bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymorphism of the Myostatin (MSTN) Gene in Landes and Kielecka Geese Breeds
Authors: Smołucha Grzegorz , Kozubska-Sobocińska Anna , Koseniuk Anna , Żukowski Kacper , Lisowski Mirosław , Grajewski Bartosz
Published: December 2019

Myostatin, also known as growth differentiation factor 8 (GDF8), belongs to the TGF- β superfamily of proteins. MSTN is a highly conserved protein that acts as a negative regulator of skeletal muscle growth. Loss of myostatin functionality causes the phenotype to appear in the form of ‘double musculature’, among others in cattle, sheep, and house mice. The presented results of the research were carried out on two geese breeds—Landes and Kielecka. The aim of the study was to identify mutations in the MSTN gene and study their impact on body weight in both geese breeds in different periods of life. Analysis of the obtained results showed the existence of polymorphism in exon 3 (c.1231C>T) and suggested a possible association (p < 0.05) between BW and genotype in 12 weeks of life in male Kielecka geese breed. The identified polymorphism may be one of the factors important for improving body weight in the studied Kielecka breed, therefore, it is necessary to conduct further research on a larger population of geese breeds in order to more accurately estimate the effect of the identified SNP c.1231C>T on BW in geese.
Effects of B-Wave Ultraviolet Supplementation Using Light-Emitting Diodes on Caged Laying Hens during the Later Phase of the Laying Cycle
Authors: Wei Yongxiang , Zheng Weichao , Li Baoming , Tong Qin , Shi Haipeng , Li Xuanyang
Published: December 2019

Caged laying hens are prone to calcium deficiencies, resulting in osteoporosis and egg quality deterioration during the later phase of the laying cycle. Fluorescent light and light-emitting diodes (LEDs), which are widely used in poultry houses now, are both deficient in ultraviolet (UV) light, the lack of which is detrimental to chickens’ welfare and health. This study was conducted to investigate the effects of UVB light supplementation using LEDs on the bone traits, blood parameters, laying performance, and egg quality for caged laying hens at 68–75 weeks. In total, 120 Jingfen laying hens were randomly assigned to four different groups, with three replicates in each group (10 hens in each cage as a replicate). UVB-LED lamps installed under the feed troughs were used to provide UVB light (296–316 nm) for the birds in the three treatment groups (1 h, 2 h, and 3 h UVB supplementation per day, respectively), while the control group was not exposed to UVB-LED light. Bone traits, egg quality, and amounts of calcium (Ca), phosphorus (P), 25-hydroxyvitamin D3 (25(OH)D3), 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and 7-dehydrocholesterol (7-DHC) in both the serum and egg yolks were tested during the experiment. The results demonstrated that UVB-LED exposure significantly increased the bone mineral density (BMD), egg production, and yolk 1,25(OH)2D3 concentrations (p < 0.05), and reduced the content of serum 7-DHC (p < 0.05), especially in the 2 h/day group; however, it did not improve egg quality, vitamin D metabolites, or photoproducts in the serum and yolk 25(OH)2D3 concentrations (p > 0.05). This study concluded that UVB supplementation using LEDs had a positive effect on caged laying hens during the later phase of the laying cycle.
Weaning Performance of Beef Cattle Calves Based on Concentrate Intake
Authors: Wang Chong , Li Dongping , Yang Jinyong , Xia Yuefeng , Tu Yan , White Robin , Gao Hui , Diao Qiyu , Mao Huiling
Published: December 2019

This study was conducted to investigate the effects of weaning based upon different concentrate intake on growth performance, health, and antioxidant status of Southern Chinese Cattle. Thirty female calves were used in the trial. Weaning strategy was the primary variable of interest and treatments included weaning when a calf consumed 1000 (W1000), 750 (W750), or 500 (W500) g of starter for three consecutive days. All calves received colostrum within 4 h of birth and colostrum intake was monitored to ensure all calves consumed 1.5 L within 12 h of birth. Calves were then fed fresh milk up to 2 L/d for 7 days. Between d 7 and 13, calves were fed a liquid feed composed of 50% fresh milk, and 50% milk replacer (MR) at maximum rate of 3 L/d. For the remainder of the study, calves were provided 3 L/d MR. Concentrate (starter), and grass hay were available ad libitum starting on d 1. Milk, MR, starter, and hay intakes were recorded daily. Calf body weights and measurements were recorded at birth and every 4 wk until weaning. Average weaning ages were 48 ± 4.5, 58 ± 4.6, and 65 ± 4.8 for W500, W750, and W1000, respectively. Between wk 8 and wk 21, calves in the W500 and W750 treatments had higher (p < 0.05) starter intakes than calves in the W1000 treatment. Body height, body length, circumference of cannon bone, circumference of the chest did not differ with weaning strategy (p > 0.05). There was no difference in body weight (BW) and average daily gain (ADG) on wk 5 when any of the calves were weaned (p > 0.05). In wk 9, BW of calves in W1000 tended to be higher than that of W750 and W500 (p = 0.10). However, calves in W1000 lost their BW advantage in wk 13. Calves’ ADG was not different during the whole experiment period among treatments. Calves in W750 had higher plasma BHBA and the total antioxidant capacity which has been associated with a positive impact on health. Data in this experiment suggest that weaning when calves consume 750 g of starter can enhance ADG, DMI, feed efficiency, and selected blood parameters compared with weaning when calves consume 500 g of starter.
Isolation of Mycobacterium avium Subsp. Paratuberculosis in the Feces and Tissue of Small Ruminants Using a Non-Automated Liquid Culture Method
Authors: De Grossi Luigi , Santori Davide , Barone Antonino , Abbruzzese Silvia , Ricchi Matteo , Marcario Gaetana Anita
Published: December 2019

