IL-6 regulates epithelial ovarian cancer EMT, invasion, and metastasis by modulating Let-7c and miR-200c through the STAT3/HIF-1α pathway.

Interleukin-6 (IL-6) and hypoxia-inducible factor-1α (HIF-1α) play important roles in epithelial-mesenchymal transformation (EMT) and tumor development. Previous studies have demonstrated that IL-6 promotes EMT, invasion, and metastasis in epithelial ovarian cancer (EOC) cells by activating the STAT3/HIF-1α pathway. MicroRNA (miRNA) is non-coding small RNAs that also play an important role in tumor development. Notably, Let-7 and miR-200 families are prominently altered in EOC. However, whether IL-6 regulates the expression of Let-7 and miR-200 families through the STAT3/HIF-1α signaling to induce EMT in EOC remains poorly understood. In this study, we conducted in vitro and in vivo investigations using two EOC cell lines, SKOV3, and OVCAR3 cells. Our findings demonstrate that IL-6 down-regulates the mRNA levels of Let-7c and miR-200c while up-regulating their target genes HMGA2 and ZEB1 through the STAT3/HIF-1α signaling in EOC cells and in vivo. Additionally, to explore the regulatory role of HIF-1α on miRNAs, both exogenous HIF blockers YC-1 and endogenous high expression or inhibition of HIF-1α can be utilized. Both approaches can confirm that the downstream molecule HIF-1α inhibits the expression and function of Let-7c and miR-200c. Further mechanistic research revealed that the overexpression of Let-7c or miR-200c can reverse the malignant evolution of EOC cells induced by IL-6, including EMT, invasion, and metastasis. Consequently, our results suggest that IL-6 regulates the expression of Let-7c and miR-200c through the STAT3/HIF-1α pathway, thereby promoting EMT, invasion, and metastasis in EOC cells.

Excitatory neurons in the lateral parabrachial nucleus mediate the interruptive effect of inflammatory pain on a sustained attention task.

BACKGROUND: Attentional deficits are among the most common pain-induced cognitive disorders. Pain disrupts attention and may excessively occupy attentional resources in pathological states, leading to daily function impairment and increased disability. However, the neural circuit mechanisms by which pain disrupts attention are incompletely understood. METHODS: We used a three-choice serial reaction time task (3CSRTT) to construct a sustained-attention task model in male C57BL/6J mice. Formalin or complete Freund's adjuvant was injected into a paw to establish an inflammatory pain model. We measured changes in 3CSRTT performance in the two inflammatory pain models, and investigated the neural circuit mechanisms of pain-induced attentional deficits. RESULTS: Acute inflammatory pain impaired 3CSRTT performance, while chronic inflammatory pain had no effect. Either inhibition of the ascending pain pathway by blockade of the conduction of nociceptive signals in the sciatic nerve using the local anesthetic lidocaine or chemogenetic inhibition of Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) neurons in the lateral parabrachial nucleus (LPBN) attenuated the acute inflammatory pain-induced impairment of 3CSRTT performance, while chemogenetic activation of CaMKIIα neurons in the LPBN disrupted the 3CSRTT. Furthermore, the activity of CaMKIIα neurons in the LPBN was significantly lower on Day 2 after complete Freund's adjuvant injection than on the day of injection, which correlated with the recovery of 3CSRTT performance during chronic inflammatory pain. CONCLUSIONS: Activation of excitatory neurons in the LPBN is a mechanism by which acute inflammatory pain disrupts sustained attention. This finding has implications for the treatment of pain and its cognitive comorbidities.

Heat shock protein: a double-edged sword linking innate immunity and hepatitis B virus infection.

Heat shock proteins (HSPs), which have a variety of functions, are one of the stress protein families. In recent years, They have been reported to play a dual role in hepatitis B virus (HBV) which as persistent infection which is associated with, cirrhosis and liver cancer. In this article, we have summarized the regulatory mechanisms between HSPs and viruses, especially HBV and associated diseases based on HSP biological functions of in response to viral infections. In view of their potential as broad-spectrum antiviral targets, we have also discuss current progress and challenges in drug development based on HSPs, as well as the potential applications of agents that have been evaluated clinically in HBV treatment.

Folic acid: a potential inhibitor against SARS-CoV-2 nucleocapsid protein.

