bluuebunny/crossref_metadata_2025 huggingface dataset:
Colorectal Cancer, Liver Metastases and Biotherapies
Authors: Osei-Bordom Daniel-Clement , Kamarajah Sivesh , Christou Niki
Published: July 2021

(1) Background: colorectal cancer (CRC) is one of the deadliest causes of death by cancer worldwide. Its first main metastatic diffusion spreads to the liver. Different mechanisms such as the epithelial–mesenchymal transition and angiogenesis are the characteristics of this invasion. At this stage, different options are possible and still in debate, especially regarding the use of targeted therapeutics and biotherapies. (2) Methods: A review of the literature has been done focusing on the clinical management of liver metastasis of colorectal cancer and the contribution of biotherapies in this field. (3) Results: In a clinical setting, surgeons and oncologists consider liver metastasis in CRC into two groups to launch adapted therapeutics: resectable and non-resectable. Around these two entities, the combination of targeted therapies and biotherapies are of high interest and are currently tested to know in which molecular and clinical conditions they have to be applied to impact positively both on survival and quality of life of patients.
SPR-Based Kinetic Analysis of the Early Stages of Infection in Cells Infected with Human Coronavirus and Treated with Hydroxychloroquine
Authors: Genova-Kalou Petia , Dyankov Georgi , Marinov Radoslav , Mankov Vihar , Belina Evdokiya , Kisov Hristo , Strijkova-Kenderova Velichka , Kantardjiev Todor
Published: July 2021

Cell-based assays are a valuable tool for examination of virus–host cell interactions and drug discovery processes, allowing for a more physiological setting compared to biochemical assays. Despite the fact that cell-based SPR assays are label-free and thus provide all the associated benefits, they have never been used to study viral growth kinetics and to predict drug antiviral response in cells. In this study, we prove the concept that the cell-based SPR assay can be applied in the kinetic analysis of the early stages of viral infection of cells and the antiviral drug activity in the infected cells. For this purpose, cells immobilized on the SPR slides were infected with human coronavirus HCov-229E and treated with hydroxychloroquine. The SPR response was measured at different time intervals within the early stages of infection. Methyl Thiazolyl Tetrazolium (MTT) assay was used to provide the reference data. We found that the results of the SPR and MTT assays were consistent, and SPR is a reliable tool in investigating virus–host cell interaction and the mechanism of action of viral inhibitors. SPR assay was more sensitive and accurate in the first hours of infection within the first replication cycle, whereas the MTT assay was not so effective. After the second replication cycle, noise was generated by the destruction of the cell layer and by the remnants of dead cells, and masks useful SPR signals.
Death Anxiety and Attitudes towards Death in Patients with Multiple Sclerosis: An Exploratory Study
Authors: Francalancia Jara , Mavrogiorgou Paraskevi , Juckel Georg , Mitrovic Tina , Kuhle Jens , Naegelin Yvonne , Kappos Ludwig , Calabrese Pasquale
Published: July 2021

Background: Death and the anxiety of it becomes more apparent when confronted with a chronic disease. Even though multiple sclerosis (MS) is a treatable condition today, it is still accompanied by a multitude of impairments, which in turn may intensify of death anxiety. Objective: The aim of this study is to explore the relationship between depression, anxiety and death anxiety in individuals with MS. Methods: Fifty-six MS patients were recruited at the Department of Neurology of the University Clinic in Basel. Death anxiety was assessed using the Bochumer Questionnaire on attitude to death and death anxiety 2.0 (BOFRETTA 2.0). Results: Scores of death anxiety towards it in MS patients were low. Only disability (EDSS) was moderately correlated with death anxiety. Depression in MS was significantly correlated with fatigue and disability, but not with the BOFRETTA 2.0. Conclusion: Scores of death anxiety and the attitude towards death are low in this MS cohort. It was shown that both psychopathological and neurological deficits impact the subject of death with respect to multiple sclerosis.
Sleep, Behavior, and Adaptive Function in KAT6A Syndrome
Authors: Smith Clay , Harris Jacqueline
Published: July 2021

KAT6A syndrome is a Mendelian Disorder of the Epigenetic Machinery characterized by intellectual disability and profound expressive language impairment. This study aimed to further characterize behavior and sleep in this syndrome. 26 participants between the ages of 3 and 35 years with KAT6A syndrome were assessed via parental informant using the Adaptive Behavior Assessment System version 3 (ABAS-3), Achenbach Child or Adult Behavior Checklist (CBCL/ABCL), and a Modified Simonds and Parraga Sleep Questionnaire (MSPSQ). The ABAS reports conceptual, social, and practical domains of adaptive function as well as a general composite score for adaptive function. The CBCL/ABCL is an inventory that measures internalizing, externalizing, and DSM-oriented problem domains. The MSPSQ is a mix of qualitative and quantitative sleep information that includes behavioral and medical sleep problems. Mean values for all domains of the ABAS-3 were in the extremely low range. Additionally, sleep was very dysfunctional in this cohort. Sixty percent of respondents reported feeling there was a sleep problem, 64% take medication for sleep, and 68% have sought treatment or advice for sleep. Only 12% of these participants have sleep apnea suggesting that sleep problems in this disorder are unrelated to sleep-disordered breathing. Interestingly, there were extremely low rates of all types of behaviors reported among participants on the CBCL/ABCL. No significant differences were seen based on genotype grouping in adaptive function, sleep, or behavior. This study further delineates the phenotype of the KAT6A syndrome and emphasizes the need for supports for adaptive functioning as well as detailed attention to the behavioral aspects of sleep in this condition.
Comparison of Brain Activation Patterns during Olfactory Stimuli between Recovered COVID-19 Patients and Healthy Controls: A Functional Near-Infrared Spectroscopy (fNIRS) Study
Authors: Ho Roger C. , Sharma Vijay K. , Tan Benjamin Y. Q. , Ng Alison Y. Y. , Lui Yit-Shiang , Husain Syeda Fabeha , Ho Cyrus S. , Tran Bach X. , Pham Quang-Hai , McIntyre Roger S. , Chan Amanda C. Y.
Published: July 2021

