bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Exercise on Secondary Sarcopenia: A Comprehensive Literature Review
Authors: Supriya Rashmi , Singh Kumar Purnendu , Gao Yang , Gu Yaodong , Baker Julien S.
Published: December 2021

Background: Sarcopenia has been recognized as an inevitable part of aging. However, its severity and the age at which it begins cannot be predicted by age alone. The condition can be categorized into primary or age-related sarcopenia and secondary sarcopenia. Sarcopenia is diagnosed as primary when there are no other specific causes. However, secondary sarcopenia occurs if other factors, including malignancy or organ failure, are evident in addition to aging. The prevalence of secondary sarcopenia is far greater than that of primary sarcopenia and requires special attention. To date, nutrition and exercise have proven to be the best methods to combat this disease. The impact of exercise on subjects suffering from sarcopenia with a specific morbidity is worthy of examination for understanding and prevention. The purpose of this review, therefore, is to summarize recent research that has investigated the impact of exercise in patients with secondary sarcopenia, specifically with one comorbidity. Methods: Pubmed, Web of Science, Embase and Medline databases were searched comprehensively with no date limit for randomized controlled trials. The literature was specifically searched for clinical trials in which subjects were sarcopenic with only one comorbidity participating in an exercise intervention. The most visible comorbidities identified and used in the search were lung disease, kidney disease, heart disease, type 2 diabetes, cancer, neurological diseases, osteoporosis and arthritis. Results: A total of 1752 studies were identified that matched the keywords. After removing duplicates, there were 1317 articles remaining. We extracted 98 articles for full screening. Finally, we included 21 relevant papers that were used in this review. Conclusion: Despite a strong rationale for using exercise to improve muscle mass, quality or physical function in subjects with cancer, type 2 diabetes, kidney disease, lung disease and many more, baseline sarcopenia evaluation has been reported in very few trials. The limited number of studies does not allow us to conclude that exercise can improve sarcopenia in patients with other comorbidities. This review highlights the necessity for wide-ranging research initiatives involving secondary sarcopenic patients.
Dynamics of the Actin Cytoskeleton at Adhesion Complexes
Authors: Cronin Nicholas M. , DeMali Kris A.
Published: December 2021

The shape of cells is altered to allow cells to adapt to their changing environments, including responding to internally generated and externally applied force. Force is sensed by cell surface adhesion proteins that are enriched in sites where cells bind to the extracellular matrix (focal adhesions) and neighboring cells (cell–cell or adherens junctions). Receptors at these adhesion sites stimulate intracellular signal transduction cascades that culminate in dramatic changes in the actin cytoskeleton. New actin filaments form, and/or new and existing filaments can be cleaved, branched, or bundled. Here, we discuss the actin cytoskeleton and its functions. We will examine the current understanding for how the actin cytoskeleton is tethered to adhesion sites. Finally, we will highlight recent studies describing how the actin cytoskeleton at these adhesion sites is remodeled in response to force.
Interactions of Pleiotrophin with a Structurally Defined Heparin Hexasaccharide
Authors: Ryan Eathen O. , Jiang Zhoumai , Nguyen Hoa , Wang Xu
Published: December 2021

Pleiotrophin (PTN) is a potent cytokine that plays an important role in neural generation, angiogenesis, inflammation, and cancers. Its interactions with the polysaccharide glycosaminoglycan (GAG) are crucial to PTN’s biological activities. In this study, we investigated the interaction of selectively protonated PTN with the heparin hexasaccharide ΔUA2S-(GlcNS6S-IdoA2S)2-GlcNS6S using solution NMR. The use of a structurally defined oligosaccharide and selectively protonated PTN enabled us to obtain intermolecular contacts using unfiltered NOESY experiments, significantly increasing the amount of high-resolution structural information obtainable. Our data showed that PTN’s arginines, lysines, and tryptophans in the two structured domains have strong interactions with the 2-O-sulfated uronate protons in the heparin hexasaccharide. Consistent with the NMR data is the observation that 2-O-desulfation and N-desulfation/N-acetylation significantly decreased heparin hexasaccharides’ affinity for PTN, while 6-O-desulfation only modestly affected the interactions with PTN. These results allowed us to hypothesize that PTN has a preference for sulfate clusters centered on the GlcNS6S-IdoA2S disaccharide. Using these data and the fact that PTN domains mostly bind heparin hexasaccharides independently, models of the PTN-heparin complex were constructed.
Irisin Association with Ki-67, MCM3 and MT-I/II in Squamous Cell Carcinomas of the Larynx
Authors: Pinkowska Agnieszka , Nowinska Katarzyna , Ciesielska Urszula , Podhorska-Okolow Marzenna
Published: December 2021

Background: Current studies indicate irisin role in carcinogenesis. The aim of the study was to investigate the expression of irisin in LSCCs and to determine its association with clinicopathological factors, as well as recognized markers of proliferation, i.e., Ki-67 and MCM3,5,7 and MT-I/II proteins. Material and methods: The research material consisted of 140 cases of LSCCs, 57 cases of laryngeal papillomas (BLs) and 14 controls (benign hypertrophic changes). Tissue microarrays were used to perform IHC. Western blot and immunofluorescence were performed in laryngeal cancer cell lines and normal keratinocytes. Results: Irisin expression levels were significantly increased in LSCC compared to BLs (p < 0.0001) and controls (p = 0.001). We noted a positive moderate and weak correlation between irisin and Ki-67, MCM3 and MT-I/II. We observed an elevated level of irisin expression with increasing tumor size (T1–2 vs. T3–4; p = 0.0348). The levels of irisin were higher in N0 than in N1 and N2–3 (p = 0.0031 and p = 0.0457, respectively). Our in vitro study revealed a higher level of irisin in Larynx Epidermoid Carcinoma 2 (HEp-2) cells compared to the control Normal Human Keratinocyte (HaCat) cell line. Conclusions: Increased irisin expression levels in LSCC and its correlation with clinicopathological and proliferation factors may indicate the potential role of irisin as a biomarker in the diagnostic process of LSCC.
Materials for Dentoalveolar Bioprinting: Current State of the Art
Authors: Salar Amoli Mehdi , EzEldeen Mostafa , Jacobs Reinhilde , Bloemen Veerle
Published: December 2021

