bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of Personal Experience and Acquired Knowledge With Intent to Recommend Adjunctive Osteopathic Manipulative Treatment or Yoga for Patients With Chronic Low Back Pain
Authors: Seffinger Michael A. , Hurwitz Eric , Quiamas John , Kitch Antoinette , Mervyn-Cohen Vanessa , Lin Edward
Published: November 2018

Context

Osteopathic manipulative treatment (OMT) and yoga are both recommended by systematic reviews in the evidence-based research literature for low back pain management. It is unknown, to the authors’ knowledge, what the effect of personal experience with OMT or yoga, reading research articles on OMT or yoga, or both will have on medical students’ recommendations for these treatment options to future patients with chronic low back pain.

Objective

To evaluate the likelihood of osteopathic medical students recommending OMT or yoga to treat patients with chronic low back pain based on their personal experience or reading research articles that recommend OMT or yoga for patients with chronic low back pain.

Methods

In this prospective cohort study, researchers administered an anonymous 18-question online survey for osteopathic medical students. The survey included a patient vignette, 2 evidence-based articles, and multiple choice, yes/no, and Likert-type questions. Participants were recruited via email from all 4 years of medical school. Between-group differences in proportions were assessed with descriptive statistics and χ2 tests; differences within groups were assessed with the McNemar test; and Fischer exact tests were used when expected cell counts were less than 5.

Results

A total of 180 participants (100 male, 80 female) completed the study. Personal experience increased the likelihood of osteopathic medical students recommending OMT (P<.018) or yoga (P<.001) to a future patient or to a patient in a case vignette (P<.05) with chronic low back pain. Students who read research articles were more likely to recommend OMT to the case patient and future patients before and after reading the intervention article regardless of their experience (P<.001).

Conclusion

Personal experience and reading evidence-based research may increase the likelihood that osteopathic medical students will recommend OMT to future patients with chronic low back pain.
Public Health and Interprofessional Education as Critical Components in the Evolution of Osteopathic Medical Education
Authors: Eduardo Velasco-Mondragon H. , Menini Teresita , West Catherine , Clearfield Michael
Published: November 2018

Public health and interprofessional education (IPE) are included among the osteopathic core competencies and Entrustable Professional Activities that should be reflected in osteopathic medical curricula. Cognizant of the importance of these 2 areas, Touro University College of Osteopathic Medicine-CA (TUCOM) has developed initiatives to advance them on campus as well as within its academic curriculum. The authors acknowledge the importance of incorporating public health content into osteopathic medicine as well as expanding IPE in the health professions as part of a larger project to impart a unique identity and relevance to osteopathic medical education at TUCOM. The authors describe TUCOM's public health and IPE initiatives and outcomes in the context of current and future relevance for osteopathic medicine. Future directions to assess the quality and impact of these programs that may be of value for other colleges of osteopathic medicine are also discussed.
Structural and functional analysis of the roles of the HCV 5′ NCR miR122-dependent long-range association and SLVI in genome translation and replication
Authors: Bentley Kirsten , Cook Jonathan P. , Tuplin Andrew K. , Evans David J.
Published: November 2018

The hepatitis C virus RNA genome possesses a variety of conserved structural elements, in both coding and non-coding regions, that are important for viral replication. These elements are known or predicted to modulate key life cycle events, such as translation and genome replication, some involving conformational changes induced by long-range RNA–RNA interactions. One such element is SLVI, a stem-loop (SL) structure located towards the 5′ end of the core protein-coding region. This element forms an alternative RNA–RNA interaction with complementary sequences in the 5′ untranslated regions that are independently involved in the binding of the cellular microRNA 122 (miR122). The switch between ‘open’ and ‘closed’ structures involving SLVI has previously been proposed to modulate translation, with lower translation efficiency associated with the ‘closed’ conformation. In the current study, we have used selective 2′-hydroxyl acylation analysed by primer extension to validate this RNA–RNA interaction in the absence and presence of miR122. We show that the long-range association (LRA) only forms in the absence of miR122, or otherwise requires the blocking of miR122 binding combined with substantial disruption of SLVI. Using site-directed mutations introduced to promote open or closed conformations of the LRA we demonstrate no correlation between the conformation and the translation phenotype. In addition, we observed no influence on virus replication compared to unmodified genomes. The presence of SLVI is well-documented to suppress translation, but these studies demonstrate that this is not due to its contribution to the LRA. We conclude that, although there are roles for SLVI in translation, the LRA is not a riboswitch regulating the translation and replication phenotypes of the virus.
New Learning, New Teaching, New Entrepreneurship, New Eco-sphere
Authors: Shaoyou Ji
Published: November 2018

As it is known, China is a country with a long history, and in this Internet Age, changes are taking place in China at high speed. The new leadership of China is faced with a series of complex challenges. In September 2013, Chinese President Xi Jinping proposed a Silk Road Economic Belt and in October a 21st-Century Maritime Silk Road; together now referred to as the Belt and Road Initiative. The Initiative aims at building a community of shared interests, responsibility and destiny with mutual political trust, economic integration and cultural inclusiveness. Investments and trade cooperations are major tasks in building the Belt and Road. As a member of higher education community, how could we be of any assistance in solving the employment problem for the government, upgrade the traditional foreign trade for the enterprises and train innovative students for the society? Consequently, I select the theme Disruptive Innovation: Shifting the way of learning. And the title of my sharing is “New Learning, New Teaching, New Entrepreneurship & New Eco-sphere”.
Núcleo de Estudo Geempiano do Distrito Federal: um olhar “de dentro para fora”
Authors: Oliveira Ândrea De Queiroz , Da Rocha Carla Borba , Medeiros Marques Yone Martins , Tuboiti Nair Cristina Da Silva
Published: November 2018

