bluuebunny/crossref_metadata_2025 huggingface dataset:
Population status and feeding ecology of common bushbuck (Tragelaphus scriptus) in Moledo Forest, west Gojjam, Ethiopia
Authors: Sinshaw Aynalem , Tamene Mesele
Published: May 2020

Background Common Bushbuck (Tragelaphus scriptus) is one of the most widely distributed antelope species in African continent and use a wide variety of habitat types. A study on population status and feeding ecology of common bushbuck in Moledo Forest, West Gojjam, Ethiopia was carried out from September 2017 to August 2018 during wet and dry seasons. Data were collected using total count method and focal sampling technique. Then, the collected data were analyzed using descriptive statistics and compared with t-test for population status and percentage contribution of food items. Plant species consumed were compared with Chi-square test between seasons.Results The result indicated that the total numbers of bushbuck population were 18 and 28 during dry and wet seasons, respectively. There was a significant difference (t = 0.61, df = 4, p < 0.05) in bushbuck population during both seasons. Sex ratio of adult male to adult female was1.4:1. On the other hand, 20 plant species belonging to 11 families were recorded as food for study animal. Food items were significantly differed between seasons ({{\chi }}^{2}= 930.88, df = 1, p < 0.05). Their food items mainly constituted 50% shrub, 30% herb and 20% tree. Young leaves contributed to 40% of their diet followed by mature leaves 26%. On the other hand, flowers contributed the least (6%) for their diet. There was a significant variation ( {{\chi }}^{2} = 98, df = 10, p < 0.05) in parts of plant consumed by common bushbuck in the study area.Conclusion There are some threats associated with common bushbuck in the study area such as livestock grazing, habitat encroachment, fire wood collection, predation and hunting. Therefore, immediate attention needs to be paid to conserve the study animal in particular and other wildlife in general.
Train-the-Trainer Course for General Practitioners Identified Salient Points for Promoting Healthy Ageing – A Convergent Mixed-Methods Study
Authors: Yang Daya , Yuan Gang , Tang Hao , Hill Anne-Marie , Chen Wei , Wang Jingsong , Kuang Ming , Xiao Haipeng , Xu Dan
Published: May 2020

Background General practitioners (GPs) in China are playing an increasingly important role in geriatric care. In the context of GP training in geriatrics, the current study sought to explore the perception of local GP trainers regarding how GP training can better serve the purpose of healthy ageing promotion.Methods In this convergent mixed-methods design study, a convenience sample of local senior GP trainers were enrolled in a Train-the-Trainer (TTT) course in Guangzhou China. A series of lectures was conducted and followed by individual surveys via an on-line platform at the end of the course with participants providing quantitative and qualitative feedback. Course satisfaction ratings and salient points with respect to the gaps and needs for GP trainers were recorded regarding healthy ageing promotion.Results Participants (n=20) reported high levels of overall satisfaction with the course (91.3%), and rated the course as relevant (97.5%) and contemporary (up-to-date) (96.7%).Six geriatric-related topics were presented: (1) polypharmacy and de-prescribing, (2) dementia, (3) antibiotic stewardship, (4) fall prevention and frailty assessment, (5) vaccination, (6) atrial fibrillation. Participants identified salient points for inclusion into GP training programs in each topic. These salient learning points were categorized into personal, interpersonal, and societal domains. Conclusions The TTT course for GP trainers provided an excellent platform for academic exchange regarding healthy ageing promotion. Salient points identified from course feedback may inform future training, research and collaboration initiatives for GPs' roles as health advocate for the older adult population.
Undiagnosed Depression among Hypertensive Individuals in Gaza: A Cross-sectional Survey from Palestine
Authors: Khadoura Khalid Jamal , Shakibazadeh Elham , Mansournia Mohammad Ali , Aljeesh Yousef , Fotouhi Akbar
Published: May 2020

Background

The aim of this study was to estimate the prevalence and to determine the associated factors of undiagnosed depression amongst hypertensive patients (HTNP) at primary health care centers (PHCC) in Gaza.
Methods

A cross-sectional survey was conducted including 538 HTNP as a recruitment phase of a clustered randomized controlled trial. Data were collected through a face to face structured interview and depression status was assessed by Beck's Depression Inventory (BDI-II). Data were analyzed by STATA version 14 using standard complex survey analyses, accounted for unresponsiveness and clustering approach. Linear regression analysis was performed to assess associations.
Results

The prevalence of undiagnosed clinical depression was 11.6% (95% confidence interval [CI]: 8.1, 16.3). Moreover, prevalence of 15.4% (95% CI: 10.8, 21.6) was found for mild depression symptoms. We found that non-adherent to antihypertensive medications (AHTNM) (β = 0.9, 95% CI: 0.17, 1.7), having more health-care system support (β = 2.8, 95% CI: 1.6, 3.9) and number of AHTNM (β = 1.5, 95% CI: 0.6, 2.5) remain significantly positive associated with BDI-II score. While, older age (β = -0.1, 95% CI: -0.2, -0.02), having better social support (β = -6.8, 95% CI: -8.9, -4.7) and having stronger patient-doctor relationship (β = -4.1, 95% CI: -6.9, -1.2) kept significantly negative association.
Conclusion

The prevalence of undiagnosed depression was about one-quarter of all cases; half of them were moderate to severe. Routine screening of depression status should be a part of care of HTNP in PHCC.
Development and Validation of the Psychometric Properties of the Perceived Barriers of Mammography Scale
Authors: Shirzadi Shayesteh , Asghari-jafarabadi Mohammad , Harison Mahnaz M , Allahverdipour Hamid
Published: May 2020

