bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical Fractionation Joint to In-Mixture NMR Analysis for Avoiding the Hepatotoxicity of Teucrium chamaedrys L. subsp. chamaedrys
Authors: Piccolella Simona , Scognamiglio Monica , D’Abrosca Brigida , Esposito Assunta , Fiorentino Antonio , Pacifico Severina
Published: May 2021

Dietary supplements based on Teucrium chamaedrys L. subsp. chamaedrys aerial parts were banned, due to the hepatotoxicity of furan-containing neo-clerodane constituents. Indeed, the plant leaf content in phenolic compounds could be further exploited for their antioxidant capability. Accordingly, bio-guided fractionation strategies have been applied, obtaining seven partially purified extracts. These latter were chemically investigated through 1D and 2D NMR techniques and tested for their antiradical, reducing and cytotoxic capability. Data acquired highlighted that, through a simple phytochemical approach, a progressive neo-clerodane depletion occurred, while maximizing phenylethanoid glycosides in alcoholic fractions. Thus, although the plant cannot be used as a botanical remedy as such, it is suggested as a source of healthy compounds, pure or in mixture, to be handled in pharmaceutical, nutraceutical and/or cosmeceutical sectors.
Role of RNA in Molecular Diagnosis of MADD Patients
Authors: Nogueira Célia , Silva Lisbeth , Marcão Ana , Sousa Carmen , Fonseca Helena , Rocha Hugo , Campos Teresa , Teles Elisa Leão , Rodrigues Esmeralda , Janeiro Patrícia , Gaspar Ana , Vilarinho Laura
Published: May 2021

The electron-transfer flavoprotein dehydrogenase gene (ETFDH) encodes the ETF-ubiquinone oxidoreductase (ETF-QO) and has been reported to be the major cause of multiple acyl-CoA dehydrogenase deficiency (MADD). In this study, we present the clinical and molecular diagnostic challenges, at the DNA and RNA levels, involved in establishing the genotype of four MADD patients with novel ETFDH variants: a missense variant, two deep intronic variants and a gross deletion. RNA sequencing allowed the identification of the second causative allele in all studied patients. Simultaneous DNA and RNA investigation can increase the number of MADD patients that can be confirmed following the suggestive data results of an expanded newborn screening program. In clinical practice, accurate identification of pathogenic mutations is fundamental, particularly with regard to diagnostic, prognostic, therapeutic and ethical issues. Our study highlights the importance of RNA studies for a definitive molecular diagnosis of MADD patients, expands the background of ETFDH mutations and will be important in providing an accurate genetic counseling and a prenatal diagnosis for the affected families.
Association of Calcitriol Supplementation with Reduced COVID-19 Mortality in Patients with Chronic Kidney Disease: A Population-Based Study
Authors: Oristrell Joaquim , Oliva Joan Carles , Subirana Isaac , Casado Enrique , Domínguez Didier , Toloba Andrea , Aguilera Patricia , Esplugues Joan , Fafián Pilar , Grau Maria
Published: May 2021

Treatment with calcitriol, the hormonal form of vitamin D, has shown beneficial effects in experimental models of acute lung injury. In this study, we aimed to analyze the associations between calcitriol supplementation and the risk of SARS-CoV2 infection or COVID-19 mortality. Individuals ≥18 years old living in Catalonia and supplemented with calcitriol from April 2019 to February 2020 were compared with propensity score matched controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality. Associations between calcitriol supplementation and outcome variables were analyzed using multivariable Cox proportional regression. A total of 8076 patients were identified as being on calcitriol treatment. Advanced chronic kidney disease and hypoparathyroidism were the most frequent reasons for calcitriol supplementation in our population. Calcitriol use was associated with reduced risk of SARS-CoV2 infection (HR 0.78 [CI 95% 0.64–0.94], p = 0.010), reduced risk of severe COVID-19 and reduced COVID-19 mortality (HR 0.57 (CI 95% 0.41–0.80), p = 0.001) in patients with advanced chronic kidney disease. In addition, an inverse association between mean daily calcitriol dose and COVID-19 severity or mortality was observed in treated patients, independently of renal function. Our findings point out that patients with advanced chronic kidney disease could benefit from calcitriol supplementation during the COVID-19 pandemic.
Effect of Oxidized Low-Density Lipoprotein on Head and Neck Squamous Cell Carcinomas
Authors: Kindt Nadège , Journé Fabrice , Carlier Stéphane , Trelcat Anne , Scalia Alessandro , Saussez Sven
Published: May 2021

Cardiovascular disease (CVD) and cancer are two major causes of death worldwide. The question is, “Could there be a link between these two pathologies in addition to their shared, common risk factors?” To find some answers, we studied the effect of oxidized low-density lipoproteins (oxLDL) on head and neck cancer (HNC) cell lines, since oxLDL is a major contributor to atherosclerosis and the principal cause of CVD. In this study, we exposed three HNC cell lines (Detroit 562, UPCI-SCC-131 and FaDu) to oxLDL. We investigated two oxLDL receptors, CD36 and Lox-1, using immunofluorescence. Cancer cell migration was evaluated using Boyden chambers and the Wnt/β-catenin pathway was investigated using Western blotting. We demonstrated that the expression of CD36 and Lox-1 significantly increases after exposure to oxLDL. Moreover, we found that oxLDL reduces the migration of HNC cell lines, an observation that is in line with an increased degradation of β-catenin under oxLDL. Finally, the inhibition of CD36 with sulfosuccinimidyl oleate (SSO) reverses the inhibition of cell migration. In conclusion, we report that oxLDL seems to induce an increase in CD36 expression on HNC cell lines, enhancing the uptake of these lipids in cells to finally decrease cancer cell migration via the CD36/β-catenin pathway.
Deep Learning Optimal Control for a Complex Hybrid Energy Storage System
Authors: Zsembinszki Gabriel , Fernández Cèsar , Vérez David , Cabeza Luisa F.
Published: May 2021