Diante de altos índices de analfabetismo, principalmente no que se refere a alunos oriundos de classes populares, em torno de 50% ao final de três anos de estudos, ou seja, crianças aos 8 anos de idade, nosso questionamento se direciona para a necessidade de mudança em busca da qualidade na educação no Ensino Fundamental, prioritariamente nas escolas públicas. Sendo assim, esse relato de experiência objetiva abordar aspectos estruturais da formação e as interferências no processo de aprendizagem dos professores ao ensinarem seus alunos, chegando, ao final de cada ano letivo, a índices de 100% de alfabetização em suas turmas. Nosso estudo apresenta o relato de profissionais pertencentes ao Núcleo de Estudo Geempiano do Distrito Federal que, composto por professoras vinculadas à Secretaria de Educação do Distrito Federal, ao longo de 13 anos, vem construindo uma trajetória de profissionalização enquanto alfabetizadoras. Utilizam-se da proposta didático-pedagógica pós-construtivista, que tem como ponto de partida, o princípio da igualdade das inteligências e o processo psicogenético de cada aluno, dentro de um Campo Conceitual de conhecimentos relacionados à leitura e à escrita. Comprovamos a formação de professores alfabetizadores, junto à proposta didático-pedagógica pós-construtivista, como uma opção na busca da melhoria e da democratização das aprendizagens, uma vez que possuem uma trajetória bem sucedida de alfabetização em turmas de classes populares.
Narrativas sobre a Centralidade da Mulher numa Sociedade Atual: Perspectivas Bororo
Authors: Campos Neide Da Silva , Grando Beleni Saléte
Published: November 2018

Neste artigo, fruto de uma pesquisa de doutorado em andamento que visa compreender as trajetórias das professoras da etnia Bororo na educação escolar indígena, trazemos as primeiras aproximações da temática a partir do diálogo com mulheres e liderança a fim de pensar as relações entre os diferentes papeis da mulher professora e mulher bororo considerando sua estrutura social matrilinear. Apresentaremos neste ensaio, dados preliminares a partir de três fontes de dados distintas, que nos permitem compreender o lugar da mulher Boe a partir da  cosmovisão Bororo e nisso analisar sentidos e significados atribuídos às mulheres na sociedade Bororo, considerando toda a especificidade da organização social e cultural do povo cuja estrutura social é centrada na mulher. A educação tradicional articula os mundos que constituem a cosmologia Bororo, na qual se vinculam as dimensões material e imaterial num processo binário de estruturação e organização social, a fim de educar o corpo-ser aredu (mulher) e o corpo-ser imedu (homem). Na concepção Bororo de ver o mundo, há sempre duas metades, dois lados, que não são antagônicos, mas complementares e co-dependentes, no sentido de que um clã, uma metade exogâmica, não pode sobreviver sem a outra, pois uma dá visibilidade à outra, permitindo o reconhecimento de diferença e pertencimento de cada pessoa na sociedade a partir do seu grupo social clânico matrilinear.

 
CDC report highlights role of stimulants in overdose deaths
Authors: Knopf Alison
Published: November 2018

It's essential to pay attention to other substances, even in the midst of an opioid epidemic, especially when stimulants such as cocaine are being mixed with illicit fentanyl, which is responsible for the huge increase in overdose mortality.
The role of synthetic P (MMA‐co‐MAH) as compatibilizer in the preparation of chlorinated polyethylene/polysodium acrylate water‐swelling rubber
Authors: Fang Zhengping , Zhang Xingning , Xia Meng , Luo Wei , Hu Huiling , Wang Zhiguo , He Peixin , Zhang Yuhong
Published: November 2018

By multicomponent mechanical blending technology, water‐swelling rubber (WSR) was prepared through choosing chlorinated polyethylene (CPE), a superabsorbent polymer (cross‐linking poly(sodium acrylate), CPNaAA), and compatibilizer (poly(methyl methacrylate‐co‐maleic anhydride), P (MMA‐co‐MAH)) along with other minor additives. P (MMA‐co‐MAH) was synthesized by grafting maleic anhydride (MAH) onto methyl methacrylate (MMA). Microstructure, water‐absorbent properties, and mechanical properties of WSR were investigated. The results showed that P (MMA‐co‐MAH) boosted the dispersibility between CPNaAA and CPE and led to the increase in Shore A hardness, tensile strength, tensile stress at 100%, and water‐swelling behavior, whereas the elongation at break and weight loss were decreased with P (MMA‐co‐MAH) content. When the content of P (MMA‐co‐MAH) reached 8 phr, the tensile strength, hardness, and water‐swelling ability of dry‐state WSR exhibited a maximum value and the percentage loss ratio of CPNaAA reached a relatively low value.
Genetically inspired prognostic scoring system (GIPSS) outperforms dynamic international prognostic scoring system (DIPSS) in myelofibrosis patients
Authors: Kuykendall Andrew T. , Talati Chetasi , Padron Eric , Sweet Kendra , Sallman David , List Alan F. , Lancet Jeffrey E. , Komrokji Rami S.
Published: November 2018