CONTEXT: Coronavirus disease 2019 is a global pandemic. Studies suggest that folic acid has antiviral effects. Molecular docking shown that folic acid can act on SARS-CoV-2 Nucleocapsid Phosphoprotein (SARS-CoV-2 N). OBJECTIVE: To identify novel molecular therapeutic targets for SARS-CoV-2. MATERIALS AND METHODS: Traditional Chinese medicine targets and virus-related genes were identified with network pharmacology and big data analysis. Folic acid was singled out by molecular docking, and its potential target SARS-CoV-2 N was identified. Inhibition of SARS-CoV-2 N of folic acid was verified at the cellular level. RESULTS: In total, 8355 drug targets were potentially involved in the inhibition of SARS-CoV-2. 113 hub genes were screened by further association analysis between targets and virus-related genes. The hub genes related compounds were analysed and folic acid was screened as a potential new drug. Moreover, molecular docking showed folic acid could target on SARS-CoV-2 N which inhibits host RNA interference (RNAi). Therefore, this study was based on RNAi to verify whether folic acid antagonises SARS-CoV-2 N. Cell-based experiments shown that RNAi decreased mCherry expression by 81.7% (p < 0.001). This effect was decreased by 8.0% in the presence of SARS-CoV-2 N, indicating that SARS-CoV-2 N inhibits RNAi. With increasing of folic acid concentration, mCherry expression decreased, indicating that folic acid antagonises the regulatory effect of SARS-CoV-2 N on host RNAi. DISCUSSION AND CONCLUSIONS: Folic acid may be an antagonist of SARS-CoV-2 N, but its effect on viruses unclear. In future, the mechanisms of action of folic acid against SARS-CoV-2 N should be studied.

Long Non-coding RNA and mRNA Expression Change in Spinal Dorsal Horn After Exercise in Neuropathic Pain Rats.

Exercise can help inhibition of neuropathic pain (NP), but the related mechanism remains being explored. In this research, we performed the effect of swimming exercise on the chronic constriction injury (CCI) rats. Compared with CCI group, the mechanical withdrawal threshold of rats in the CCI-Swim group significantly increased on the 21st and 28th day after CCI surgery. Second-generation RNA-sequencing technology was employed to investigate the transcriptomes of spinal dorsal horns in the Sham, CCI, and CCI-Swim groups. On the 28th day post-operation, 306 intersecting long non-coding RNAs (lncRNAs) and 173 intersecting mRNAs were observed between the CCI vs Sham group and CCI-Swim vs CCI groups. Then, the biological functions of lncRNAs and mRNAs in the spinal dorsal horn of CCI rats were then analyzed. Taking the results together, this study could provide a novel perspective for the treatment for NP.

Crosstalk Between MicroRNAs and Circular RNAs in Human Diseases: A Bibliographic Study.

Background: Crosstalk of circular RNAs (circRNAs) and microRNAs (miRNAs) refers to the communication and co-regulation between them. circRNAs can act as miRNAs sponges, and miRNAs can mediate circRNAs. They interact to regulate gene expression and participate in the occurrence and development of various human diseases. Methods: Publications on the crosstalk between miRNAs and circRNAs in human diseases were collected from Web of Science. The collected material was limited to English articles and reviews. CiteSpace and Microsoft Excel were used for bibliographic analysis. Results: A total of 1,013 papers satisfied the inclusion criteria. The publication outputs and types of researched diseases were analyzed, and bibliographic analysis was used to characterize the most active journals, countries, institutions, keywords, and references. The annual number of publications remarkably increased from 2011 to 2020. Neoplasm was the main research hotspot (n = 750 publications), and Biochemical and Biophysical Research Communications published the largest number of papers (n = 64) on this topic. Nanjing Medical University ranked first among institutions actively engaged in this field by publishing 72 papers, and China contributed 96.84% of the 1,013 papers (n = 981 publications) analyzed. Burst keywords in recent years included glioblastoma, miR-7, skeletal muscle, and non-coding RNA. Conclusion: Crosstalk between miRNAs and circRNAs in human diseases is a popular research topic. This study provides important clues on research trends and frontiers.

Interactions Among lncRNA/circRNA, miRNA, and mRNA in Musculoskeletal Degenerative Diseases.

Musculoskeletal degenerative diseases (MSDDs) are pathological conditions that affect muscle, bone, cartilage, joint and connective tissue, leading to physical and functional impairments in patients, mainly consist of osteoarthritis (OA), intervertebral disc degeneration (IDD), rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are novel regulators of gene expression that play an important role in biological regulation, involving in chondrocyte proliferation and apoptosis, extracellular matrix degradation and peripheral blood mononuclear cell inflammation. Research on MSDD pathogenesis, especially on RA and AS, is still in its infancy and major knowledge gaps remain to be filled. The effects of lncRNA/circRNA-miRNA-mRNA axis on MSDD progression help us to fully understand their contribution to the dynamic cellular processes, provide the potential OA, IDD, RA and AS therapeutic strategies. Further studies are needed to explore the mutual regulatory mechanisms between lncRNA/circRNA regulation and effective therapeutic interventions in the pathology of MSDD.