Paratuberculosis is a chronic disease of ruminants caused by Mycobacterium avium subsp. Paratuberculosis (MAP). Since isolation of MAP type I (S) is rarely reported in Italy, our research was aimed at isolating, by an inexpensive liquid culture manual method, this type of MAP isolates. At first, we used an ELISA to point out to serologically positive samples from five flocks. Secondly, we used a fecal direct IS900-qPCR on the ELISA positive samples, in order to detect shedder animals. Feces from IS900-qPCR positive samples were inoculated in solid and liquid culture media. IS900-qPCR was further used to test the growth of MAP isolates in liquid medium, which were further confirmed by f57-qPCR and submitted to typing by specific PCR in order to identify the MAP type. Twenty-eight samples (24 fecal and four tissutal samples) were processed by culture methods, resulting in the isolation of six type I MAP field isolates. Notably, no isolates were recovered by solid media, underlining the utility of this liquid method. Few data about this type of MAP are currently available in Italy, and further analyses should be carried out in order to study the origin and epidemiology of type I strains circulating in Italy.
Optimising the Efficacy of Equine Welfare Communications: Do Equine Stakeholders Differ in Their Information-Seeking Behaviour and Communication Preferences?
Authors: Pickering Persephone , Hockenhull Jo
Published: December 2019

Information on the management of animals within domestic environments is freely available to animal owners and caregivers either online, or in paper form by request. However, awareness is growing within the animal welfare sector that simply providing written guidelines or educational material is not enough to affect a positive change in owners in relation to animal welfare. In the quest to improve equine welfare, understanding the way that owners and other stakeholders seek information and their communication preferences is key to effective dissemination of up to date equine welfare information and research findings. Three UK equine stakeholder groups—horse owners, livery yard owners, and equine veterinarians—were surveyed online to find out where they sought equine information. Their awareness of equine welfare Codes of Practice, how they respond when they are asked to give advice to horse owners and their communication preferences were included within the survey. All three stakeholder groups tended to seek information from people rather than from organisations, or digital and printed resources. Veterinarians were the most used information source across all three stakeholder groups This highlighted the importance of ensuring that equine veterinarians have access to up to date, evidence-based equine welfare information. While the majority of participants were aware of the equine welfare Code of Practice, fewer had actually read it, this was true particularly amongst horse owners. The primary reasons for this were the features of the Code as well as the issuing organisation. The stakeholders expressed a preference for information to be communicated in a neutral or positive way rather than focusing on negative aspects. Our findings suggest that industry professionals, particularly veterinarians, have an important role to play in knowledge transfer and the dissemination of research findings to horse owners. The efficacy of equine welfare communication could be improved if the information delivery preferences of equine stakeholders are were taken into consideration.
Impact of Sodium Nitrite Reduction on Lipid Oxidation and Antioxidant Properties of Cooked Meat Products
Authors: Karwowska Małgorzata , Kononiuk Anna , Wójciak Karolina M.
Published: December 2019

Oxidation processes are responsible for reduction of the sensory and nutritional quality of meat and meat products, thus affecting consumer acceptance. The use of sodium nitrite in meat processing is an important factor limiting these changes. Therefore, eliminating this substance from the recipe of meat products to increase their nutritional value is not an easy challenge. The aim of this study was to determine the effect of sodium nitrite reduction on the lipid oxidation (peroxide value, thiobarbituric acid reactive substances), and color parameters (CIE L*a*b*, total heme pigment and heme iron, nitrosylmyoglobin) in cooked meat products during 15 days of vacuum storage. The antioxidant properties of products and isolated peptides (2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS•), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferric-reducing antioxidant power) were also evaluated. Experimental material included four different sample groups of cooked meat products produced with various percentages of sodium nitrite (0, 50, 100, and 150 mg kg−1). It was shown that the sodium nitrite dose had no statistically significant effect on lightness (L*) and redness (a*) values, as well as nitrosylmyoglobin content. Along with decreasing the share of sodium nitrite in the samples, the thiobarbituric acid reactive substances (TBARS) value increased from 0.43 mg kg−1 for samples with 150 mg kg−1 at day 0 to 3.14 mg kg−1 for samples without nitrite at day 15. The total ABTS scavenging capacity of the cooked meat samples was in the range 2.48 to 4.31 eqv. mM Trolox per g of product throughout the entire storage period. During storage, the ferric-reducing antioxidant power of samples with nitrite increased from 0.25 to 0.38 eqv. mg/mL ascorbic acid per g of product. In conclusion, reduction of nitrite to the level of 50 mg kg−1 seemed to be comparable with the traditional use of nitrite in meat products in terms of the physicochemical properties and properties related to lipid oxidation, as well as total antioxidant capacity and peptide antioxidant capacity.
Influence of Approaching Excavation on Adjacent Segments for Twin Tunnels
Authors: Li Shaohua , Li Pengfei , Zhang Mingju , Liu Yi
Published: December 2019