Impaired sense of smell occurs in a fraction of patients with COVID-19 infection, but its effect on cerebral activity is unknown. Thus, this case report investigated the effect of COVID-19 infection on frontotemporal cortex activity during olfactory stimuli. In this preliminary study, patients who recovered from COVID-19 infection (n = 6) and healthy controls who never contracted COVID-19 (n = 6) were recruited. Relative changes in frontotemporal cortex oxy-hemoglobin during olfactory stimuli was acquired using functional near-infrared spectroscopy (fNIRS). The area under curve (AUC) of oxy-hemoglobin for the time interval 5 s before and 15 s after olfactory stimuli was derived. In addition, olfactory function was assessed using the Sniffin’ Sticks 12-identification test (SIT-12). Patients had lower SIT-12 scores than healthy controls (p = 0.026), but there were no differences in oxy-hemoglobin AUC between healthy controls and patients (p > 0.05). This suggests that past COVID-19 infection may not affect frontotemporal cortex function, and these preliminary results need to be verified in larger samples.
Transcriptomic Data Analysis Reveals a Down-Expression of Galectin-8 in Schizophrenia Hippocampus
Authors: Petralia Maria Cristina , Ciurleo Rosella , Bramanti Alessia , Bramanti Placido , Saraceno Andrea , Mangano Katia , Quattropani Maria Catena , Nicoletti Ferdinando , Fagone Paolo
Published: July 2021

Schizophrenia (SCZ) is a severe psychiatric disorder with several clinical manifestations that include cognitive dysfunction, decline in motivation, and psychosis. Current standards of care treatment with antipsychotic agents are often ineffective in controlling the disease, as only one-third of SCZ patients respond to medications. The mechanisms underlying the pathogenesis of SCZ remain elusive. It is believed that inflammatory processes may play a role as contributing factors to the etiology of SCZ. Galectins are a family of β-galactoside-binding lectins that contribute to the regulation of immune and inflammatory responses, and previous reports have shown their role in the maintenance of central nervous system (CNS) homeostasis and neuroinflammation. In the current study, we evaluated the expression levels of the galectin gene family in post-mortem samples of the hippocampus, associative striatum, and dorsolateral prefrontal cortex from SCZ patients. We found a significant downregulation of LGALS8 (Galectin-8) in the hippocampus of SCZ patients as compared to otherwise healthy donors. Interestingly, the reduction of LGALS8 was disease-specific, as no modulation was observed in the hippocampus from bipolar nor major depressive disorder (MDD) patients. Prediction analysis identified TBL1XR1, BRF2, and TAF7 as potential transcription factors controlling LGALS8 expression. In addition, MIR3681HG and MIR4296 were negatively correlated with LGALS8 expression, suggesting a role for epigenetics in the regulation of LGALS8 levels. On the other hand, no differences in the methylation levels of LGALS8 were observed between SCZ and matched control hippocampus. Finally, ontology analysis of the genes negatively correlated with LGALS8 expression identified an enrichment of the NGF-stimulated transcription pathway and of the oligodendrocyte differentiation pathway. Our study identified LGALS8 as a disease-specific gene, characterizing SCZ patients, that may in the future be exploited as a potential therapeutic target.
Stopping a Response When You Really Care about the Action: Considerations from a Clinical Perspective
Authors: Morein-Zamir Sharon , Anholt Gideon
Published: July 2021

Response inhibition, whether reactive or proactive, is mostly investigated in a narrow cognitive framework. We argue that it be viewed within a broader frame than the action being inhibited, i.e., in the context of emotion and motivation of the individual at large. This is particularly important in the clinical domain, where the motivational strength of an action can be driven by threat avoidance or reward seeking. The cognitive response inhibition literature has focused on stopping reactively with responses in anticipation of clearly delineated external signals, or proactively in limited contexts, largely independent of clinical phenomena. Moreover, the focus has often been on stopping efficiency and its correlates rather than on inhibition failures. Currently, the cognitive and clinical perspectives are incommensurable. A broader context may explain the apparent paradox where individuals with disorders characterised by maladaptive action control have difficulty inhibiting their actions only in specific circumstances. Using Obsessive Compulsive Disorder as a case study, clinical theorising has focused largely on compulsions as failures of inhibition in relation to specific internal or external triggers. We propose that the concept of action tendencies may constitute a useful common denominator bridging research into motor, emotional, motivational, and contextual aspects of action control failure. The success of action control may depend on the interaction between the strength of action tendencies, the ability to withhold urges, and contextual factors.
NUPR1: A Critical Regulator of the Antioxidant System
Authors: Huang Can , Santofimia-Castaño Patricia , Iovanna Juan
Published: July 2021