Although current treatments can successfully address a wide range of complications in the dentoalveolar region, they often still suffer from drawbacks and limitations, resulting in sub-optimal treatments for specific problems. In recent decades, significant progress has been made in the field of tissue engineering, aiming at restoring damaged tissues via a regenerative approach. Yet, the translation into a clinical product is still challenging. Novel technologies such as bioprinting have been developed to solve some of the shortcomings faced in traditional tissue engineering approaches. Using automated bioprinting techniques allows for precise placement of cells and biological molecules and for geometrical patient-specific design of produced biological scaffolds. Recently, bioprinting has also been introduced into the field of dentoalveolar tissue engineering. However, the choice of a suitable material to encapsulate cells in the development of so-called bioinks for bioprinting dentoalveolar tissues is still a challenge, considering the heterogeneity of these tissues and the range of properties they possess. This review, therefore, aims to provide an overview of the current state of the art by discussing the progress of the research on materials used for dentoalveolar bioprinting, highlighting the advantages and shortcomings of current approaches and considering opportunities for further research.
Triglyceride Saturation in Patients at Risk of NASH and NAFLD: A Cross-Sectional Study
Authors: Bydder Mark , Chavez Tanya , Lam Jessica , Henderson Walter , Pinto Nick , Chavarria Roxana , Pham Alex D. , Loomba Rohit , Schwimmer Jeff , Sirlin Claude , Hamilton Gavin
Published: December 2021

Chemical shift magnetic resonance imaging (MRI) is commonly used to estimate the amount of fat in tissues, namely the proton density fat fraction (PDFF). In addition to PDFF, the type of fat can be inferred and characterized in terms of the number of double bonds (NDB), number of methylene-interrupted double bonds (NMIDB) and the chain length (CL) of the fatty acid chains. The saturation index is potentially a marker for metabolic disorders. This study assesses the feasibility of estimating these parameters independently or in a constrained manner. Correlations with spectroscopy were measured in 109 subjects’ subcutaneous and visceral fat depots (p = 2 × 10−28), and with the NAFLD Activity Score (NAS) from histological evaluation of biopsies. The findings indicate that imaging estimates are comparable to spectroscopy (p = 0.0002), but there is no significant association of NDB with NAS (p = 0.1).
Novel SH-SAW Biosensors for Ultra-Fast Recognition of Growth Factors
Authors: Matatagui Daniel , Bastida Ágatha , Horrillo M. Carmen
Published: December 2021

In this study, we investigated a label-free time efficient biosensor to recognize growth factors (GF) in real time, which are of gran interesting in the regulation of cell division and tissue proliferation. The sensor is based on a system of shear horizontal surface acoustic wave (SH-SAW) immunosensor combined with a microfluidic chip, which detects GF samples in a dynamic mode. In order to prove this method, to our knowledge not previously used for this type of compounds, two different GFs were tested by two immunoreactions: neurotrophin-3 and fibroblast growth factor-2 using its polyclonal antibodies. GF detection was conducted via an enhanced sequential workflow to improve total test time of the immunoassay, which shows that this type of biosensor is a very promising method for ultra-fast recognition of these biomolecules due to its great advantages: portability, simplicity of use, reusability, low cost, and detection within a relatively short period of time. Finally, the biosensor is able to detect FGF-2 growth factor in a concentration wide range, from 1–25 µg/mL, for a total test time of ~15 min with a LOD of 130 ng/mL.
On-Line Monitoring of Biofilm Accumulation on Graphite-Polypropylene Electrode Material Using a Heat Transfer Sensor
Authors: Netsch Andreas , Horn Harald , Wagner Michael
Published: December 2021

Biofilms growing on electrodes are the heart piece of bioelectrochemical systems (BES). Moreover, the biofilm morphology is key for the efficient performance of BES and must be monitored and controlled for a stable operation. For the industrial use of BES (i.e., microbial fuel cells for energy production), monitoring of the biofilm accumulation directly on the electrodes during operation is desirable. In this study a commercially available on-line heat transfer biofilm sensor is applied to a graphite-polypropylene (C-PP) pipe and compared to its standard version where the sensor is applied to a stainless-steel pipe. The aim was to investigate the transferability of the sensor to a carbonaceous material (C-PP), that are preferably used as electrode materials for bioelectrochemical systems, thereby enabling biofilm monitoring directly on the electrode surface. The sensor signal was correlated to the gravimetrically determined biofilm thickness in order to identify the sensitivity of the sensor for the detection and quantification of biofilm on both materials. Results confirmed the transferability of the sensor to the C-PP material, despite the sensor sensitivity being decreased by a factor of approx. 5 compared to the default biofilm sensor applied to a stainless-steel pipe.
Family-Based Whole-Exome Analysis of Specific Language Impairment (SLI) Identifies Rare Variants in BUD13, a Component of the Retention and Splicing (RES) Complex
Authors: Andres Erin M. , Earnest Kathleen Kelsey , Zhong Cuncong , Rice Mabel L. , Raza Muhammad Hashim
Published: December 2021

