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Dencker Hill opublikował 1 rok, 8 miesięcy temu
© The author(s).Syndecan-4 is a member of the polysaccharide syndecan family and plays a vital role in intervertebral disc development. Several studies have demonstrated the positive relationship between syndecan-4 expression and intervertebral disc degeneration. However, the detailed molecular mechanism by which syndecan-4 affects the degeneration of nucleus pulposus cells (NPCs) remains unclear. In this study, cell viability was determined by CCK-8 assay, mRNA level was determined by qPCR, and protein expression was determined by western blot. Molecular interaction was determined by chromatin immunoprecipitation assay. A rabbit intervertebral disc degeneration model was established to test for syndecan in vivo. We found that the morphology and viability of NPCs were not affected by the expression of syndecan-4 in the long term. While the NPC function were affected, which results in the degeneration of intervertebral disc. Syndecan-4 overexpression promoted the degeneration of NPCs. Syndecan-4 also activated the JNK signaling pathway and downstream p53 pathways, and promoted degeneration. Inhibition of the JNK pathway, which down-regulated p53 expression, alleviated the degeneration. In an in vivo study, syndecan-4 siRNA injection stopped the development of rabbit disc degeneration, and even created a reverse effect, in which JNK/p53 played a role. Syndecan-4 may be a novel therapeutic target for intervertebral disc degeneration via suppressing the JNK/p53 pathway. © The author(s).Acetaminophen (APAP) refers to a medication used to manage pain and fever symptoms, but it always causes liver injury when overdosed. Zhishi, dried young fruit of Citrus aurantium L., is a famous Citrus herbal medicine in Asian countries which is rich in dietary phenolic substances. In this study, the mechanism of Zhishi protected against APAP-induced liver injury was studied more deeply by metabolomic strategy and pharmacological study. The metabolomics results demonstrated that Zhishi can prevent the APAP-induced liver injury model by regulating liver metabolic disorders in glycerophospholipid metabolism, fatty acid biosynthesis and glycerolipid metabolism. Moreover, it is confirmed that Zhishi blocked apoptosis of APAP-induced BRL-3A cell by simultaneously regulating p53 up-regulated apoptosis regulator (PUMA), AMPK-SIRT1 and JNK1 signaling pathways. Our findings indicated that Zhishi exhibited a hepaprotective effect against APAP-induced liver necrosis by inhibiting the PUMA and reversing disorder of liver lipid metabolism which could assist in improving the clinical outcomes of chemical-induced liver injury. © The author(s).The highly conserved protease TASP1 not only takes part in critical site-specific proteolysis, but also plays an important role in numerous liquid and solid malignancies. However, the TASP1 expression and its biological regulation function in malignant gallbladder carcinoma (GBC) remain fully unknown. Here we observed that TASP1 levels were substantially overexpressed in GBC samples compared with non-tumor tissues. High TASP1 level was closely associated with T stage and metastasis, and was also correlated with poor prognosis in GBC patients. The depletion of TASP1 inhibited GBC cell proliferation and metastasis in vitro and in vivo. Furthermore, we first revealed that FAM49B had biological function and was positively regulated by TASP1 activating PI3K/AKT signaling pathway in GBC. At the same time, FAM49B also promoted GBC cell proliferation and migration. Inhibition of PI3K/AKT with LY294002 or FAM49B expression abrogated Myc-TASP1/Lv-shTASP1-induced GBC cell proliferation and motility. In conclusion, these findings demonstrate that TASP1 is critical for GBC progression via TASP1-PI3K/AKT-FAM49B axis and it may be a novel prognostic factor. The therapeutic targeting TASP1 may be a potential treatment approach for GBC patients. © The author(s).The Wnt signaling pathway plays important roles in organ development and disease processes. Secreted frizzled-related protein 2 (sFRP2), a vital molecule of Wnt signaling, can regulate cardiac development and cardiovascular disease. Recent studies have suggested that sFRP2 is not only an antagonist of the canonical Wnt signaling pathway, but also has a more complex relationship in myocardial fibrosis, angiogenesis, cardiac hypertrophy and cardiac regeneration. Here, we review the role of sFRP2 and Wnt signaling in cardiac development and cardiovascular disease. © The author(s).Snakebite envenomation is a serious public health concern in rural areas of Uganda. Snakebites are poorly documented in Uganda because most occur in rural settings where traditional therapists end up being the first-line defense for treatment. Ethnobotanical surveys in Uganda have reported that some plants are used to antagonize the activity of various snake venoms. This review was sought to identify antivenin plants in Uganda and some pharmacological evidence supporting their use. A literature survey done in multidisciplinary databases revealed that 77 plant species belonging to 65 genera and 42 families are used for the treatment of snakebites in Uganda. The majority of these species belong to family Fabaceae (31%), Euphorbiaceae (14%), Asteraceae (12%), Amaryllidaceae (10%) and Solanaceae (10%). The main growth habit of the species is shrubs (41%), trees (33%) and herbs (18%). Antivenin extracts are usually prepared from roots (54%) and leaves (23%) through decoctions, infusions, powders, and juices, and are administered orally (67%) or applied topically (17%). The most frequently encountered species were Allium cepa, Carica