Deep Reinforcement Learning (DRL) proved to be successful for solving complex control problems and has become a hot topic in the field of energy systems control, but for the particular case of thermal energy storage (TES) systems, only a few studies have been reported, all of them with a complexity degree of the TES system far below the one of this study. In this paper, we step forward through a DRL architecture able to deal with the complexity of an innovative hybrid energy storage system, devising appropriate high-level control operations (or policies) over its subsystems that result optimal from an energy or monetary point of view. The results show that a DRL policy in the system control can reduce the system operating costs by more than 50%, as compared to a rule-based control (RBC) policy, for cooling supply to a reference residential building in Mediterranean climate during a period of 18 days. Moreover, a robustness analysis was carried out, which showed that, even for large errors in the parameters of the system simulation models corresponding to an error multiplying factors up to 2, the average cost obtained with the original model deviates from the optimum value by less than 3%, demonstrating the robustness of the solution over a wide range of model errors.
Inelastic Dynamic Eccentricities in Pushover Analysis Procedure of Multi-Story RC Buildings
Authors: Bakalis Athanasios , Makarios Triantafyllos , Athanatopoulou Asimina
Published: May 2021

A documented pushover procedure on asymmetric, single-story, reinforced concrete (RC) buildings using inelastic dynamic eccentricities is extending in this paper on asymmetric multi-story RC buildings, aiming at the Near Collapse state. The floor lateral static forces of the pushover procedure are applied eccentric to the Mass Centers using appropriate inelastic dynamic or design eccentricities (dynamic plus accidental ones) to safely estimate the ductility demands of both the flexible and stiff sides of the building due to the coupled torsional/translational response. All eccentricities are applied with respect to the “Capable Near Collapse Principal System” of multi-story buildings, which is defined appropriately using the well-known methodology of the torsional optimum axis. Moreover, two patterns of lateral forces are used for performing the analysis, where in the second one an additional top-force is applied to consider the higher-mode effects. A six-story, asymmetric, torsionally-sensitive RC building is examined to verify the proposed pushover procedure relative to the results of non-linear dynamic analysis. The outcomes indicate that the proposed pushover procedure can safely predict the seismic ductility demands at the flexible and stiff sides, providing reliable estimates for the peak inter-story drift-ratios throughout the building as well as a good prediction of the plastic mechanism.
Targeting BRAF and RAS in Colorectal Cancer
Authors: Bellio Helene , Fumet Jean David , Ghiringhelli Francois
Published: May 2021

Colorectal cancer (CRC) is still one of the most frequent forms of cancer in the world in terms of incidence. Around 40% of CRC patients carry a mutation of the Kirsten rat sarcoma (KRAS) gene, while 10% have a mutation in the B-Raf proto-oncogene serine/threonine kinase (BRAF) gene. These mutations are responsible for dysregulation of the mitogen-associated protein kinase (MAPK) pathway, leading to the proliferation, differentiation, angiogenesis, and resistance to apoptosis of cells. Activation of the MAPK pathway results in adaptive therapeutic resistance, rendering EGFR inhibitors ineffective. This review aims to highlight the recent findings that have improved our understanding of KRAS and BRAF mutations in colorectal cancer and to describe new targeted therapies, used alone or in combination.
RLIP76: A Structural and Functional Triumvirate
Authors: Cornish Jasmine , Owen Darerca , Mott Helen R.
Published: May 2021

RLIP76/RalBP1 is an ATP-dependent transporter of glutathione conjugates, which is overexpressed in various human cancers, but its diverse functions in normal cells, which include endocytosis, stress response and mitochondrial dynamics, are still not fully understood. The protein can be divided into three distinct regions, each with its own structural properties. At the centre of the protein are two well-defined domains, a GTPase activating protein domain targeting Rho family small G proteins and a small coiled-coil that binds to the Ras family small GTPases RalA and RalB. In engaging with Rho and Ral proteins, RLIP76 bridges these two distinct G protein families. The N-terminal region is predicted to be disordered and is rich in basic amino acids, which may mediate membrane association, consistent with its role in transport. RLIP76 is an ATP-dependent transporter with ATP-binding sites within the N-terminus and the Ral binding domain. Furthermore, RLIP76 is subject to extensive phosphorylation, particularly in the N-terminal region. In contrast, the C-terminal region is thought to form an extensive coiled-coil that could mediate dimerization. Here, we review the structural features of RLIP76, including experimental data and computational predictions, and discuss the implications of its various post-translational modifications.
Prognostic Significance of BIRC5/Survivin in Breast Cancer: Results from Three Independent Cohorts
Authors: Oparina Nina , Erlandsson Malin C. , Fäldt Beding Anna , Parris Toshima , Helou Khalil , Karlsson Per , Einbeigi Zakaria , Bokarewa Maria I.
Published: May 2021