A genetically inspired prognostic scoring system (GIPSS) that stratifies primary myelofibrosis (PMF) patients by genetic variants alone was recently proposed. While non‐inferior to the dynamic international prognostic scoring system (DIPSS), the lack of overlapping prognostic variables between the models leads to increased risk for disagreement between two valid prognostic models and presents a challenging clinical situation. In an external cohort of 266 molecularly annotated myelofibrosis (MF) patients, we demonstrated that the GIPSS model significantly differentiated between four risk groups (low, int‐1, int‐2, high) with median OS that was not reached, not reached, 60.5 and 28.9 months, respectively. High‐risk patients had significantly inferior leukemia‐free survival (LFS) (P < 0.0001). We identified a cohort of prognostically ambiguous patients (n = 39) in which GIPSS and DIPSS models differed by ≥2 risk groups. Among these patients, a similar proportion were up‐staged by DIPSS (n = 19) and GIPSS (n = 20). Patients upstaged by GIPSS (genetically high‐risk) had a trend toward inferior OS compared with patients upstaged by DIPSS (clinically high‐risk) (P = .08) and significantly worse LFS (P = .04). Patients deemed intermediate‐2 and high‐risk by GIPSS who underwent allogeneic transplant had improved OS compared with those that did not (P = .04). GIPSS is a valid disease‐specific prognostic system and outperforms DIPSS in patients where the two models disagree. Additionally, while GIPSS was developed for PMF; the current study shows, however, that the contemporary genetic model performs equally well for both primary and secondary myelofibrosis.
Repellent action and contact toxicity mechanisms of the essential oil extracted from Chinese chive against Plutella xylostella larvae
Authors: Gao Quan , Song Li , Sun Jia , Cao Hai‐Qun , Wang Likun , Lin Huafeng , Tang Feng
Published: November 2018

Botanical pesticides play increasingly important roles in the control of agricultural pests. In this study, the insecticidal effects, specifically the repellent action and contact toxicity, of the essential oil extracted from Chinese chive (EOC) against Plutella xylostella larvae were confirmed. The mechanisms of repellent’s action were studied using electroantennograms (EAGs), and the effects on glutathione
S‐transferase (GST), carboxylesterase (CarE), and acetyl cholinesterase were investigated after EOC treatments. The EOC affected the EAG results and inhibited the activities of GST and CarE in treated
P. xylostella larvae, which could explain its insecticidal effects. And, four pyrazines showed greater repellent activities than that of the EOC, which was confirmed as the main active compounds of EOC.
Interleukin‐17A Inhibition Diminishes Inflammation and New Bone Formation in Experimental Spondyloarthritis
Authors: van Tok Melissa N. , van Duivenvoorde Leonie M. , Kramer Ina , Ingold Peter , Pfister Sabina , Roth Lukas , Blijdorp Iris C. , van de Sande Marleen G. H. , Taurog Joel D. , Kolbinger Frank , Baeten Dominique L.
Published: November 2018

Objective

It remains unclear if and how inflammation and new bone formation in spondyloarthritis (SpA) are coupled. We undertook this study to assess the hypothesis that interleukin‐17A (IL‐17A) is a pivotal driver of both processes.

Methods

The effect of tumor necrosis factor (TNF) and IL‐17A on osteogenesis was tested in an osteoblastic differentiation assay using SpA fibroblast‐like synoviocytes (FLS) differentiated with dexamethasone, β‐glycophosphatase, and ascorbic acid. IL‐17A blockade was performed in HLA–B27/human β2‐microglobulin (hβ2m)–transgenic rats, which served as a model for SpA in both prophylactic and therapeutic settings. Inflammation and new bone formation were evaluated by micro–computed tomography imaging, histologic analysis, and gene expression profiling.

Results

TNF and IL‐17A significantly increased in vitro osteoblastic differentiation. In vivo, prophylactic blockade of IL‐17A significantly delayed spondylitis and arthritis development and decreased arthritis severity. Anti–IL‐17A treatment was also associated with prevention of bone loss and periosteal new bone formation. Therapeutic targeting of IL‐17A after the initial inflammatory insult also significantly reduced axial and peripheral joint inflammation. This treatment was again associated with a marked reduction in spinal and peripheral structural damage, including new bone formation. RNA sequencing of target tissue confirmed that IL‐17A is a key driver of the molecular signature of disease in this model and that therapeutic anti–IL‐17A treatment reversed the inflammatory signature and the selected gene expression related to bone damage.

Conclusion

Both prophylactic and therapeutic inhibition of IL‐17A diminished inflammation and new bone formation in HLA‐B27/hβ2m–transgenic rats. Taken together with the ability of IL‐17A to promote osteoblastic differentiation of human SpA FLS, these data suggest a direct link between IL‐17A–driven inflammation and pathologic new bone formation in SpA.
Clinical anatomy of pelvic pain in women
Authors: Eid Seif , Loukas Marios , Tubbs R. Shane
Published: November 2018

Pelvic pain is a common symptom that affects women worldwide and usually presents with variable range of severity, duration, and location. Several gynecological conditions may result in pelvic pain, and may have a variable presentation among patients. Pelvic pain creates a significant challenge and frustration to both patients and clinicians, which also creates a significant burden on the economy. It is necessary to tailor the management of pelvic pain to each individual patient to achieve optimal outcomes. Endometriosis, adenomyosis, and fibroids result in pelvic pain and may occur simultaneously. This review highlights some of the common gynecological etiologies of pelvic pain with a focus on anatomy, diagnosis, and management. Clin. Anat. 9999:1–5, 2018. © 2018 Wiley Periodicals, Inc.
Efficacy and safety of liraglutide added to insulin therapy in elderly patients with type 2 diabetes
Authors: Tonoike Mie , Chujo Daisuke , Noda Mitsuhiko
Published: November 2018

Introduction

The combination of GLP‐1 receptor agonists and insulin is effective in type 2 diabetes (T2D) treatment. However, its longitudinal efficacy and safety in elderly patients have not been established. We evaluated whether liraglutide (Lira) added to insulin therapy safely improved glycaemic control in T2D patients aged >65 years.