This paper aims at influence analysis of approaching excavation on adjacent segments for twin tunnels with variable clear spacing located in Beijing, China. A series of numerical simulations have been conducted to investigate the influence of approaching excavation on ground displacements and mechanical responses of segments. What’s more, on-site monitoring was conducted at the position of the minimum spacing between the twin tunnels. It is found that the deformation of the measured segment presents a pronounced asymmetric ovalization when the second tunnel approaches the measured cross-section. During the approaching excavation of the second tunnel, the normal force increases gradually, whereas the bending moment first decreases and then increases. The maximum increments of internal forces in the measured segment are both located at the regions near the second tunnel, in which the springline and shoulder of the segment are mainly subject to the effect of the circumferential compression and axial tension. The approaching excavation reduces the horizontal displacements of the ground between twin tunnels and increases the ground settlements as well as the horizontal displacements of the ground on both sides. The actual tunneling case of first along the curved trajectory and then along the straight-line trajectory can reduce internal forces of the segment.
Analysis of the Influence of High Peening Coverage on Almen Intensity and Residual Compressive Stress
Authors: Yang Zhaorui , Lee Youngseog , He Shangwen , Jia Wenzhen , Zhao Jun
Published: December 2019

The effectiveness of shot peening is mainly determined by the peening coverage. The peening coverage is required to be 100% for current technical standards of shot peening. With the increase of material strength, higher peening coverage is required in shot peening process. However, the influence of high peening coverage on Almen intensity and residual compressive stress is unclear, the difficulty mainly lies in the lack of quantitative description of peening coverage in finite element analysis. To analyze the influence of high peening coverage on Almen intensity and residual compressive stress, firstly an approximate quantitative description of peening coverage based on dent size, the distance of shots and shot numbers is proposed in this study. Based on this quantitative description of peening coverage, the arc height and residual stress of the Almen test are simulated with the finite element method. The simulation results of arc height and saturation curve agree well with that of the Almen test, by which the effectiveness of the quantitative description and FE simulation are proved. The further study indicates that in shot peening processes, the excessive peening coverage doesn’t improve Almen intensity and residual compressive stress.
Value Stream Analysis in Military Logistics: The Improvement in Order Processing Procedure
Authors: Acero Raquel , Torralba Marta , Pérez-Moya Roberto , Pozo José Antonio
Published: December 2019

Military logistics is a complex process where response times, demand uncertainty, wide variety of material references, and cost-effectiveness are decisive for combat capability. The demanding flexibility can only be achieved by improving supply chain management (SCM) to minimize lead times. To cope with these requirements, lean thinking can be extended to military organizations. This research justifies and proposes the use of lean methodologies to improve logistics processes with the case study of a military unit. In particular, the article presents the results obtained using value stream mapping (VSM) and value stream design (VSD) tools to improve the order processing lead time of spare items. The procedure starts with an order generation from a military unit that requests the material and ends before transportation to the final destination. The whole project was structured, considering the define–measure–analyze–improve–control (DMAIC) problem-solving methodology. The results show that the future state map might increase added-value activities from 44% to 70%. After implementation, it was demonstrated that the methodology applied reduced the lead-time average and deviation up to 69.6% and 61.9%, respectively.
Tribology Properties of Synthesized Multiscale Lamellar WS2 and Their Synergistic Effect with Anti-Wear Agent ZDDP
Authors: Wu Na , Hu Ningning , Wu Jinhe , Zhou Gongbo
Published: December 2019

The microscale/nanoscale lamellar-structure WS2 particles with sizes of 2 µm and 500 nm were synthesized by solid-phase reaction method and characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The synergies between microscale/nanoscale WS2 particles and ZDDP as lubricating oil additives was evaluated by means of UMT-2 tribometer at room temperature. The wear scars were examined with SEM and electron-probe micro-analyzer (EPMA). The results show that the anti-wear properties were improved and the friction coefficient was greatly decreased with the simultaneous addition of WS2 particles and ZDDP, and the largest reduction of friction coefficient was 47.2% compared with that in base oil. Moreover, the presence of ZDDP additive in the lubricant further enhances the friction-reduction and anti-wear effect of microscale/nanoscale WS2. This confirms that there is a synergistic effect between WS2 particles and ZDDP.
Stepwise Assessment of Different Saltation Theories in Comparison with Field Observation Data
Authors: Lee Haeju , Park Sung Hoon
Published: December 2019

Wind-blown dust models use input data, including soil conditions and meteorology, to interpret the multi-step wind erosion process and predict the quantity of dust emission. Therefore, the accuracy of the wind-blown dust models is dependent on the accuracy of each input condition and the robustness of the model schemes for each elemental step of wind erosion. A thorough evaluation of a wind-blown model thus requires validation of the input conditions and the elemental model schemes. However, most model evaluations and intercomparisons have focused on the final output of the models, i.e., the vertical dust emission. Recently, a delicate set of measurement data for saltation flux and friction velocity was reported from the Japan-Australia Dust Experiment (JADE) Project, which enabled the step-by-step evaluation of wind-blown dust models up to the saltation step. When all the input parameters were provided from the observations, both the two widely used saltation schemes showed very good agreement with measurements, with the correlation coefficient and the agreement of index both being larger than 0.9, which demonstrated the strong robustness of the physical schemes for saltation. However, using the meteorology model to estimate the input conditions such as weather and soil conditions, considerably degraded the models’ performance. The critical reason for the model failure was determined to be the inaccuracy in the estimation of the threshold friction velocity (representing soil condition), followed by inaccurate estimation of surface wind speed. It was not possible to determine which of the two saltation schemes was superior, based on the present study results. Such differentiation will require further evaluation studies using more measurements of saltation flux and vertical dust emissions.
Direct Numerical Simulation of Fog: The Sensitivity of a Dissipation Phase to Environmental Conditions
Authors: Karimi Mona
Published: December 2019