Nuclear protein 1 (NUPR1) is a small intrinsically disordered protein (IDP) activated in response to various types of cellular stress, including endoplasmic reticulum (ER) stress and oxidative stress. Reactive oxygen species (ROS) are mainly produced during mitochondrial oxidative metabolism, and directly impact redox homeostasis and oxidative stress. Ferroptosis is a ROS-dependent programmed cell death driven by an iron-mediated redox reaction. Substantial evidence supports a maintenance role of the stress-inducible protein NUPR1 on cancer cell metabolism that confers chemotherapeutic resistance by upregulating mitochondrial function-associated genes and various antioxidant genes in cancer cells. NUPR1, identified as an antagonist of ferroptosis, plays an important role in redox reactions. This review summarizes the current knowledge on the mechanism behind the observed impact of NUPR1 on mitochondrial function, energy metabolism, iron metabolism, and the antioxidant system. The therapeutic potential of genetic or pharmacological inhibition of NUPR1 in cancer is also discussed. Understanding the role of NUPR1 in the antioxidant system and the mechanisms behind its regulation of ferroptosis may promote the development of more efficacious strategies for cancer therapy.
Collapse of Intra-Tumor Cooperation Induced by Engineered Defector Cells
Authors: Archetti Marco
Published: July 2021

Anti-cancer therapies promote clonal selection of resistant cells that evade treatment. Effective therapy must be stable against the evolution of resistance. A potential strategy based on concepts from evolutionary game theory is to impair intra-tumor cooperation using genetically modified cells in which genes coding for essential growth factors have been knocked out. Such engineered cells would spread by clonal selection, driving the collapse of intra-tumor cooperation and a consequent reduction in tumor growth. Here, I test this idea in vitro in four cancer types (neuroendocrine pancreatic cancer, mesothelioma, lung adenocarcinoma and multiple myeloma). A reduction, or even complete eradication, of the producer clone and the consequent reduction in cell proliferation, is achieved in some but not all cases by introducing a small fraction of non-producer cells in the population. I show that the collapse of intra-tumor cooperation depends on the cost/benefit ratio of growth factor production. When stable cooperation among producer and non-producer cells occurs, its collapse can be induced by increasing the number of growth factors available to the cells. Considerations on nonlinear dynamics in the framework of evolutionary game theory explain this as the result of perturbation of the equilibrium of a system that resembles a public goods game, in which the production of growth factors is a cooperative phenotype. Inducing collapse of intra-tumor cooperation by engineering cancer cells will require the identification of growth factors that are essential for the tumor and that have a high cost of production for the cell.
Targeted Alpha-Particle Radiotherapy and Immune Checkpoint Inhibitors Induces Cooperative Inhibition on Tumor Growth of Malignant Melanoma
Authors: Li Mengshi , Liu Dijie , Lee Dongyoul , Cheng Yinwen , Baumhover Nicholas J. , Marks Brenna M. , Sagastume Edwin A. , Ballas Zuhair K. , Johnson Frances L. , Morris Zachary S. , Schultz Michael K.
Published: July 2021

Radiotherapy can facilitate the immune recognition of immunologically “cold” tumors and enhance the efficacy of anti-PD-1 and anti-CTLA-4 immune checkpoint inhibitors (ICIs) in melanoma. Systemic administration of receptor-targeted radionuclide therapy has the potential to selectively deliver radionuclides to multiple tumors throughout the body in metastatic settings. By triggering immunologic cell death and increasing the immune susceptibility of surviving tumor cells in these locations, targeted radionuclide therapies may overcome resistance to ICIs and render immunologically “cold” tumors throughout the body responsive to ICIs and immunologically “hot”. Here, we show the anti-tumor cooperation of targeted α-particle radionuclide therapy (α-TRT) and ICIs in preclinical models of melanoma. Melanocortin 1 receptor (MC1R)-targeted radiopeptide [212Pb]VMT01 was employed to deliver α-radiation to melanoma tumors in mice. A single injection of 4.1 MBq [212Pb]VMT01 significantly slowed the tumor growth of B16-F10 melanoma and the combination of [212Pb]VMT01 and ICIs induced a cooperative anti-tumor effect leading to 43% complete tumor response with no sign of malignancy on autopsy. Animals with complete response developed anti-tumor immunity to reject further tumor inoculations. This therapeutic cooperation was completely abolished in RAG1 KO mice, which are deficient in T-cell maturation. In addition, the anti-tumor cooperation was compromised when fractionated [212Pb]VMT01 was used in the combination. We also demonstrated that [212Pb]VMT01 induced immunogenic cell death in tumor vaccination assays and in vitro exposure to [212Pb]VMT01 sensitized immunotolerant melanoma to ICIs treatment in vivo. Enhanced tumor infiltrating CD3+, CD4+, CD8+ lymphocytes were observed following injection of 1.4 MBq [212Pb]VMT01. Overall, we demonstrated anti-tumor cooperation between α-TRT and ICIs in melanoma that is mediated by tumor specific immunity.
Keratinocyte Carcinoma and Photoprevention: The Protective Actions of Repurposed Pharmaceuticals, Phytochemicals and Vitamins
Authors: Pihl Celina , Togsverd-Bo Katrine , Andersen Flemming , Haedersdal Merete , Bjerring Peter , Lerche Catharina Margrethe
Published: July 2021