Methods

Twenty T2D patients receiving insulin were recruited, and Lira was added to their treatment regimen. Before and 6 months after Lira was added, we assessed the metabolic parameters and continuous glucose monitoring (CGM) data.

Results

Six months after Lira was added, the levels of HbA1c and glycated albumin and body weight were significantly improved, despite the daily doses and number of insulin injections per day being reduced. CGM analysis revealed that the SD and AUC of glucose >180 mg/dL were significantly decreased; the proportion of hypoglycaemic events was not increased.

Conclusion

Lira administration safely improved glycaemic control and reduced body weight. Lira added to insulin therapy may improve the quality of life in elderly T2D patients undergoing insulin therapy, especially those requiring social support.
Estimation of magnesium level in type 2 diabetes mellitus and its correlation with HbA1c level
Authors: Saeed Hajar , Haj Safer , Qasim Bayar
Published: November 2018

Background

Type 2 diabetes mellitus (T2DM) is a common disease; the total number of diabetes patients is expected to reach 366 million by 2030. Magnesium has received considerable attention for its potential role in improving insulin sensitivity and preventing diabetes and its cardiovascular complications. Hypomagnesaemia is linked to poor control of type 2 diabetes mellitus, and depletion of serum magnesium occurs exponentially with duration of disease. The aim of this study was to measure serum magnesium level and the correlation of magnesium level with HbA1c in type 2 diabetes mellitus.

Methods

In this cross‐sectional study, we included 100 diabetic patients; blood is taken for measurement of both magnesium and HbA1c levels. Patients with risk factors of magnesium deficiency were not included.

Results

Of the total 100 patients recruited in our study, majority had diabetes for 8.0 years duration. The mean age of the patients was 53.97 ± 10.65 years, most of them were on oral hypoglycaemic agents (84.9%) followed by combination of oral hypoglycaemic agents and insulin (10.5%), and a small percentage were on insulin alone (4.7%). The mean of serum magnesium and HbA1c levels was 1.88 ± 0.25 mg/dL and 8.38% ± 1.53%, respectively. The majority of the patients had a normal level of magnesium (95.0%); however, most of them had uncontrolled blood glucose (82.0%). The study showed that the serum magnesium level and HbA1c are not significantly correlated (P = 0.462).

Conclusion

Normal magnesium levels were observed in majority of patients, there is no significant correlation between serum magnesium and HbA1c levels in patients with T2DM, but larger‐scale clinical trials are needed in future.
One Pot Sequential Synthesis of N‐[2‐(Phenylsulfinyl)phenyl]acetamides: A Ring Opening Rearrangement Functionalization (RORF)
Authors: Behera Ahalya , Rakshit Amitava , Sahoo Ashish K. , Patel Bhisma K.
Published: November 2018

A CuII catalyzed one‐pot sequential synthesis of N‐[2‐(phenylthio)phenyl]acetamides from benzo[d]thiazol‐2‐amines, iodoarenes and carboxylic acids (RCOOH) has been accomplished via ring opening rearrangement functionalization (RORF). Here, the ring opening is associated with the loss of carbon and nitrogen atoms with concurrent S‐arylation and N‐acylation leading to ortho‐bifunctionalized products. A further sequential addition of tert‐butyl hydroperoxide (TBHP) results in the formation of a sulfur oxidized product, N‐[2‐(phenylsulfinyl)phenyl]acetamide. A plausible mechanism has been proposed for this unprecedented ring opening rearrangement functionalization (RORF).
Interrater reliability in visual identification of interictal high‐frequency oscillations on electrocorticography and scalp EEG
Authors: Nariai Hiroki , Wu Joyce Y. , Bernardo Danilo , Fallah Aria , Sankar Raman , Hussain Shaun A.
Published: November 2018

High‐frequency oscillations (HFOs), including ripples (Rs) and fast ripples (FRs), are promising biomarkers of epileptogenesis, but their clinical utility is limited by the lack of a standardized approach to identification. We set out to determine whether electroencephalographers experienced in HFO analysis can reliably identify and quantify interictal HFOs. Two blinded raters independently reviewed 10 intraoperative electrocorticography (ECoG) samples from epilepsy surgery cases, and 10 scalp EEG samples from epilepsy monitoring unit evaluations. HFOs were visually marked using bandpass filters (R, 80–250 Hz; FR, 250–500 Hz) with a sampling frequency of 2,000 Hz. There was agreement as to the presence or absence of epileptiform discharges (EDs), Rs, and FRs, in 17, 18, and 18 cases, respectively. Interrater reliability (IRR) was favorable with κ = 0.70, 0.80, and 0.80, respectively, and similar for ECoG and scalp electroencephalography (EEG). Furthermore, interclass correlation for rates of Rs (0.99, 95% confidence interval [CI] 0.96–0.99) and FRs (0.77, 95% CI 0.41–0.91) were superior in comparison to EDs (0.37, 95% CI −0.60 to 0.75). Our data suggest that HFO identification and quantification are reliable among experienced electroencephalographers. Our findings support the reliability of utilizing HFO data in both research and clinical arenas.
RGD‐modified dihydrolipoamide dehydrogenase as a molecular bridge for enhancing the adhesion of bone forming cells to titanium dioxide implant surfaces
Authors: Dayan Avraham , Lamed Raphael , Benayahu Dafna , Fleminger Gideon
Published: November 2018