Specific language impairment (SLI) is a common neurodevelopmental disorder (NDD) that displays high heritability estimates. Genetic studies have identified several loci, but the molecular basis of SLI remains unclear. With the aim to better understand the genetic architecture of SLI, we performed whole-exome sequencing (WES) in a single family (ID: 489; n = 11). We identified co-segregating rare variants in three new genes: BUD13, APLP2, and NDRG2. To determine the significance of these genes in SLI, we Sanger sequenced all coding regions of each gene in unrelated individuals with SLI (n = 175). We observed 13 additional rare variants in 18 unrelated individuals. Variants in BUD13 reached genome-wide significance (p-value < 0.01) upon comparison with similar variants in the 1000 Genomes Project, providing gene level evidence that BUD13 is involved in SLI. Additionally, five BUD13 variants showed cohesive variant level evidence of likely pathogenicity. Bud13 is a component of the retention and splicing (RES) complex. Additional supportive evidence from studies of an animal model (loss-of-function mutations in BUD13 caused a profound neural phenotype) and individuals with an NDD phenotype (carrying a CNV spanning BUD13), indicates BUD13 could be a target for investigation of the neural basis of language.
Mapping Actuarial Criteria for Parkinson’s Disease-Mild Cognitive Impairment onto Data-Driven Cognitive Phenotypes
Authors: Kenney Lauren E. , Ratajska Adrianna M. , Lopez Francesca V. , Price Catherine C. , Armstrong Melissa J. , Bowers Dawn
Published: December 2021

Prevalence rates for mild cognitive impairment in Parkinson’s disease (PD-MCI) remain variable, obscuring the diagnosis’ predictive utility of greater dementia risk. A primary factor of this variability is inconsistent operationalization of normative cutoffs for cognitive impairment. We aimed to determine which cutoff was optimal for classifying individuals as PD-MCI by comparing classifications against data-driven PD cognitive phenotypes. Participants with idiopathic PD (n = 494; mean age 64.7 ± 9) completed comprehensive neuropsychological testing. Cluster analyses (K-means, Hierarchical) identified cognitive phenotypes using domain-specific composites. PD-MCI criteria were assessed using separate cutoffs (−1, −1.5, −2 SD) on ≥2 tests in a domain. Cutoffs were compared using PD-MCI prevalence rates, MCI subtype frequencies (single/multi-domain, executive function (EF)/non-EF impairment), and validity against the cluster-derived cognitive phenotypes (using chi-square tests/binary logistic regressions). Cluster analyses resulted in similar three-cluster solutions: Cognitively Average (n = 154), Low EF (n = 227), and Prominent EF/Memory Impairment (n = 113). The −1.5 SD cutoff produced the best model of cluster membership (PD-MCI classification accuracy = 87.9%) and resulted in the best alignment between PD-MCI classification and the empirical cognitive profile containing impairments associated with greater dementia risk. Similar to previous Alzheimer’s work, these findings highlight the utility of comparing empirical and actuarial approaches to establish concurrent validity of cognitive impairment in PD.
Cognitive Rehabilitation in Multiple Sclerosis in the Period from 2013 and 2021: A Narrative Review
Authors: Brochet Bruno
Published: December 2021

Background: In recent years, several blinded randomized controlled trials (RCT) have been conducted on cognitive rehabilitation (CR) in adults with multiple sclerosis (MS). Objective: To review all blinded RCTs on CR in MS published since 2013. Methods: The National Library of Medicine database (Medline) and PSYCINFO were searched using the keywords MS and CR or cognitive training or NP rehabilitation or memory rehabilitation or attention rehabilitation. Results: After the exclusion of some papers not specifically focused on CR, a final list of 26 studies was established. The papers belong to three main categories: individual specific rehabilitation (8studies), group rehabilitation (4 studies), and computerized training (CT) (14 studies), while one study combined group rehabilitation and CT. Among the individual rehabilitation studies, 5 were devoted to memory, and most of the 19 other selected studies were about several cognitive domains. Most of the studies mainly concerned RRMS patients, except for 2 studies that were carried out exclusively in progressive forms. Despite the methodological limitations of some studies and the great heterogeneity of the protocols, the results are generally in favor of the efficacy of CR in neuropsychological tests. Conclusion: Recent blinded RCTs about CR in MS show promising results.
Responsible Genes for Neuronal Migration in the Chromosome 17p13.3: Beyond Pafah1b1(Lis1), Crk and Ywhae(14-3-3ε)
Authors: Liu Xiaonan , Bennison Sarah A. , Robinson Lozen , Toyo-oka Kazuhito
Published: December 2021

The 17p13.3 chromosome region is often deleted or duplicated in humans, resulting in severe neurodevelopmental disorders such as Miller–Dieker syndrome (MDS) and 17p13.3 duplication syndrome. Lissencephaly can also be caused by gene mutations or deletions of a small piece of the 17p13.3 region, including a single gene or a few genes. PAFAH1B1 gene, coding for LIS1 protein, is a responsible gene for lissencephaly and MDS and regulates neuronal migration by controlling microtubules (MTs) and cargo transport along MTs via dynein. CRK is a downstream regulator of the reelin signaling pathways and regulates neuronal migration. YWHAE, coding for 14-3-3ε, is also responsible for MDS and regulates neuronal migration by binding to LIS1-interacting protein, NDEL1. Although these three proteins are known to be responsible for neuronal migration defects in MDS, there are 23 other genes in the MDS critical region on chromosome 17p13.3, and little is known about their functions in neurodevelopment, especially in neuronal migration. This review will summarize the recent progress on the functions of LIS1, CRK, and 14-3-3ε and describe the recent findings of other molecules in the MDS critical regions in neuronal migration.
Influence of the Process of Synthesis of Zeolites from Volcanic Ash in Its Synergistic Action as a Flame-Retardant for Polypropylene Composites
Authors: Almirón Jonathan , Vargas María , Tupayachy-Quispe Danny , Duquesne Sophie , Roudet Francine , Silva-Vela Alejandro
Published: December 2021