Breast cancer (BC) histological and molecular classifications significantly improved the treatment strategy and prognosis. Inhibitor of apoptosis BIRC5/survivin is often overexpressed in cancers, however, indications of its importance in BC are inconsistent. We integrate BIRC5 protein and mRNA measures with clinical associates and long-term outcome in three independent cohorts Protein levels of BIRC5 were measured in primary lysates of 845 patients of the West Swedish BC cohort (VGR-BC) and linked to 5- and 27-years survival. The results were externally validated in transcriptomic data from METABRIC and SCAN-B cohorts. Survival analysis showed that high levels of BIRC5 were consistently associated with a poor probability of 5-year overall survival. High BIRC5 in VGR-BC contributed negatively to the disease-specific survival at 5 and 27 years. Subsets with different status by ER (estrogen receptor) expression and presence of nodal metastasis supported independent association of high BIRC5 with poor prognosis in all cohorts. In METABRIC and SCAN-B cohorts, high levels of BIRC5 mRNA were associated with the basal-like and luminal B molecular BC subtypes and with increasing histologic grade. BIRC5 is a sensitive survival marker that acts independent of ER and nodal status, and its levels need to be considered when making treatment decisions.
Gut Microbiota as Potential Biomarker and/or Therapeutic Target to Improve the Management of Cancer: Focus on Colibactin-Producing Escherichia coli in Colorectal Cancer
Authors: Veziant Julie , Villéger Romain , Barnich Nicolas , Bonnet Mathilde
Published: May 2021

The gut microbiota is crucial for physiological development and immunological homeostasis. Alterations of this microbial community called dysbiosis, have been associated with cancers such colorectal cancers (CRC). The pro-carcinogenic potential of this dysbiotic microbiota has been demonstrated in the colon. Recently the role of the microbiota in the efficacy of anti-tumor therapeutic strategies has been described in digestive cancers and in other cancers (e.g., melanoma and sarcoma). Different bacterial species seem to be implicated in these mechanisms: F. nucleatum, B. fragilis, and colibactin-associated E. coli (CoPEC). CoPEC bacteria are prevalent in the colonic mucosa of patients with CRC and they promote colorectal carcinogenesis in susceptible mouse models of CRC. In this review, we report preclinical and clinical data that suggest that CoPEC could be a new factor predictive of poor outcomes that could be used to improve cancer management. Moreover, we describe the possibility of using these bacteria as new therapeutic targets.
Coordination Properties of Non-Rigid Phosphinoyldithioformate Complexes of the [Mo2O2(µ-S)2]2+ Cation in Catalytic Sulfur Transfer Reactions with Thiiranes
Authors: Razinkov Dmitrii , Ingvarsdottir Hafdís I. , Kvaran Ágúst , Jonsdottir Sigridur , Suman Sigridur G.
Published: May 2021

Two “Mo2O2S2”-based complexes with phosphinoyldithioformate ligands were synthesized from the metathesis reaction of [R2P(O)CS2]− with (Me4N)2[Mo2O2(µ-S)2(Cl)4] to give [Mo2O2(µ-S)2{R2P(O)CS2}2] (1; R = Ph, 2; R = Bn). The complexes were fully characterized, including the X-ray crystal structure for 1. Variable temperatures 31P NMR of 1 and 2 exhibit non-rigid behavior in solution where three and two coordination isomers were present, respectively. The organic substituent on the P atom greatly impacts the complex non-rigid properties and behavior. The catalytic activity of 1 and 2 towards sulfur atom transfer (SAT) using propylene sulfide and cyclohexene sulfide was explored, employing homogeneous reaction conditions at an ambient temperature on the NMR scale. The complexes showed distinctly different properties along with high conversions in short reaction times. A catalytic cycle consistent with the results is proposed.
A Review: Scanning Electrochemical Microscopy (SECM) for Visualizing the Real-Time Local Catalytic Activity
Authors: Preet Anant , Lin Tzu-En
Published: May 2021

Scanning electrochemical microscopy (SECM) is a powerful scanning probe technique for measuring the in situ electrochemical reactions occurring at various sample interfaces, such as the liquid-liquid, solid-liquid, and liquid-gas. The tip/probe of SECM is usually an ultramicroelectrode (UME) or a nanoelectrode that can move towards or over the sample of interest controlled by a precise motor positioning system. Remarkably, electrocatalysts play a crucial role in addressing the surge in global energy consumption by providing sustainable alternative energy sources. Therefore, the precise measurement of catalytic reactions offers profound insights for designing novel catalysts as well as for enhancing their performance. SECM proves to be an excellent tool for characterization and screening catalysts as the probe can rapidly scan along one direction over the sample array containing a large number of different compositions. These features make SECM more appealing than other conventional methodologies for assessing bulk solutions. SECM can be employed for investigating numerous catalytic reactions including the oxygen reduction reaction (ORR), oxygen evolution reaction (OER), hydrogen evolution reaction (HER), water oxidation, glucose oxidation reaction (GOR), and CO2 reduction reaction (CO2RR) with high spatial resolution. Moreover, for improving the catalyst design, several SECM modes can be applied based on the catalytic reactions under evaluation. This review aims to present a brief overview of the recent applications of electrocatalysts and their kinetics as well as catalytic sites in electrochemical reactions, such as oxygen reduction, water oxidation, and methanol oxidation.
The Genomic Landscape of Thyroid Cancer Tumourigenesis and Implications for Immunotherapy
Authors: Singh Amandeep , Ham Jeehoon , Po Joseph William , Niles Navin , Roberts Tara , Lee Cheok Soon
Published: May 2021

