The BH3 mimetic ABT-737 increases treatment efficiency of paclitaxel against hepatoblastoma

<p>Abstract</p> <p>Background</p> <p>The primary goal of current chemotherapy in hepatoblastoma (HB) is reduction of tumour volume and vitality to enable complete surgical resection and reduce risk of recurrence or metastatic disease. Drug resistance remains a major challenge for HB treatment. In some malignancies inhibition of anti-apoptotic pathways using small BH3 mimetic molecules like ABT-737 shows synergistic effects in combination with cystotoxic agents in vitro. Now we analysed toxicology and synergistic effects of this approach in HB cells and HB xenografts.</p> <p>Methods</p> <p>Viability was monitored in HB cells (HUH6 and HepT1) and fibroblasts treated with paclitaxel, ABT-737 and a combination of both in a MTT assay. HUH6 xenotransplants in NOD/LtSz-scid IL2Rγnull mice (NSG) were treated accordingly. Tumour volume and body weight were monitored. Xenografted tumours were analysed by histology and immunohistochemistry (Ki-67 and TUNEL assay).</p> <p>Results</p> <p>ABT-737 reduced viability in HUH6 and HepT1 cells cultures at concentrations above 1 μM and also enhanced the cytotoxic effect of paclitaxel when used in combination. Thereby paclitaxel could be reduced tenfold to achieve similar reduction of viability of tumour cells. In contrast no toxicity in fibroblasts was observed at the same regiments. Subcutaneous HB (HUH6) treated with paclitaxel (12 mg/kg body weight, n = 7) led to delayed tumour growth in the beginning of the experiment. However, tumour volume was similar to controls (n = 5) at day 25. Combination treatment with paclitaxel and ABT-737 (100 mg/kg, n = 8) revealed significantly 10 fold lower relative tumour volumes compared to control and paclitaxel groups. Paclitaxel dependent toxicity was observed in this mice strain.</p> <p>Conclusions</p> <p>Our results demonstrate enhancement of chemotherapy by using modulators of apoptosis. Further analyses should include improved pharmacological formulations of paclitaxel and BH3 mimetics in order to reduce toxicological effects. Sensitising HB to apoptosis may also render resistant HB susceptible to established chemotherapy regimens.</p

Leptin and Adiponectin: new players in the field of tumor cell and leukocyte migration

Adipose tissue is no longer considered to be solely an energy storage, but exerts important endocrine functions, which are primarily mediated by a network of various soluble factors derived from fat cells, called adipocytokines. In addition to their responsibility to influence energy homeostasis, new studies have identified important pathways linking metabolism with the immune system, and demonstrating a modulatory role of adipocytokines in immune function. Additionally, epidemiological studies underline that obesity represents a significant risk factor for the development of cancer, although the exact mechanism of this relationship remains to be determined. Whereas a possible influence of adipocytokines on the proliferation of tumor cells is already known, new evidence has come to light elucidating a modulatory role of this signaling substances in the regulation of migration of leukocytes and tumor cells. The migration of leukocytes is a key feature to fight cancer cells, whereas the locomotion of tumor cells is a prerequisite for tumor formation and metastasis. We herein review the latest tumor biological findings on the role of the most prominent adipocytokines leptin and adiponectin, which are secreted by fat cells, and which are involved in leukocyte migration, tumor growth, invasion and metastasis. This review thus accentuates the complex, interactive involvement of adipocytokines in the regulation of migration of both leukocytes and tumor cells, and gives an insight in the underlying molecular mechanisms

Posttraumatic levels of liver enzymes can reduce the need for CT in children: a retrospective cohort study

BACKGROUND: Computed tomography (CT) is the gold standard in the initial evaluation of the hemodynamically stable patient with suspected liver trauma. However, the adverse effects of radiation exposure are of specific concern in the pediatric population. It is therefore desirable to explore alternative diagnostic modalities. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are hepatic enzymes, which are elevated in peripheral blood in relation to liver injury. The aim of the present study was to investigate a potential role of normal liver transaminase levels in the decision algorithm in suspected pediatric blunt liver trauma. METHODS: Retrospective analysis of consecutively collected data from children (0–17 years) with blunt liver trauma, admitted to a single trauma centre in Denmark, between 2000 and 2013. Patients underwent abdominal CT during initial evaluation, and initial AST and/or ALT was measured. Based on local guidelines, we set the threshold for blood AST and ALT level to 50 IU/L. Nonparametric statistical tests were used. RESULTS: Sixty consecutive children with liver injury following blunt abdominal trauma were enrolled in the study. All patients with normal AST and/or ALT level were treated conservatively with success. Information on both AST and ALT was available in 47 children. Of these 47 children, three children had AST and ALT levels ≤50 IU/L. These children suffered from grade I liver injuries, and were treated conservatively with no complications. DISCUSSION: All children who presented with blunt liver injury and AST and ALT levels ≤50 IU/L did not require treatment. These findings indicate that AST and ALT could be included in an updated management algorithm as a screening method to avoid abdominal CT. Notable limitations to the study was the retrospective method of data collection, without inclusion of a control group. CONCLUSIONS: CT seems superfluous in the initial evaluation of hemodynamically stable children with suspected blunt liver injury and blood AST and ALT levels ≤50 IU/L

The TREAT-NMD DMD Global Database: Analysis of more than 7,000 Duchenne Muscular Dystrophy mutations

Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations)

