bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced Organ-on-a-Chip Devices to Investigate Liver Multi-Organ Communication: Focus on Gut, Microbiota and Brain
Authors: Boeri Lucia , Izzo Luca , Sardelli Lorenzo , Tunesi Marta , Albani Diego , Giordano Carmen
Published: September 2019

The liver is a key organ that can communicate with many other districts of the human body. In the last few decades, much interest has focused on the interaction between the liver and the gut microbiota, with their reciprocal influence on biosynthesis pathways and the integrity the intestinal epithelial barrier. Dysbiosis or liver disorders lead to0 epithelial barrier dysfunction, altering membrane permeability to toxins. Clinical and experimental evidence shows that the permeability hence the delivery of neurotoxins such as LPS, ammonia and salsolinol contribute to neurological disorders. These findings suggested multi-organ communication between the gut microbiota, the liver and the brain. With a view to in vitro modeling this liver-based multi-organ communication, we describe the latest advanced liver-on-a-chip devices and discuss the need for new organ-on-a-chip platforms for in vitro modeling the in vivo multi-organ connection pathways in physiological and pathological situations.
Enhanced Solubility and Anticancer Potential of Mansonone G By β-Cyclodextrin-Based Host-Guest Complexation: A Computational and Experimental Study
Authors: Mahalapbutr Panupong , Wonganan Piyanuch , Charoenwongpaiboon Thanapon , Prousoontorn Manchumas , Chavasiri Warinthorn , Rungrotmongkol Thanyada
Published: September 2019

Mansonone G (MG), a plant-derived compound isolated from the heartwood of Mansonia gagei, possesses a potent antitumor effect on several kinds of malignancy. However, its poor solubility limits the use for practical applications. Beta-cyclodextrin (βCD), a cyclic oligosaccharide composed of seven (1→4)-linked α-D-glucopyranose units, is capable of encapsulating a variety of poorly soluble compounds into its hydrophobic interior. In this work, we aimed to enhance the water solubility and the anticancer activity of MG by complexation with βCD and its derivatives (2,6-di-O-methyl-βCD (DMβCD) and hydroxypropyl-βCD). The 90-ns molecular dynamics simulations and MM/GBSA-based binding free energy results suggested that DMβCD was the most preferential host molecule for MG inclusion complexation. The inclusion complex formation between MG and βCD(s) was confirmed by DSC and SEM techniques. Notably, the MG/βCDs inclusion complexes exerted significantly higher cytotoxic effect (~2–7 fold) on A549 lung cancer cells than the uncomplexed MG.
The Involvement of the Banana F-Box Protein MaEBF1 in Regulating Chilling-Inhibited Starch Degradation through Interaction with a MaNAC67-Like Protein
Authors: Song Zunyang , Qin Jiajia , Zheng Qiuli , Ding Xiaochun , Chen Weixin , Lu Wangjin , Li Xueping , Zhu Xiaoyang
Published: September 2019

Low-temperature storage is a common strategy for preserving and transporting vegetables and fruits. However, many fruits are hypersensitive to chilling injury, including bananas. In the present study, storage conditions of 11 °C delayed the ripening of Fenjiao (Musa ABB Pisang Awak) banana, and the pulp could be softened after ethephon treatment. Storage conditions of 7 °C prevented fruit from fully softening, and fruit contained a significantly higher starch content and lower soluble sugar content. MaEBF1, a critical gene component in the ethylene signaling pathway, was repressed during ripening after fruit had been stored for 12 days at 7 °C. The expression of a series of starch degradation-related genes and a MaNAC67-like gene were also severely repressed. Both MaEBF1 and MaNAC67-like genes were ethylene-inducible and localized in the nucleus. MaNAC67-like protein was able to physically bind to the promoter of genes associated with starch degradation, including MaBAM6, MaSEX4, and MaMEX1. Yeast two-hybrid, GST-pull down, and BiFC assays showed that MaEBF1 interacted with the MaNAC67-like protein, and their interaction further activated the promoters of MaBAM6 and MaSEX4. The current study indicates that MaNAC67-like is a direct regulator of starch degradation and potential for involvement in regulating chilling-inhibited starch degradation by interacting with the ethylene signaling components in banana fruit. The present work paves the way for further functional analysis of MaEBF1 and MaNAC67-like in banana, which will be useful for understanding the regulation of banana starch metabolism and fruit ripening.
Transgenic Plant Detection Using an AuNPs Based SPR Biosensor
Authors: Grześkowiak Bartosz F. , Tuśnio Karol , Woźniak Anna , Szalata Marlena , Lipiński Daniel , Jurga Stefan , Słomski Ryszard
Published: September 2019

The intensive development and commercialization of genetically modified plants observed over the last decade has led to the development of transgenic detection methods that are rapid and sensitive. Among the strategies used for the detection/monitoring of genetically modified organisms (GMOs), surface plasmon resonance (SPR) meets the necessary criteria. This optical technique measures the changes in the refractive index in the vicinity of thin metal layers (i.e., gold) in response to biomolecular interactions occurring at a flat metal‒solution interface. Additionally, it allows the application of functionalized gold nanoparticles (AuNPs) in SPR research to enhance the signal intensity. In the present study, an SPR method, enhanced by the application of AuNPs, was developed to detect transgenic tobacco plants carrying a Streptococcus mutans antigen. The basis for the detection of the target DNA was the hybridization between the genomic DNA isolated from the leaves, stems, and roots of the transgenic tobacco and the biotinylated oligonucleotide probes immobilized onto a streptavidin (SA) sensor chip. SA-functionalized AuNPs coated with a second type of biotinylated probe were applied to increase the sensitivity of the detection method. Analysis of the results indicated that the constructed SPR-based sensor chip can potentially recognize complementary standard fragments (nonamplified genomic DNA) at concentrations as low as 1 pM. Thus, nonamplified transgenic DNA was detected using a label-free and real-time AuNPs-enhanced SPR biosensing method. This unique approach could be used to detect GMOs with high efficiency, even at a low detection limit, high repeatability, and with less time and a lower cost needed for each analysis.
Advances in Directly Amplifying Nucleic Acids from Complex Samples
Authors: Walker Faye M. , Hsieh Kuangwen
Published: September 2019