Thyroid cancer is the most prevalent endocrine malignancy that comprises mostly indolent differentiated cancers (DTCs) and less frequently aggressive poorly differentiated (PDTC) or anaplastic cancers (ATCs) with high mortality. Utilisation of next-generation sequencing (NGS) and advanced sequencing data analysis can aid in understanding the multi-step progression model in the development of thyroid cancers and their metastatic potential at a molecular level, promoting a targeted approach to further research and development of targeted treatment options including immunotherapy, especially for the aggressive variants. Tumour initiation and progression in thyroid cancer occurs through constitutional activation of the mitogen-activated protein kinase (MAPK) pathway through mutations in BRAF, RAS, mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway and/or receptor tyrosine kinase fusions/translocations, and other genetic aberrations acquired in a stepwise manner. This review provides a summary of the recent genetic aberrations implicated in the development and progression of thyroid cancer and implications for immunotherapy.
Imaging the Renal Microcirculation in Cell Therapy
Authors: Apelt Katerina , Bijkerk Roel , Lebrin Franck , Rabelink Ton J.
Published: May 2021

Renal microvascular rarefaction plays a pivotal role in progressive kidney disease. Therefore, modalities to visualize the microcirculation of the kidney will increase our understanding of disease mechanisms and consequently may provide new approaches for evaluating cell-based therapy. At the moment, however, clinical practice is lacking non-invasive, safe, and efficient imaging modalities to monitor renal microvascular changes over time in patients suffering from renal disease. To emphasize the importance, we summarize current knowledge of the renal microcirculation and discussed the involvement in progressive kidney disease. Moreover, an overview of available imaging techniques to uncover renal microvascular morphology, function, and behavior is presented with the associated benefits and limitations. Ultimately, the necessity to assess and investigate renal disease based on in vivo readouts with a resolution up to capillary level may provide a paradigm shift for diagnosis and therapy in the field of nephrology.
Calcium Signaling in Plant Programmed Cell Death
Authors: Ren Huimin , Zhao Xiaohong , Li Wenjie , Hussain Jamshaid , Qi Guoning , Liu Shenkui
Published: May 2021

Programmed cell death (PCD) is a process intended for the maintenance of cellular homeostasis by eliminating old, damaged, or unwanted cells. In plants, PCD takes place during developmental processes and in response to biotic and abiotic stresses. In contrast to the field of animal studies, PCD is not well understood in plants. Calcium (Ca2+) is a universal cell signaling entity and regulates numerous physiological activities across all the kingdoms of life. The cytosolic increase in Ca2+ is a prerequisite for the induction of PCD in plants. Although over the past years, we have witnessed significant progress in understanding the role of Ca2+ in the regulation of PCD, it is still unclear how the upstream stress perception leads to the Ca2+ elevation and how the signal is further propagated to result in the onset of PCD. In this review article, we discuss recent advancements in the field, and compare the role of Ca2+ signaling in PCD in biotic and abiotic stresses. Moreover, we discuss the upstream and downstream components of Ca2+ signaling and its crosstalk with other signaling pathways in PCD. The review is expected to provide new insights into the role of Ca2+ signaling in PCD and to identify gaps for future research efforts.
ARCGHR Neurons Regulate Muscle Glucose Uptake
Authors: de Lima Juliana Bezerra Medeiros , Debarba Lucas Kniess , Rupp Alan C. , Qi Nathan , Ubah Chidera , Khan Manal , Didyuk Olesya , Ayyar Iven , Koch Madelynn , Sandoval Darleen A. , Sadagurski Marianna
Published: May 2021

The growth hormone receptor (GHR) is expressed in brain regions that are known to participate in the regulation of energy homeostasis and glucose metabolism. We generated a novel transgenic mouse line (GHRcre) to characterize GHR-expressing neurons specifically in the arcuate nucleus of the hypothalamus (ARC). Here, we demonstrate that ARCGHR+ neurons are co-localized with agouti-related peptide (AgRP), growth hormone releasing hormone (GHRH), and somatostatin neurons, which are activated by GH stimulation. Using the designer receptors exclusively activated by designer drugs (DREADD) technique to control the ARCGHR+ neuronal activity, we demonstrate that the activation of ARCGHR+ neurons elevates a respiratory exchange ratio (RER) under both fed and fasted conditions. However, while the activation of ARCGHR+ promotes feeding, under fasting conditions, the activation of ARCGHR+ neurons promotes glucose over fat utilization in the body. This effect was accompanied by significant improvements in glucose tolerance, and was specific to GHR+ versus GHRH+ neurons. The activation of ARCGHR+ neurons increased glucose turnover and whole-body glycolysis, as revealed by hyperinsulinemic-euglycemic clamp studies. Remarkably, the increased insulin sensitivity upon the activation of ARCGHR+ neurons was tissue-specific, as the insulin-stimulated glucose uptake was specifically elevated in the skeletal muscle, in parallel with the increased expression of muscle glycolytic genes. Overall, our results identify the GHR-expressing neuronal population in the ARC as a major regulator of glycolysis and muscle insulin sensitivity in vivo.
AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review
Authors: Višnjić Dora , Lalić Hrvoje , Dembitz Vilma , Tomić Barbara , Smoljo Tomislav
Published: May 2021

5-Aminoimidazole-4-carboxamide ribonucleoside (AICAr) has been one of the most commonly used pharmacological modulators of AMPK activity. The majority of early studies on the role of AMPK, both in the physiological regulation of metabolism and in cancer pathogenesis, were based solely on the use of AICAr as an AMPK-activator. Even with more complex models of AMPK downregulation and knockout being introduced, AICAr remained a regular starting point for many studies focusing on AMPK biology. However, there is an increasing number of studies showing that numerous AICAr effects, previously attributed to AMPK activation, are in fact AMPK-independent. This review aims to give an overview of the present knowledge on AMPK-dependent and AMPK-independent effects of AICAr on metabolism, hypoxia, exercise, nucleotide synthesis, and cancer, calling for caution in the interpretation of AICAr-based studies in the context of understanding AMPK signaling pathway.
Control of Macrophage Inflammation by P2Y Purinergic Receptors
Authors: Klaver Dominik , Thurnher Martin
Published: May 2021