Background To improve women’s participation in early detection of breast cancer we need to understand women’s perceived barriers to Mammography. Due to lack of women participation in referrals to mammography centers, this study aims to develop and test the psychometric properties of the Perceived Barriers of Mammography Scale (PBMS-23) for Iranian women.Methods A mixed method design was performed to develop the PBMS-23 during 2016–2017. The item pool was mainly generated through qualitative data and literature review. Next, the developed questionnaire was answered by 500 women ages 40 to 69 years. The internal consistency, test-retest reliability, content and face validity and construct validity (both exploratory and confirmatory) were assessed.Results Twenty eight items were initially extracted and next, based on content validity assessment, twenty three items (PBMS-23) were remained. The exploratory factor analysis revealed eight factors of believe in fate and destiny, breast conflict, defense avoidance, inconveniences/difficulties of mammography screening, contrasting/competing priorities, fear, distrust of mammography, and lack of knowledge in the PBMS-23 that accounted for 59.20 of the total variance. The confirmatory factor analysis also showed a model with appropriate fitness for the data. The Cronbach’s alpha coefficient and the intra-class correlation coefficient were 0.68, 0.90 respectively.Conclusion The findings showed that the developed PBMS-23 instrument was a valid and reliable instrument for assessing perceived barriers of mammography screening that can be used both in practice and in future studies especially in the Middle East.
Chinese herbal medicine for the treatment of chronic rhinosinusitis: protocol for a systematic review and meta-analysis
Authors: Hu Shouliang , Li Lu , Zhu Xin , Fu Yijie , Li Hui , Zhu Tianmin
Published: May 2020

Background: In east Asian countries, the traditional treatment is to treat chronic rhinosinusitis(CRS) with some herbal formulas. However, there is a lack of clinical evidence to support the effect of the drug. Here, we describe a randomized controlled trial to investigate the efficacy and safety of herbal formulations for the treatment of CRS.Methods: We will search electronic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical Literature Database (CBM), PubMed, Embase, Chinese Science and Technology Periodical Database (VIP), China National Knowledge Infrastructure (CNKI), and Wanfang database using keywords related to CRS and Chinese herbal medicine. Extensive database search was carried out for CRS related randomized controlled trials.Two reviewers(SH and LL) will independently filter the search results to determine eligible articles, complete data collection.The quality of individual trials will be assessed by(XZ and YF) using the Cochrane collaborative bias risk assessment tool. We will calculate the relative risk and 95% confidence interval(CI) of the dichotomy results and the weighted average difference, as well as the corresponding 95% confidence interval of the continuous results. Statistical methods such as subgroup analysis and sensitivity analysis will be used to investigate the sources of heterogeneity.Discussion: The systematic review and meta-analysis will provide evidence for the quality of life and the safety of traditional Chinese medicine in CRS patients.This study will provide a high quality research method for the therapeutic effect of Chinese herbal medicine on CRS, and will also help broaden research horizons for the complementary and alternative therapy of CRS.Systematic review registrationPROSPERO registration number: CRD42019123047(https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019123047).
Do different doses of acupuncture matter on autonomic nervous activity and symptom management in dysmenorrhea? A randomized controlled trial.
Authors: Chien Tsai-Ju , Huang Yi-Shuo , Kuo Chun-Yu , Cho Yu-Ching , Chen Hsin-Yu , Chu Chi-Chang , Cheng Ting-Yu
Published: May 2020

Background The study examined whether the acupuncture dose (number of acupoints stimulated) impacted the efficacy of acupuncture on dysmenorrhea and the relationship with autonomic nervous system regulation.Methods This three-arm randomized controlled study included a high-dose acupuncture (12 acupoints, N = 23), low-dose acupuncture (6 acupoints, N = 30) and control (N = 30) arm. The treatment course was three months. We set heart rate variation (HRV) and analgesics dependence as the primary outcome measurements; Visual Analog Scale (VAS) score, Verbal Multidimensional Scoring System (VMSS) and the 12-Item Short Form Health Survey (SF-12) quality of life questionnaires were set as secondary outcomes. SPSS version 24 was used for data analysis.Results Low-dose acupuncture was superior to high-dose in analgesics dependence (p value: low/high/control: p = 0.043/p = 0.056/p = 0.376); symptom relief (VMSS: low/high/control: p < 0.001/p = 0.007/p = 0.109); and physical quality of life (low/high/control: p < 0.001/p = 0.01/p = 0.007). The groups did not differ in HRV parameters (p > 0.05). In intergroup analysis, more significant changes were noted in the high-dose than in the low-dose group. The scattered nature of the significant changes implies that acupuncture may have a short-term effect on HRV parameters which does not correlate with the acupuncture dose.Conclusions Acupuncture can effectively treat dysmenorrheal pain, improve symptoms and reduce analgesic dependence, but the effect does not correlate with the number of acupoints stimulated. The acupuncture has short-term effect on HRV; yet whether its efficacy on dysmenorrhea is directly related to adjusting the autonomic nervous system may need more large-scale study. It is a safe and effective alternative therapy for dysmenorrhea.Trial: The Efficacy of Different Doses of Acupuncture in Dysmenorrhea, NCT03881319 at ClinicalTrials.gov,
Dynamics of structural and functional changes in gut microbiota during treatment with a microalgal β- glucan, paramylon and the impact on gut inflammation
Authors: Taylor Harrison , Gudi Radhika , Brown Robert , Vasu Chenthamarakshan
Published: May 2020