The sensitivity of fog dissipation to the environmental changes in radiation, liquid-water lapse rate, free tropospheric temperature and relative humidity was studied through numerical experiments designed based on the 2007-Paris Fog observations. In particular, we examine how much of the stratocumulus-thinning mechanism can be extended to the near-surface clouds or fog. When the free troposphere is warmed relative to the reference case, fog-top descends and become denser. Reducing the longwave radiative cooling via a more emissive free troposphere favors thickening the physical depth of fog, unlike cloud-thinning in a stratocumulus cloud. Drying the free troposphere allows fog thinning and promotes fog dissipation while sustaining the entrainment rate. The numerical simulation results suggest that the contribution of entrainment drying is more effective than the contribution of entrainment warming yielding the reduction in liquid water path tendency and promoting the onset of fog depletion relative to the reference case studied here. These sensitivity experiments indicate that the fog lifting mechanism can enhance the effect of the inward mixing at the fog top. However, to promote fog dissipation, an inward mixing mechanism only cannot facilitate removing humidity in the fog layer unless a sufficient entrainment rate is simultaneously sustained.
Challenges Faced with Small Molecular Modulators of Potassium Current Channel Isoform Kv1.5
Authors: Zhao Zefeng , Ruan Songsong , Ma Xiaoming , Feng Qian , Xie Zhuosong , Nie Zhuang , Fan Peinan , Qian Mingcheng , He Xirui , Wu Shaoping , Zhang Yongmin , Zheng Xiaohui
Published: December 2019

The voltage-gated potassium channel Kv1.5, which mediates the cardiac ultra-rapid delayed-rectifier (IKur) current in human cells, has a crucial role in atrial fibrillation. Therefore, the design of selective Kv1.5 modulators is essential for the treatment of pathophysiological conditions involving Kv1.5 activity. This review summarizes the progress of molecular structures and the functionality of different types of Kv1.5 modulators, with a focus on clinical cardiovascular drugs and a number of active natural products, through a summarization of 96 compounds currently widely used. Furthermore, we also discuss the contributions of Kv1.5 and the regulation of the structure-activity relationship (SAR) of synthetic Kv1.5 inhibitors in human pathophysiology. SAR analysis is regarded as a useful strategy in structural elucidation, as it relates to the characteristics that improve compounds targeting Kv1.5. Herein, we present previous studies regarding the structural, pharmacological, and SAR information of the Kv1.5 modulator, through which we can assist in identifying and designing potent and specific Kv1.5 inhibitors in the treatment of diseases involving Kv1.5 activity.
Platinum Derivatives Effects on Anticancer Immune Response
Authors: Rébé Cédric , Demontoux Lucie , Pilot Thomas , Ghiringhelli François
Published: December 2019

Along with surgery and radiotherapy, chemotherapeutic agents belong to the therapeutic arsenal in cancer treatment. In addition to their direct cytotoxic effects, these agents also impact the host immune system, which might enhance or counteract their antitumor activity. The platinum derivative compounds family, mainly composed of carboplatin, cisplatin and oxaliplatin, belongs to the chemotherapeutical arsenal used in numerous cancer types. Here, we will focus on the effects of these molecules on antitumor immune response. These compounds can induce or not immunogenic cell death (ICD), and some strategies have been found to induce or further enhance it. They also regulate immune cells’ fate. Platinum derivatives can lead to their activation. Additionally, they can also dampen immune cells by selective killing or inhibiting their activity, particularly by modulating immune checkpoints’ expression.
PARP1 Inhibition Augments UVB-Mediated Mitochondrial Changes—Implications for UV-Induced DNA Repair and Photocarcinogenesis
Authors: Hegedűs Csaba , Boros Gábor , Fidrus Eszter , Kis Gréta Nikoletta , Antal Miklós , Juhász Tamás , Janka Eszter Anna , Jankó Laura , Paragh György , Emri Gabriella , Bai Péter , Remenyik Éva
Published: December 2019