Ultraviolet radiation (UVR) arising from sun exposure represents a major risk factor in the development of keratinocyte carcinomas (KCs). UVR exposure induces dysregulated signal transduction, oxidative stress, inflammation, immunosuppression and DNA damage, all of which promote the induction and development of photocarcinogenesis. Because the incidence of KCs is increasing, better prevention strategies are necessary. In the concept of photoprevention, protective compounds are administered either topically or systemically to prevent the effects of UVR and the development of skin cancer. In this review, we provide descriptions of the pathways underlying photocarcinogenesis and an overview of selected photoprotective compounds, such as repurposed pharmaceuticals, plant-derived phytochemicals and vitamins. We discuss the protective potential of these compounds and their effects in pre-clinical and human trials, summarising the mechanisms of action involved in preventing photocarcinogenesis.
Recent Advances in Glioma Therapy: Combining Vascular Normalization and Immune Checkpoint Blockade
Authors: Ho Rachel L. Y. , Ho Ivy A. W.
Published: July 2021

Glioblastoma (GBM) accounts for more than 50% of all primary malignancies of the brain. Current standard treatment regimen for GBM includes maximal surgical resection followed by radiation and adjuvant chemotherapy. However, due to the heterogeneity of the tumor cells, tumor recurrence is often inevitable. The prognosis of patients with glioma is, thus, dismal. Glioma is a highly angiogenic tumor yet immunologically cold. As such, evolving studies have focused on designing strategies that specifically target the tyrosine kinase receptors of angiokines and encourage immune infiltration. Recent promising results from immunotherapies on other cancer types have prompted further investigations of this therapy in GBM. In this article, we reviewed the pathological angiogenesis and immune reactivity in glioma, as well as its target for drug development, and we discussed future directions in glioma therapy.
Correction: Earl et al. Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival. Cancers 2021, 13, 1612
Authors: Earl Julie , Barreto Emma , Castillo María , Fuentes Raquel , Rodríguez-Garrote Mercedes , Ferreiro Reyes , Reguera Pablo , Muñoz Gloria , Garcia-Seisdedos David , López Jorge , Sainz Bruno , Malats Nuria , Carrato Alfredo
Published: July 2021

The authors wish to make the following corrections to this paper [...]
Breast Cancer Drug Resistance: Overcoming the Challenge by Capitalizing on MicroRNA and Tumor Microenvironment Interplay
Authors: Cosentino Giulia , Plantamura Ilaria , Tagliabue Elda , Iorio Marilena V. , Cataldo Alessandra
Published: July 2021

The clinical management of breast cancer reaches new frontiers every day. However, the number of drug resistant cases is still high, and, currently, this constitutes one of the major challenges that cancer research has to face. For instance, 50% of women affected with HER2 positive breast cancer presents or acquires resistance to trastuzumab. Moreover, for patients affected with triple negative breast cancer, standard chemotherapy is still the fist-line therapy, and often patients become resistant to treatments. Tumor microenvironment plays a crucial role in this context. Indeed, cancer-associated stromal cells deliver oncogenic cues to the tumor and vice versa to escape exogenous insults. It is well known that microRNAs are among the molecules exploited in this aberrant crosstalk. Indeed, microRNAs play a crucial function both in the induction of pro-tumoral traits in stromal cells and in the stroma-mediated fueling of tumor aggressiveness. Here, we summarize the most recent literature regarding the involvement of miRNAs in the crosstalk between tumor and stromal cells and their capability to modulate tumor microenvironment characteristics. All up-to-date findings suggest that microRNAs in the TME could serve both to reverse malignant phenotype of stromal cells, modulating response to therapy, and as predictive/prognostic biomarkers.
Overview of Oral Potentially Malignant Disorders: From Risk Factors to Specific Therapies
Authors: Lorini Luigi , Bescós Atín Coro , Thavaraj Selvam , Müller-Richter Urs , Alberola Ferranti Margarita , Pamias Romero Jorge , Sáez Barba Manel , de Pablo García-Cuenca Alba , Braña García Irene , Bossi Paolo , Nuciforo Paolo , Simonetti Sara
Published: July 2021

Oral squamous cell carcinoma (OSCC) is a very aggressive cancer, representing one of the most common malignancies worldwide. Oral potentially malignant disorders (OPMDs) regroup a variegate set of different histological lesions, characterized by the potential capacity to transform in OSCC. Most of the risk factors associated with OSCC are present also in OPMDs’ development; however, the molecular mechanisms and steps of malignant transformation are still unknown. Treatment of OSCC, including surgery, systemic therapy and radiotherapy (alone or in combination), has suffered a dramatic change in last years, especially with the introduction of immunotherapy. However, most cases are diagnosed during the advanced stage of the disease, decreasing drastically the survival rate of the patients. Hence, early diagnosis of premalignant conditions (OPMDs) is a priority in oral cancer, as well as a massive education about risk factors, the understanding of mechanisms involved in malignant progression and the development of specific and more efficient therapies. The aim of this article is to review epidemiological, clinical, morphological and molecular features of OPMDs, with the purpose to lay the foundation for an exhaustive comprehension of these lesions and their ability of malignant transformation and for the development of more effective and personalized treatments.
Combined Inhibition of AKT and KIT Restores Expression of Programmed Cell Death 4 (PDCD4) in Gastrointestinal Stromal Tumor
Authors: Kozinova Marya , Joshi Shalina , Ye Shuai , Belinsky Martin G. , Sharipova Dinara , Farma Jeffrey M. , Reddy Sanjay S. , Litwin Samuel , Devarajan Karthik , Campos Alex Rosa , Yu Yi , Schwartz Brian , von Mehren Margaret , Rink Lori
Published: July 2021