Macrophages comprise a phenotypically and functionally diverse group of hematopoietic cells. Versatile macrophage subsets engage to ensure maintenance of tissue integrity. To perform tissue stress surveillance, macrophages express many different stress-sensing receptors, including purinergic P2X and P2Y receptors that respond to extracellular nucleotides and their sugar derivatives. Activation of G protein-coupled P2Y receptors can be both pro- and anti-inflammatory. Current examples include the observation that P2Y14 receptor promotes STAT1-mediated inflammation in pro-inflammatory M1 macrophages as well as the demonstration that P2Y11 receptor suppresses the secretion of tumor necrosis factor (TNF)-α and concomitantly promotes the release of soluble TNF receptors from anti-inflammatory M2 macrophages. Here, we review macrophage regulation by P2Y purinergic receptors, both in physiological and disease-associated inflammation. Therapeutic targeting of anti-inflammatory P2Y receptor signaling is desirable to attenuate excessive inflammation in infectious diseases such as COVID-19. Conversely, anti-inflammatory P2Y receptor signaling must be suppressed during cancer therapy to preserve its efficacy.
Psoriasis and Liver Damage in HIV-Infected Patients
Authors: Busca Arenzana Carmen , Quintana Castanedo Lucía , Chiloeches Fernández Clara , Nieto Rodríguez Daniel , Herranz Pinto Pedro , Delgado Hierro Ana Belén , Olveira Martín Antonio , Montes Ramírez María Luisa
Published: May 2021

Background/objectives: Psoriasis is the most frequent skin disease in HIV-infected patients. Nonalcohol fatty liver disease (NAFLD) is more prevalent in patients with psoriasis. We report the prevalence of psoriasis and NAFLD and investigate risk factors of liver damage in HIV-infected patients with psoriasis. Methods: We performed a retrospective observational study. Steatosis was defined as indicative abdominal ultrasound findings, CAP (controlled attenuated parameter by transient elastography) > 238 dB/m, and/or triglyceride and glucose index (TyG) > 8.38. Significant (fibrosis ≥ 2) and advanced liver fibrosis (fibrosis ≤ F3) were studied by transient elastography (TE) and/or FIB-4 using standard cutoff points. FIB-4 (Fibrosis 4 score) results were adjusted for hepatitis C (HCV)-coinfected patients. Results: We identified 80 patients with psoriasis (prevalence, 1.5%; 95% CI, 1.1–1.8). Psoriasis was severe (PASI > 10 and/or psoriatic arthritis) in 27.5% of cases. The prevalence of steatosis was 72.5% (95% CI, 65–85). Severe psoriasis was an independent risk factor for steatosis (OR, 12; 95% CI, 1.2–120; p = 0.03). Significant liver fibrosis (p < 0.05) was associated with HCV coinfection (OR 3.4; 95% CI, 1.1–10.6), total CD4 (OR 0.99; 95% CI, 0.99–1), and time of efavirenz exposure (OR 1.2; 95% CI, 1.0–1.3). Conclusions: The prevalence of psoriasis in HIV-infected patients was similar to that of the general population. Steatosis is highly prevalent, and severe psoriasis is an independent risk factor for steatosis in HIV-infected patients.
Glycosylation of Immune Receptors in Cancer
Authors: Sun Ruoxuan , Kim Alyssa Min Jung , Lim Seung-Oe
Published: May 2021

Evading host immune surveillance is one of the hallmarks of cancer. Immune checkpoint therapy, which aims to eliminate cancer progression by reprogramming the antitumor immune response, currently occupies a solid position in the rapidly expanding arsenal of cancer therapy. As most immune checkpoints are membrane glycoproteins, mounting attention is drawn to asking how protein glycosylation affects immune function. The answers to this fundamental question will stimulate the rational development of future cancer diagnostics and therapeutic strategies.
HDAC8 Activates AKT through Upregulating PLCB1 and Suppressing DESC1 Expression in MEK1/2 Inhibition-Resistant Cells
Authors: Ha Soon-Duck , Lewin Naomi , Li Shawn S. C. , Kim Sung-Ouk
Published: May 2021

Inhibition of the RAF-MEK1/2-ERK signaling pathway is an ideal strategy for treating cancers with NRAS or BRAF mutations. However, the development of resistance due to incomplete inhibition of the pathway and activation of compensatory cell proliferation pathways is a major impediment of the targeted therapy. The anthrax lethal toxin (LT), which cleaves and inactivates MEKs, is a modifiable biomolecule that can be delivered selectively to tumor cells and potently kills various tumor cells. However, resistance to LT and the mechanism involved are yet to be explored. Here, we show that LT, through inhibiting MEK1/2-ERK activation, inhibits the proliferation of cancer cells with NRAS/BRAF mutations. Among them, the human colorectal tumor HT-29 and murine melanoma B16-BL6 cells developed resistance to LT in 2 to 3 days of treatment. These resistant cells activated AKT through a histone deacetylase (HDAC) 8-dependent pathway. Using an Affymetrix microarray, followed by qPCR validation, we identified that the differential expression of the phospholipase C-β1 (PLCB1) and squamous cell carcinoma-1 (DESC1) played an important role in HDAC8-mediated AKT activation and resistance to MEK1/2-ERK inhibition. By using inhibitors, small interference RNAs and/or expression vectors, we found that the inhibition of HDAC8 suppressed PLCB1 expression and induced DESC1 expression in the resistant cells, which led to the inhibition of AKT and re-sensitization to LT and MEK1/2 inhibition. These results suggest that targeting PLCB1 and DESC1 is a novel strategy for inhibiting the resistance to MEK1/2 inhibition.
The Anti-Infectious Role of Sphingosine in Microbial Diseases
Authors: Wu Yuqing , Liu Yongjie , Gulbins Erich , Grassmé Heike
Published: May 2021