Vegetal fibers in polymeric composites: a review

The need to develop and commercialize materials containing vegetal fibers has grown in order to reduce environmental impact and reach sustainability. Large amounts of lignocellulosic materials are generated around the world from several human activities. The lignocellulosic materials are composed of cellulose, hemicellulose, lignin, extractives and ashes. Recently these constituents have been used in different applications; in particular, cellulose has been the subject of numerous works on the development of composite materials reinforced with natural fibers. Many studies have led to composite materials reinforced with fibers to improve the mechanical, physical, and thermal properties. Furthermore, lignocellulosic materials have been treated to apply in innovative solutions for efficient and sustainable systems. This paper aims to review the lignocellulosic fibers characteristics, as well as to present their applications as reinforcement in composites of different polymeric matrices.Fundação Cearense de Apoio ao Desenvolvimento Cientifico e TecnologicoFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Embrapa Agroind Trop, Fortaleza, Ceara, BrazilUniv Estadual Paulista UNESP, Fac Engn Guaratingueta, Dept Mat &Tecnol, Guaratingueta, SP, BrazilCtr Univ Volta Redonda UniFOA, Volta Redonda, RJ, BrazilDepartamento de Materiais e Tecnologia, Faculdade de Engenharia de Guaratinguetá, Universidade Estadual Paulista – UNESP, Guaratinguetá, SP, BrazilFundacao Cearense deApoio ao Desenvolvimento Cientifico e Tecnologico: DCR-0024-00522.01.00/12FAPESP: 2011/14.153-

Serum ferritin, iron levels and iron binding capacity in asymmetric SGA babies

The concentration of serum ferritin reflects the extent of iron stores in premature infants. We aimed to determine serum ferritin levels and iron status in asymmetric small for gestational age (SGA) babies. This study was performed on 21 SGA babies and 19 appropriate for gestational age (AGA) babies. Hemoglobin, iron, iron binding capacity and ferritin levels were investigated in the first six hours after the birth. Hemoglobin levels in the SGA and control groups were 20.9 +/- 1.3 (19.4-23.4 g/dl) and 19.6 +/- 0.8 (18.5-21.5 g/dl), respectively (p = 0.001). Serum ferritin levels in the SGA and AGA groups were 58.36 +/- 20.1 ng/ml and 90.46 +/- 30.5 ng/ml, respectively. Ferritin levels were found lower in the SGA group (p 0.05). Decreased ferritin levels may result from either impaired iron transport associated with uteroplacental vascular insufficiency or increased iron utilization during enhanced erythropoiesis in conditions characterized by chronic fetal hypoxia. Our results stress the significance of iron supplementation and careful anemia follow-up in term SGA babies. Because anemia progress early, beginning iron therapy as soon as possible is a necessity in SGA babies as in prematures

ASSESSMENT of CRACK INITIATION and PROPAGATION in BONE USING ACOUSTIC EMISSION (AE) TECHNIQUES

Acoustic emission (AE) is a nondestructive testing (NDT) technique used for detecting damages, cracks, and leaks in different structures such as metals, composites, wood, fiberglass, ceramics, plastics, etc. In recent years, AE has gained popularity within the field of biomedical applications. The structure of bone is similar to composite materials, therefore, it is advantageous to use NDT technique. Thus, it can be used for monitoring the fracture behavior, crack initiation/propagation, and fatigue detection in bones. The goal of this study was to determine the usefulness of AE techniques in fracture detection phase of bones and to develop an NDT methodology for the monitoring of crack initiation and propagation in bones. This study describes AE activity during fracture of bone tissue under tensile loads. The experiments were carried out in vitro techniques using intact and fracture-simulated bovine tibias. The specimens were loaded to failure in tension using a mechanical testing machine. During the mechanical tests, AE signals were measured and recorded by using AE system processor equipped with two wideband piezoelectric sensors fixed to the surfaces of both ends of the test specimens. By superposing the load-time curve and the cumulative AE event-time curve, AE activities of crack initiation and propagation were identified. In all experiments, the cumulative AE number for each period of time rose up exponentially with the incremental tensile load. Load for AE initiation demonstrated a convincing linear interaction with AE event generation. © 2018 World Scientific Publishing Company.This study was funded by Cukurova University Scientific Research Department under the Project No. FYL 20166515. The authors also wish to thank Dursun DÖĞER (Executive of Tekprom Uygunluk Değerlendirme ve Gozetim Hizm.Ltd.Şti.) for supplying AE processor system and other instruments in AET

A cross-validation study of Turkish sentiment analysis datasets and tools

In recent years, sentiment analysis has gained increasing significance, prompting researchers to explore datasets in various languages, including Turkish. However, the limited availability and reuse of Turkish datasets across studies has yielded highly diverse outcomes. To address this, we conducted a systematic review of sentiment analysis studies on Turkish text. Our search identified 78 relevant studies, from which we extracted over 80 datasets. These studies were labeled using a comprehensive sentiment analysis taxonomy, and the dataset details were compiled into a structured repository. Furthermore, we evaluated the performance of four stateof-the-art models-XLM-T, BERTurk (fine-tuned with the BounTi dataset), TSAM, and TurkishBERTweet-on four widely-used Turkish datasets. Among the models, XLM-T achieved the highest performance with an accuracy of 0.92 and F1 score of 0.95 on the Twt dataset, while TSAM reached 0.97 accuracy and F1 score on the Humir dataset. Our empirical results demonstrate that model performance varies significantly based on dataset characteristics such as domain, balance, and linguistic structure. Our review revealed key research gaps, including the limited application of emotion-based and concept-based sentiment analysis techniques and the lack of domain diversity in Turkish sentiment datasets. By highlighting such gaps and compiling a centralized repository, this study provides a comprehensive and publicly accessible resource to guide future research in Turkish sentiment analysis.Publisher versio