The majority of gastrointestinal stromal tumor (GIST) patients develop resistance to the first-line KIT inhibitor, imatinib mesylate (IM), through acquisition of secondary mutations in KIT or bypass signaling pathway activation. In addition to KIT, AKT is a relevant target for inhibition, since the PI3K/AKT pathway is crucial for IM-resistant GIST survival. We evaluated the activity of a novel pan-AKT inhibitor, MK-4440 (formerly ARQ 751), as monotherapy and in combination with IM in GIST cell lines and preclinical models with varying IM sensitivities. Dual inhibition of KIT and AKT demonstrated synergistic effects in IM-sensitive and -resistant GIST cell lines. Proteomic analyses revealed upregulation of the tumor suppressor, PDCD4, in combination treated cells. Enhanced PDCD4 expression correlated to increased cell death. In vivo studies revealed superior efficacy of MK-4440/IM combination in an IM-sensitive preclinical model of GIST compared with either single agent. The combination demonstrated limited efficacy in two IM-resistant models, including a GIST patient-derived xenograft model possessing an exon 9 KIT mutation. These studies provide strong rationale for further use of AKT inhibition in combination with IM in primary GIST; however, alternative agents will need to be tested in combination with AKT inhibition in the resistant setting.
Biocatalytic Silylation: The Condensation of Phenols and Alcohols with Triethylsilanol
Authors: Sparkes Emily I. , Egedeuzu Chisom S. , Lias Billie , Sung Rehana , Caslin Stephanie A. , Tabatabaei Dakhili S. Yasin , Taylor Peter G. , Quayle Peter , Wong Lu Shin
Published: July 2021

Silicatein-α (Silα), a hydrolytic enzyme derived from siliceous marine sponges, is one of the few enzymes in nature capable of catalysing the metathesis of silicon–oxygen bonds. It is therefore of interest as a possible biocatalyst for the synthesis of organosiloxanes. To further investigate the substrate scope of this enzyme, a series of condensation reactions with a variety of phenols and aliphatic alcohols were carried out. In general, it was observed that Silα demonstrated a preference for phenols, though the conversions were relatively modest in most cases. In the two pairs of chiral alcohols that were investigated, it was found that the enzyme displayed a preference for the silylation of the S-enantiomers. Additionally, the enzyme’s tolerance to a range of solvents was tested. Silα had the highest level of substrate conversion in the nonpolar solvents n-octane and toluene, although the inclusion of up to 20% of 1,4-dioxane was tolerated. These results suggest that Silα is a potential candidate for directed evolution toward future application as a robust and selective biocatalyst for organosiloxane chemistry.
Uniform Distribution of Pd on GO-C Catalysts for Enhancing the Performance of Air Cathode Microbial Fuel Cell
Authors: Wang Jingzhen , Mu Kaijie , Zhao Xuedong , Luo Dianliang , Yu Xiaodi , Li Wenpeng , Chu Jie , Yang Jing , Yang Qinzheng
Published: July 2021

Metal, as a high-performance electrode catalyst, is a research hotspot in the construction of a high-performance microbial fuel cell (MFC). However, metal catalyst nanoparticles and their dispersed carriers are prone to aggregation, producing catalytic electrodes with inferior qualities. In this study, Pd is uniformly dispersed on the graphene framework supported by carbon black to form nanocomposite catalysts (Pd/GO-C catalysts). The effect of the palladium loading amount in the catalyst on the catalytic performance of the air cathode was further studied. The optimized metal loading afforded a reduced resistance and improved accessibility of Pd particles for the ORR. The maximum current output of the 0.250 Pd (mg/cm2) MFC was 1645 mA/m2, which is 4.2-fold higher than that of the carbon paper cathode. Overall, our findings provide a novel protocol for the preparation of high-efficient ORR catalyst for MFCs.
The Expanding Role of Mitochondria, Autophagy and Lipophagy in Steroidogenesis
Authors: Bassi Geetika , Sidhu Simarjit Kaur , Mishra Suresh
Published: July 2021

The fundamental framework of steroidogenesis is similar across steroidogenic cells, especially in initial mitochondrial steps. For instance, the START domain containing protein-mediated cholesterol transport to the mitochondria, and its conversion to pregnenolone by the enzyme P450scc, is conserved across steroidogenic cells. The enzyme P450scc localizes to the inner mitochondrial membrane, which makes the mitochondria essential for steroidogenesis. Despite this commonality, mitochondrial structure, number, and dynamics vary substantially between different steroidogenic cell types, indicating implications beyond pregnenolone biosynthesis. This review aims to focus on the growing roles of mitochondria, autophagy and lipophagy in cholesterol uptake, trafficking and homeostasis in steroidogenic cells and consequently in steroidogenesis. We will focus on these aspects in the context of the physiological need for different steroid hormones and cell-intrinsic inherent features in different steroidogenic cell types beyond mitochondria as a mere site for the beginning of steroidogenesis. The overall goal is to provide an authentic and comprehensive review on the expanding role of steroidogenic cell-intrinsic processes in cholesterol homeostasis and steroidogenesis, and to bring attention to the scientific community working in this field on these promising advancements. Moreover, we will discuss a novel mitochondrial player, prohibitin, and its potential role in steroidogenic mitochondria and cells, and consequently, in steroidogenesis.
Personalized Armored TCR-Redirected T Cell Therapy for Liver/Organ Transplant with Recurrent Cancer
Authors: Hafezi Morteza , Tan Anthony , Bertoletti Antonio
Published: July 2021