Titanium and its alloys are widely used in dental‐ and orthopedic implants, the outer surface of which is often oxidized to titanium dioxide (TiO2). To achieve efficient osseointegration with bone‐forming cells, it is desirable to counter the formation of the soft fibrous tissue around the implant by creating strong and stable interactions between the implant surface and bone‐forming osteoblasts. To address this challenge, a bioactive coating had to be designed. Protein adsorption to TiO2 is well known in the literature, but it is mostly characterized by weak associations, rendering less efficient implant osseointegration. We have previously demonstrated the unique conjugation between the dihydrolipoamide dehydrogenase (DLDH) protein and TiO2 surfaces, based on specific coordinative bonding via Cys–His–Glu–Asp motif residues. To enhance cell binding to DLDH and facilitate osseointegration, DLDH was bioengineered to include Arg–Gly–Asp (RGD) moieties (DLDHRGD). Coating TiO2 disks with DLDHRGD led to improved adherence of integrin‐expressing osteogenic MBA‐15 to the surface of the disks. Following the enhanced adsorption, higher proliferation rates of the adherent cells, as well as faster mineralization were observed, compared to controls. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 545–551, 2019.
Combinational effects of mechanical forces and substrate surface characteristics on esophageal epithelial differentiation
Authors: Wu Yanru , Kang Yun Gyeong , Cho Hana , Kim In Gul , Chung Eun‐Jae , Shin Jung‐Woog
Published: November 2018

Even the efficacy of substrate and mechanical stimuli in addition to biochemical cues have been recognized in many studies of stem cell differentiation, few studies have been reported on the differentiation into esophageal epithelial cells. Therefore, the aim of this study was set to propose a method of differentiating stem cells into esophageal epithelial cells according to biochemical reagent concentration, substrate properties, and mechanical forces. After the concentration of all‐trans retinoic acid was determined as 5 μM by a baseline experiment, the degree of differentiation was compared in three different kinds of substrates: cover glass, polyurethane (PU) membrane, and electrospun PU sheet (ePU). Then, on the substrate showing the more positive results, that is, ePU, two types of mechanical forces, intermittent hydrostatic pressure (IHP), and shear stress (SS), were applied individually at different magnitudes for the latter 7 days of an overall incubation period of 14 days. Following various biological assays, the lower IHP (50 mmHg) resulted in greater positive effects than the others. Even with cessation of the mechanical force, the relevant markers were remarkably increased. Although the range of factors regulating differentiation was limited, this study nonetheless demonstrated the combinational effects of mechanical force along with substrate type for the first time in related studies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 552–560, 2019.
Peptide‐modified methacrylated glycol chitosan hydrogels as a cell‐viability supporting pro‐angiogenic cell delivery platform for human adipose‐derived stem/stromal cells
Authors: Dhillon Jobanpreet , Young Stuart A. , Sherman Stephen E. , Bell Gillian I. , Amsden Brian G. , Hess David A. , Flynn Lauren E.
Published: November 2018

Cell‐based therapies involving the injection of adipose‐derived stem/stromal cells (ASCs) within rationally designed biomaterials are a promising approach for stimulating angiogenesis. With this focus, the current work explored the effects of incorporating integrin‐binding RGD or IKVAV peptides within in situ‐gelling N‐methacrylate glycol chitosan (MGC) hydrogels on the response of encapsulated human ASCs. Initial studies focused on hydrogel characterization to validate that the MGC, MGC‐RGD, and MGC‐IKVAV hydrogels had similar biomechanical properties. ASC viability following encapsulation and culture under 2% O2 was significantly impaired in the MGC‐IKVAV group relative to the MGC and MGC‐RGD groups. In contrast, sustained viability, along with enhanced cell spreading and metabolic activity were observed in the MGC‐RGD group. Investigation of angiogenic transcription suggested that the incorporation of the peptide groups did not substantially alter the pro‐angiogenic gene expression profile of the encapsulated ASCs after 7 days of culture under 2% O2. Consistent with the in vitro findings, preliminary in vivo characterization following subcutaneous implantation into NOD/SCID mice showed that ASC retention was enhanced in the MGC‐RGD hydrogels relative to the MGC‐IKVAV group at 14 days. Further, the encapsulated ASCs in the MGC and MGC‐RGD groups promoted murine CD31+ endothelial cell recruitment to the peri‐implant region. Overall, the results indicate that the MGC‐RGD and MGC hydrogels are promising platforms for ASC delivery, and suggest that strategies that support long‐term ASC viability can augment in vivo angiogenesis through paracrine mechanisms. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 571–585, 2019.
Surface mineralized hybrid nanofibrous scaffolds based on poly(l‐lactide) and alginate enhances osteogenic differentiation of stem cells
Authors: Ataie Maryam , Shabani Iman , Seyedjafari Ehsan
Published: November 2018

Surface mineralized nanofibrous scaffolds hold great potential for bone tissue engineering applications. In this study, a new hybrid nanofibrous scaffold composed of alginate/poly(l‐lactide) nanofibers was fabricated using electrospinning method and then crosslinking process was employed. Hydroxyapatite crystal formation took place using in situ precipitation by immersion of the scaffolds in simulated body fluid solution for 10 days at 37°C. The morphologies of the scaffolds were observed using scanning electron microscope. Hydroxyapatite crystal formation on the surface of nanofibers was confirmed using scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, Fourier transform infrared spectroscopy and X‐ray diffraction analysis. The biocompatibility of the fabricated scaffolds was evaluated using mesenchymal stem cell culture and MTT assay. According to alkaline phosphatase activity and calcium content assays, it was concluded that the osteogenic differentiation of stem cells was considerable on scaffolds containing hydroxyapatite crystals in comparison with other specimens. The results showed biocompatibility of the scaffolds and their support from stem cell adhesion, growth and osteogenic differentiation, so the hydroxyapatite‐coated poly(l‐lactide)/alginate hybrid nanofibrous scaffolds hold suitable characteristics for bone tissue engineering applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 586–596, 2019.
miR‐124‐3p attenuates neuropathic pain induced by chronic sciatic nerve injury in rats via targeting EZH2
Authors: Zhang Yang , Liu Hai‐Lin , An Li‐Jun , Li Lin , Wei Meng , Ge Dong‐Jian , Su Zhen
Published: November 2018