In this research, the influence of natural zeolites obtained from the volcanic ash of the Ubinas volcano has been studied as synergistic agents in a flame-retardant system (composed of ammonium polyphosphate, pentaerythritol, and polypropylene). Four zeolites were synthesized from volcanic ash, including those that had been calcined and those that had not. These were then placed in an alkaline solution at three synthesis temperatures. Zeolites were characterized through X-ray diffraction, specific surface area by nitrogen adsorption analysis (Brunauer–Emmett–Teller) and scanning electron microscopy. Polypropylene matrix composites were prepared with ammonium polyphosphate, pentaerythritol and zeolites at 1, 5 and 9%. Its thermal stability and fire resistance were evaluated by thermogravimetric analysis, limiting oxygen index, vertical burning test and cone calorimeter and its morphological structure by scanning electron microscopy. It was determined that the synthesis temperature and the use of calcined and without calcined volcanic ash have an influence on the characteristics of the zeolites and on its synergistic action.
Management of Advanced Squamous Cell Carcinoma of the Vulva
Authors: Rogers Linda J.
Published: December 2021

Vulvar cancer is a rare gynaecological malignancy, accounting for 2–5% of cancers of the female genital tract. Squamous cell carcinoma is the most frequently occurring subtype and, historically, has been a disease of older post-menopausal women, occurring with a background of lichen sclerosus and other epithelial conditions of the vulvar skin that may be associated with well-differentiated vulvar intra-epithelial neoplasia (dVIN). An increase in human papillomavirus (HPV) infections worldwide has led to an increase in vulvar squamous carcinomas in younger women, resulting from HPV-associated high-grade vulvar squamous intra-epithelial lesions (vHSIL). Surgical resection is the gold standard for the treatment of vulvar cancer. However, as approximately 30% of patients present with locally advanced disease, which is either irresectable or will require radical surgical resection, possibly with a stoma, there has been a need to investigate alternative forms of treatment such as chemoradiation and targeted therapies, which may minimise the psychosexual morbidity of radical surgery. This review aims to provide an update on management strategies for women with advanced vulvar cancer. It is hoped that investigation of the molecular biologies of the two different pathways to vulvar squamous cell carcinoma (HPV-associated and non-HPV-associated) will lead to the development of targeted therapeutic agents.
Prognostic Value of the B12/CRP Index in Older Systemically Treatable Cancer Patients
Authors: Montegut Coline , Correard Florian , Nouguerède Emilie , Rey Dominique , Chevalier Thomas , Meurer Marie , Deville Jean-Laurent , Baciuchka Marjorie , Pradel Vincent , Greillier Laurent , Villani Patrick , Couderc Anne-Laure
Published: December 2021

Background: While comprehensive geriatric assessment (CGA) in older patients treated for cancer assesses several related domains, it does not include standardized biological tests. The present study aimed to: (1) assess the prognosis value of the B12/CRP index (BCI) in a population of systemically treatable older patients with cancer and (2) analyze the association between BCI value and pre-existing geriatric frailty. Method: We conducted a retrospective observational study between January 2016 and June 2020 at Marseille University Hospital. All consecutive cancer patients aged 70 years and over before initiating systemic therapy were included. Results: Of the 863 patients included, 60.5% were men and 42.5% had metastatic stage cancer. Mean age was 81 years. The low-BCI group (≤10,000) had a significantly longer survival time than the mid-BCI (10,000 < BCI ≤ 40,000) and high-BCI (BCI > 40,000) groups (HR = 0.327, CI95% [0.26–0.42], p-value = 0.0001). Mid- and high-BCI (BCI > 40,000) values were associated with impaired functional status and malnutrition. Conclusion: A BCI > 10,000 would appear to be a good biological prognostic factor for poor survival times and pre-existing geriatric impairment in older cancer patients before they initiate systemic treatment.
Retinal Glial Cells in Von Hippel–Lindau Disease: A Novel Approach in the Pathophysiology of Retinal Hemangioblastoma
Authors: Pilotto Elisabetta , Midena Giulia , Torresin Tommaso , De Mojà Gilda , Bacelle Maria Laura , Ferrara Alfonso Massimiliano , Zovato Stefania , Midena Edoardo
Published: December 2021