Hepatitis B virus-related hepatocellular carcinoma recurrence after liver transplantation (LT) is notoriously difficult to manage and fatal. As a therapeutic option, adoptive cell therapy with HBV-specific TCR-redirected T cells could be employed to target and control relapses in these patients. However, indispensable immunosuppressive medications post-transplantation can significantly hinder the optimum efficacy of such therapy in the clinic. Here we report a new class of Armored TCR T cells which are able to attack recurrent cancer cells in liver transplanted recipients, while temporarily evading immunosuppressant drugs. We believe this strategy could open up new opportunities for treating pathologies under immunosuppressant treatment.
Oxidative Stress Induces Telomere Dysfunction and Shortening in Human Oocytes of Advanced Age Donors
Authors: Kordowitzki Paweł
Published: July 2021

Research from the past decades provided strong evidence that in humans the pool of oocytes starts to decline already before the birth of a female individual, and from menarche to menopause the oocyte is exposed to different environmental stimuli. Since more and more women of the 21st century in developed countries wish to postpone the first pregnancy to their thirties, higher rates of miscarriage and chromosomal non-disjunction might occur. In oocytes of advanced maternal age, meaning above 35 years of age, characteristics such as chromosomal instabilities/abnormalities, spindle defects, decreased mitochondrial function and telomere shortening become more prevalent than in younger counterparts. Telomere attrition belongs to the so-called “hallmarks of aging” which are also relevant for the female germ-line cells. In oocytes, telomeres shorten with advancing maternal age due to the effects of reactive oxygen species and not upon replicative senescence, similar to how it is common in dividing cells.
Mitophagy Regulates Neurodegenerative Diseases
Authors: Cen Xufeng , Zhang Manke , Zhou Mengxin , Ye Lingzhi , Xia Hongguang
Published: July 2021

Mitochondria play an essential role in supplying energy for the health and survival of neurons. Mitophagy is a metabolic process that removes dysfunctional or redundant mitochondria. This process preserves mitochondrial health. However, defective mitophagy triggers the accumulation of damaged mitochondria, causing major neurodegenerative disorders. This review introduces molecular mechanisms and signaling pathways behind mitophagy regulation. Furthermore, we focus on the recent advances in understanding the potential role of mitophagy in the pathogenesis of major neurodegenerative diseases (Parkinson’s, Alzheimer’s, Huntington’s, etc.) and aging. The findings will help identify the potential interventions of mitophagy regulation and treatment strategies of neurodegenerative diseases.
A New Supported Manganese-Based Coordination Complex as a Nano-Catalyst for the Synthesis of Indazolophthalazinetriones and Investigation of Its Antibacterial Activity
Authors: Ariannezhad Maryam , Habibi Davood , Heydari Somayyeh , Khorramabadi Vahideh
Published: July 2021

A new magnetic supported manganese-based coordination complex (Fe3O4@SiO2@CPTMS@MBOL@ Mn) was prepared in consecutive stages and characterized via various techniques (VSM, SEM, TEM, XRD, FT-IR, EDX, TG-DTA, and ICP). To evaluate its application, it was used for synthesis of divers Indazolophthalazinetriones in a simple procedure via the one-pot three-component condensation reaction of aldehydes, dimedone, and phthalhydrazide in ethanol under reflux conditions. The Mn catalyst can be recycled without any noticeable loss in catalytic activity. Additionally, the antibacterial properties of the nano-catalyst were studied against some bacterial strains.
Glucose Biosensor Based on Dendritic Gold Nanostructures Electrodeposited on Graphite Electrode by Different Electrochemical Methods
Authors: Ramanaviciene Almira , German Natalija , Kausaite-Minkstimiene Asta , Ramanavicius Arunas
Published: July 2021

In this research, we have demonstrated a one-step electrochemical deposition of dendritic gold nanostructures (DGNs) on a graphite rod (GR) electrode without any template, seeds, surfactants, or stabilizers. Three electrochemical methods, namely, constant potential amperometry (CPA), pulse amperometry, and differential pulse voltammetry, were used for DGN synthesis on GR electrode and further application in enzymatic glucose biosensors. Formed gold nanostructures, including DGNs, were characterized by a field emission scanning electron microscopy. The optimal concentration of HAuCl4 (6.0 mmol L−1), duration of DGNs synthesis (400 s), electrodeposition potential (−0.4 V), and the best electrochemical method (CPA) were determined experimentally. Then the enzyme, glucose oxidase, was adsorbed on the surface of DGNs and covalently cross-linked with glutaraldehyde vapor. The enzymatic glucose biosensor based on DGNs electrodeposited at optimal conditions and modified with glucose oxidase showed a quick response (less than 3 s), a high saturation current (291 μA), appropriate linear range (up to 9.97 mmol L−1 of glucose, R2 = 0.9994), good repeatability (RSD 2.4, 2.2 and 1.5% for 2, 30, 97 mmol L−1 of glucose), low limit of detection (0.059 mmol L−1, S/N = 3) and good stability. Additionally, this biosensor could be successfully applied for glucose determination in real samples with good accuracy. These results proved the principle of enzymatic glucose biosensor development based on DGNs as the basis for further investigations.
Bi2S3/rGO Composite Based Electrochemical Sensor for Ascorbic Acid Detection
Authors: Qu Chengling , Li He , Zhou Shuang , Li Guodong , Wang Cheng , Snyders Rony , Bittencourt Carla , Li Wenjiang
Published: July 2021