Sphingolipids are important structural membrane components and, together with cholesterol, are often organized in lipid rafts, where they act as signaling molecules in many cellular functions. They play crucial roles in regulating pathobiological processes, such as cancer, inflammation, and infectious diseases. The bioactive metabolites ceramide, sphingosine-1-phosphate, and sphingosine have been shown to be involved in the pathogenesis of several microbes. In contrast to ceramide, which often promotes bacterial and viral infections (for instance, by mediating adhesion and internalization), sphingosine, which is released from ceramide by the activity of ceramidases, kills many bacterial, viral, and fungal pathogens. In particular, sphingosine is an important natural component of the defense against bacterial pathogens in the respiratory tract. Pathologically reduced sphingosine levels in cystic fibrosis airway epithelial cells are normalized by inhalation of sphingosine, and coating plastic implants with sphingosine prevents bacterial infections. Pretreatment of cells with exogenous sphingosine also prevents the viral spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from interacting with host cell receptors and inhibits the propagation of herpes simplex virus type 1 (HSV-1) in macrophages. Recent examinations reveal that the bactericidal effect of sphingosine might be due to bacterial membrane permeabilization and the subsequent death of the bacteria.
Fibrotic Events in the Progression of Cholestatic Liver Disease
Authors: Wu Hanghang , Chen Chaobo , Ziani Siham , Nelson Leonard J. , Ávila Matías A. , Nevzorova Yulia A. , Cubero Francisco Javier
Published: May 2021

Cholestatic liver diseases including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are associated with active hepatic fibrogenesis, which can ultimately lead to the development of cirrhosis. However, the exact relationship between the development of liver fibrosis and the progression of cholestatic liver disease remains elusive. Periductular fibroblasts located around the bile ducts seem biologically different from hepatic stellate cells (HSCs). The fibrotic events in these clinical conditions appear to be related to complex crosstalk between immune/inflammatory mechanisms, cytokine signalling, and perturbed homeostasis between cholangiocytes and mesenchymal cells. Several animal models including bile duct ligation (BDL) and the Mdr2-knockout mice have improved our understanding of mechanisms underlying chronic cholestasis. In the present review, we aim to elucidate the mechanisms of fibrosis in order to help to identify potential diagnostic and therapeutic targets.
Apigenin and Structurally Related Flavonoids Allosterically Potentiate the Function of Human α7-Nicotinic Acetylcholine Receptors Expressed in SH-EP1 Cells
Authors: Shabbir Waheed , Yang Keun-Hang Susan , Sadek Bassem , Oz Murat
Published: May 2021

Phytochemicals, such as monoterpenes, polyphenols, curcuminoids, and flavonoids, are known to have anti-inflammatory, antioxidant, neuroprotective, and procognitive effects. In this study, the effects of several polyhydroxy flavonoids, as derivatives of differently substituted 5,7-dihydroxy-4H-chromen-4-one including apigenin, genistein, luteolin, kaempferol, quercetin, gossypetin, and phloretin with different lipophilicities (cLogP), as well as topological polar surface area (TPSA), were tested for induction of Ca2+ transients by α7 human nicotinic acetylcholine (α7 nACh) receptors expressed in SH-EP1 cells. Apigenin (10 μM) caused a significant potentiation of ACh (30 μM)-induced Ca2+ transients, but did not affect Ca2+ transients induced by high K+ (60 mM) containing solutions. Co-application of apigenin with ACh was equally effective as apigenin preincubation. However, the effect of apigenin significantly diminished by increasing ACh concentrations. The flavonoids tested also potentiated α7 nACh mediated Ca2+ transients with descending potency (highest to lowest) by genistein, gossypetin, kaempferol, luteolin, phloretin, quercetin, and apigenin. The specific binding of α7 nACh receptor antagonist [125I]-bungarotoxin remained unchanged in the presence of any of the tested polyhydroxy flavonoids, suggesting that these compounds act as positive allosteric modulators of the α7-nACh receptor in SH-EP1 cells. These findings suggest a clinical potential for these phytochemicals in the treatment of various human diseases from pain to inflammation and neural disease.
Cross-Reactivity and Sequence Homology Between Alpha-Synuclein and Food Products: A Step Further for Parkinson’s Disease Synucleinopathy
Authors: Vojdani Aristo , Lerner Aaron , Vojdani Elroy
Published: May 2021