Advances in nucleic acid amplification technologies have revolutionized diagnostics for systemic, inherited, and infectious diseases. Current assays and platforms, however, often require lengthy experimental procedures and multiple instruments to remove contaminants and inhibitors from clinically-relevant, complex samples. This requirement of sample preparation has been a bottleneck for using nucleic acid amplification tests (NAATs) at the point of care (POC), though advances in “lab-on-chip” platforms that integrate sample preparation and NAATs have made great strides in this space. Alternatively, direct NAATs—techniques that minimize or even bypass sample preparation—present promising strategies for developing POC diagnostic tools for analyzing real-world samples. In this review, we discuss the current status of direct NAATs. Specifically, we surveyed potential testing systems published from 1989 to 2017, and analyzed their performances in terms of robustness, sensitivity, clinical relevance, and suitability for POC diagnostics. We introduce bubble plots to facilitate our analysis, as bubble plots enable effective visualization of the performances of these direct NAATs. Through our review, we hope to initiate an in-depth examination of direct NAATs and their potential for realizing POC diagnostics, and ultimately transformative technologies that can further enhance healthcare.
Short- and Mid-Term Improvement of Postural Balance after a Neurorehabilitation Program via Hippotherapy in Patients with Sensorimotor Impairment after Cerebral Palsy: A Preliminary Kinetic Approach
Authors: Viruega Hélène , Gaillard Inès , Carr John , Greenwood Bill , Gaviria Manuel
Published: September 2019

There is still a lack of studies focused on trunk neurorehabilitation. Accordingly, it is unclear which therapeutic modalities are the most effective in improving static/dynamic balance after brain damage. We designed a pilot study on hippotherapy to assess its short- and mid-term effect on dynamic postural balance in patients with moderate-to-severe sensorimotor impairment secondary to cerebral palsy. Five patients aged 15.4 ± 6.1 years old were recruited. All of them had moderate-to-severe alterations of the muscle tone with associated postural balance impairment. Standing and walking were also impaired. Ten minutes horse riding simulator followed by twenty minutes hippotherapy session were conducted during five session days separated by one week each. We analyzed the displacement of the Center of Pressure (COP) on the sitting surface of the simulator’s saddle by means of a customized pressure pad. We measured the general behavior of the COP displacement as well as the postural adjustments when pace changed from walk to trot to walk during the sessions and among sessions. Statistical analysis revealed an improved postural control both by the end of the session and from session 1 to session 5. These results suggest that hippotherapy might support regularization of postural control in a long-term neurorehabilitation context.
Hospital Outcomes in Antepartum Mental Disorders: A Study on 897,397 Pregnant Inpatients
Authors: Bhimanadham Narmada N. , Mainali Pranita , Robert Chris A. , Masroor Anum , Onyeaka Henry K. , Hossain Sadaf , Patel Rikinkumar S.
Published: September 2019

Objective: To evaluate the impact of antepartum mental disorders (AMD) in medical and psychiatric comorbidities, and inpatient outcomes during hospitalizations for pregnancy/birth-related complications. Methods: We used the national inpatient sample (NIS) data and included 19,170,562 female patients (age, 12–40 years) with a principal diagnosis of pregnancy/birth-related complications and grouped by co-diagnoses of AMD (N = 897,397). We used a binomial logistic regression model to evaluate the odds ratio (OR) for major severity of illness and adjusted for demographic confounders. Results: The hospitalizations with AMD increased by 22.1% (p < 0.001) from 2010 to 2014. White females (66.1%) and those from low-income families (<25th percentile, 31.8%) majorly had comorbid AMD. Depression (43.8%) and drug abuse (27%) were prevalent psychiatric disorders in AMD inpatients. Comorbid AMD inpatients had a higher likelihood for major severity of illness (OR 2.475, 95% CI 2.459–2.491, p < 0.001). They also had a longer hospitalization stay with a mean difference of 0.486 days (95% CI 0.480–0.491) and higher total charges by $1889.420 per admission (95% CI 1852.670–1926.170) than non-AMD inpatients. Conclusions: AMD is associated with worsening of severity of illness in pregnancy/birth-related complications and require acute inpatient care. Mental health assessment and treatment of AMD, and education about efficacy and safety of psychiatric medications may help to improve outcomes in these patients.
Sustainable Strategies for the Adaptive Reuse of Religious Heritage: A Social Opportunity
Authors: Lo Faro Alessandro , Miceli Alessia
Published: September 2019