Background
Previously, we have shown that oral administration of yeast derived β-1,3/1,6-D-glucan, a complex dietary polysaccharide, enhances immune regulation, reduces gut inflammation and alters the composition of the gut microbiota. However, it is not known if other structurally distinct β-glucans have similar properties. The aim of this study was, using B6 mice, to investigate the ability of a microalgae derived β-1,3-D-glucan, paramylon (PM), a widely used dietary supplement, in shaping the gut microbiota and modulating the susceptibility to gut inflammation.
Results
The community structure within the gut microbiota, based on 16S rRNA sequencing data, showed progressive changes including selective enrichment of specific communities and lowered community richness and diversity during prolonged oral treatment with PM. Compared to control mice, the gut microbiota of PM treated mice had significantly higher abundance of Verrucomicrobia (+ 16.46%; p = 0.002) and lower abundance of Firmicutes (-7.53%; p = 0.0147). Specific taxa that were significantly more abundant in PM treated mice include Akkermansia muciniphila (p = 0.037) and several Bacteroides members. Predictive functional analysis revealed overrepresentation of carbohydrate metabolism function in general (p = 0.0058) and glycosaminoglycan degradation (p = 0.015), fatty acid biosynthesis (p = 0.0082), and sugar (fructose, mannose) metabolism (p = 0.0065) in particular in the fecal microbiota of PM recipients compared to controls, and many of these functions were linked to Bacteroides spp. Pretreatment with PM not only diminished susceptibility to dextran sulfate sodium (DSS) to induced colitis severity (colon inflammation score; p = 0.029), but also caused enhanced immune regulation through increasing Foxp3 + T-cells (p = 0.0108) and IL10- producing cells (p = 0.0159), and decreasing IFNγ producing cells (p = 0.0224).
Conclusions
The use of PM as an oral dietary supplement effectively alters the composition of gut microbiota by enriching certain microbial communities such as Bacteroides spp. and carbohydrate metabolism function. These changes promote an anti-inflammatory/regulatory immune response which suppresses susceptibility to gut inflammation. Overall, this study demonstrates the prebiotic properties of PM and the potential benefits of its prolonged oral consumption to gut health.
Changes to Chiropractic Practice in Response to COVID-19: a survey of all 50 United States
Authors: Neff Shawn M , Roecker Christopher B , Okamoto Casey S , Holguin Samuel L , Napuli Jason G , Mattox Ross , Hinkeldey Nathan A , Paris David J
Published: May 2020

Introduction:
The COVID-19 pandemic led to unprecedented changes, as many individual state and local governments enacted stay-at-home orders and nonessential businesses were closed. State chiropractic licensing boards play an important role in protecting the public via regulation of licensure and provision of guidance regarding standards of practice, especially during times of change or uncertainty.
Objective
The purpose of this study was to summarize the guidance provided in each of the 50 United States, related to chiropractic practice during the COVID-19 pandemic.
Methods
A review of the public facing websites of Governors and state chiropractic licensing boards was conducted for each of the United States. Data was collected regarding the official guidance provided by each state’s chiropractic licensing board as well as the issuance of stay at home orders and designations of essential personnel by state Governors. Descriptive statistics were used to report the findings from this project.
Results
Each of the 50 state Governor’s websites and individual state chiropractic licensing board’s websites were surveyed. Stay-at-home or shelter-in-place orders were issued in 86% of all states. Chiropractors were classified as essential providers in 54% of states, non-essential in one state (2%), and no guidance was provided in the remaining 44% of all states. Fourteen states (28%) recommended restricting visits to only urgent cases and the remaining states (72%) provided no guidance. Twenty-seven states (54%) provided information regarding protecting against infectious disease and the remaining states (46%) provided no guidance. Twenty-two states (44%) provided recommendations regarding chiropractic telehealth and the remaining states (56%) provided no guidance. Seventeen states (34%) altered license renewal requirements and eight states (16%) issued warnings against advertising misleading or false information regarding spinal manipulation and protection from COVID-19.
Conclusion
Individual state guidance during the COVID-19 pandemic was heterogenous, widely variability in accessibility, and often no guidance was provided by state chiropractic licensing boards. Some state chiropractic licensing boards chose to assemble guidance for licensees into a single location, which we identified as a best practice for future situations where changes in chiropractic practice must be quickly communicated.
Lactate oxidative phosphorylation by annulus fibrosus cells: Evidence for lactate-dependent metabolic symbiosis in intervertebral discs
Authors: Wang Dong , Hartman Robert , Han Chao , Zhou Chaoming , Couch Brandon , Malkamaki Matias , Roginskava Vera , Houten Bennett Van , Mullet Steven , Wendell Stacy , Jurczak Michael , Kang James , Lee Joon , Sowa Gwendolyn , Vo Nam
Published: May 2020