Keratinocytes provide the first line of defense of the human body against carcinogenic ultraviolet (UV) radiation. Acute and chronic UVB-mediated cellular responses were widely studied. However, little is known about the role of mitochondrial regulation in UVB-induced DNA damage. Here, we show that poly (ADP-ribose) polymerase 1 (PARP1) and ataxia-telangiectasia-mutated (ATM) kinase, two tumor suppressors, are important regulators in mitochondrial alterations induced by UVB. Our study demonstrates that PARP inhibition by ABT-888 upon UVB treatment exacerbated cyclobutane pyrimidine dimers (CPD) accumulation, cell cycle block and cell death and reduced cell proliferation in premalignant skin keratinocytes. Furthermore, in human keratinocytes UVB enhanced oxidative phosphorylation (OXPHOS) and autophagy which were further induced upon PARP inhibition. Immunoblot analysis showed that these cellular responses to PARP inhibition upon UVB irradiation strongly alter the phosphorylation level of ATM, adenosine monophosphate-activated kinase (AMPK), p53, protein kinase B (AKT), and mammalian target of rapamycin (mTOR) proteins. Furthermore, chemical inhibition of ATM led to significant reduction in AMPK, p53, AKT, and mTOR activation suggesting the central role of ATM in the UVB-mediated mitochondrial changes. Our results suggest a possible link between UVB-induced DNA damage and metabolic adaptations of mitochondria and reveal the OXPHOS-regulating role of autophagy which is dependent on key metabolic and DNA damage regulators downstream of PARP1 and ATM.
Hypertonicity-Affected Genes Are Differentially Expressed in Clear Cell Renal Cell Carcinoma and Correlate with Cancer-Specific Survival
Authors: Kandabarau Siarhei , Leiz Janna , Krohn Knut , Winter Stefan , Bedke Jens , Schwab Matthias , Schaeffeler Elke , Edemir Bayram
Published: December 2019

The heterogeneity of renal cell carcinoma (RCC) subtypes reflects the cell type of origin in the nephron, with consequences for therapy and prognosis. The transcriptional cues that determine segment-specific gene expression patterns are poorly understood. We recently showed that hypertonicity in the renal medulla regulates nephron-specific gene expression. Here, we analyzed a set of 223 genes, which were identified in the present study by RNA-Seq to be differentially expressed by hypertonicity, for the prediction of cancer-specific survival (CSS). Cluster analyses of these genes showed discrimination between tumor and non-tumor samples of clear cell RCC (ccRCC). Refinement of this gene signature to a four-gene score (OSM score) through statistical analyses enabled prediction of CSS in ccRCC patients of The Cancer Genome Atlas (TCGA) (n = 436) in univariate (HR = 4.1; 95% CI: 2.78−6.07; p = 4.39 × 10−13), and multivariate analyses including primary tumor (T); regional lymph node (N); distant metastasis (M); grading (G)(p = 2.3 × 10−5). The OSM score could be validated in an independent ccRCC study (n = 52) in univariate (HR = 1.29; 95% CI = 1.05–1.59; p = 0.011) and multivariate analyses (p = 0.016). Cell culture experiments using RCC cell lines demonstrated that the expression of the tumor suppressor ELF5 could be restored by hypertonicity. The innovation of our novel gene signature is that these genes are physiologically regulated only by hypertonicity, thereby providing the possibility to be targeted for therapy.
Overcoming Drug Resistance by Taking Advantage of Physical Principles: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)
Authors: Nadiradze Giorgi , Horvath Philipp , Sautkin Yaroslav , Archid Rami , Weinreich Frank-Jürgen , Königsrainer Alfred , Reymond Marc A.
Published: December 2019

Theoretical considerations as well as comprehensive preclinical and clinical data suggest that optimizing physical parameters of intraperitoneal drug delivery might help to circumvent initial or acquired resistance of peritoneal metastasis (PM) to chemotherapy. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a novel minimally invasive drug delivery system systematically addressing the current limitations of intraperitoneal chemotherapy. The rationale behind PIPAC is: (1) optimizing homogeneity of drug distribution by applying an aerosol rather than a liquid solution; (2) applying increased intraperitoneal hydrostatic pressure to counteract elevated intratumoral interstitial fluid pressure; (3) limiting blood outflow during drug application; (4) steering environmental parameters (temperature, pH, electrostatic charge etc.) in the peritoneal cavity for best tissue target effect. In addition, PIPAC allows repeated application and objective assessment of tumor response by comparing biopsies between chemotherapy cycles. Although incompletely understood, the reasons that allow PIPAC to overcome established chemoresistance are probably linked to local dose intensification. All pharmacological data published so far show a superior therapeutic ratio (tissue concentration/dose applied) of PIPAC vs. systemic administration, of PIPAC vs. intraperitoneal liquid chemotherapy, of PIPAC vs. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) or PIPAC vs. laparoscopic HIPEC. In the initial introduction phase, PIPAC has been used in patients who were quite ill and had already failed multiple treatment regimes, but it may not be limited to that group of patients in the future. Rapid diffusion of PIPAC in clinical practice worldwide supports its potential to become a game changer in the treatment of chemoresistant isolated PM of various origins.
miR-10a-5p and miR-29b-3p as Extracellular Vesicle-Associated Prostate Cancer Detection Markers
Authors: Worst Thomas Stefan , Previti Christopher , Nitschke Katja , Diessl Nicolle , Gross Julia Christina , Hoffmann Lena , Frey Lisa , Thomas Vanessa , Kahlert Christoph , Bieback Karen , Torres Crigna Adriana , Fricke Fabia , Porubsky Stefan , Westhoff Niklas , von Hardenberg Jost , Nuhn Philipp , Erben Philipp , Michel Maurice Stephan , Boutros Michael
Published: December 2019