The legacy of built heritage is one of the most critical questions of our time—the objective of preserving its immaterial values and exploiting its original vocation brings about challenges related to the history, the identity, and the quality of life of the concerned territory. This especially applies to religious buildings given their strong bond with collective memory. The aim of this research is to determine whether allocating new uses that pursuit social benefits for the community is a possible implementation of the aforementioned purposes and whether it better addresses a broader view of sustainable development, which encompasses equity and well-being. The methodology combines careful knowledge of the building, comparing residual performances of the fabric with new functions. We present a case study, with focus on healthcare-related accommodation facilities and the issue of healthcare migration, which aims to convert a dismissed capuchin convent, located in Villagonia (Taormina, Italy), into a shelter house to host families whose relatives are being treated at the neighbourhood medical centre. This proposal shows that heritage buildings, especially religious ones, have outstanding material and immaterial potential and, through good reuse practices, they provide a valuable opportunity to address the overarching objective of social sustainability.
N6-Isopentenyladenosine Inhibits Colorectal Cancer and Improves Sensitivity to 5-Fluorouracil Targeting FBXW7 Tumor Suppressor
Authors: Fiore Donatella , Piscopo Chiara , Proto Maria , Vasaturo Michele , Dal Piaz Fabrizio , Fusco Bruno , Pagano Cristina , Laezza Chiara , Bifulco Maurizio , Gazzerro Patrizia
Published: September 2019

N6-isopentenyladenosine has been shown to exert potent in vitro antitumor activity on different human cancers, including colorectal cancer. Although some potential biochemical targets have been identified, its precise mechanism of action remains unclear. We found that N6-isopentenyladenosine affects colorectal cancer proliferation in in vitro models carrying different mutational status of FBXW7 and TP53 genes, and in HCT116 xenografts in SCID mice, by increasing the expression of the well-established tumor suppressor FBXW7, a component of the SCF-E3 ubiquitin ligase complex that promotes degradation of various oncoproteins and transcription factors, such as c-Myc, SREBP and Mcl1. Corroborating our previous studies, we identified for the first time the FBXW7/SREBP/FDPS axis as a target of the compound. Pull down of ubiquitinated proteins, immunoprecipitation and luciferase assays, reveal that through the increase of FBXW7/c-Myc binding, N6-isopentenyladenosine induces the ubiquitination of c-Myc, inhibiting its transcriptional activity. Moreover, in FBXW7- and TP53-wild type cells, N6-isopentenyladenosine strongly synergizes with 5-Fluorouracil to inhibit colon cancer growth in vitro. Our results provide novel insights into the molecular mechanism of N6-isopentenyladenosine, revealing its multi-targeting antitumor action, in vitro and in vivo. Restoring of FBXW7 tumor-suppressor represents a valid therapeutic tool, enabling N6-isopentenyladenosine as optimizable compound for patient-personalized therapies in colorectal cancer.
PTEN and Gynecological Cancers
Authors: Nero Camilla , Ciccarone Francesca , Pietragalla Antonella , Scambia Giovanni
Published: September 2019

PTEN is a tumour suppressor gene, and its loss of function is frequently observed in both heritable and sporadic cancers. It is involved in a great variety of biological processes, including maintenance of genomic stability, cell survival, migration, proliferation and metabolism. A better understanding of PTEN activity and regulation has therefore emerged as a subject of primary interest in cancer research. Gynaecological cancers are variously interested by PTEN deregulation and many perspective in terms of additional prognostic information and new therapeutic approaches can be explored. Here, we present the most significant findings on PTEN in gynaecological cancers (ovarian, endometrial, cervical, vulvar and uterine cancer) focusing on PTEN alterations incidence, biological role and clinical implications.
FADD in Cancer: Mechanisms of Altered Expression and Function, and Clinical Implications
Authors: Marín-Rubio José L , Vela-Martín Laura , Fernández-Piqueras José , Villa-Morales María
Published: September 2019

FADD was initially described as an adaptor molecule for death receptor-mediated apoptosis, but subsequently it has been implicated in nonapoptotic cellular processes such as proliferation and cell cycle control. During the last decade, FADD has been shown to play a pivotal role in most of the signalosome complexes, such as the necroptosome and the inflammasome. Interestingly, various mechanisms involved in regulating FADD functions have been identified, essentially posttranslational modifications and secretion. All these aspects have been thoroughly addressed in previous reviews. However, FADD implication in cancer is complex, due to pleiotropic effects. It has been reported either as anti- or protumorigenic, depending on the cell type. Regulation of FADD expression in cancer is a complex issue since both overexpression and downregulation have been reported, but the mechanisms underlying such alterations have not been fully unveiled. Posttranslational modifications also constitute a relevant mechanism controlling FADD levels and functions in tumor cells. In this review, we aim to provide detailed, updated information on alterations leading to changes in FADD expression and function in cancer. The participation of FADD in various biological processes is recapitulated, with a mention of interesting novel functions recently proposed for FADD, such as regulation of gene expression and control of metabolic pathways. Finally, we gather all the available evidence regarding the clinical implications of FADD alterations in cancer, especially as it has been proposed as a potential biomarker with prognostic value.
Risk of Hematologic Malignant Neoplasms after Postoperative Treatment of Breast Cancer
Authors: Jabagi Marie Joelle , Goncalves Anthony , Vey Norbert , Le Tri Thien , Zureik Mahmoud , Dray-Spira Rosemary
Published: September 2019

