This study considered all articles published in six Public Library of Science (PLOS) journals in 2012 and Web of Science citations for these articles as of May 2015. A total of 2,406 articles were ...analyzed to examine the relationships between Altmetric Attention Scores (AAS) and Web of Science citations. The AAS for an article, provided by Altmetric aggregates activities surrounding research outputs in social media (news outlet mentions, tweets, blogs, Wikipedia, etc.). Spearman correlation testing was done on all articles and articles with AAS. Further analysis compared the stratified datasets based on percentile ranks of AAS: top 50%, top 25%, top 10%, and top 1%. Comparisons across the six journals provided additional insights. The results show significant positive correlations between AAS and citations with varied strength for all articles and articles with AAS (or social media mentions), as well as for normalized AAS in the top 50%, top 25%, top 10%, and top 1% datasets. Four of the six PLOS journals, Genetics, Pathogens, Computational Biology, and Neglected Tropical Diseases, show significant positive correlations across all datasets. However, for the two journals with high impact factors, PLOS Biology and Medicine, the results are unexpected: the Medicine articles showed no significant correlations but the Biology articles tested positive for correlations with the whole dataset and the set with AAS. Both journals published substantially fewer articles than the other four journals. Further research to validate the AAS algorithm, adjust the weighting scheme, and include appropriate social media sources is needed to understand the potential uses and meaning of AAS in different contexts and its relationship to other metrics.
Although hepatitis B virus (HBV) has been documented to cause hepatocellular carcinoma (HCC), the exact role of HBV in the development of HCC remains enigmatic. Several hypotheses have been proposed ...to explain the potential mechanism, including insertional mutagenesis of HBV genomes and transcriptional activators of HBV gene products such as hepatitis B x protein (HBx) and truncated middle S mutants. In the past few years, we have identified two types of large HBV surface antigens (LHBs) with deletions at the pre‐S1 (ΔS1‐LHBs) and pre‐S2 (ΔS2‐LHBs) regions in ground glass hepatocytes. The pre‐S mutant LHBs are retained in the endoplasmic reticulum (ER) and escape from immune attack. The pre‐S mutants, particularly ΔS2‐LHBs, are increasingly prevalent in patients with hepatitis B e antigen (HBeAg)‐positive chronic HBV infection, ranging from 6% before the 3rd decade to 35% in the 6th decade. In HCC patients, the two pre‐S mutants were detected in 60% of HCC patients, in the serum and in HCC tissues. Pre‐S mutant LHBs can initiate ER stress to induce oxidative DNA damage and genomic instability. Furthermore, pre‐S mutant LHBs can upregulate cyclooxygenase‐2 and cyclin A to induce cell cycle progression and proliferation of hepatocytes. In transgenic mice, the pre‐S mutants can induce dysplasia of hepatocytes and development of HCC. In a nested control study, the presence of pre‐S mutants carried a high risk of developing HCC in HBV carriers. In summary, the findings we describe in this review suggest a potential role for HBV pre‐S mutants in HBV‐related hepatocarcinogenesis, providing a model of viral carcinogenesis associated with ER stress. (Cancer Sci 2006; 97: 683–688)
Microsatellite instability (MSI) is the primary predictive biomarker for therapeutic efficacies of cancer immunotherapies. Establishment of the MSI detection methods with high sensitivity and ...accessibility is important. Because MSI is mainly caused by defects in DNA mismatch repair (MMR), immunohistochemical (IHC) staining for the MMR proteins has been widely employed to predict the responses to immunotherapies. Thus, due to the high sensitivity of PCR, the MSI-PCR analysis has also been recommended as the primary approach as MMR IHC. This study aimed to develop a sensitive and convenient platform for daily MSI-PCR services. The routine workflow used a non-labeling QIAxcel capillary electrophoresis system which did not need the fluorescence labeling of the DNA products or usage of a multi-color fluorescence reader. Furthermore, the 15 and 1000 bp size alignment markers were used to precisely detect the size of the DNA product. A cohort of 336 CRC cases was examined by MSI-PCR on the five mononucleotide MSI markers recommended by ESMO. The PCR products were analyzed in the screening gels, followed by high-resolution gel electrophoresis for confirmation if needed. In the MSI-PCR tests, 90.1% (303/336) cases showed clear major shift patterns in the screening gels, and only 33 cases had to be re-examined using the high-resolution gels. The cohort was also analyzed by MMR IHC is, which revealed 98.5% (331/336) concordance with MSI-PCR. In the five discordant cases, 4 (3 MSI-L and 1 MSS) showed MSH6 loss. Besides, one case exhibited MSI-H but no loss in the MMR IHC. Further NGS analysis, in this case, found that missense and frameshift mutations in the PMS2 and MSH6 genes occurred, respectively. In conclusion, the non-labeling MSI-PCR capillary electrophoresis revealed high concordance with the MMR IHC analysis and is cost- and time-effective. Therefore, it shall be highly applicable in clinical laboratories.