Extracellular vesicles (EVs) are shed by many different cell types. Their nucleic acids content offers new opportunities for biomarker research in different solid tumors. The role of EV RNA in prostate cancer (PCa) is still largely unknown. EVs were isolated from different benign and malignant prostate cell lines and blood plasma from patients with PCa (n = 18) and controls with benign prostatic hyperplasia (BPH) (n = 7). Nanoparticle tracking analysis (NTA), Western blot, electron microscopy, and flow cytometry analysis were used for the characterization of EVs. Non-coding RNA expression profiling of PC3 metastatic PCa cells and their EVs was performed by next generation sequencing (NGS). miRNAs differentially expressed in PC3 EVs were validated with qRT-PCR in EVs derived from additional cell lines and patient plasma and from matched tissue samples. 92 miRNAs were enriched and 48 miRNAs were depleted in PC3 EVs compared to PC3 cells, which could be confirmed by qRT-PCR. miR-99b-5p was significantly higher expressed in malignant compared to benign EVs. Furthermore, expression profiling showed miR-10a-5p (p = 0.018) and miR-29b-3p (p = 0.002), but not miR-99b-5p, to be overexpressed in plasma-derived EVs from patients with PCa compared with controls. In the corresponding tissue samples, no significant differences in the miRNA expression could be observed. We thus propose that EV-associated miR-10a-5p and miR-29b-3p could serve as potential new PCa detection markers.
N-Terminal Truncated Myb with New Transcriptional Activity Produced Through Use of an Alternative MYB Promoter in Salivary Gland Adenoid Cystic Carcinoma
Authors: Frerich Candace A. , Sedam Hailey N. , Kang Huining , Mitani Yoshitsugu , El-Naggar Adel K. , Ness Scott A.
Published: December 2019

Adenoid cystic carcinoma (ACC) is an aggressive salivary gland tumor that frequently displays perineural invasion and is often associated with translocations or overexpression of the MYB oncogene. Detailed analyses of MYB transcripts from ACC patient samples revealed that ACC tumors utilize an alternative MYB promoter, which is rarely used in normal cells or other tumor types. The alternative promoter transcripts produce N-terminally truncated Myb proteins lacking a highly conserved and phosphorylated domain, which includes the pS11 epitope that is frequently used to detect Myb proteins. In RNA-seq assays, Myb isoforms lacking the N-terminal domain displayed unique transcriptional activities, regulating many genes differently than full-length Myb. Thus, a regulatory pathway unique to ACC activates the alternative MYB promoter, leading to the production of a truncated Myb protein with altered transcriptional activities. This could provide new therapeutic opportunities for ACC patients.
Honokiol: A Review of Its Anticancer Potential and Mechanisms
Authors: Ong Chon Phin , Lee Wai Leong , Tang Yin Quan , Yap Wei Hsum
Published: December 2019

Cancer is characterised by uncontrolled cell division and abnormal cell growth, which is largely caused by a variety of gene mutations. There are continuous efforts being made to develop effective cancer treatments as resistance to current anticancer drugs has been on the rise. Natural products represent a promising source in the search for anticancer treatments as they possess unique chemical structures and combinations of compounds that may be effective against cancer with a minimal toxicity profile or few side effects compared to standard anticancer therapy. Extensive research on natural products has shown that bioactive natural compounds target multiple cellular processes and pathways involved in cancer progression. In this review, we discuss honokiol, a plant bioactive compound that originates mainly from the Magnolia species. Various studies have proven that honokiol exerts broad-range anticancer activity in vitro and in vivo by regulating numerous signalling pathways. These include induction of G0/G1 and G2/M cell cycle arrest (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins), epithelial–mesenchymal transition inhibition via the downregulation of mesenchymal markers and upregulation of epithelial markers. Additionally, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases (activation of 5′ AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling), inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)). Combining these studies provides significant insights for the potential of honokiol to be a promising candidate natural compound for chemoprevention and treatment.
Dose Intensity/Body Surface Area Ratio is a Novel Marker Useful for Predicting Response to Lenvatinib against Hepatocellular Carcinoma
Authors: Eso Yuji , Nakano Shigeharu , Mishima Masako , Arasawa Soichi , Iguchi Eriko , Nakamura Fumiyasu , Takeda Haruhiko , Takai Atsushi , Takahashi Ken , Taura Kojiro , Seno Hiroshi
Published: December 2019

Lenvatinib was recently approved as a novel first-line molecular targeted agent (MTA) for treating hepatocellular carcinoma (HCC). The importance of relative dose intensity (RDI) has been shown in the treatment of various types of cancers. However, RDI may not accurately reflect the treatment intensity of lenvatinib, as it is the first oral MTA where the dose is based on the patient’s weight. We aimed to evaluate the utility of 2M-DBR (the delivered dose intensity/body surface area ratio at 60 days) by comparing the relationship between 2M-DBR, 2M-RDI (RDI at 60 days), and the therapeutic response. The therapeutic response to lenvatinib was evaluated in 45 patients who underwent computed tomography 8–12 weeks after treatment initiation. We also investigated the clinical factors associated with high 2M-DBR. The area under the receiver operating characteristic of 2M-DBR that predicts the response to lenvatinib was higher than that of 2M-RDI (0.8004 vs. 0.7778). Patients with high 2M-DBR achieved significantly better objective responses and disease control rates than those with low 2M-DBR (p < 0.0001 and 0.0008). Patients with high 2M-DBR experienced significantly longer progression-free survival (PFS) than those with low 2M-DBR (p = 0.0001), while there was no significant correlation between 2M-RDI levels and PFS (p = 0.2198). Patients who achieved higher levels of 2M-DBR had a significantly better modified ALBI grade (p = 0.0437), better CONUT score (p = 0.0222), and higher BTR (p = 0.0281). Multivariate analysis revealed that high 2M-DBR was the only significant factor associated with longer PFS. In conclusion, 2M-DBR could be an important factor that reflects treatment intensity and useful for predicting the response to lenvatinib against HCC, instead of 2M-RDI.
Application of an Artificial Intelligence Algorithm to Prognostically Stratify Grade II Gliomas
Authors: Cesselli Daniela , Ius Tamara , Isola Miriam , Del Ben Fabio , Da Col Giacomo , Bulfoni Michela , Turetta Matteo , Pegolo Enrico , Marzinotto Stefania , Scott Cathryn Anne , Mariuzzi Laura , Di Loreto Carla , Beltrami Antonio Paolo , Skrap Miran
Published: December 2019