An indirect consequence of the improved long-term survival seen in patients with breast cancer (BC) is the increased risk of hematologic malignant neoplasms (HM). This study aimed to analyze the role of postoperative treatment for BC in the development of subsequent HM. Using the French National Health Data System, we examined the HM risks in patients diagnosed with an incident primary breast cancer between 2007 and 2015, who underwent surgery as first-line treatment for BC. Main outcomes were acute myeloid leukemia (AML), Myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), multiple myeloma (MM), Hodgkin’s lymphoma or non-Hodgkin’s lymphoma (HL/NHL), and acute lymphoblastic leukemia or lymphocytic lymphoma (ALL/LL). Analyses were censored at HM occurrence, death, loss to follow up, or December 2017. The risk of each type of HM was compared according to the initial postoperative treatment of breast cancer. Of a total of 324,056 BC survivors, 15.5% underwent surgery only, 46.7% received radiotherapy after surgery, 4.3% received chemotherapy after surgery, and 33.5% received all three modalities. Overall, 2236 cases of hematologic malignancies occurred. Compared to the surgery alone group, AML was significantly increased after surgery plus radiation (aHR, 1.5; 95% CI, 1.0–2.1), surgery plus chemotherapy (aHR, 2.1; 95% CI, 1.2–3.6) and all modalities (aHR, 3.3; 95% CI, 2.3–4.7). MDS was significantly increased after surgery plus chemotherapy (aHR, 1.7; 95% CI, 1.1–2.5) or after all modalities (aHR, 1.4; 95% CI, 1.1–1.8). HL/NHL were significantly increased only in the radiotherapy and surgery group (aHR, 1.3; 95% CI, 1.0–1.6). A nonsignificant increase of ALL/LL (aHR, 1.8; 95% CI, 0.6–3.5) was noted after chemotherapy and with all three modalities (aHR, 1.4; 95% CI, 0.7–2.8). Our population based study revealed increased risks of various HM associated with postoperative BC treatment. The added benefit of chemotherapy and radiation therapy should take into consideration these long-term complications.
Autophagy Function and Dysfunction: Potential Drugs as Anti-Cancer Therapy
Authors: Cuomo Francesca , Altucci Lucia , Cobellis Gilda
Published: September 2019

Autophagy is a highly conserved catabolic and energy-generating process that facilitates the degradation of damaged organelles or intracellular components, providing cells with components for the synthesis of new ones. Autophagy acts as a quality control system, and has a pro-survival role. The imbalance of this process is associated with apoptosis, which is a “positive” and desired biological choice in some circumstances. Autophagy dysfunction is associated with several diseases, including neurodegenerative disorders, cardiomyopathy, diabetes, liver disease, autoimmune diseases, and cancer. Here, we provide an overview of the regulatory mechanisms underlying autophagy, with a particular focus on cancer and the autophagy-targeting drugs currently approved for use in the treatment of solid and non-solid malignancies.
Lower Extremity Lymphedema in Gynecologic Cancer Patients: Propensity Score Matching Analysis of External Beam Radiation versus Brachytherapy
Authors: Chang Won Ick , Kang Hyun-Cheol , Wu Hong-Gyun , Kim Hak Jae , Jeon Seung Hyuck , Lee Maria , Kim Hee Seung , Chung Hyun Hoon , Kim Jae Weon , Park Noh Hyun , Song Yong Sang , Seo Kwan-Sik
Published: September 2019

The goal of this study is to compare the risk of lower extremity lymphedema (LEL) between pelvic external beam radiation therapy (EBRT) and vaginal brachytherapy, and to identify risk factors for LEL in gynecologic cancer patients treated with adjuvant radiation therapy (RT) after radical surgery. A total of 263 stage I–III gynecologic cancer patients who underwent adjuvant RT were retrospectively reviewed. One-to-one case-matched analysis was conducted with propensity scores generated from patient, tumor, and treatment characteristics. Using the risk factors found in this study, high- and low-risk groups were identified. With a median follow-up of 36.0 months, 35 of 263 (13.3%) patients developed LEL. In multivariate analysis, laparoscopic surgery (HR 2.548; p = 0.024), harvesting more than 30 pelvic lymph nodes (HR 2.246; p = 0.028), and para-aortic lymph node dissection (PALND, HR 2.305; p = 0.014) were identified as independent risk factors for LEL. After propensity score matching, the LEL incidence of the brachytherapy group was significantly lower than the EBRT group (p = 0.025). In conclusion, high-risk patients with risk factors such as laparoscopic surgery, harvesting more than 30 pelvic lymph nodes, PALND, and adjuvant pelvic EBRT require closer observation for LEL.
Exosomal microRNAs from Longitudinal Liquid Biopsies for the Prediction of Response to Induction Chemotherapy in High-Risk Neuroblastoma Patients: A Proof of Concept SIOPEN Study ‖
Authors: Morini Martina , Cangelosi Davide , Segalerba Daniela , Marimpietri Danilo , Raggi Federica , Castellano Aurora , Fruci Doriana , Font de Mora Jaime , Cañete Adela , Yáñez Yania , Viprey Virginie , Corrias Maria Valeria , Carlini Barbara , Pezzolo Annalisa , Schleiermacher Gudrun , Mazzocco Katia , Ladenstein Ruth , Sementa Angela Rita , Conte Massimo , Garaventa Alberto , Burchill Susan , Luksch Roberto , Bosco Maria Carla , Eva Alessandra , Varesio Luigi
Published: September 2019

Despite intensive treatment, 50% of children with high-risk neuroblastoma (HR-NB) succumb to their disease. Progression through current trials evaluating the efficacy of new treatments for children with HR disease usually depends on an inadequate response to induction chemotherapy, assessed using imaging modalities. In this study, we sought to identify circulating biomarkers that might be detected in a simple blood sample to predict patient response to induction chemotherapy. Since exosomes released by tumor cells can drive tumor growth and chemoresistance, we tested the hypothesis that exosomal microRNA (exo-miRNAs) in blood might predict response to induction chemotherapy. The exo-miRNAs expression profile in plasma samples collected from children treated in HR-NBL-1/SIOPEN before and after induction chemotherapy was compared to identify a three exo-miRs signature that could discriminate between poor and good responders. Exo-miRNAs expression also provided a chemoresistance index predicting the good or poor prognosis of HR-NB patients.
Improvement of the Photocatalytic Activity of ZnO/Burkeite Heterostructure Prepared by Combustion Method
Authors: Luna-Flores A. , Morales M.A. , Agustín-Serrano R. , Portillo R. , Luna-López J.A. , Pérez-Sánchez G.F. , Luz A.D. Hernández-de la , Tepale N.
Published: September 2019