Elevated levels of plasma free fatty acid (FFA) and disturbed mitochondrial dynamics play crucial roles in the pathogenesis of diabetic kidney disease (DKD). However, the mechanisms by which FFA ...leads to mitochondrial damage in glomerular podocytes of DKD and the effects of Berberine (BBR) on podocytes are not fully understood.
: Using the db/db diabetic mice model and cultured mouse podocytes, we investigated the molecular mechanism of FFA-induced disturbance of mitochondrial dynamics in podocytes and testified the effects of BBR on regulating mitochondrial dysfunction, podocyte apoptosis and glomerulopathy in the progression of DKD.
: Intragastric administration of BBR for 8 weeks in db/db mice significantly reversed glucose and lipid metabolism disorders, podocyte damage, basement membrane thickening, mesangial expansion and glomerulosclerosis. BBR strongly inhibited podocyte apoptosis, increased reactive oxygen species (ROS) generation, mitochondrial fragmentation and dysfunction both
and
. Mechanistically, BBR could stabilize mitochondrial morphology in podocytes via abolishing palmitic acid (PA)-induced activation of dynamin-related protein 1 (Drp1).
: Our study demonstrated for the first time that BBR may have a previously unrecognized role in protecting glomerulus and podocytes via positively regulating Drp1-mediated mitochondrial dynamics. It might serve as a novel therapeutic drug for the treatment of DKD.
Depression is a global health problem with growing prevalence rates and serious impacts on the daily life of patients. However, the side effects of currently used antidepressants greatly reduce the ...compliance of patients. Quercetin is a flavonol present in fruits, vegetables, and Traditional Chinese medicine (TCM) that has been proved to have various pharmacological effects such as anti-depressant, anti-cancer, antibacterial, antioxidant, anti-inflammatory, and neuroprotective. This review summarizes the evidence for the pharmacological application of quercetin to treat depression. We clarified the mechanisms of quercetin regulating the levels of neurotransmitters, promoting the regeneration of hippocampal neurons, improving hypothalamic-pituitary-adrenal (HPA) axis dysfunction, and reducing inflammatory states and anti-oxidative stress. We also summarized the antidepressant effects of some quercetin glycoside derivatives to provide a reference for further research and clinical application.
Abstract Over the past decade, learning engagement has received increasing attention from researchers. As a critical factor in college students’ academic achievement, learning engagement is ...significant in students’ long-term future development and social creativity. Present studies show that the overall level of college students’ learning engagement is low, which is highly unfavourable to educational quality and long-term development. There is no doubt about the position of the university library in academic circles. However, the influence of the university library environment on college students’ learning engagement has not been fully explored. The data in this study came from a survey of 45 Chinese universities. This paper investigates the relationship between the university library environment, students’ interaction, and students’ learning engagement. The results showed differences in Chinese college students’ learning engagement in liberal arts and sciences majors. The learning engagement of liberal arts majors is much lower than that of science students. We found that the library environment has an important influence on college students’ learning engagement. And the library environment can affect college students’ learning engagement through the intermediary role of interactive participation among students. In addition, for liberal arts students, the direct effect of the library environment on their learning engagement is more significant. However, for science students, the influence of the library environment on their learning engagement is more strongly intermediated by the students’ interaction. Therefore, future construction and renovation of library environments should cater not only to the diverse needs of different academic disciplines, especially liberal arts students who need special attention but also guide more students to interact friendly through the spatial characteristics of the library so as to improve the overall learning engagement of college students.
The incidence of diabetes mellitus (DM) and depression is increasing year by year around the world, bringing a serious burden to patients and their families. Jiao-tai-wan (JTW), a well-known ...traditional Chinese medicine (TCM), has been approved to have hypoglycemic and antidepressant effects, respectively, but whether JTW has such dual effects and its potential mechanisms is still unknown. This study is to evaluate the dual therapeutic effects of JTW on chronic restraint stress (CRS)-induced DM combined with depression mice, and to explore the underlying mechanisms through network pharmacology.
CRS was used on db/db mice for 21 days to induce depression-like behaviors, so as to obtain the DM combined with depression mouse model. Mice were treated with 0.9% saline (0.1 ml/10 g), JTW (3.2 mg/kg) and Fluoxetine (2.0 mg/kg), respectively. The effect of JTW was accessed by measuring fasting blood glucose (FBG) levels, conducting behavioral tests and observing histopathological change. The ELISA assay was used to evaluate the levels of inflammatory cytokines and the UHPLC-MS/MS method was used to determine the depression-related neurotransmitters levels in serum. The mechanism exploration of JTW against DM and depression were performed via a network pharmacological method.