Background: Von Hippel–Lindau (VHL) disease is a neoplastic syndrome caused by a mutation of the VHL tumor suppressor gene. Retinal hemangioblastoma (RH) is a vascularized tumor and represents the most common ocular manifestation of this disease. At the retinal level, VHL protein is able to regulate tumor growth, angiogenic factors, and neuroinflammation, probably stimulating retinal glial cells. The aim of the present study was to analyze in vivo the optical coherence tomography (OCT) biomarkers of retinal macroglia and microglia in a cohort of VHL patients. Methods: The mean thicknesses of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), and peripapillary retinal nerve fiber layer (pRNFL) were measured with OCT as biomarkers of retinal macroglia. OCT images were also analyzed to detect and quantify hyperreflective retinal foci (HRF), a biomarker of retinal activated microglia. Results: 61 eyes of 61 VHL patients (22 eyes (36.07%) with peripheral RH and 39 eyes (63.93%) without RH) and 28 eyes of 28 controls were evaluated. pRNFL was thinner in VHL patients (p < 0.05) and in VHL without RH (p < 0.01) compared to controls, and thicker in VHL patients with RH than in those without RH (p < 0.05). The thickness of mRNFL (p < 0.0001) and GCL (p < 0.05) was reduced in VHL patients and in VHL without RH compared to controls, whereas mRNFL (p < 0.0001) and GCL (p < 0.05) were increased in VHL patients with RH compared to those without RH. HRF were significantly higher in number in VHL patients and in VHL without RH, than in controls, and significantly lower (p < 0.05) in the eyes of VHL patients with RH, than in those without RH. Conclusions: The OCT analysis, which detects and allows to quantify the biomarkers of retinal microglia (HRF) and macroglia (pRNFL, mRNFL and GCL), showed a different behavior of these two retinal glial cells populations in VHL patients, related to the presence or absence of peripheral RH. These data allow to hypothesize a novel pathophysiologic pathway of retinal hemangioblastoma in VHL disease.
The Tumour Suppressor CYLD Is Required for Clathrin-Mediated Endocytosis of EGFR and Cetuximab-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma
Authors: Liu Rin , Shinriki Satoru , Maeshiro Manabu , Hirayama Mayumi , Jono Hirofumi , Yoshida Ryoji , Nakayama Hideki , Matsui Hirotaka
Published: December 2021

Epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) and is a target for the therapeutic antibody cetuximab (CTX). However, because only some patients have a significant clinical response to CTX, identification of its predictive biomarkers and potentiation of CTX-based therapies are important. We have recently reported a frequent downregulation of cylindromatosis (CYLD) in primary HNSCC, which led to increased cell invasion and cisplatin resistance. Here, we show that CYLD located mainly in lipid rafts was required for clathrin-mediated endocytosis (CME) and degradation of the EGFR induced by EGF and CTX in HNSCC cells. The N-terminus containing the first cytoskeleton-associated protein-glycine domain of CYLD was responsible for this regulation. Loss of CYLD restricted EGFR to lipid rafts, which suppressed CTX-induced apoptosis without impeding CTX’s inhibitory activity against downstream signalling pathways. Disruption of the lipid rafts with cholesterol-removing agents overcame this resistance by restoring CME and the degradation of EGFR. Regulation of EGFR trafficking by CYLD is thus critical for the antitumour activity of CTX. Our findings suggest the usefulness of a combination of cholesterol-lowering drugs with anti-EGFR antibody therapy in HNSCC.
E-Cadherin-Deficient Epithelial Cells Are Sensitive to HDAC Inhibitors
Authors: Decourtye-Espiard Lyvianne , Bougen-Zhukov Nicola , Godwin Tanis , Brew Tom , Schulpen Emily , Black Michael A. , Guilford Parry
Published: December 2021

Inactivating germline mutations in the CDH1 gene (encoding the E-cadherin protein) are the genetic hallmark of hereditary diffuse gastric cancer (HDGC), and somatic CDH1 mutations are an early event in the development of sporadic diffuse gastric cancer (DGC) and lobular breast cancer (LBC). In this study, histone deacetylase (HDAC) inhibitors were tested for their ability to preferentially inhibit the growth of human cell lines (MCF10A and NCI-N87) and murine organoids lacking CDH1 expression. CDH1−/− breast and gastric cells were more sensitive to the pan-HDAC inhibitors entinostat, pracinostat, mocetinostat and vorinostat than wild-type cells, with an elevated growth inhibition that was, in part, attributable to increased apoptosis. CDH1-null cells were also sensitive to more class-specific HDAC inhibitors, but compared to the pan-inhibitors, these effects were less robust to genetic background. Increased sensitivity to entinostat was also observed in gastric organoids with both Cdh1 and Tp53 deletions. However, the deletion of Tp53 largely abrogated the sensitivity of the Cdh1-null organoids to pracinostat and mocetinostat. Finally, entinostat enhanced Cdh1 expression in heterozygous Cdh1+/− murine organoids. In conclusion, entinostat is a promising drug for the chemoprevention and/or treatment of HDGC and may also be beneficial for the treatment of sporadic CDH1-deficient cancers.
Recent Advances in the Genetic of MALT Lymphomas
Authors: Rodríguez-Sevilla Juan José , Salar Antonio
Published: December 2021

Mucosa-associated lymphoid tissue (MALT) lymphomas are a diverse group of lymphoid neoplasms with B-cell origin, occurring in adult patients and usually having an indolent clinical behavior. These lymphomas may arise in different anatomic locations, sharing many clinicopathological characteristics, but also having substantial variances in the aetiology and genetic alterations. Chromosomal translocations are recurrent in MALT lymphomas with different prevalence among different sites, being the 4 most common: t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). Several chromosomal numerical abnormalities have also been described, but probably represent secondary genetic events. The mutational landscape of MALT lymphomas is wide, and the most frequent mutations are: TNFAIP3, CREBBP, KMT2C, TET2, SPEN, KMT2D, LRP1B, PRDM1, EP300, TNFRSF14, NOTCH1/NOTCH2, and B2M, but many other genes may be involved. Similar to chromosomal translocations, certain mutations are enriched in specific lymphoma types. In the same line, variation in immunoglobulin gene usage is recognized among MALT lymphoma of different anatomic locations. In the last decade, several studies have analyzed the role of microRNA, transcriptomics and epigenetic alterations, further improving our knowledge about the pathogenic mechanisms in MALT lymphoma development. All these advances open the possibility of targeted directed treatment and push forward the concept of precision medicine in MALT lymphomas.
Bak and Bcl-xL Participate in Regulating Sensitivity of Solid Tumor Derived Cell Lines to Mcl-1 Inhibitors
Authors: Senichkin Viacheslav V. , Pervushin Nikolay V. , Zamaraev Alexey V. , Sazonova Elena V. , Zuev Anton P. , Streletskaia Alena Y. , Prikazchikova Tatiana A. , Zatsepin Timofei S. , Kovaleva Olga V. , Tchevkina Elena M. , Zhivotovsky Boris , Kopeina Gelina S.
Published: December 2021