The engineering of an efficient electrochemical sensor based on a bismuth sulfide/reduced graphene oxide (Bi2S3/rGO) composite to detect ascorbic acid (AA) is reported. The Bi2S3 nanorods/rGO composite was synthesized using a facile hydrothermal method. By varying the amount of graphene oxide (GO) added to the synthesis, the morphology and size of Bi2S3 nanorods anchored on the surface of rGO can be tuned. Compared to a bare glassy carbon electrode (GCE), the GCE modified with Bi2S3/rGO composite presented enhanced electrochemical performance, which was attributed to the optimal electron transport between the rGO support and the loaded Bi2S3 as well as to an increase in the number of active catalytic sites. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) analysis of Bi2S3/rGO/GCE demonstrate that the active Bi2S3/rGO layer on GCE plays an important role in the electrochemical behavior of the sensor. In particular, the Bi2S3/rGO/GCE sensor shows a wide detecting range (5.0–1200 μM), low detection limit (2.9 µM), good sensitivity (268.8 μA mM−1 cm−2), and sufficient recovery values (97.1–101.6%) for the detection of ascorbic acid.
How Chemoresistive Sensors Can Learn from Heterogeneous Catalysis. Hints, Issues, and Perspectives
Authors: Monter-Guzmán Jessica Yazmín Monter , Chu Xiangfeng , Comini Elisabetta , Epifani Mauro , Zanella Rodolfo
Published: July 2021

The connection between heterogeneous catalysis and chemoresistive sensors is emerging more and more clearly, as concerns the well-known case of supported noble metals nanoparticles. On the other hand, it appears that a clear connection has not been set up yet for metal oxide catalysts. In particular, the catalytic properties of several different oxides hold the promise for specifically designed gas sensors in terms of selectivity towards given classes of analytes. In this review, several well-known metal oxide catalysts will be considered by first exposing solidly established catalytic properties that emerge from related literature perusal. On this basis, existing gas-sensing applications will be discussed and related, when possible, with the obtained catalysis results. Then, further potential sensing applications will be proposed based on the affinity of the catalytic pathways and possible sensing pathways. It will appear that dialogue with heterogeneous catalysis may help workers in chemoresistive sensors to design new systems and to gain remarkable insight into the existing sensing properties, in particular by applying the approaches and techniques typical of catalysis. However, several divergence points will appear between metal oxide catalysis and gas-sensing. Nevertheless, it will be pointed out how such divergences just push to a closer exchange between the two fields by using the catalysis knowledge as a toolbox for investigating the sensing mechanisms.
Consequences of COVID-19 Lockdown on Children and Their Pets: Dangerous Increase of Dog Bites among the Paediatric Population
Authors: Parente Giovanni , Gargano Tommaso , Di Mitri Marco , Cravano Sara , Thomas Eduje , Vastano Marzia , Maffi Michela , Libri Michele , Lima Mario
Published: July 2021

Background: The SARS-CoV-2 pandemic has not only put our national health systems to the test, but it also notably hit the economy, the society and the psychology of the people. Our pets have been subjected to the pandemic related stress too. The aim of the study was to evaluate whether the stress induced on domestic dogs resulted in an increase of dog bites in the paediatric population. Methods: A retrospective study was conducted on all patients admitted to our paediatric emergency department for dog bite from January 2014 and December 2020. We compared the total mean dog bites of the years 2014–2019 and the mean number per single month with the respective 2020 data. The bites were divided between bites from family dogs and bites from stranger dogs. Continuous data were analysed using single sample t test while categorical values with chi-squared test, considering statistically significant a p value < 0.05. Results: From January 2014 to December 2019, we recorded a mean of 41 ± 5.9 dog bites (range: 30–46) of which a mean 13 ± 2.6 (range: 10–17) were due to family dogs (32%) and a mean of 28 ± 2.4 (range: 25–31) were due to stranger dogs (68%); the male-to-female ratio was 3:2 and 43% of the injuries concerned the head and face, 26% the lower limbs, 25% the upper limbs, 3% the genitalia and 3% the torso. From January 2020 to December 2020, 30 children were admitted for dog bites: 22 were from family dogs (73%) and 8 from stranger dogs (27%); the male-to-female ratio was 14:11 and 72% of the injuries concerned the head and face, 16% the upper limbs, 8% the lower limbs and 4% the torso. The 2020 data’s higher number of family dog bites compared with the mean of those in the 2014–2019 period was statistically significant (p < 0.01) such as the 2020 data’s lower number of stranger dog bites when compared with the mean number of stranger dog bites in the 2014–2019 period (p < 0.01). Between 2014 and 2019, a mean of 9 ± 2 (range: 6–12) of the wounds needed to be sutured (22%), while 32 ± 3 (range: 28–35) wounds were discharged after application of Steri Strips (78%). On the other hand, in 2020, 21 wounds needed to be sutured (70%), and 9 received just Steri Strips application (41%). The frequency distribution of the treatments required (stitches vs. Steri Strips) between the 2014 to 2019 period and the 2020 period was statistically significant (p < 0.0001). Conclusions: The number of family dog bites in children increased in 2020, especially during the lockdown period. Paediatricians should pay a lot of attention now more than ever to educate parents on the importance of always supervising children who are playing with dogs.
Nutrition and Physical Activity Behavior in 11–14-Year-Old Schoolchildren in Serbia
Authors: Cvetković Biljana , Cvetković Milan , Petrušič Tanja , Đorđić Višnja , Bubanj Saša , Popović Boris , Andrašić Slobodan , Buišić Svetlana , Bogataj Špela
Published: July 2021