(1) Background: Recently, it has been shown that the extent of resection (EOR) and molecular classification of low-grade gliomas (LGGs) are endowed with prognostic significance. However, a prognostic stratification of patients able to give specific weight to the single parameters able to predict prognosis is still missing. Here, we adopt classic statistics and an artificial intelligence algorithm to define a multiparametric prognostic stratification of grade II glioma patients. (2) Methods: 241 adults who underwent surgery for a supratentorial LGG were included. Clinical, neuroradiological, surgical, histopathological and molecular data were assessed for their ability to predict overall survival (OS), progression-free survival (PFS), and malignant progression-free survival (MPFS). Finally, a decision-tree algorithm was employed to stratify patients. (3) Results: Classic statistics confirmed EOR, pre-operative- and post-operative tumor volumes, Ki67, and the molecular classification as independent predictors of OS, PFS, and MPFS. The decision tree approach provided an algorithm capable of identifying prognostic factors and defining both the cut-off levels and the hierarchy to be used in order to delineate specific prognostic classes with high positive predictive value. Key results were the superior role of EOR on that of molecular class, the importance of second surgery, and the role of different prognostic factors within the three molecular classes. (4) Conclusions: This study proposes a stratification of LGG patients based on the different combinations of clinical, molecular, and imaging data, adopting a supervised non-parametric learning method. If validated in independent case studies, the clinical utility of this innovative stratification approach might be proved.
Influence of Impurities in a Methanol Solvent on the Epoxidation of Propylene with Hydrogen Peroxide over Titanium Silicalite-1
Authors: Wang Gang , Li Yue , Zhu Quanren , Li Gang , Zhang Chao , Guo Hongchen
Published: December 2019

The recycled methanol solvent of the HPPO (liquid-phase epoxidation of propylene and hydrogen peroxide to propylene oxide) process usually contains many kinds of trace impurities, such as fusel alcohol, aldehyde, ketone, ester, acetal, and amine. In this study, the influence of these impurities on the catalytic performance of titanium silicalite-1 (TS-1) in the liquid-phase epoxidation of propylene with H2O2 was investigated with a batch reactor and simulated methanol solvents. The results show that amine and acetone are the most hazardous impurities, as they could remarkably suppress the conversion of H2O2. Furthermore, competitive adsorption experiments and IR and UV-Raman spectroscopic studies indicate that the suppression effect of impurities on the catalytic activity of TS-1 can be attributed to the competitive adsorption of the impurities on the tetra-coordination framework Ti sites. With this funding, the suppression mechanism of different impurities in a methanol solvent on the catalytic activity of TS-1 in the liquid-phase epoxidation of propylene was discussed.
microRNA: The Impact on Cancer Stemness and Therapeutic Resistance
Authors: Jiao Xueqiao , Qian Xianling , Wu Longyuan , Li Bo , Wang Yi , Kong Xinyu , Xiong Lixia
Published: December 2019

Cancer ranks as the second leading cause of death worldwide, causing a large social and economic burden. However, most anti-cancer treatments face the problems of tumor recurrence and metastasis. Therefore, finding an effective cure for cancer needs to be solved urgently. Recently, the discovery of cancer stem cells (CSCs) provides a new orientation for cancer research and therapy. CSCs share main characteristics with stem cells and are able to generate an entire tumor. Besides, CSCs usually escape from current anti-cancer therapies, which is partly responsible for tumor recurrence and poor prognosis. microRNAs (miRNAs) belong to small noncoding RNA and regulate gene post-transcriptional expression. The dysregulation of miRNAs leads to plenty of diseases, including cancer. The aberrant miRNA expression in CSCs enhances stemness maintenance. In this review, we summarize the role of miRNAs on CSCs in the eight most common cancers, hoping to bridge the research of miRNAs and CSCs with clinical applications. We found that miRNAs can act as tumor promoter or suppressor. The dysregulation of miRNAs enhances cell stemness and contributes to tumor metastasis and therapeutic resistance via the formation of feedback loops and constitutive activation of carcinogenic signaling pathways. More importantly, some miRNAs may be potential targets for diagnosis, prognosis, and cancer treatments.
Engineered Maturation Approaches of Human Pluripotent Stem Cell-Derived Ventricular Cardiomyocytes
Authors: Ge Feixiang , Wang Zetian , Xi Jianzhong Jeff
Published: December 2019