Bibliometric Analysis of Studies on Neuropathic Pain Associated With Depression or Anxiety Published From 2000 to 2020.

Objective: Neuropathic pain (NP) associated with depression or anxiety is highly prevalent in clinical practice. Publications about NP associated with depression or anxiety increased exponentially from 2000 to 2020. However, studies that applied the bibliometric method in analyzing global scientific research about NP associated with depression or anxiety are rare. This work used the bibliometric method to analyze the publications on NP associated with depression or anxiety between 2000 and 2020. Method: Publications from 2000 and 2020 were identified from the Thomson Reuters Web of Science (WoS) database. We employed CiteSpace V to conduct the bibliometric study. Results: A total of 915 articles or reviews were obtained from the WoS database. The number of publications has increased over the last two decades. The USA was the most productive among countries or regions in the field. According to the burst key words, neuroinflammation, hippocampus, safety, and modulation were the hot global research issues in the domain. Conclusion: Publications about NP associated with depression or anxiety have remarkably increased from 2000 to 2020. These historical opinions about NP associated with depression or anxiety could be an important practical basis for further research into potential development trends.

[Effects of polystyrene microplastics (PS-MPs) on the growth, physiology, and biochemical characteristics of Hydrilla verticillata]. / 聚苯乙烯微塑料对黑藻生长及生理生化特征的影响.

In order to evaluate the effects of polystyrene microplastics (PS-MPs) on the growth, physiology, and biochemical characteristics of submerged plants, we exposed a typical submerged plant, Hydrilla verticillata, to a series of concentrations (i.e. 0, 5, 10, 30, 50, 100 mg·L-1) of 3 µm polystyrene microplastics (PS-MPs) and measured parameters including height, biomass, chlorophyll content, antioxidant enzyme activity, photosynthetic fluorescence. The results showed that the height of H. Verticillata significantly decreased at the high PS-MP concentrations (50 to 100 mg·L-1), while the fresh weight significantly increased at the low PS-MP concentration (5 mg·L-1). The fresh weight of H. verticillata gradually decreased with the increasing PS-MP concentration but the dry weight did not change. The total amount of chlorophyll, chlorophyll a, and chlorophyll a/b significantly decreased with the increases of the PS-MP concentrations, while the chlorophyll b did not change. PS-MPs affected the antioxidant enzyme activities of H. verticillata. The activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were first increased and then decreased with the increasing PS-MP concentration. The chlorophyll fluorescence parameters (Fo, Fm, Fv/Fm) decreased with the increasing concentration of PS-MP and the 1-Qp-Lss value (reflective of the closing of PSⅡ reaction center) was increased under the stable state, probably due to the inhibited PSⅡ reaction center. The overall intensity of fluorescence imaging of H. verticillata decreased with the increasing concentration of PS-MPs. When the PS-MP concentration was lower than 10 mg·L-1, the photosynthetic activity of the leaves was normal. In contrast, when the PS-MP concentration was higher than 30 mg·L-1, it caused significant adverse effects on leaves, including weaker photosynthetic intensity and the presence of yellow or withered leaves. Our results suggested that H. verticillata could tolerate PS-MP pollution but its growth and photosynthesis would be inhibited at high concentrations (>30 mg·L-1). Our results provided basic information to better understand the eco-physiological effects of PS-MPs in the freshwater environment.

microRNA-Based Network and Pathway Analysis for Neuropathic Pain in Rodent Models.

Neuropathic pain (NP) is poorly managed, and in-depth mechanisms of gene transcriptome alterations in NP pathogenesis are not yet fully understood. To determine microRNA-related molecular mechanisms of NP and their transcriptional regulation in NP, PubMed, Embase, Web of Science and CINAHL Complete (EBSCO) were searched from inception to April 2021. Commonly dysregulated miRNAs in NP were assessed. The putative targets of these miRNAs were determined using TargetScan, Funrich, Cytoscape and String database. A total of 133 literatures containing miRNA profiles studies and experimentally verify studies were included. Venn analysis, target gene prediction analysis and functional enrichment analysis indicated several miRNAs (miR-200b-3p, miR-96, miR-182, miR-183, miR-30b, miR-155 and miR-145) and their target genes involved in known relevant pathways for NP. Targets on transient receptor potential channels, voltage-gated sodium channels and voltage-gated calcium channels may be harnessed for pain relief. A further delineation of signal processing and modulation in neuronal ensembles is key to achieving therapeutic success in future studies.