The results of blood glucose measurement showed that JTW has a therapeutic effect on db/db mice. Behavioral tests and the levels of depression-related neurotransmitters proved that JTW can effectively ameliorate depression-like symptoms in mice induced by CRS. In addition, JTW can also improve the inflammatory state and reduce the number of apoptotic cells in the hippocampus. According to network pharmacology, 28 active compounds and 484 corresponding targets of JTW, 1407 DM targets and 1842 depression targets were collected by screening the databases, and a total of 117 targets were obtained after taking the intersection. JTW plays a role in reducing blood glucose level and antidepressant mainly through active compounds such as quercetin, styrene, cinnamic acid, ethyl cinnamate, (R)-Canadine, palmatine and berberine, etc., the key targets of its therapeutic effect include INS, AKT1, IL-6, VEGF-A, TNF and so on, mainly involved in HIF-1 signal pathway, pathways in cancer, Hepatitis B, TNF signal pathway, PI3K-Akt signal pathway and MAPK signaling pathway, etc. CONCLUSION: Our experimental study showed that JTW has hypoglycemic and antidepressant effects. The possible mechanism was explored by network pharmacology, reflecting the characteristics of multi-component, multi-target and multi-pathway, which provides a theoretical basis for the experimental research and clinical application of JTW in the future.
Adenosine 2A receptor (A2AR) exerts protective roles in endotoxin‐ and/or ischemia‐induced tissue damage. However, the role for A2AR in nonalcoholic fatty liver disease (NAFLD) remains largely ...unknown. We sought to examine the effects of global and/or myeloid cell‐specific A2AR disruption on the aspects of obesity‐associated NAFLD and to elucidate the underlying mechanisms. Global and/or myeloid cell–specific A2AR‐disrupted mice and control mice were fed a high‐fat diet (HFD) to induce NAFLD. In addition, bone marrow–derived macrophages and primary mouse hepatocytes were examined for inflammatory and metabolic responses. Upon feeding an HFD, both global A2AR‐disrupted mice and myeloid cell–specific A2AR‐defcient mice revealed increased severity of HFD‐induced hepatic steatosis and inflammation compared with their respective control mice. In in vitro experiments, A2AR‐deficient macrophages exhibited increased proinflammatory responses, and enhanced fat deposition of wild‐type primary hepatocytes in macrophage–hepatocyte cocultures. In primary hepatocytes, A2AR deficiency increased the proinflammatory responses and enhanced the effect of palmitate on stimulating fat deposition. Moreover, A2AR deficiency significantly increased the abundance of sterol regulatory element‐binding protein 1c (SREBP1c) in livers of fasted mice and in hepatocytes upon nutrient deprivation. In the absence of A2AR, SREBP1c transcription activity was significantly increased in mouse hepatocytes. Conclusion: Taken together, our results demonstrate that disruption of A2AR in both macrophage and hepatocytes accounts for increased severity of NAFLD, likely through increasing inflammation and through elevating lipogenic events due to stimulation of SREBP1c expression and transcription activity. (Hepatology 2018;68:48‐61).
Jiao-tai-wan (JTW) has been often used to treat insomnia and diabetes mellitus. Recent studies found its antidepressant activity, but the related mechanism is not clear. This study is to evaluate the ...therapeutic effects of JTW on chronic restraint stress (CRS)-induced depression mice and explore the potential mechanisms.
CRS was used to set up a depression model. Mice in different groups were treated with 0.9 % saline, JTW and fluoxetine. After the last day of CRS, the behavioral tests were conducted. The levels of neurotransmitters, inflammatory cytokines and HPA axis index were detected and the protein expressions of NLRP3 inflammasome complex were determined. H&E, NISSL, TUNEL and immunofluorescence staining were used to observe histopathological changes and the activation of microglia and astrocytes. The potential mechanisms were explored via network pharmacology and verified by Western blot.
The assessment of liver and kidney function showed that JTW was non-toxic. Behavioral tests proved that JTW can effectively ameliorate depression-like symptoms in CRS mice, which may be related to the inhibition of NLRP3 inflammasome activation. JTW can also improve the inflammatory state and HPA axis hyperactivity in mice, and has a protective effect on CRS-induced hippocampal neurons damage. The network pharmacology analysis and the results of Western blot suggested that the antidepressant effects of JTW may be related to the MAPK signaling pathway.
Our findings indicated that JTW may exert antidepressant effects in CRS-induced mice by inhibiting NLRP3 inflammasome activation and improving inflammatory state, and MAPK signaling pathway may also be involved.
•Jiao-tai-wan can effectively ameliorate depression-like behaviors induced by chronic restraint stress.•Jiao-tai-wan has a protective effect on chronic restraint stress-induced hippocampal neurons damage.•The antidepressant effects of Jiao-tai-wan may be related to the MAPK signaling pathway.
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