In this work, a novel route is discussed to produce in one step ZnO/Burkeite powders by the modified solution combustion method. The ZnO particles enhance the photocatalytic activity in the degradation of Rhodamine B, in which Burkeite mineral acts as a support due to the pH-dependent morphology of the particle aggregates of the as-synthesized powders. The X-ray diffraction (XRD) characterization shows the presence of a heterostructure: ZnO/Burkeite. The Scanning Electron Microscopy (SEM) image shows a morphological dependence with the pH of the solution used for the synthesis. The results show that the system with the highest degradation (92.4%) corresponds to the case in which ZnO/Burkeite heterostructure was synthesized with a pH 11.
Surface Modification of Nanocrystalline TiO2 Materials with Sulfonated Porphyrins for Visible Light Antimicrobial Therapy
Authors: Sułek Adam , Pucelik Barbara , Kobielusz Marcin , Łabuz Przemysław , Dubin Grzegorz , Dąbrowski Janusz M.
Published: September 2019

Highly-active, surface-modified anatase TiO2 nanoparticles were successfully synthesized and characterized. The morphological and optical properties of the obtained (metallo)porphyrin@qTiO2 materials were evaluated using absorption and fluorescence spectroscopy, scanning electron microscopy (SEM) imaging, and dynamic light scattering (DLS). These hybrid nanoparticles efficiently generated reactive oxygen species (ROS) under blue-light irradiation (420 ± 20 nm) and possessed a unimodal size distribution of 20–70 nm in diameter. The antimicrobial performance of the synthetized agents was examined against Gram-negative and Gram-positive bacteria. After a short-term incubation of microorganisms with nanomaterials (at 1 g/L) and irradiation with blue-light at a dose of 10 J/cm2, 2–3 logs of Escherichia coli, and 3–4 logs of Staphylococcus aureus were inactivated. A further decrease in bacteria viability was observed after potentiation photodynamic inactivation (PDI), either by H2O2 or KI, resulting in complete microorganism eradication even when using low material concentration (from 0.1 g/L). SEM analysis of bacteria morphology after each mode of PDI suggested different mechanisms of cellular disruption depending on the type of generated oxygen and/or iodide species. These data suggest that TiO2-based materials modified with sulfonated porphyrins are efficient photocatalysts that could be successfully used in biomedical strategies, most notably, photodynamic inactivation of microorganisms.
Rh(III)-Catalyzed C–H Bond Activation for the Construction of Heterocycles with sp3-Carbon Centers
Authors: Wang Run , Xie Xiong , Liu Hong , Zhou Yu
Published: September 2019

Rh(III)-catalyzed C–H activation features mild reaction conditions, good functional group tolerance, high reaction efficiency, and regioselectivity. Recently, it has attracted tremendous attention and has been employed to synthesize various heterocycles, such as indoles, isoquinolines, isoquinolones, pyrroles, pyridines, and polyheterocycles, which are important privileged structures in biological molecules, natural products, and agrochemicals. In this short review, we attempt to present an overview of recent advances in Rh(III)-mediated C–H bond activation to generate diverse heterocyclic scaffolds with sp3 carbon centers.
Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo
Authors: Alberca Custodio Ricardo W. , Mirotti Luciana , Gomes Eliane , Nunes Fernanda P.B. , S. Vieira Raquel , Graça Luís , R. Almeida Rafael , S. Câmara Niels O. , Russo Momtchilo
Published: September 2019

Elevated levels of immunoglobulin E (IgE) are associated with allergies and other immunological disorders. Sensitization with alum adjuvant favours IgE production while CpG-ODN adjuvant, a synthetic toll-like receptor 9 (TLR9) agonist, inhibits it. The cellular mechanisms underlying in vivo TLR regulation of immunoglobulin production, specially IgE, are still controversial. Specifically, TLR-mediated IgE regulation in vivo is not yet known. In this study we showed that augmented levels of IgE induced by sensitizations to OVA with or without alum adjuvant or with OVA-pulsed dendritic cells (DCs) were inhibited by co-administration of CpG. Notably, CpG-mediated suppression of IgE production required MyD88-expression on DCs but not on B-cells. This finding contrasts with previous in vitro studies reporting regulation of IgE by a direct action of CpG on B cells via MyD88 pathway. In addition, we showed that CpG also inhibited IgE production in a MyD88-dependent manner when sensitization was performed with OVA-pulsed DCs. Finally, CpG signalling through MyD88 pathway was also necessary and sufficient to prevent anaphylactic antibody production involved in active cutaneous anaphylaxis.
Reciprocal Regulation of TRPS1 and miR-221 in Intervertebral Disc Cells
Authors: Penolazzi Letizia , Lambertini Elisabetta , Scussel Bergamin Leticia , Gandini Carlotta , Musio Antonio , De Bonis Pasquale , Cavallo Michele , Piva Roberta
Published: September 2019