BH3 mimetics represent a promising tool in cancer treatment. Recently, the drugs targeting the Mcl-1 protein progressed into clinical trials, and numerous studies are focused on the investigation of their activity in various preclinical models. We investigated two BH3 mimetics to Mcl-1, A1210477 and S63845, and found their different efficacies in on-target doses, despite the fact that both agents interacted with the target. Thus, S63845 induced apoptosis more effectively through a Bak-dependent mechanism. There was an increase in the level of Bcl-xL protein in cells with acquired resistance to Mcl-1 inhibition. Cell lines sensitive to S63845 demonstrated low expression of Bcl-xL. Tumor tissues from patients with lung adenocarcinoma were characterized by decreased Bcl-xL and increased Bak levels of both mRNA and proteins. Concomitant inhibition of Bcl-xL and Mcl-1 demonstrated dramatic cytotoxicity in six of seven studied cell lines. We proposed that co-targeting Bcl-xL and Mcl-1 might lead to a release of Bak, which cannot be neutralized by other anti-apoptotic proteins. Surprisingly, in Bak-knockout cells, inhibition of Mcl-1 and Bcl-xL still resulted in pronounced cell death, arguing against a sole role of Bak in the studied phenomenon. We demonstrate that Bak and Bcl-xL are co-factors for, respectively, sensitivity and resistance to Mcl-1 inhibition.
On the Effect of Cobalt Promotion over Ni/CeO2 Catalyst for CO2 Thermal and Plasma Assisted Methanation
Authors: Hasrack Golshid , Bacariza Maria Carmen , Henriques Carlos , Da Costa Patrick
Published: December 2021

In recent years, carbon dioxide hydrogenation leading to synthetic fuels and value-added molecules has been proposed as a promising technology for stabilizing anthropogenic greenhouse gas emissions. Methanation or Sabatier are possible reactions to valorize the CO2. In the present work, thermal CO2 methanation and non-thermal plasma (NTP)-assisted CO2 methanation was performed over 15Ni/CeO2 promoted with 1 and 5 wt% of cobalt. The promotion effect of cobalt is proven both for plasma and thermal reaction and can mostly be linked with the basic properties of the materials.
Spectral, Entropy and Bifurcation Analysis of the Dynamics of a Catalyst Chemical Reverse-Flow Tubular Reactor
Authors: Berezowski Marek , Kozioł Natalia , Lawnik Marcin
Published: December 2021

Oscillations, including chaotic ones, can spontaneously appear in chemical reactors or lean premixed combustors. Such behavior of the system is undesirable and should be identified at the stage of its modeling. This article analyzes the behavior of reverse-flow tubular chemical reactor with longitudinal dispersion in terms of chaotic oscillations. The purpose of using reverse flow is to increase the conversion degree. For the analysis of the reactor, among others, spectral analysis, entropy, and bifurcation analysis were used. The obtained results show the chaotic behavior of the reactor in a wide range of changes in the parameter’s values.
Sulfide-Based Photocatalysts Using Visible Light, with Special Focus on In2S3, SnS2 and ZnIn2S4
Authors: Conesa José C.
Published: December 2021

Sulfides are frequently used as photocatalysts, since they absorb visible light better than many oxides. They have the disadvantage of being more easily photocorroded. This occurs mostly in oxidizing conditions; therefore, they are commonly used instead in reduction processes, such as CO2 reduction to fuels or H2 production. Here a summary will be presented of a number of sulfides used in several photocatalytic processes; where appropriate, some recent reviews will be presented of their behaviour. Results obtained in recent years by our group using some octahedral sulfides will be shown, showing how to determine their wavelength-dependent photocatalytic activities, checking their mechanisms in some cases, and verifying how they can be modified to extend their wavelength range of activity. It will be shown here as well how using photocatalytic or photoelectrochemical setups, by combining some enzymes with these sulfides, allows achieving the photo-splitting of water into H2 and O2, thus constituting a scheme of artificial photosynthesis.
Morphological Characteristics of Idiopathic Inflammatory Myopathies in Juvenile Patients
Authors: Schänzer Anne , Rager Leonie , Dahlhaus Iris , Dittmayer Carsten , Preusse Corinna , Della Marina Adela , Goebel Hans-Hilmar , Hahn Andreas , Stenzel Werner
Published: December 2021

Background: In juvenile idiopathic inflammatory myopathies (IIMs), morphological characteristic features of distinct subgroups are not well defined. New treatment strategies require a precise diagnosis of the subgroups in IIM, and, therefore, knowledge about the pathomorphology of juvenile IIMs is warranted. Methods: Muscle biopsies from 15 patients (median age 8 (range 3–17) years, 73% female) with IIM and seven controls were analyzed by standard methods, immunohistochemistry, and transmission electron microscopy (TEM). Detailed clinical and laboratory data were accessed retrospectively. Results: Proximal muscle weakness and skin symptoms were the main clinical symptoms. Dermatomyositis (DM) was diagnosed in 9/15, antisynthetase syndrome (ASyS) in 4/15, and overlap myositis (OM) in 2/15. Analysis of skeletal muscle tissues showed inflammatory cells and diffuse upregulation of MHC class I in all subtypes. Morphological key findings were COX-deficient fibers as a striking pathology in DM and perimysial alkaline phosphatase positivity in anti-Jo-1-ASyS. Vascular staining of the type 1 IFN-surrogate marker, MxA, correlated with endothelial tubuloreticular inclusions in both groups. None of these specific morphological findings were present in anti-PL7-ASyS or OM patients. Conclusions: Morphological characteristics discriminate IIM subtypes in juvenile patients, emphasizing differences in aetiopathogenesis and supporting the notion of individual and targeted therapeutic strategies.
MFUM-BrTNBC-1, a Newly Established Patient-Derived Triple-Negative Breast Cancer Cell Line: Molecular Characterisation, Genetic Stability, and Comprehensive Comparison with Commercial Breast Cancer Cell Lines
Authors: Skok Kristijan , Gradišnik Lidija , Čelešnik Helena , Milojević Marko , Potočnik Uroš , Jezernik Gregor , Gorenjak Mario , Sobočan Monika , Takač Iztok , Kavalar Rajko , Maver Uroš
Published: December 2021