Heart diseases such as myocardial infarction and myocardial ischemia are paroxysmal and fatal in clinical practice. Cardiomyocytes (CMs) differentiated from human pluripotent stem cells provide a promising approach to myocardium regeneration therapy. Identifying the maturity level of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is currently the main challenge for pathophysiology and therapeutics. In this review, we describe current maturity indicators for cardiac microtissue and microdevice cultivation technologies that accelerate cardiac maturation. It may provide insights into regenerative medicine, drug cardiotoxicity testing, and preclinical safety testing.
Splicing Dysregulation as Oncogenic Driver and Passenger Factor in Brain Tumors
Authors: Bielli Pamela , Pagliarini Vittoria , Pieraccioli Marco , Caggiano Cinzia , Sette Claudio
Published: December 2019

Brain tumors are a heterogeneous group of neoplasms ranging from almost benign to highly aggressive phenotypes. The malignancy of these tumors mostly relies on gene expression reprogramming, which is frequently accompanied by the aberrant regulation of RNA processing mechanisms. In brain tumors, defects in alternative splicing result either from the dysregulation of expression and activity of splicing factors, or from mutations in the genes encoding splicing machinery components. Aberrant splicing regulation can generate dysfunctional proteins that lead to modification of fundamental physiological cellular processes, thus contributing to the development or progression of brain tumors. Herein, we summarize the current knowledge on splicing abnormalities in brain tumors and how these alterations contribute to the disease by sustaining proliferative signaling, escaping growth suppressors, or establishing a tumor microenvironment that fosters angiogenesis and intercellular communications. Lastly, we review recent efforts aimed at developing novel splicing-targeted cancer therapies, which employ oligonucleotide-based approaches or chemical modulators of alternative splicing that elicit an impact on brain tumor biology.
Depolarization-Associated CircRNA Regulate Neural Gene Expression and in Some Cases May Function as Templates for Translation
Authors: Mahmoudi Ebrahim , Kiltschewskij Dylan , Fitzsimmons Chantel , Cairns Murray J.
Published: December 2019

Circular RNAs (circRNAs) are a relatively new class of RNA transcript with high abundance in the mammalian brain. Here, we show that circRNAs expression in differentiated neuroblastoma cells were significantly altered after depolarization with 107 upregulated and 47 downregulated circRNAs. This coincided with a global alteration in the expression of microRNA (miRNA) (n = 269) and mRNA (n = 1511) in depolarized cells, suggesting a regulatory axis of circRNA–miRNA–mRNA is involved in the cellular response to neural activity. In support of this, our in silico analysis revealed that the circular transcripts had the capacity to influence mRNA expression through interaction with common miRNAs. Loss-of-function of a highly expressed circRNA, circ-EXOC6B, resulted in altered expression of numerous mRNAs enriched in processes related to the EXOC6B function, suggesting that circRNAs may specifically regulate the genes acting in relation to their host genes. We also found that a subset of circRNAs, particularly in depolarized cells, were associated with ribosomes, suggesting they may be translated into protein. Overall, these data support a role for circRNAs in the modification of gene regulation associated with neuronal activity.
(–)-Catechin-7-O-β-d-Apiofuranoside Inhibits Hepatic Stellate Cell Activation by Suppressing the STAT3 Signaling Pathway
Authors: Park Yong Joo , Kim Dong Min , Jeong Mi Ho , Yu Jae Sik , So Hae Min , Bang In Jae , Kim Ha Ryong , Kwon Seung-Hwan , Kim Ki Hyun , Chung Kyu Hyuck
Published: December 2019

Hepatic fibrosis is characterized by the abnormal deposition of extracellular matrix (ECM) proteins. During hepatic fibrogenesis, hepatic stellate cell (HSC) activation followed by chronic injuries is considered a key event in fibrogenesis, and activated HSCs are known to comprise approximately 90% of ECM-producing myofibroblasts. Here, we demonstrated that (–)-catechin-7-O-β-d-apiofuranoside (C7A) significantly inhibited HSC activation via blocking the signal transducer and activator of transcription 3 (STAT3) signaling pathway. This is the first study to show the hepatic protective effects of C7A with possible mechanisms in vitro and in vivo. In our bioactivity screening, we figured out that the EtOH extract of Ulmus davidiana var. japonica root barks, which have been used as a Korean traditional medicine, inhibited collagen synthesis in HSCs. Four catechins isolated from the EtOAc fraction of the EtOH extract were compared with each other in terms of reduction in collagen, which is considered as a marker of hepatic protective effects, and C7A showed the strongest inhibitory effects on HSC activation in protein and qPCR analyses. As a possible mechanism, we investigated the effects of C7A on the STAT3 signaling pathway, which is known to activate HSCs. We found that C7A inhibited phosphorylation of STAT3 and translocation of STAT3 to nucleus. C7A also inhibited expressions of MMP-2 and MMP-9, which are downstream genes of STAT3 signaling. Anti-fibrotic effects of C7A were evaluated in a thioacetamide (TAA)-induced liver fibrosis model, which indicated that C7A significantly inhibited ECM deposition through inhibiting STAT3 signaling. C7A decreased serum levels of aspartate amino transferase and alanine transaminase, which were markedly increased by TAA injection. Moreover, ECM-associated proteins and mRNA expression were strongly suppressed by C7A. Our study provides the experimental evidence that C7A has inhibitory effects on HSC activation after live injury and has preventive and therapeutic potentials for the management of hepatic fibrosis.