Emerging evidence has suggested that microRNAs play a critical role in neuropathic pain development. However, the biological role of miRNAs in regulating neuropathic pain remains barely known. In our present study, we found that miR‐124‐3p was significantly downregulated in rats after chronic sciatic nerve injury (CCI). In addition, it was showed that overexpression of miR‐124‐3p obviously repressed mechanical allodynia and heat hyperalgesia. Meanwhile, it has been reported that neuroinflammation can contribute a lot to neuropathic pain progression. Here, we found that inflammatory cytokine (IL‐6, IL‐1β, and TNF‐⍺) protein expression in rats after CCI greatly increased and miR‐124‐3p mimics depressed inflammation cytokine levels. Consistently, miR‐124‐3p alleviated inflammation production in lipopolysaccharide‐incubated spinal microglial cells. Bioinformatics analysis revealed that EZH2 acted as a direct target of miR‐124‐3p, which participated in the miR‐124‐3p‐modulated effects on neuropathic pain development and neuroinflammation. We observed that miR‐124‐3p was able to promote neuroinflammation and neuropathic pain through targeting EZH2. The direct correlation between them was validated in our current study using dual‐luciferase reporter assays. Subsequently, it was manifested that EZH2 abrogated the inhibitory role of miR‐124‐3p on neuropathic pain progression in CCI rats. Taken these together, our findings highlighted a novel contribution of miR‐124‐3p to neuropathic pain and indicated the possibilities for developing novel therapeutic options for neuropathic pain.
Theaflavin and epigallocatechin‐3‐gallate synergistically induce apoptosis through inhibition of PI3K/Akt signaling upon depolymerizing microtubules in HeLa cells
Authors: Chakrabarty Subhendu , Nag Debasish , Ganguli Arnab , Das Amlan , Ghosh Dastidar Debabrata , Chakrabarti Gopal
Published: November 2018

Theaflavin (TF) and epigallocatechin‐3‐gallate (EGCG) both have been reported previously as microtubule depolymerizing agents that also have anticancer effects on various cancer cell lines and in animal models. Here, we have applied TF and EGCG in combination on HeLa cells to investigate if they can potentiate each other to improve their anticancer effect in lower doses and the underlying mechanism. We found that TF and EGCG acted synergistically, in lower doses, to inhibit the growth of HeLa cells. We found the combination of 50 µg/mL TF and 20 µg/mL EGCG to be the most effective combination with a combination index of 0.28. The same combination caused larger accumulation of cells in the G
2/M phase of the cell cycle, potent mitochondrial membrane potential loss, and synergistic augmentation of apoptosis. We have shown that synergistic activity might be due to stronger microtubule depolymerization by simultaneous binding of TF and EGCG at different sites on tubulin: TF binds at vinblastine binding site on tubulin, and EGCG binds near colchicines binding site on tubulin. A detailed mechanistic analysis revealed that stronger microtubule depolymerization caused effective downregulation of PI3K/Akt signaling and potently induced mitochondrial apoptotic signals, which ultimately resulted in the apoptotic death of HeLa cells in a synergistic manner.
Molecular mechanism and role of microRNA‐93 in human cancers: A study based on bioinformatics analysis, meta‐analysis, and quantitative polymerase chain reaction validation
Authors: Gao Yun , Deng Kaifeng , Liu Xuexiang , Dai Meiyu , Chen Xiaoli , Chen Jifei , Chen Jianming , Huang Yujie , Dai Shengming , Chen Jingfan
Published: November 2018

Introduction

Currently, studies have shown that microRNA‐93 (miR‐93) can be an oncogene or a tumor suppressor in different kinds of cancers. The role of miR‐93 in human cancers is inconsistent and the underlying mechanism on the aberrant expression of miR‐93 is complicated.

Methods

We first conducted gene enrichment analysis to give insight into the prospective mechanism of miR‐93. Second, we performed a meta‐analysis to evaluate the clinical value of miR‐93. Finally, a validation test based on quantitative polymerase chain reaction (qPCR) was performed to further investigate the role of miR‐93 in pan‐cancer.

Results

Gene Ontology (GO) enrichment analysis results showed that the target genes of miR‐93 were closely related to transcription, and MAPK1, RBBP7 and Smad7 became the hub genes. In the diagnostic meta‐analysis, the overall sensitivity, specificity, and area under the curve were 0.76 (0.64‐0.85), 0.82 (0.64‐0.92), and 0.85 (0.82‐0.88), respectively, which suggested that miR‐93 had excellent performance on the diagnosis for human cancers. In the prognostic meta‐analysis, dysregulated miR‐93 was found to be associated with poor OS in cancer patients. In the qPCR validation test, the serum levels of miR‐93 were upregulated in breast cancer, breast hyperplasia, lung cancer, chronic obstructive pulmonary disease, nasopharyngeal cancer, hepatocellular cancer, gastric ulcer, endometrial cancer, esophageal cancer, laryngeal cancer, and prostate cancer compared with healthy controls.