BackgroundIntervertebral disc degeneration contributes to low back pain. The avascular intervertebral disc consists of a central hypoxic nucleus pulpous (NP) surrounded by the more oxygenated annulus fibrosus (AF). Lactate, an abundant end-product of NP glycolysis, has long been viewed as a harmful waste that acidifies disc tissue and decreases cell viability and function. The objective of this study was to determine whether lactate could be used by AF cells as a carbon source rather than being removed from disc tissue as a waste byproduct.Methods.Import and conversion of lactate to tricarboxylic acid (TCA) cycle intermediates and amino acids in rabbit AF cells were measured by heavy-isotope (13C-lactate) tracing experiments using mass spectrometry. Levels of protein expression of lactate converting enzymes, lactate importer and exporter in NP and AF tissues were quantified by Western blots. Effects of lactate on proteoglycan (35S-sulfate) and collagen (3H-proline) matrix protein synthesis and oxidative phosphorylation (Seahorse XFe96 Extracellular Flux Analyzer) in AF cells were assessed.Results.Heavy-isotope tracing experiments revealed that AF cells imported and converted lactate into TCA cycle intermediates and amino acids using in vitro cell culture and in vivo models. Addition of exogenous lactate (4 mM) in culture media induced expression of the lactate importer MCT1, and increased oxygen consumption rate by 50%, mitochondrial ATP-linked respiration by 30%, and collagen synthesis by 50% in AF cell cultures grown under physiologic oxygen (5% O2) and glucose concentration (1 mM). AF tissue highly expresses MCT1, LDH-H, an enzyme that preferentially converts lactate to pyruvate, and PDH, an enzyme that converts pyruvate to acetyl-coA. In contrast, NP tissue highly expresses MCT4, a lactate exporter, and LDH-M, an enzyme that preferentially converts pyruvate to lactate.Conclusions.These findings support disc lactate-dependent metabolic symbiosis in which lactate produced by the hypoxic, glycolytic NP cells is utilized by the more oxygenated AF cells via oxidative phosphorylation for energy and matrix production, thus shifting the current research paradigm of viewing disc lactate as a waste product to considering it as an important biofuel. These scientifically impactful results suggest novel therapeutic targets in disc metabolism and degeneration.
Preparation and Performance Analysis of a Spray Dust Suppressant for Coking Coal Dust
Authors: Jiang Jiuhong , Wang Pengfei , Pei Ye , Liu Ronghua , Liu Liming , He Yunchu
Published: May 2020

Coking coal dust has strong hydrophobicity, and it is difficult to combine with droplets in the air and settle. In order to improve the ability of droplets to collect coking coal dusts, a spray dust suppressant for coking coal dusts was studied. Based on monomer optimization and compounding experiments, two types of surfactant monomers, fatty alcohol ether sodium sulfate (AES) and sodium dodecyl benzene sulfonate (SDBS), were selected as the surfactant components for the dust suppressant. Meanwhile, the surfactant monomers were combined with four inorganic salts and the reverse osmosis moisture absorption of each solution was measured. By combining the results of both reverse osmosis moisture absorption and the water retention experiments, CaCl 2 was selected as the inorganic salt auxiliary component for the dust suppressant. Finally, the best concentration combination of the three components were obtained using orthogonal experiments, i.e., AES (0.05%), SDBS (0.03%), and CaCl 2 (0.6%). The dust suppressant solution constituted by this scheme had a high moisture absorption and great performance.
Syngas production by chemical-looping gasification of waste activated carbon with iron-based oxygen carrier
Authors: Li Xiao , Mei An , Wu Man , Li Jinshuai , Zhang Xiuli , Wu Jilai , Yuan Sijie , Guo Qingjie
Published: May 2020

Waste activated carbon (WAC), as a typical solid waste, can be utilized by chemical looping gasification (CLG) technology with an iron-based oxygen carrier to produce valuable synthesis gas. A series of experiments on WAC of the CLG process have been carried out in a fixed-bed reactor. The operation parameters involving the OC/WAC mole ratio, steam flow rate and reaction temperature during CLG reactions have been investigated in detail. Further, the cyclic performance within 10 cycles has been also discussed. Fresh and cyclic reaction oxygen carrier samples have been analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). In order to obtain high-quality syngas with high carbon conversion, the optimal of OC/WAC mole ratio, steam flow rate and reaction temperature are 0.15, 0.10 mL/min, and 950 °C, respectively. The iron-based oxygen carrier exhibits a stable cyclic performance during the multiple tests, following the reaction path of Fe2O3→Fe0.98O in the individual reduction process. Moreover, the iron-based oxygen carrier could be oxidized almost to its initial state after 10 redox tests. No obvious sintering and agglomeration phenomena are observed. The WAC of CLG presents a new approach for the comprehensive utilization and disposal of solid waste, especially with low volatile feedstock.
Pyrolysis kinetic modelling of abundant plastic waste (PET) and in-situ emissions monitoring
Authors: Osman Ahmed I. , Farrell Charlie , Al-Muhtaseb Ala'a H. , Al-Fatesh Ahmed S. , Harrison John , Rooney David W.
Published: May 2020

Background: Recycling the ever-increasing plastic waste has become an urgent global concern. One of the most convenient methods for plastic recycling is pyrolysis, owing to its environmentally friendly nature and its intrinsic properties. Understanding the pyrolysis process and the degradation mechanism is crucial for scale-up and reactor design. Therefore, we studied kinetic modelling of the pyrolysis process for one of the most common plastics, polyethylene terephthalate (PET). The focus was to better understand and predict PET pyrolysis when transitioning to a low carbon economy and adhering to environmental and governmental legislation. This work aims at presenting for the first time, the kinetic triplet (activation energy, pre-exponential constant and reaction rate) for the PET pyrolysis using the differential iso-conversional method. This is coupled with the in-situ online tracking of the gaseous emissions using mass spectrometry. Results: The differential iso-conversional method showed activation energy (E a ) values of 165-195 kJ.mol -1 , R 2 = 0.99659. While the ASTM-E698 showed 165.6 kJ.mol -1 and integral methods such as Flynn-Wall and Ozawa (FWO) (166-180 kJ.mol -1 ). The in-situ MS results showed the pyrolysis gaseous emissions which are C 1 -hydrocarbon and H-O-C=O along with C 2 hydrocarbons, C 5 - C 6 hydrocarbons, acetaldehyde, the fragment of O-CH=CH 2 , hydrogen and water. Conclusions: The kinetic triplet along with the in-situ monitoring of the gaseous emissions of PET pyrolysis can benefit in the process modelling of this system to help better understand the process at scale. This ultimately aids in reactor optimization and design at scale, as it gives a better insight into the reaction mechanism. This can be used by plastic recyclers worldwide and the predictions made in this study can be used to determine how the rate of reaction changes based on temperature and heating rate beyond experimental results both isothermally, non-isothermally and in stepwise heating regimes.
MiR-185-5p targets RAB35 gene to regulate tumor cell-derived exosomes mediated proliferation, migration and invasion of non-small cell lung cancer cells
Authors: Wang Dan , Yu Shufang , Yi Shasha , Liu Sichan
Published: May 2020