Intervertebral disc (IVD), a moderately moving joint located between the vertebrae, has a limited capacity for self-repair, and treating injured intervertebral discs remains a major challenge. The development of innovative therapies to reverse IVD degeneration relies primarily on the discovery of key molecules that, occupying critical points of regulatory mechanisms, can be proposed as potential intradiscal injectable biological agents. This study aimed to elucidate the underlying mechanism of the reciprocal regulation of two genes differently involved in IVD homeostasis, the miR-221 microRNA and the TRPS1 transcription factor. Human lumbar IVD tissue samples and IVD primary cells were used to specifically evaluate gene expression and perform functional analysis including the luciferase gene reporter assay, chromatin immunoprecipitation, cell transfection with hTRPS1 overexpression vector and antagomiR-221. A high-level expression of TRPS1 was significantly associated with a lower pathological stage, and TRPS1 overexpression strongly decreased miR-221 expression, while increasing the chondrogenic phenotype and markers of antioxidant defense and stemness. Additionally, TRPS1 was able to repress miR-221 expression by associating with its promoter and miR-221 negatively control TRPS1 expression by targeting the TRPS1-3′UTR gene. As a whole, these results suggest that, in IVD cells, a double-negative feedback loop between a potent chondrogenic differentiation suppressor (miR-221) and a regulator of axial skeleton development (TRPS1) exists. Our hypothesis is that the hostile degenerated IVD microenvironment may be counteracted by regenerative/reparative strategies aimed at maintaining or stimulating high levels of TRPS1 expression through inhibition of one of its negative regulators such as miR-221.
Wnt Signaling in Neural Crest Ontogenesis and Oncogenesis
Authors: Ji Yu , Hao Hongyan , Reynolds Kurt , McMahon Moira , Zhou Chengji J.
Published: September 2019

Neural crest (NC) cells are a temporary population of multipotent stem cells that generate a diverse array of cell types, including craniofacial bone and cartilage, smooth muscle cells, melanocytes, and peripheral neurons and glia during embryonic development. Defective neural crest development can cause severe and common structural birth defects, such as craniofacial anomalies and congenital heart disease. In the early vertebrate embryos, NC cells emerge from the dorsal edge of the neural tube during neurulation and then migrate extensively throughout the anterior-posterior body axis to generate numerous derivatives. Wnt signaling plays essential roles in embryonic development and cancer. This review summarizes current understanding of Wnt signaling in NC cell induction, delamination, migration, multipotency, and fate determination, as well as in NC-derived cancers.
Syncytiotrophoblast of Placentae from Women with Zika Virus Infection Has Altered Tight Junction Protein Expression and Increased Paracellular Permeability
Authors: Miranda Jael , Martín-Tapia Dolores , Valdespino-Vázquez Yolotzin , Alarcón Lourdes , Espejel-Nuñez Aurora , Guzmán-Huerta Mario , Muñoz-Medina José Esteban , Shibayama Mineko , Chávez-Munguía Bibiana , Estrada-Gutiérrez Guadalupe , Lievano Samuel , Ludert Juan Ernesto , González-Mariscal Lorenza
Published: September 2019

The cytotrophoblast of human placenta transitions into an outer multinucleated syncytiotrophoblast (STB) layer that covers chorionic villi which are in contact with maternal blood in the intervillous space. During pregnancy, the Zika virus (ZIKV) poses a serious prenatal threat. STB cells are resistant to ZIKV infections, yet placental cells within the mesenchyme of chorionic villi are targets of ZIKV infection. We seek to determine whether ZIKV can open the paracellular pathway of STB cells. This route is regulated by tight junctions (TJs) which are present in the uppermost portion of the lateral membranes of STB cells. We analyzed the paracellular permeability and expression of E-cadherin, occludin, JAMs –B and –C, claudins -1, -3, -4, -5 and -7, and ZO-1, and ZO-2 in the STB of placentae from ZIKV-infected and non-infected women. In ZIKV-infected placentae, the pattern of expression of TJ proteins was preserved, but the amount of claudin-4 diminished. Placentae from ZIKV-infected women were permeable to ruthenium red, and had chorionic villi with a higher mean diameter and Hofbauer hyperplasia. Finally, ZIKV added to the basolateral surface of a trophoblast cell line reduced the transepithelial electrical resistance. These results suggest that ZIKV can open the paracellular pathway of STB cells.
Photosensitizer Activation Drives Apoptosis by Interorganellar Ca2+ Transfer and Superoxide Production in Bystander Cancer Cells
Authors: Nardin Chiara , Peres Chiara , Mazzarda Flavia , Ziraldo Gaia , Salvatore Anna Maria , Mammano Fabio
Published: September 2019

In cells, photosensitizer (PS) activation by visible light irradiation triggers reactive oxygen species (ROS) formation, followed by a cascade of cellular responses involving calcium (Ca2+) and other second messengers, resulting in cell demise. Cytotoxic effects spread to nearby cells not exposed to light by poorly characterized so-called “bystander effects”. To elucidate the mechanisms involved in bystander cell death, we used both genetically encoded biosensors and fluorescent dyes. In particular, we monitored the kinetics of interorganellar Ca2+ transfer and the production of mitochondrial superoxide anion (O2−∙) and hydrogen peroxide (H2O2) in irradiated and bystander B16-F10 mouse melanoma cancer cells. We determined that focal PS photoactivation in a single cell triggers Ca2+ release from the endoplasmic reticulum (ER) also in the surrounding nonexposed cells, paralleled by mitochondrial Ca2+ uptake. Efficient Ca2+ efflux from the ER was required to promote mitochondrial O2−∙ production in these bystander cells. Our results support a key role for ER–mitochondria communication in the induction of ROS-mediated apoptosis in both direct and indirect photodynamical cancer cell killing.
Insights into Biological Role of LncRNAs in Epithelial-Mesenchymal Transition
Authors: Cheng Jun-Ting , Wang Lingzhi , Wang Hong , Tang Feng-Ru , Cai Wen-Qi , Sethi Gautam , Xin Hong-Wu , Ma Zhaowu
Published: September 2019