Introduction: Parkinson’s disease is characterized by non-motor/motor dysfunction midbrain neuronal death and α-synuclein deposits. The accepted hypothesis is that unknown environmental factors induce α-synuclein accumulation in the brain via the enteric nervous system. Material and Methods: Monoclonal antibodies made against recombinant α-synuclein protein or α-synuclein epitope 118–123 were applied to the antigens of 180 frequently consumed food products. The specificity of those antibody-antigen reactions was confirmed by serial dilution and inhibition studies. The Basic Local Alignment Search Tool sequence matching program was used for sequence homologies. Results: While the antibody made against recombinant α-synuclein reacted significantly with 86/180 specific food antigens, the antibody made against α-synuclein epitope 118–123 reacted with only 32/180 tested food antigens. The food proteins with the greatest number of peptides that matched with α-synuclein were yeast, soybean, latex hevein, wheat germ agglutinin, potato, peanut, bean agglutinin, pea lectin, shrimp, bromelain, and lentil lectin. Conclusions: The cross-reactivity and sequence homology between α-synuclein and frequently consumed foods, reinforces the autoimmune aspect of Parkinson’s disease. It is hypothesized that luminal food peptides that share cross-reactive epitopes with human α-synuclein and have molecular similarity with brain antigens are involved in the synucleinopathy. The findings deserve further confirmation by extensive research.
Adipose Tissue-Derived Stem Cell Yield Depends on Isolation Protocol and Cell Counting Method
Authors: Prantl Lukas , Eigenberger Andreas , Brix Eva , Kempa Sally , Baringer Magnus , Felthaus Oliver
Published: May 2021

In plastic surgery, lipofilling is a frequent procedure. Unsatisfactory vascularization and impaired cell vitality can lead to unpredictable take rates in the fat graft. The proliferation and neovascularization inducing properties of adipose tissue-derived stem cells may contribute to solve this problem. Therefore, the enrichment of fat grafts with stem cells is studied intensively. However, it is difficult to compare these studies because many factors—often not precisely described—are influencing the results. Our study summarizes some factors which influence the cell yield like harvesting, isolation procedure and quantification. Stem cells were isolated after liposuction. Quantification was done using a cell chamber, colony counting, or flow cytometry with changes to one parameter, only, for each comparison. Quantification of cells isolated after liposuction at the same harvesting site from the same patient can vary greatly depending on the details of the isolation protocol and the method of quantification. Cell yield can be influenced strongly by many factors. Therefore, a comparison of different studies should be handled with care.
Dual Transduction of H2O2 Detection Using ZnO/Laser-Induced Graphene Composites
Authors: Zanoni Julia , Moura Jorge P. , Santos Nuno F. , Carvalho Alexandre F. , Fernandes António J. S. , Monteiro Teresa , Costa Florinda M. , Pereira Sónia O. , Rodrigues Joana
Published: May 2021

Zinc oxide (ZnO)/laser-induced graphene (LIG) composites were prepared by mixing ZnO, grown by laser-assisted flow deposition, with LIG produced by laser irradiation of a polyimide, both in ambient conditions. Different ZnO:LIG ratios were used to infer the effect of this combination on the overall composite behavior. The optical properties, assessed by photoluminescence (PL), showed an intensity increase of the excitonic-related recombination with increasing LIG amounts, along with a reduction in the visible emission band. Charge-transfer processes between the two materials are proposed to justify these variations. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy evidenced increased electron transfer kinetics and an electrochemically active area with the amount of LIG incorporated in the composites. As the composites were designed to be used as transducer platforms in biosensing devices, their ability to detect and quantify hydrogen peroxide (H2O2) was assessed by both PL and CV analysis. The results demonstrated that both methods can be employed for sensing, displaying slightly distinct operation ranges that allow extending the detection range by combining both transduction approaches. Moreover, limits of detection as low as 0.11 mM were calculated in a tested concentration range from 0.8 to 32.7 mM, in line with the values required for their potential application in biosensors.
White Nail as a Static Physical Finding: Revitalization of Physical Examination
Authors: Ohta Ryuichi , Sano Chiaki
Published: May 2021

Physical examinations are critical for diagnosis and should be differentiated into static and dynamic categories. One of the static findings is white nail, such as Terry’s and Lindsay’s nails. Here, we report the cases of two older patients with acute diseases who had nail changes that aided evaluation of their clinical course. Two elderly women who presented with acute conditions were initially thought to have normal serum albumin levels. They were found to have white nail with differences in nail involvement of the first finger, which subsequently revealed their hypoalbuminemia. The clinical courses were different following the distribution of nail whitening. Our findings show that examination of a white nail could indicate the previous clinical status more clearly than laboratory data. It can be useful for evaluating preclinical conditions in patients with acute diseases. Further evaluation is needed to establish the relationship between clinical outcomes and the presence of white nail in acute conditions among older patients.
The Role of Astaxanthin on Chronic Diseases
Authors: Zhang Xueqi , Hou Yachen , Li Jingan , Wang Jianfeng
Published: May 2021

Natural astaxanthin exists widely in algae, fungi, shrimp and crab, and, as a strong antioxidant, has potential effects on cardiovascular diseases, cancer, liver diseases and other physical health diseases. The treatment of many diseases involves the body’s signal transduction to regulate the body’s antioxidant defense system and inflammation. Astaxanthin is usually used as a dietary supplement, which plays an antioxidant and anti-inflammatory role in the organism. This article reviews the structure, source of astaxanthin and how it plays an anti-inflammatory and anti-oxidant role in organisms, especially in treating diabetes.
Structural Phase Transition in (NH4)3GeF7–Raman Spectroscopy Data
Authors: Gerasimova Yulia , Laptash Natalia , Krylov Alexander , Vonog Vita , Vtyurin Alexander
Published: May 2021