Background: Non-small cell lung cancer (NSCLC) is the most common malignant tumor, and its recurrence and metastasis are the main causes of death. Recently, there are evidences that tumor derived exosomes play an important role in the occurrence and development of non-small cell lung cancer.Material/Methods: First, miR-185-5p and RAB35 expression in tumor tissues, paracancerous healthy tissues, lung cancer cell lines and normal bronchial epithelial cell line were detected. Then, miR-185-5p and RAB35 were over-expressed/knocked down to study their effects on A549 cells and H2170 cells proliferation, migration and invasion . Next, bioinformatics analysis and luciferase reporter gene analysis verified the targeting relationships of miR-185-5p and RAB35 , respectively. Finally, the exosomes secreted by tumor cells with RAB35 gene downregulated or miR-185-5p overexpression were co cultured with their parent cells to verify the regulatory effect of RAB35 on the secretion and function of exosomes.Results: The miR-185-5p expression was downregulated, while RAB35 expression was prominently upregulated in NSCLC tissues and cell lines. Moreover, miR-185-5p overexpression or RAB35 downregulated suppressed cells proliferation, migration and invasion. Furthermore, we clarified that RAB35 was a direct target of miR-185-5p. Additionally, exosomes derived from tumor cells could restore cells proliferation, migration and invasion, while exosomes secreted by tumor cells with RAB35 downregulated or mR-185-5p overexpression lose the ability to restore cells proliferation, migration and invasion.Conclusions: Our findings indicate that miR-185-5p targets RAB35 gene to regulate tumor cell-derived exosomes-mediated proliferation, migration and invasion of NSCLC cells.
Novel Potential Binding Sites for Selective Inhibitor Design of Human Soluble Epoxide Hydrolase
Authors: Bzówka Maria , Mitusińska Karolina , Góra Artur
Published: May 2020

Human soluble epoxide hydrolase (hsEH) has been known to be involved in the hydrolysis of epoxyeicosatrienoic acids (EETs), which are anti-inflammatory and cardioprotective signalling molecules. Since the conversion of EETs into the corresponding diols generates non-bioactive molecules, the enzyme’s inhibition would be beneficial. hsEH quickly became the molecular target, however, the proposed inhibitors directed toward this enzyme have not undergone clinical trials, mostly due to their low solubility in water. Our goal is to indicate new regions, distinct from those already investigated, that could be considered during the development of novel and perhaps more soluble inhibitors of hsEH. To fulfil this goal, we used a combination of classical and mixed-solvent molecular dynamics (cMD and MixMD) simulations and a ligand tracking approach. Such a strategy, considers conformational changes in the interior of the enzyme, extends conformational space of binding cavities, and provides insight into different sets of potential binding modes. By analysis of the local distribution of different molecular probes (water and organic cosolvent molecules), we were able to identify potential binding sites (hot-spots), which can indicate the location of the most important functional groups for the binding of designed inhibitors. The uniqueness of the binding spots was examined by superpositioning the indicated hot-spots with a map of chemical interactions between the known inhibitors and hsEH. We analysed all available crystal structures of hsEHs with inhibitors deposited in the PDB database to gain insight into the binding modes of the known inhibitors and to find similarities and dissimilarities between them. By comparing the results obtained based on the map of chemical interactions, with the regions identified by using cMD and MixMD, we were able to identify regions that have not been targeted by ligands until now and which are promising possible binding sites for polar groups that would be beneficial for inhibitors solubility.
Children with oligoarticular Juvenile Idiopathic Arthritis have skewed synovial monocyte polarization pattern with functional impairment – a distinct inflammatory pattern for oligoarticular juvenile arthritis
Authors: Schmidt Tobias , Berthold Elisabet , Arve-Butler Sabine , Gullstrand Birgitta , Mossberg Anki , Kahn Fredrik , Bengtsson Anders A , Månsson Bengt , Kahn Robin
Published: May 2020