[Roles of autophagy onself-renewal and differentiation of mesenchymal stem cells].

Mesenchymal stem cells (MSCs), which have the potential of self-replication and differentiation, are a very valuable cell source for stem cell-based medical therapy. Their application has opened up a new way for disease research. Although MSCs can maintain cell stemness through self-renewal, with the prolongation of cell passage and culture time, the stemness of MSCs gradually decays, and the cell aging and differentiation potential decreases gradually. Autophagy is a highly conserved cytological process that degrades the modified, excess, and deleterious cytoplasmic components in autophagosomes, which are then degraded by fusion with lysosomes. As the main intracellular degradation and recycling pathway, autophagy plays an active role in maintaining cell homeostasis, self-renewal and pluripotency. In this paper, the role of autophagy in self-renewal and maintenance of multidirectional differentiation potential of MSCs was reviewed, which laid a theoretical foundation and practical basis for the research and application of MSCs.

Bibliometric Analysis of Exercise and Neuropathic Pain Research.

BACKGROUND: Neuropathic pain, a type of chronic pain, is difficult to treat clinically. Mounting evidence suggests that exercise can effectively ease neuropathic pain, and the number of publications related to exercise and neuropathic pain has increased over time. However, bibliometrics is rarely used in analyzing the general aspects of studies on exercise and neuropathic pain. The present study aims to provide a systematic overview of global scientific research related to exercise and neuropathic pain from 2005 to 2019. METHODS: Publications on Science Citation Index - Expanded of Web of Science from 2005 to 2019 were searched, and those related to exercise and neuropathic pain were analyzed. Only English papers were included without specific species restrictions. RESULTS: A total of 676 papers were included in accordance with our adopted criteria. Linear regression analysis showed a statistically meaningful increase in the number of publications on exercise and neuropathic pain study over time (p< 0.001). The subject categories of the 676 papers mainly focused on neuroscience (29.88%), clinical neurology (18.79%) and rehabilitation (10.06%) in Web of Science. In terms of contribution to scientific research on exercise and neuropathic pain, the United States led the first echelon and had the largest numbers of published papers, citations and H-index. CONCLUSION: The findings in our study may provide researchers useful information about research trends and frontiers, cooperators and cooperative institutions.

[Correlation Between Nursing Work Environment and Nurse Burnout, Job Satisfaction, and Turnover Intention in the Western Region of Mainland China].

BACKGROUND: Nurse burnout and low job satisfaction are main reasons that cause nurses to leave their current position. Improving the nursing work environment may reduce the severity of job burnout and of job dissatisfaction and thus decrease the turnover intention of nursing staff. PURPOSE: The aim of this study was to explore the correlation between the nursing work environment and the outcome variables of burnout, job satisfaction, and turnover intention in the western region of Mainland China. METHODS: This is a cross-sectional descriptive study. Survey data were collected between February and December 2012 from 1,112 clinical nurses working at 83 medical, surgical, and intensive care units in 20 hospitals across the western region of Mainland China. Multistage sampling was conducted on some of the participants. The research instruments that were used included the Practice Environment Scale of the Nursing Work Index, Maslach Burnout Inventory, Nurse Job Satisfaction Scale, and the self-developed basic information and turnover intention questionnaire. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 19.0. The level of statistical significance was set at p<.05. RESULTS: Among the five dimensions of the nursing work environment, collegial nurse-physician relations earned the most favorable mean scores (3.57±0.68; total=4 points), whereas adequacy of staffing and resources earned the lowest (3.21±0.82). Over half of the participants (58.4%) reported experiencing a high level of emotional exhaustion (EE) burnout, 45.2% reported experiencing a high level of depersonalization (DP) burnout, and 24.6% reported experiencing a high level of personal accomplishment (PA) burnout. About 59% of the participants were satisfied with their work and 3.8% reported intention to leave. Participants in self-reported "favorable" work environments were less likely to report high burnout, less likely to report intention to leave, and more likely to report job satisfaction than their peers in self-reported "poor" work environments. The odds ratio (OR) values were 0.64 (EE), 0.66 (DP), 0.57 (PA), 0.19, and 2.26. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results of the present study support that the nursing work environment affects nurse burnout, job satisfaction, and turnover intention. Therefore, nursing managers should work to improve nursing work environments in order to reduce the turnover intent among their nursing staff.