Triple-negative breast cancer (TNBC) is a breast cancer (BC) subtype that accounts for approximately 15–20% of all BC cases. Cancer cell lines (CLs) provide an efficient way to model the disease. We have recently isolated a patient-derived triple-negative BC CL MFUM-BrTNBC-1 and performed a detailed morphological and molecular characterisation and a comprehensive comparison with three commercial BC CLs (MCF-7, MDA-MB-231, MDA-MB-453). Light and fluorescence microscopy were used for morphological studies; immunocytochemical staining for hormone receptor, p53 and Ki67 status; RNA sequencing, qRT-PCR and STR analysis for molecular characterisation; and biomedical image analysis for comparative phenotypical analysis. The patient tissue-derived MFUM-BrTNBC-1 maintained the primary triple-negative receptor status. STR analysis showed a stable and unique STR profile up to the 6th passage. MFUM-BrTNBC-1 expressed EMT transition markers and displayed changes in several cancer-related pathways (MAPK, Wnt and PI3K signalling; nucleotide excision repair; and SWI/SNF chromatin remodelling). Morphologically, MFUM-BrTNBC-1 differed from the commercial TNBC CL MDA-MB-231. The advantages of MFUM-BrTNBC-1 are its isolation from a primary tumour, rather than a metastatic site; good growth characteristics; phenotype identical to primary tissue; complete records of origin; a unique identifier; complete, unique STR profile; quantifiable morphological properties; and genetic stability up to (at least) the 6th passage.
Interleukin-8 in Melanoma Pathogenesis, Prognosis and Therapy—An Integrated View into Other Neoplasms and Chemokine Networks
Authors: Filimon Anca , Preda Iulia A. , Boloca Adina F. , Negroiu Gabriela
Published: December 2021

Cutaneous melanoma accounts for only about 7% of skin cancers but is causing almost 90% of deaths. Melanoma cells have a distinct repertoire of mutations from other cancers, a high plasticity and degree of mimicry toward vascular phenotype, stemness markers, versatility in evading and suppress host immune control. They exert a significant influence on immune, endothelial and various stromal cells which form tumor microenvironment. The metastatic stage, the leading cause of mortality in this neoplasm, is the outcome of a complex, still poorly understood, cross-talk between tumor and other cell phenotypes. There is accumulating evidence that Interleukin-8 (IL-8) is emblematic for advanced melanomas. This work aimed to present an updated status of IL-8 in melanoma tumor cellular complexity, through a comprehensive analysis including data from other chemokines and neoplasms. The multiple processes and mechanisms surveyed here demonstrate that IL-8 operates following orchestrated programs within signaling webs in melanoma, stromal and vascular cells. Importantly, the yet unknown molecularity regulating IL-8 impact on cells of the immune system could be exploited to overturn tumor fate. The molecular and cellular targets of IL-8 should be brought into the attention of even more intense scientific exploration and valorization in the therapeutical management of melanoma.
Establishing F1A-CreERT2 Mice to Trace Fgf1 Expression in Adult Mouse Cardiomyocytes
Authors: Hsu Yi-Chao , Chung Yu-Fen , Chen Mei-Shu , Wang Chi-Kuang , Jiang Si-Tse , Chiu Ing-Ming
Published: December 2021

Fibroblast growth factor 1 (FGF1) regulates many biological and physiological processes. In mice, Fgf1 gene contains at least three upstream promoters and are alternatively spliced to the first protein coding exon, giving rise to different Fgf1 mRNA variants (1A, 1B and 1G). Among them, the Fgf1A transcript is predominantly expressed in the heart. FGF1 can induce cardiomyocyte regeneration and cardiogenesis in vitro and in vivo. Here, we generated a novel mouse line using the Fgf1A promoter (F1A) driving the expression of the inducible Cre recombinase (CreERT2). We firstly demonstrated that the highest mRNA expression of CreERT2 were detected in the heart specifically of F1A-CreERT2 mice, similar to that of Fgf1A mRNA. The F1A-CreERT2 mice were crossed with ROSA26 mice, and the F1 mice were analyzed. The LacZ-positive signals were detected exclusively in the heart after tamoxifen administration. The CreERT2-mediated recombination in the tissues is monitored through LacZ-positive signals, indicating the in situ localization of F1A-positive cells. Consistently, these F1A-positive cells with RFP-positive signals or LacZ-positive blue signals were co-localized with cardiomyocytes expressing cardiac troponin T, suggesting cardiomyocyte-specific activation of Fgf1A promoter. Our data suggested that the F1A-CreERT2 mouse line could be used for time-dependent and lineage tracing of Fgf1A-expressing cells in vivo.
Aspirin Inhibition of Group VI Phospholipase A2 Induces Synthetic Lethality in AAM Pathway Down-Regulated Gingivobuccal Squamous Carcinoma
Authors: Pansare Kshama , Mohanty Bhabani , Dhotre Ranjeeta , Pettiwala Aafrin M. , Parab Saili , Gupta Neha , Gera Poonam , Gardi Nilesh , Dugge Rucha , Sahu Priyanka , Alhans Ruby , Kowtal Pradnya , Chaudhari Pradip , Sarin Rajiv
Published: December 2021