Long non-coding RNAs (lncRNAs) are versatile regulators of gene expression and play crucial roles in diverse biological processes. Epithelial-mesenchymal transition (EMT) is a cellular program that drives plasticity during embryogenesis, wound healing, and malignant progression. Increasing evidence shows that lncRNAs orchestrate multiple cellular processes by modulating EMT in diverse cell types. Dysregulated lncRNAs that can impact epithelial plasticity by affecting different EMT markers and target genes have been identified. However, our understanding of the landscape of lncRNAs important in EMT is far from complete. Here, we summarize recent findings on the mechanisms and roles of lncRNAs in EMT and elaborate on how lncRNAs can modulate EMT by interacting with RNA, DNA, or proteins in epigenetic, transcriptional, and post-transcriptional regulation. This review also highlights significant EMT pathways that may be altered by diverse lncRNAs, thereby suggesting their therapeutic potential.
Update on the Genetics of Systemic Lupus Erythematosus: Genome-Wide Association Studies and Beyond
Authors: Kwon Young-Chang , Chun Sehwan , Kim Kwangwoo , Mak Anselm
Published: September 2019

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of complex etiology that primarily affects women of childbearing age. The development of SLE is attributed to the breach of immunological tolerance and the interaction between SLE-susceptibility genes and various environmental factors, resulting in the production of pathogenic autoantibodies. Working in concert with the innate and adaptive arms of the immune system, lupus-related autoantibodies mediate immune-complex deposition in various tissues and organs, leading to acute and chronic inflammation and consequent end-organ damage. Over the past two decades or so, the impact of genetic susceptibility on the development of SLE has been well demonstrated in a number of large-scale genetic association studies which have uncovered a large fraction of genetic heritability of SLE by recognizing about a hundred SLE-susceptibility loci. Integration of genetic variant data with various omics data such as transcriptomic and epigenomic data potentially provides a unique opportunity to further understand the roles of SLE risk variants in regulating the molecular phenotypes by various disease-relevant cell types and in shaping the immune systems with high inter-individual variances in disease susceptibility. In this review, the catalogue of SLE susceptibility loci will be updated, and biological signatures implicated by the SLE-risk variants will be critically discussed. It is optimistically hoped that identification of SLE risk variants will enable the prognostic and therapeutic biomarker armamentarium of SLE to be strengthened, a major leap towards precision medicine in the management of the condition.
An Agonist of the CXCR4 Receptor Strongly Promotes Regeneration of Degenerated Motor Axon Terminals
Authors: Negro Samuele , Zanetti Giulia , Mattarei Andrea , Valentini Alice , Megighian Aram , Tombesi Giulia , Zugno Alessandro , Dianin Valentina , Pirazzini Marco , Fillo Silvia , Lista Florigio , Rigoni Michela , Montecucco Cesare
Published: September 2019

The activation of the G-protein coupled receptor CXCR4 by its ligand CXCL12α is involved in a large variety of physiological and pathological processes, including the growth of B cells precursors and of motor axons, autoimmune diseases, stem cell migration, inflammation, and several neurodegenerative conditions. Recently, we demonstrated that CXCL12α potently stimulates the functional recovery of damaged neuromuscular junctions via interaction with CXCR4. This result prompted us to test the neuroregeneration activity of small molecules acting as CXCR4 agonists, endowed with better pharmacokinetics with respect to the natural ligand. We focused on NUCC-390, recently shown to activate CXCR4 in a cellular system. We designed a novel and convenient chemical synthesis of NUCC-390, which is reported here. NUCC-390 was tested for its capability to induce the regeneration of motor axon terminals completely degenerated by the presynaptic neurotoxin α-Latrotoxin. NUCC-390 was found to strongly promote the functional recovery of the neuromuscular junction, as assayed by electrophysiology and imaging. This action is CXCR4 dependent, as it is completely prevented by AMD3100, a well-characterized CXCR4 antagonist. These data make NUCC-390 a strong candidate to be tested in human therapy to promote nerve recovery of function after different forms of neurodegeneration.
Visual Narrative of the Loss of Energy after Natural Disasters
Authors: Castañeda-Garza Gerardo , Valerio-Ureña Gabriel , Izumi Takako
Published: September 2019

Concerns exists regarding natural disasters, but what about the resulting power outages? This study investigates the characteristics of a digital visual narrative depicting the loss of electrical power after a natural disaster to identify how such situations are represented in images found on the internet. A qualitative approach with an exploratory scope was taken using digital methods. Six events in different places were selected, and 4691 images were analyzed using the Google Cloud Vision API. A constant comparison method was used to identify categories from these images. Then, a manual analysis was performed on a sample of the images of each event, and then categorized. It was found that more than half of the images refer to categories such as infrastructure, nature, and hazards, while the energy category was represented in 13.02% of the images. Most images were photographs; however, the non-photographic images found contained useful information regarding energy. Even when all events featuring power outages, few focused on the lack of energy and more on impacts to the infrastructure, despite energy being required for cities’ recovery.
Multi-Layered Mesoporous TiO2 Thin Films: Photoelectrodes with Improved Activity and Stability
Authors: Gent Enno , Taffa Dereje H. , Wark Michael
Published: September 2019