Conclusions

miR‐93 could act as an effective diagnostic and prognostic factor for cancer patients. Its clinical value for cancer early diagnosis and survival prediction is promising.
Activation of mammalian terget of rapamycin kinase and glycogen synthase kinase‐3β accompanies abnormal accumulation of cholesterol in fibroblasts from Niemann‐Pick type C patients
Authors: Wos Marcin , Komiażyk Magdalena , Pikula Slawomir , Tylki‐Szymanska Anna , Bandorowicz‐Pikula Joanna
Published: November 2018

Background

Niemann Pick type C (NPC) lysosomal disorder is linked to the disruption of cholesterol transport. Recent data suggest that the molecular background of this disease is more complex. It was found that accumulation of cholesterol and glycolipids in the late endosomal/lysosomal compartment of NPC1 cells may affect mitochondrial functions.

Materials and Methods

In this study, primary skin fibroblasts derived from skin biopsies of two anonymous patients with NPC‐carrying mutations in the NPC1 gene, characterized by a high total cholesterol content, as well as two healthy donors were used. The presence of signaling proteins in the whole cell lysates and mitochondrial fractions were examined by Western blotting assay.

Results

In this report, we provide experimental evidence that in NPC1 cells, dysfunction of mitochondria and cellular metabolism, as reported by Wos et al in 2016, coexist with alterations in signal transduction pathways, such as the mammalian target of rapamycin, AKT, phosphoinositide‐dependent protein kinase‐1, glycogen synthase kinase‐3 β, and Jun amino‐terminal kinase, leading to abnormal cholesterol accumulation and distribution.

Conclusion

Differences in signal transduction between control and NPC1 cells may suggest that the latter cells experienced significant alterations in the complex molecular mechanisms that control cellular energy metabolism and vesicular transport.
Inhibitor of growth 4 inhibits cell proliferation, migration, and induces apoptosis of renal cell carcinoma cells
Authors: Sun Jiping , Xie Liyi , Lv Jing , Zhang Wenjing , Lv Jia , Liang Yu , Geng Yingzhou , Li Xudong
Published: November 2018

The inhibitor of growth 4 (ING4) is known as a tumor suppressor. The expressions of ING4 were markedly reduced in human renal clear cell carcinoma (ccRCC) tissues. However, the role of ING4 in renal cell carcinoma (RCC) remains unknown. The aim of the current study was to detect the ING4 expression level and its potential role in human RCC cell lines. Our results showed that ING4 was lowly expressed in human RCC cell lines compared with that in proximal tubular cell line. Ectopic overexpression of ING4 inhibited the proliferation, migration, and invasion properties, and as well as prevented epithelial‐mesenchymal transition (EMT) phenotype of RCC cells. In addition, ING4 overexpression induced cell apoptosis and autophagy in RCC cells. Furthermore, ING4 overexpression suppressed the activation of PI3K/Akt pathway in RCC cells. The activator of PI3K/Akt, insulin‐like growth factor 1, abolished the effects of ING4 on RCC cells. These findings indicated that ING4 presented anticancer activity in RCC cells. The effects of ING4 on RCC cells were mediated by regulating the PI3K/Akt pathway. These findings suggested that ING4 could be used for gene therapy of RCC.
A curcumin derivative hydrazinobenzoylcurcumin suppresses stem‐like features of glioblastoma cells by targeting Ca2+/calmodulin‐dependent protein kinase II
Authors: Shin Hee Jeong , Lee Sanghun , Jung Hye Jin
Published: November 2018

Glioblastoma multiforme (GBM) is the most aggressive and common type of human primary brain tumor. Glioblastoma stem‐like cells (GSCs) have been proposed to contribute to tumor initiation, progression, recurrence, and therapeutic resistance of GBM. Therefore, targeting GSCs could be a promising strategy to treat this refractory cancer. Calmodulin (CaM), a major regulator of Ca2+‐dependent signaling, controls various cellular functions via interaction with multiple target proteins. Here, we investigated the anticancer effect of hydrazinobenzoylcurcumin (HBC), a Ca
2+/CaM antagonist, against GSCs derived from U87MG and U373MG cells. HBC significantly inhibited not only the self‐renewal capacity, such as cell growth and neurosphere formation but also the metastasis‐promoting ability, such as migration and invasion of GSCs. HBC induced apoptosis of GSCs in a caspase‐dependent manner. Notably, HBC repressed the phosphorylation of Ca
2+/CaM‐dependent protein kinase II (CaMKII), c‐Met, and its downstream signal transduction mediators, thereby reducing the expression levels of GSC markers, such as CD133, Nanog, Sox2, and Oct4. In addition, the knockdown of CaMKIIγ remarkably decreased the cancer stem cell‐like phenotypes as well as the expression of stemness markers by blocking c‐Met signaling pathway in U87MG GSCs. These results suggest that HBC suppresses the stem‐like features of GBM cells via downregulation of CaM/CaMKII/c‐Met axis and therefore CaMKII may be a novel therapeutic target to eliminate GSCs.
Icaritin inhibits glioblastoma cell viability and glycolysis by blocking the IL‐6/Stat3 pathway
Authors: Li Hongchao , Liang Qinghua , Wang Lin
Published: November 2018