Background: To elucidate the role of iPLA2/PLA2G6 in gingivobuccal squamous cell carcinoma (GB-SCC) and to ascertain the synthetic lethality-based chemoprevention role of aspirin in arachidonic acid metabolism (AAM) pathway down-regulated GB-SCC. Methods: The in vitro efficacy of aspirin on GB-SCC cells (ITOC-03 and ITOC-04) was assessed by cell proliferation, colony formation, apoptosis, cell migration, cell cycle assay and RNA-seq, while inhibition of PLA2G6 and AAM pathway components was affirmed by qPCR, Western blot and immunofluorescence staining. The in vivo effect of aspirin was evaluated using NOD-SCID mice xenografts and immunohistochemical analysis. Results: We found that aspirin, which has been reported to act through the COX pathway, is inhibiting PLA2G6, and thereby the COX and LOX components of the AAM pathway. The findings were validated using PLA2G6 siRNA and immunohistochemical marker panel. Moreover, a pronounced effect in ITOC-04 cells and xenografts implied aspirin-induced synthetic lethality in the AAM pathway down-regulated GB-SCC. Conclusions: This study reveals that aspirin induces the anti-tumor effect by a previously unrecognized mechanism of PLA2G6 inhibition. In addition, the effect of aspirin is influenced by the baseline AAM pathway status and could guide precision prevention clinical trials of AAM pathway inhibitors.
A Fluorescence-Based Chemical Sensor for Detection of Melamine in Aqueous Solutions
Authors: Radha Remya , Vitor Rute F. , Al-Sayah Mohammad Hussein
Published: December 2021

Melamine, an industrial chemical, receives wide attention nowadays because of its unethical usage as a nitrogen enhancer in protein-rich foods and dairy products. Since most of the existing melamine detection methods are highly expensive and time-consuming, high sensitivity biosensor-based detection methods have arisen in the scientific literature as promising alternatives. This study reports the design, synthesis, and fluorescent investigations of a carbazole-based sensor (CB) for the detection of melamine in aqueous solutions. The titration studies and microplate experiments on a CB-cyanuric acid mixture (CB-CA) with melamine suggested that the novel sensor could detect melamine even at very low concentrations in both aqueous solutions and dairy samples.
The Influence of Grain Boundaries on Crystal Structure and Tensile Mechanical Properties of Al0.1CoCrFeNi High-Entropy Alloys Studied by Molecular Dynamics Method
Authors: Liu Cuixia , Wang Rui , Jian Zengyun
Published: December 2021

The mechanical properties of high-entropy alloys are superior to those of traditional alloys. However, the key problem of finding a strengthening mechanism is still challenging. In this work, the molecular dynamics method is used to calculate the tensile properties of face-centered cubic Al0.1CoCrFeNi high-entropy alloys containing Σ3 grain boundaries and without grain boundary. The atomic model was established by the melting rapid cooling method, then stretched by the static drawing method. The common neighbor analysis and dislocation extraction algorithm are used to analyze the crystal evolution mechanism of Σ3 grain boundaries to improve the material properties of high-entropy alloys during the tensile test. The results show that compared with the mechanical properties Al0.1CoCrFeNi high-entropy alloys without grain boundary, the yield strength and Young’s modulus of a high-entropy alloy containing Σ3 grain boundary are obviously larger than that of high-entropy alloys without grain boundary. Dislocation type includes mainly 1/6<112> Shockley partial dislocations, a small account of 1/6<110> Stair-rod, 1/2<110>perfect dislocation, and 1/3<111> Hirth dislocations. The mechanical properties of high-entropy alloys are improved by dislocation entanglement and accumulation near the grain boundary.
Interfacial Stabilities, Electronic Properties and Interfacial Fracture Mechanism of 6H-SiC Reinforced Copper Matrix Studied by the First Principles Method
Authors: Shu Yao , Zhang Shaowen , Xiong Yongnan , Luo Xing , He Jiazhen , Yin Cuicui , Ding Xiaoyong , Zheng Kaihong
Published: December 2021

The interfacial mechanics and electrical properties of SiC reinforced copper matrix composites were studied via the first principles method. The work of adhesion (Wad) and the interfacial energies were calculated to evaluate the stabilities of the SiC/Cu interfacial models. The carbon terminated (CT)-SiC/Cu interfaces were predicted to be more stable than those of the silicon terminated (ST)-SiC/Cu from the results of the Wad and interfacial energies. The interfacial electron properties of SiC/Cu were studied via charge density distribution, charge density difference, electron localized functions and partial density of the state. Covalent C–Cu bonds were formed based on the results of electron properties, which further explained the fact that the interfaces of the CT-SiC/Cu are more stable than those of the ST-SiC/Cu. The interfacial mechanics of the SiC/Cu were investigated via the interfacial fracture toughness and ultimate tensile stress, and the results indicate that both CT- and ST-SiC/Cu interfaces are hard to fracture. The ultimate tensile stress of the CT-SiC/Cu is nearly 23 GPa, which is smaller than those of the ST-SiC/Cu of 25 GPa. The strains corresponding to their ultimate tensile stresses of the CT- and ST-SiC/Cu are about 0.28 and 0.26, respectively. The higher strains of CT-SiC/Cu indicate their stronger plastic properties on the interfaces of the composites.