We obtained Raman spectra of (NH4)3GeF7 crystals with a wide range of frequencies (10–3400 cm−1) and temperatures (8–300 K), including phase transition, which was accompanied by a symmetry increase with a temperature decrease. The internal vibrations of the GeF62− group were classified by the positional symmetry method. Considerable transformations of the Raman spectra were observed at the lower frequency range of lattice vibrations and the ranges of the internal vibrations of the ammonium ions. In contrast, the internal modes of the GeF62− groups changed only slightly due to their resonance splitting in the multiplied unit cell, which agreed well with the proposed phase transition mechanism induced by ammonium group ordering.
Chronic Kidney Disease Is Associated with High Mortality Risk in Patients with Diabetes after Primary Shoulder Arthroplasty: A Nationwide Population-Based Cohort Study
Authors: Lin Meng-Hao , Lin Su-Ju , Kuo Liang-Tseng , Chen Tien-Hsing , Chen Chi-Lung , Yu Pei-An , Tsai Yao-Hung , Hsu Wei-Hsiu
Published: May 2021

The number of diabetic patients with chronic kidney disease (CKD) undergoing shoulder arthroplasty is growing. This study aims to compare perioperative outcomes of shoulder arthroplasty in diabetic patients at different renal function stages. Between 1998 and 2013, a total of 4443 diabetic patients with shoulder arthroplasty were enrolled: 1174 (26%) had CKD without dialysis (CKD group), 427 (9%) underwent dialysis (dialysis group), and 3042 (68%) had no CKD (non-CKD group). Compared with the non-CKD group, the CKD (odds ratio [OR], 4.69; 95% confidence interval [CI], 2.02–10.89) and dialysis (OR, 6.71; 95% CI, 1.63–27.73) groups had a high risk of in-hospital death. The dialysis group had a high risk of infection after shoulder arthroplasty compared with the CKD (subdistribution hazard ratio [SHR], 1.69; 95% CI, 1.07–2.69) and non-CKD (SHR, 1.76; 95% CI, 1.14–2.73) groups. The dialysis group showed higher risks of all-cause readmission and mortality than the CKD and non-CKD groups after a 3-month follow-up. In conclusion, CKD was associated with worse outcomes after shoulder arthroplasty. Compared with those without CKD, CKD patients had significantly increased readmission and mortality risks but did not have an increased risk of surgical complications, including superficial infection or implant removal.
CT-Guided Drainage of Fluid Collections Following Liver Resection: Technical and Clinical Outcome of 143 Patients during a 14-Year Period
Authors: Winter Katharina S. , Greif Veronika , Crispin Alexander , Burgard Caroline , Forbrig Robert , Liebig Thomas , Trumm Christoph G. , Stahl Robert
Published: May 2021

Purpose: To retrospectively evaluate the technical and clinical outcome of patients with symptomatic postoperative fluid collections following liver resection treated with CT-guided drainage (CTD). Methods: 143 suitable patients were examined between 2004 and 2017. Technical success was defined as (a) sufficient drainage of the fluid collection and (b) the non-occurrence of peri-interventional complications requiring surgical treatment with minor or prolonged hospitalization. Clinical success was defined as (a) decreasing or normalization of specific blood parameters within 30 days after intervention and (b) no surgical revision in addition to intervention required. C-reactive protein (CRP), leukocytes and Total Serum Bilirubin (TSB) were assessed. Dose length product (DLP) for the intervention parts was determined. Results: Technical success was achieved in 99.5% of 189 performed interventions. Clinical success was reached in 74% for CRP, in 86.7% for Leukocytes and in 62.1% for TSB. The median of successful decrease was 6.0 days for CRP, 3.5 days for Leukocytes and 5.5 days for TSB. In 90.2%, no surgical revision was necessary. Total DLP was significantly lower in the second half of the observation period (median 536.0 mGy*cm between years 2011 and 2017 vs. median 745.5 mGy*cm between years 2004 and 2010). Conclusions: Technical success rate of CTD was very high, and clinical success rate was fair to good. Reduction of the radiation dose reflects developments of CT technology and increased experience of the interventional radiologists.
Mesonephric-Like Carcinosarcoma of the Ovary Associated with Low-Grade Serous Carcinoma: A Case Report
Authors: d’Amati Antonio , Pezzuto Federica , Serio Gabriella , Marzullo Andrea , Fortarezza Francesco , Lettini Teresa , Cazzato Gerardo , Cormio Gennaro , Resta Leonardo
Published: May 2021

Mesonephric adenocarcinomas are rare tumors of the female genital tract, thought to arise from embryonic mesonephric remnants, primarily in the cervix and vagina. Conversely, endometrial and ovarian mesonephric adenocarcinomas may have a different pathogenesis, probably originating from transdifferentiated Müllerian carcinomas, as demonstrated by the association of these neoplasms with endometriosis and ovarian serous tumors. For this reason, in the endometrium and in the ovary, they are defined as “mesonephric-like adenocarcinomas”. Some cases of mesonephric carcinomas of the female genital tract have been reported to show a sarcomatous component and have been defined as “mesonephric carcinosarcomas”, characterized by poor prognosis and high metastatic behavior, but this entity has never been described in the ovary. The case herein presented is of a 74-year-old female with abdominal discomfort and a complex ovarian mass. Histological and immunohistochemical analysis showed features of ovarian mesonephric-like carcinoma combined with a low-grade serous component, in support of the theory of a Müllerian origin of these neoplasms. The tumor also revealed foci of chondrosarcomatous differentiation, never before reported in the ovary, showing a similar immunohistochemical profile to the mesonephric-like elements. This work thus describes the first reported case of ovarian mesonephric-like carcinosarcoma.