papaya, Securidaca longipedunculata, Harrisonia abyssinica, and Nicotiana tabacum. Species with global reports of tested antivenom activity included Allium cepa, Allium sativum, Basella alba, Capparis tomentosa, Carica papaya, Cassia occidentalis, Jatropa carcus, Vernonia cinereal, Bidens pilosa, Hoslundia opposita, Maytensus senegalensis, Securinega virosa, and Solanum incanum. There is need to identify and evaluate the antivenom compounds in the claimed plants. © The Author(s) 2020.Objective To determine the relationship between blood serum lipophilic antioxidant levels and cognitive function (CF) in older adults aged 60 and above guided by the oxidative stress theory of aging. Methods Cross-sectional data from the National Health and Nutrition Examination Survey (n = 291) for older adults aged 60 and above were examined using Pearson correlation coefficient and multiple linear regression to determine whether blood serum antioxidant status predicted CF while controlling for age, sex, race, hypertension, smoking status, and body mass index. Results Alpha-tocopherol, retinyl palmitate, trans-lycopene, and retinyl stearate were all significantly correlated with CF. After controlling for covariates, α-tocopherol and retinyl palmitate were associated with CF. Age, sex, and current smoking status were significant predictors of CF. Conclusions The benefits of antioxidants in CF may be a part of nutritional recommendations which include α-tocopherol and retinyl palmitate for delay of CI, and subsequently a better quality of life. © The Author(s) 2020.Recovery and long-term remission are the goals of treatment for substance use disorders, yet the majority of treated adolescents never stop using or resume using substances quickly after treatment. Thus, continuing care or recovery support services are common post-treatment recommendations for this group. Almost half of people who resolved significant substance use problems did so through participation in 12-step programs like Alcoholics Anonymous or Narcotics Anonymous. These recovery support programs are available online and in communities around the world. Yet less then 2% of these programs’ members are under 21 years old. To help clinicians understand the 12-step explanatory model and facilitate clinical decision making on whether or when to refer individuals to these groups, this article summarizes the 12-step philosophy and practices and provides a concise review of research on adolescents’ involvement in 12-step groups, including qualitative work that illuminates adolescents’ reasons for resisting or engaging in 12-step practices. © The Author(s) 2020.Background Treatment demand for cannabis use disorders is increasing in Europe. Mobile phone- and internet-based interventions for cannabis users can possibly help meet the need. The purpose of this study was to examine whether a recently developed Norwegian Cannabis Cessation app reaches a broader or different user group compared to community-based Cannabis Cessation programs (CCP, Nordic abbreviation HAP). Method The app respondents (n = 148) were recruited through an online link in the app. A comparative sample (n = 102) was recruited in three municipally based CCPs in Norway. We examined whether app users differed from the CCP population in sociodemographics, substance use, mental health, and well-being. Result The app group included more women than the CCP group (46% versus 26%, χ2 = 10.9, P = .001), but otherwise the groups were similar for sociodemographic variables. Severity of cannabis use did not differ between groups, but the app sample exhibited a higher depressiveness score on the Hopkins Symptom Checklist (mean difference, 0.24; 95% CI 0.04-0.44; P = .018) and lower perceived well-being (3.4 point lower score on the Outcome Rating Scale; 95% CI -5.7 to -1.2; P = .003). Well-being was negatively associated with being in the app group, being older, and having higher levels of mental distress, and was positively associated with the perceived ability to make changes (’self-efficacy of quitting’). Conclusion The higher proportion of women in the app group indicated that the app did capture an expanded segment of the cannabis-using population. The app can be an alternative for those who are not yet prepared to seek treatment in formal healthcare services. The high level of depressive symptoms and lower levels of well-being among the app respondents suggest that some app users might need additional support. © The Author(s) 2020.Aim This study aimed to analyze the primary stability of dental implant in maxillary and mandibular anterior and posterior regions using a finite element analysis. Materials and methods CBCT images of maxillary and mandibular regions were collected from patients’ radiographic data and transformed to 3D models. A Straumann Dental implant was inserted in each bone model and then pulled-out, where amount von-Mises stress was obtained and analyzed for each. A comparison between the insertion and the pull-out was evaluated. Results Twenty-four images were randomly selected for analysis from 122 scans. In both the insertion and the pull-out of the dental implant, von-Mises stress was high in cortical as compared to the cancellous bone (p less then 0.0001). Maxillary posterior region had a low von-Mises stress (p less then 0.001). Bone plastic deformation was higher in cancellous than the cortical bone in all bone regions and was the lowest in maxillary posterior region (p less then 0.001). Bone displacement decreased from Type I to type IV bone. Conclusion Evaluation of von-Mises stress showed different measurements in maxillary and mandibular regions. Bone deformation was low in the maxillary posterior region. © 2019 The Authors.