Background
Juvenile idiopathic arthritis (JIA) is an umbrella term of inflammatory joint diseases in children. Oligoarthritis is the most common form in the Western world, representing roughly 60% of all patients. Monocytes and macrophages play an important role in adult arthritides, but their role in oligoarticular JIA is less studied. Polarization highly influences monocytes’ and macrophages’ effector functions, broadly separated into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Here, we set out to investigate the polarization pattern and functional aspects of synovial monocytes in oligoarticular juvenile idiopathic arthritis (JIA).
Methods
Paired synovial fluid, blood samples (n = 13) and synovial biopsies (n = 3) were collected from patients with untreated oligoarticular JIA. Monocytes were analyzed for polarization markers by flow cytometry and qPCR. Effector function was analyzed by a phagocytosis assay. Polarization of healthy monocytes was investigated by stimulation with synovial fluid in vitro. Monocyte/macrophage distribution, polarization and mRNA expression were investigated in biopsies by immunohistochemistry, immunofluorescence and in situ hybridization.
Results
Children with oligoarticular JIA have polarized synovial fluid monocytes of a specific M1(IFNg)/M2(IL-4)-like pattern. This was evidenced by increased surface expression of CD40 (p < 0.001), CD86 (p < 0.001) and CD206 (p < 0.001), but not CD163, as compared to paired circulating monocytes, and extensively explored at the mRNA level were synovial fluid monocytes differentially expressed classical markers of M1(IFNg)/M2(IL-4) polarization. Synovial fluid monocytes were functionally affected, as assessed by reduced capacity to phagocytose (p < 0.01). Synovial fluid induced M2 (CD16 and CD206), but not M1 (CD40 and CD86) markers in healthy monocytes and did not induce cytokine production. Single and co-expression of surface CD40 and CD206, as well as mRNA expression of IL-10 and TNF, was observed in monocytes/macrophages in synovial biopsies.
Conclusion
Children with untreated oligoarticular JIA have similar and distinct synovial fluid monocyte polarization pattern of mixed pro- and anti-inflammatory features. This pattern was not exclusively a result of the synovial fluid milieu as monocytes/macrophages in the synovial membrane show similar patterns. Our study highlights a distinct polarization pattern in oligoarticular JIA, which could be utilized for future treatment strategies.
Human Recombinant Fibroblast Growth Factor-18 (Sprifermin), Enhances Cartilage Healing in a Cartilage Injury Model
Authors: Hendesi Honey , Stewart Suzanne , Gibison Michelle L , Guehring Hans , Richardson Dean W. , Dodge George R
Published: May 2020

Background: Post traumatic osteoarthritis is a disabling condition impacting mostly young and active population. In the present study we investigated the impact of intra-articular sprifermin, a recombinant truncated fibroblast growth factor 18, on the outcome of microfracture treatment, a widely used surgical technique to enhance cartilage healing at the site of injury. Methods: For the purpose if this study, we created a cartilage defect and performed microfracture treatment in fetlock joints of 18 horses, treated joints with one of three doses of sprifermin (10, 30, or 100 mg) or with saline, hyaluronan (HA), and evaluated animals functional and structural outcomes over 24 weeks. For primary outcome measures we performed histological evaluations and performed gene expression analysis of aggrecan, collagen types I and II, and cartilage oligomeric matrix protein (COMP) in three regions of interest. As secondary outcome measures we examined animal’s lameness, performed arthroscopic, radiographic, and CT scan imaging, and gross morphology assessment. Results: We detected the highest treatment benefit following 100 mg sprifermin treatment. Overall histological assessment showed an improvement in the kissing region and expression of constitutive genes showed a concentration dependent enhancement, especially in the peri-lesion area. We detected a significant improvement in lameness scores, arthroscopic evaluations, radiography, and CT scans following sprifermin treatment when results from three dose-treatment groups were combined. Conclusion: Our results demonstrated for the first time, an enhancement in outcomes of the microfracture treatment following sprifermin treatment, suggesting a cartilage regenerative role and a potential benefit of sprifermin treatment in early cartilage injuries.
Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress
Authors: CHEN WEN , LIU ZHE , WU CHENZHOU , CHEN YAFEI , QIU LING , ZHANG ZHUOYUAN , SUN HAIBIN , CHEN SIYU , AN ZIJIAN , LI YI , LI LONGJIANG
Published: May 2020

Background
C18 ceramide (CER) plays an important role in the occurrence and development of oral squamous cell carcinoma (OSCC). However, the function of ceramide synthase 1 (CERS1), a key enzyme in C18 CER synthesis, in OSCC is still unclear. The aim of our study was to investigate the relationship between CERS1 and oral cancer.
Methods
The expression of CERS1 on 48 pairs of matching OSCC patients’ cancer and normal tissues was determined by quantitative real-time PCR (RT-PCR). A mouse OSCC model induced by 4-nitroquinolin-1-oxide (4NQO) was established on CERS1+/+ and CERS1-/- C57BL/N6 mice. The functions of CERS1 downregulated were accessed by cell counting kit-8 method, colony formation assay, EdU DNA Proliferation in vitro Detection, wound healing test and Annexin V/PI double staining. RT-PCR, Western blot and luciferase assay were performed to explore the molecular mechanisms of CERS1.
Results
In this study, we found that the expression of CERS1 was downregulated in oral cancer tissues and cell lines. In the mouse OSCC model, CERS1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, CERS1 knockdown promoted cell proliferation, migration and invasion in vitro. CERS1 knockdown caused endoplasmic reticulum stress (ER stress) and induced the activating transcription factor 4 (ATF4) pathway. ATF4 upregulated VEGFA transcription to promote tumor growth and metastasis. In addition, mild ER stress caused by CERS1 knockdown could induce cisplatin resistance.
Conclusions
Our study suggests that CERS1 is downregulated in oral cancer. The downregulation of CERS1 promotes the aggressiveness of OSCC and chemotherapeutic drug resistance by inducing mild ER stress.
The clinical value of the changes of peripheral lymphocyte subsets absolute counts in patients with non-small cell lung cancer
Authors: Xia Ying , Li Wentao , Li Yongmin , Liu Yunhe , Ye Songshan , Liu Aqing , Yu Jianchun , Jia Yingjie , Liu Xu , Chen Huayu , Guo Yongtie
Published: May 2020