Glioblastoma (GBM) is a common and aggressive brain tumor that is associated with significant increase in glycolysis for energy production. Icaritin is a natural compound and exhibits anticancer activity in GBM. However, the effect of icaritin on glycolysis in GBM cells remains unclear. The aim of the current study was to investigate the effect of icaritin on glycolysis in GBM cells. The human GBM cell lines U87 and T98G were treated with icaritin or the inhibitor of Stat3 (S3I‐201) in the presence or absence of recombinant human interleukin (IL)‐6. Cell viability was measured using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5 diphenyltetrazolium bromide (MTT) assay. The glycolysis was analyzed by detecting the glucose consumption and lactate production. The Western blot analysis was conducted to detect the expressions of hexokinase 2 (HK2), signal transducer and activator of transcription 3 (Stat3), p‐Stat3, and B lymphoma Mo‐MLV insertion region 1 (Bmi‐1). Results showed that icaritin inhibited the viability of U87 and T98G cells in a dose‐dependent manner. The decreased glucose consumption and lactate production, accompanied by reduced expressions of HK2, were found in both U87 and T98G cells. Icaritin inhibited the IL‐6/Stat3 pathway, which is evidenced by the decreased expressions of p‐Stat3 and Bmi‐1. IL‐6 treatment induced the phosphorylation of Stat3 and Bmi‐1 expression, increased cell viability, as well as elevated glucose consumption, lactate production, and HK2 expression; however, the effects of IL‐6 were attenuated by icaritin or S3I‐201 treatment. In conclusion, icaritin exerted inhibitory effects on cell viability and glycolysis in GBM cells, which was mediated by the IL‐6/Stat3 pathway.
Predictive values of obesity categories for cardiovascular disease risk factors in Chinese adult population
Authors: Yin Dong , Yan Yongxin , Xu Ning , Hui Yuan , Han Guanjun , Ma Ning , Yang Chuanhui , Wang Guofeng
Published: November 2018

Objective

Whether obesity categories can be used to predict cardiovascular disease (CVD) in Chinese adults remains unclear. This aim of this study was to examine the predictive values of obesity categories for CVD risk factors in Chinese adults.

Methods

This study comprised a sample size of 3480 men and 6364 women aged ≥25 years (age range 25‐89 years), from the medical health check‐up center of Lianyungang First People's Hospital. The following CVD risk factor outcomes were used: hypertension, diabetes, dyslipidemia, insulin resistance, and metabolic syndrome (Mets). Framingham risk scores were used to evaluate the CVD. Four categories of obesity were used, based on body mass index (BMI) and waist circumference: no risk, increased risk, high risk, and very high risk. Predictive abilities were determined by calculating the odds ratios (OR) of CVD risk.

Results

A graded linear relationship between obesity categories and CVD risk was observed across the categories, except for dyslipidemia. The people in the very high‐risk category had the highest OR of having more unfavorable CVD risk factors compared with those in the lower risk category. For example, the OR of diabetes increased with the increase in risk category (OR, 1.13, 1.36, and 1.83, respectively, for increased, high, and very high risk categories in men and OR, 1.52, 1.80, and 2.78, respectively, for increased, high, and very high risk category in women).

Conclusions

These findings suggest that obesity categories provide clinical insights into identifying multiple CVD risk factors in Chinese adults.
Pyrazinamide drug resistance in RpsA mutant (∆438A) of Mycobacterium tuberculosis: Dynamics of essential motions and free‐energy landscape analysis
Authors: Singh Aditi , Somvanshi Pallavi , Grover Abhinav
Published: November 2018

Pyrazinamide is an essential first‐line antitubercular drug which plays pivotal role in tuberculosis treatment. It is a prodrug that requires amide hydrolysis by mycobacterial pyrazinamidase enzyme for conversion into pyrazinoic acid (POA). POA is known to target ribosomal protein S1 (RpsA), aspartate decarboxylase (PanD), and some other mycobacterial proteins. Spontaneous chromosomal mutations in RpsA have been reported for phenotypic resistance against pyrazinamide. We have constructed and validated 3D models of the native and Δ438A mutant form of RpsA protein. RpsA protein variants were then docked to POA and long range molecular dynamics simulations were carried out. Per residue binding free‐energy calculations, free‐energy landscape analysis, and essential dynamics analysis were performed to outline the mechanism underlying the high‐level PZA resistance conferred by the most frequently occurring deletion mutant of RpsA. Our study revealed the conformational modulation of POA binding site due to the disruptive collective modes of motions and increased conformational flexibility in the mutant than the native form. Residue wise MMPBSA decomposition and protein‐drug interaction pattern revealed the difference of energetically favorable binding site in the wild‐type (WT) protein in comparison with the mutant. Analysis of size and shape of minimal energy landscape area delineated higher stability of the WT complex than the mutant form. Our study provides mechanistic insights into pyrazinamide resistance in Δ438A RpsA mutant, and the results arising out of this study will pave way for design of novel and effective inhibitors targeting the resistant strains of Mycobacterium tuberculosis.
Dysregulation of miR‐125b predicts poor response to therapy in pediatric acute lymphoblastic leukemia
Authors: El‐Khazragy Nashwa , Elshimy Amal Ali , Hassan Safaa Shawky , Matbouly Safa , Safwat Gehan , Zannoun Mohamed , Riad Ramez. A.
Published: November 2018

Background

Acute lymphoblastic leukemia (ALL) is the most well‐known sort of leukemia in children. In spite of favorable survival rates, some patients relapse and achieve a poor outcome.

Methods

We analyzed miR‐125b and Bcl‐2 expressions in pediatric patients with ALL and evaluated their clinical utility as molecular markers for the prediction of disease outcomes.

Results

Downregulation of miR‐125b and increased Bcl‐2 expression levels in pediatric patients with ALL were associated with poor prognosis at diagnosis. At day 28 of induction, miR‐125b was significantly increased, whereas Bcl‐2 was downregulated. Loss of miR‐125b during diagnosis and its elevation after therapy are strongly correlated with short leukemia‐free survival and worse survival. Moreover, the combination of miR‐125b with Bcl‐2 markers can clearly enhance the prediction of the disease outcome. Finally, a univariate analysis highlighted the independent prognostic value of miR‐125 in a pediatric patient with ALL.

Conclusions

miR‐125b and Bcl‐2 together are potent predictors for the prognosis and, therefore, can be used as therapeutic targets in childhood ALL.