This work aims at the identification of porous titanium dioxide thin film (photo)electrodes that represent suitable host structures for a subsequent electrodeposition of plasmonic nanoparticles. Sufficient UV absorption and electrical conductivity were assured by adjusting film thickness and TiO 2 crystallinity. Films with up to 10 layers were prepared by an evaporation-induced self-assembly (EISA) method and layer-by-layer deposition. Activities were tested towards the photoelectrochemical oxidation of water under UV illumination. Enhanced activities with each additional layer were observed and explained with increased amounts of immobilized TiO 2 and access to more active sites as a combined effect of increased surface area, better crystallinity and improved transport properties. Furthermore, films display good electrochemical and mechanical stability, which was related to the controlled intermediate thermal annealing steps, making these materials a promising candidate for future electrochemical depositions of plasmonic noble metal nanoparticles that has been further demonstrated by incorporation of gold.
Benefits of Nanomedicine for Therapeutic Intervention in Malignant Diseases
Authors: Sevastre Ani-Simona , Horescu Cristina , Carina Baloi Stefania , Cioc Catalina Elena , Vatu Bogdan Ionel , Tuta Cristian , Artene Stefan Alexandru , Danciulescu Maria Mihaela , Tudorache Stefania , Dricu Anica
Published: September 2019

Cancer remains one of the most difficult to manage healthcare problems. The last two decades have been considered the golden age of cancer research, with major breakthroughs being announced on a regular basis. However, the major problem regarding cancer treatment is the incapability to selectively target cancer cells, with certain populations of tumors still remaining alive after treatment. The main focus of researchers is to develop treatments that are both effective and selective in targeting malignant cells. In this regard, bioavailability can be increased by overcoming the biological barriers encountered in the active agent’s pathway, creating carrier vehicles that have the ability to target malignant cells and effectively release the active agent. Since its appearance, nanomedicine has provided many answers to these challenges, but still, some expectations were not satisfied. In this review, we focused on the most recent developments in targeted drug delivery. Furthermore, a summary of different types of nanoparticles used to deliver active therapeutic agents in oncology is presented, along with details on the nanodrugs that were clinically approved by the Food and Drug Administration (FDA), until April 2019.
First-Principles Calculations of Structural, Mechanical, and Electronic Properties of the B2-Phase NiTi Shape-Memory Alloy Under High Pressure
Authors: Yu Fang , Liu Yu
Published: September 2019

A first-principles calculation program is used for investigating the structural, mechanical, and electronic properties of the cubic NiTi shape-memory alloy (SMA) with the B2 phase under high pressure. Physical parameters including dimensionless ratio, elastic constants, Young’s modulus, bulk modulus, shear modulus, ductile-brittle transition, elastic anisotropy, and Poisson’s ratio are computed under different pressures. Results indicate that high pressure enhances the ability to resist volume deformation along with the ductility and metallic bonds, but the biggest resistances to elastic and shear deformation occur at P = 35   GPa for the B2-phase NiTi SMA. Meanwhile, the strong anisotropy produced by the high pressure will motivate the cross-slip process of screw dislocations, thereby improving the plasticity of the B2-phase NiTi SMA. Additionally, the results of the density of states (DOS) reveal that the B2-phase NiTi SMA is essentially characterized by the metallicity, and it is hard to induce the structural phase transition for the B2-phase NiTi SMA under high pressure, which provides valuable guidance for designing and applying the NiTi SMA under high pressure.
The Predictive Power of Different Projector-Augmented Wave Potentials for Nuclear Quadrupole Resonance
Authors: Ansari Jaafar N. , Sauer Karen L. , Glasbrenner James K.
Published: September 2019

The projector-augmented wave (PAW) method is used to calculate electric field gradients (EFG) for various PAW potentials. A variety of crystals containing reactive nonmetal, simple metal, and transition elements, are evaluated in order to determine the predictive ability of the PAW method for the determination of nuclear quadrupole resonance frequencies in previously unstudied materials and their polymorphs. All results were compared to experimental results and, where possible, to previous density functional theory (DFT) calculations. The EFG at the 14N site of NaNO2 is calculated by DFT for the first time. The reactive nonmetal elements were not very sensitive to the variation in PAW potentials, and calculations were quite close to experimental values. For the other elements, the various PAW potentials led to a clear spread in EFG values, with no one universal potential emerging. Within the spread, there was agreement with other ab initio models.
2D Monte Carlo Simulation of Patchy Particles Association and Protein Crystal Polymorph Selection
Authors: Ranguelov Bogdan , Nanev Christo
Published: September 2019

Typically, protein crystals inherit the polymorphic form selected by nuclei arising in the solution. However, a transition of a polymorphic form may also occur at a later crystal growth stage. Unfortunately, due to the molecular-scale processes involved, the earliest stages of protein crystal nucleation and polymorph selection remain poorly understood. This paper attempts to elucidate the polymorph selection and crystal growth process in proteins (and colloidal crystals) using 2D Monte Carlo simulations and a computational model with short-range attraction for ‘protein-like’ patchy particles (PPs) of a specific patch geometry, bond width and strength. A relatively narrow temperature range is established whereby parts of the PPs monomers arrange initially in a rapidly growing unstable rhombohedral lattice (Rh). Stable trimers form simultaneously from the monomers remaining in the solution and monomers released from the Rh lattice. These trimers serve as building blocks of a more stable Kagome trihexagonal lattice (TriHex), which appears after a prolonged simulation time. The step-by-step scenario of this polymorphic transition and the specific role of PPs’ geometric and interaction anisotropies are discussed in detail.