Background: Immune function strongly influences the outcome of patients with non-small cell lung cancer(NSCLC). It’s vital to understand the immune state of patients through detecting the level of lymphocyte subsets including percentage and number timely and accurately, and helpful to evaluate conditions of prognosis and adjust the treatment program for patients.Methods: Blood sample was obtained from 172 patients with NSCLC and 55 normal controls(NCs).The absolute count and percentages of CD3+,CD3+CD4+,CD3+CD8+, B and NK cells were determined by flow cytometry simultaneously with single platform technologies. Then 172 patients were followed up for the study of effects of the lymphocyte on disease progression and disease free survival(DFS). The factors affecting disease progression were analyzed by Binary Logistic regression.Calculating survivals were with the method of Kaplan-Meier. The log-rank test and proportional hazard regression model (enter method) were used for univariable and multivariable analyses respectively. Results: The absolute counts of CD3+, CD3+CD4+, CD3+CD8+, B and NK cells were significantly decreased in patients contrasted with NCs(P<0.05), no difference in percentages(P>0.05) except NK cells between patients and NCs. Relative to NCs, patients with NSCLC at stage Ⅰ and Ⅱ had lower absolute count of lymphocyte subsets(P<0.01), patients at stage Ⅲ~Ⅳ were also significantly lower compared with those in control group (P<0.01), no significant differences were observed in the percentages between patients and NCs. Compared the absolute counts of CD3+, CD3+CD4+, CD3+CD8+, B and NK cells among patients at different stages, only CD3+CD4+ was associated with clinical stages obviously. Patients with treatment of chemotherapy after surgery or only surgery showed different effects on absolute counts of CD3+CD4+,CD3+CD8+, NK and B cells . Binary Logistic regression showed CD3+CD4+ and CD3+CD8+ could contribute to favorable prognosis. Multivariate analysis of prognostic factors of DFS showed CD3+CD4+ cell was independent factor for predicting DFS .Conclusions:Compared to NCs, patients with NSCLC at different stages showed decreased absolute lymphocyte count obviously, rather than lymphocyte percentage, which persists for months or years after chemotherapy. The high level of baseline absolute CD3+CD4+ cells count(>502 cells/ul) contributed to longer disease free survival.Chinese Clinic Trial Registry number:ChiCTR-IOR-17014139; Registry date:2017/12/25
WITHDRAWN: EGFL6 Modulates WNT Signaling to Drive Esophageal Cancer Metastasis and Proliferation
Authors: Wang Yanhong , Kang Jing , Tian Jihua , Jia Hongyan , Wang Juanjuan , Shi Ruyi , Chang Sijia , Ji He , Yang Jia , Gao Yuan , Wang Guiqin , Ren Xiaojun
Published: May 2020

Background
Esophageal cancer (EC) is the sixth deadliest cancer in the world. There has been no breakthrough in the research on EC in the past few decades. Epidermal growth factor-like protein 6 (EGFL6), as a member of the epidermal growth factor superfamily, plays an important role in the occurrence and development of some tumors. However, the role of EGFL6 in the EC has never explored.
Methods
Immunohistochemical staining was used to evaluate the expression level of EGEC6 protein in human EC and its adjacent non-tumor tissues, and analyzed the correlation between the expression level of EGFL6 protein and clinical pathological indexes and survival rate. In vitro, by constructing EGFL6 silence and overexpressed EC cells,used CCK-8, clone formation, wound healing assays, transwell experiment and flow cytometry to explore the effects of EGFL6 on the proliferation, invasion, migration and apoptosis of EC. By using real-time PCR or western blot to detect the related marker genes of epithelial-mesenchymal transformation (EMT), tumor stem cells (TSCs) and Wnt/β-catenin. In vivo, established a nude mouse EC transplantation tumor model.
Results
The results showed that the expression level of EGFL6 in EC is significantly higher than that in adjacent non-tumor tissues, and is related to poor prognosis of patients. In vitro, CCK-8, clone formation, wound healing assays, transwell experiment and flow cytometry results show that EGFL6 overexpression can promotes proliferation, invasion and migration of EC cells and inhibits apoptosis. EGFL6 silencing inhibits proliferation, invasion and migration of EC cells and promotes apoptosis. Real-time PCR and Western-blot detection of EMT-related markers found that EGFL6 can induce EC cells EMT. Real-time PCR detection of esophageal cancer stem cell-related genes showed that EGFL6 may maintain the expression of esophageal cancer stem cell-like cell population. Western-blot detection of Wnt/β-catenin signaling marker genes showed that EGFL6 participated in the expression of Wnt/β-catenin signaling pathway. In vivo experiments found that knockout of EGFL6 could inhibit the formation of subcutaneous tumors in nude mice.
Conclusion
Taken together, our study identified a novel role and mechanism of EGFL6 in EC and provided epigenetic therapeutic strategies for the treatment of EC.
EZH2-mediated epigenetic silencing of ZIC4 in hepatocellular carcinoma
Authors: Wang Jinghui , Yang Zhu , Long Fengxi , Luo Li , Li Gao , Chen Changpei , Sun Dongxue , Tang Dongxin
Published: May 2020

Background: The present study aimed to explore the role of ZIC4 in human liver cancer.Methods: Illumina450 genome-wide methylation data was downloaded from The Cancer Genome Atlas for 50 available liver tumor/surrounding pairs. Wound healing test, colony formation and flow cytometry assay were utilized to analyze cell migration, survival and apoptosis. The effects of EZH2 and ZIC4 on tumor growth were also investigated through in vivo xenograft and orthotopic implantation experiments. Results: ZIC4 was hypermethylated in liver cancer tissues and cell lines. EZH2 knockdown and DZNep mediated H3K27me3 contributes to ZIC4 expression. The antitumor effect of EZH2 knockdown on hepatocellular carcinoma growth, metastasis and epithelial-mesenchymal transition progression in vitro were rescued by sh-ZIC4. Downregulation of ZIC4 also rescued the antitumor effect of DZNep in vivo.Conclusions: Epigenetic silencing of ZIC4 by EZH2 mediated H3K27me3 is an important mechanism in human liver cancer and provide a new therapeutic target for the treatment of hepatocellular carcinoma disease.
MiR-103a-3p promotes tumour glycolysis in colorectal cancer via Hippo/YAP1/HIF1A axis
Authors: Sun Zhenqiang , Zhang Qiuge , Yuan Weitang , Li Xiaoli , Chen Chen , Guo Yaxin , Shao Bo , Dang Qin , Zhou Quanbo , Wang Qisan , Wang Guixian , Liu Jinbo , Kan Quancheng
Published: May 2020

Background
Glycolysis plays an essential role in the growth and metastasis of solid cancer and has received increasing attention in recent years. However, the complex regulatory mechanisms of tumour glycolysis remain elusive. This study aimed to explore the molecular effect and mechanism of the noncoding RNA miR-103a-3p on glycolysis in colorectal cancer (CRC).
Methods
We explored the effects of miR-103a-3p on glycolysis and the biological functions of CRC cells in vitro and in vivo. Furthermore, we investigated whether miR-103a-3p regulates HIF1A expression through the Hippo/YAP1 pathway, and evaluated the role of the miR-103a-3p-LATS2/SAV1-YAP1-HIF1A axis in promoting glycolysis and angiogenesis in CRC cells and contributing to invasion and metastasis of CRC cells.
Results
We found that miR-103a-3p is highly expressed in CRC tissues and cell lines compared with matched controls and the high expression of miR-103a-3p is associated with poor patient prognosis. Under hypoxic conditions, a high level of miR-103a-3p can promote the proliferation, invasion, migration, angiogenesis and glycolysis of CRC cells. Moreover, miR-103a-3p knockdown inhibits the growth, proliferation, and glycolysis of CRC cells and promotes the Hippo-YAP signalling pathway in nude mice in a xenograft model. Here, we demonstrated that miR-103a-3p could directly target LATS2 and SAV1. Subsequently, we verified that TEAD1, a transcriptional coactivator of Yes-associated protein 1 (YAP1), directly binds to the HIF1A promoter region and the YAP1 and TEAD1 proteins could co-regulate the expression of HIF1A, thus promoting tumour glycolysis.
Conclusions
MiR-103a-3p, which is highly expressed in CRC cells, promotes HIF1A expression by targeting the core molecules LATS2 and SAV1 of the Hippo/YAP1 pathway, contributing to enhanced proliferation, invasion, migration, glycolysis and angiogenesis in CRC. Our study revealed the functional mechanisms of miR-103a-3p/YAP1/HIF1A axis in CRC glycolysis, which would provide potential intervention targets for molecular targeted therapy of CRC.
Ferroptosis induction induced by ginkgetin enhances therapeutic effect of cisplatin in EGFR wild type non-small cell lung cancer
Authors: Lou Jian-Shu , Zhao Li-Ping , Huang Zhi-Hui , Chen Xia-Yin , Xu Jing-Ting , TAI William Chi-Shing , Tsim Karl W.K. , Chen Yi-Tao , Xie Tian
Published: May 2020

Background Cisplatin (DDP) is the first-in-class drug for advanced and non-targetable non-small cell lung cancer (NSCLC). Recent study indicates that DDP could slightly induce non apoptotic cell death ferroptosis, and the cytotoxicity was promoted by ferroptosis inducer. The agents enhancing ferroptosis level therefore may increase anticancer effect of DDP. Several lines of evidence support the usage of phytochemicals in therapy of NSCLC. Ginkgetin, a bioflavonoid derived from Ginkgo biloba leaves, showed anti-cancer effect on NSCLC both in vitro and in vivo, which could strongly trigger autophagy. Ferroptosis can be triggered by autophagy, and which regulates redox homeostasis. Thus, we aim to elucidate the possible role of ferroptosis induction in accounting for synergy of ginkgetin with DDP in cancer therapy.Methods Ginkgetin promoted DDP-induced anticancer effect was observed via cytotoxicity assay and western blot. Ferroptosis triggered by ginkgetin in DDP treated NSCLC was observed via lipid peroxidation assay, labile iron pool assay, western blot, and QPCR. With ferroptosis blocking, the contribution of ferroptosis on ginkgetin + DDP induced cytotoxicity, Nrf2/HO-1 axis and apoptosis were determined via luciferase assay, immunostaining, chromatin immunoprecipitation (CHIP), and flow cytometry. The role of ferroptosis in ginkgetin + DDP treated NSCLC cells was illustrated by the application of ferroptosis inhibitor, which was further demonstrated in xenograft nude mice model.Results Ginkgetin synergized cisplatin in cytotoxicity in NSCLC cells, which concomitant with increased labile iron pool and lipid peroxidation: both these processes were the key characteristics of ferroptosis. The induction of ferroptosis, mediated by ginkgetin, was further confirmed by decline expressions of SLC7A11, GPX4 and GSH/GSSG ratio. In parallel, ginkgetin disrupted redox hemeostasis in DDP-treated cells, demonstrated by the enhanced ROS formation and inactivation on Nrf2/HO-1 axis. Ginkgetin also enhanced DDP-induced mitochondrial membrane potential (MMP) loss and apoptosis in cultured NSCLC cells. Furthermore, blocking ferroptosis reversed the gingketin-induced inactivation on Nrf2/HO-1, as well as the elevation on ROS formation, MMP loss and apoptosis in DDP-treated NSCLC cells.Conclusion This study firstly reported that ginkgetin promoted DDP-induced anticancer effect, which could be accounted by induction of ferroptosis.