Regular physical activity and healthy diet have a significant positive impact on children’s health. Lack of physical activity increases the risk of various diseases, while obesity has become an alarming health problem worldwide. The aim of this study is to investigate the patterns of physical activity and diet among 11–14-year-old school children in Serbia. The sample included 623 primary school children, of whom 333 were boys (53.45%) and 290 were girls (46.55%). The children were also divided according to their age/grade: fifth grade/11 years (24.40% (n = 152; M = 84, F = 68)), sixth grade/12 years (25.68% (n = 160; M = 91, F = 69)), seventh grade/13 years (26.81% (n = 167; M = 83, F = 84)) and eighth grade/14 years (23.11% (n = 144; M = 75, F = 69)). Children’s lifestyle was assessed using two subscales of questionnaires based on the Health-Promoting Lifestyle Profile model II. The Mann–Whitney U test showed no statistically significant difference between boys and girls in the variables Nutrition (p = 0.81) and Physical Activity (p = 0.91). The Kruskal–Wallis test was applied and showed no statistically significant differences between children of different ages, regardless of gender, in the variable Nutrition (p = 0.63). However, differences were evident in the variable Physical Activity (p < 0.001), with the highest mean scores recorded in 12- and 13-year-old children and the lowest in 14-year-old children. Additionally, no statistically significant differences were found among boys as a function of age in the variables Nutrition (p = 0.55) and Physical Activity (p = 0.15), nor among girls in the variable Nutrition (p = 0.43), but in the variable Physical Activity (p = 0.01). In general, it can be concluded that the older primary school children have relatively satisfactory dietary and physical activity habits, but that these behaviors decrease with age, especially the level of physical activity. There is a need for better and more effective education of children about the benefits and importance of proper nutrition and regular physical activity.
Prediction of Recurrence of Completely Resected Pancreatic Solid Pseudopapillary Neoplasms in Pediatric Patients: A Single Center Analysis
Authors: Son Joonhyuk , Kim Wontae , Seo Jeong-Meen , Lee Sanghoon
Published: July 2021

Background: Many previous studies have investigated the risk factors for the recurrence of pancreatic solid pseudopapillary neoplasms (SPNs), although a consensus has not yet been reached, despite this effort. We aimed to identify the predictive factors for recurrence in patients with SPNs who underwent complete surgical resection of the tumor. Methods: We retrospectively analyzed the records of pediatric patients with SPNs who underwent surgical resection at a single center between 2001 and 2018. Results: During the study period, 47 patients with SPNs underwent radical resection of the tumor. The median age of the patients was 14 (8–18) years. R0 resection was confirmed in every case and none of the patients presented with systemic metastasis at the time of diagnosis. The median follow-up period was 53.1 (30.8–150.8) months. Of the 47 patients, only two (4.2%) experienced recurrence. Using comparative analysis, we found that some factors such as a large tumor size, peripancreatic tissue invasion, and capsule invasion did not increase the risk of recurrence of SPNs. Lymph node metastasis was the only significant factor for recurrence in our study (p = 0.043). Conclusion: During our single center analysis, we found that only lymph node metastasis was a predictive factor for recurrence of SPNs among patients who underwent complete tumor resection. Long-term follow-up is required to determine whether SPNs will recur if lymph node metastasis is observed after surgery. Furthermore, therapeutic benefits of routine lymphadenectomy or sentinel lymph node biopsy should be investigated in future studies to reduce the risk of recurrence in patients with SPNs.
Long-Term Follow-Up of Renal Function in Children after Liver Transplantation—A Single Center Retrospective Study
Authors: Kowalewski Grzegorz , Kaliciński Piotr , Stefanowicz Marek , Grenda Ryszard , Czubkowski Piotr , Szymczak Marek
Published: July 2021

Chronic kidney disease (CKD) is a common complication after liver transplantation (LT). Its prevalence with modern immunosuppression regimens, especially in children, is variable depending on the transplantation era. The study included 61 pediatric patients with at least 10 years of follow-up after liver transplantation remaining under constant care of the Department of Pediatric Surgery and Organ Transplantation. The analysis included several tests: estimated glomerular function (eGFR), results of screening for renal tubular defects and blood concentrations of basic immunosuppressive drug-tacrolimus. CKD was diagnosed in 3% of children at 12 years after LT. The maintaining of tacrolimus concentrations >4 ng/mL in long-term observation was associated with a significant increase of microalbuminuria. The presence of microalbuminuria, regarded as a risk factor of CKD, confirmed the necessity of regular comprehensive assessment of patients in long-term follow-up.
Application of Combined Long Amplicon Sequencing (CoLAS) for Genetic Analysis of Neurofibromatosis Type 1: A Pilot Study
Authors: Togi Sumihito , Ura Hiroki , Niida Yo
Published: July 2021

Elaborate analyses of the status of gene mutations in neurofibromatosis type 1 (NF1) are still difficult nowadays due to the large gene sizes, broad mutation spectrum, and the various effects of mutations on mRNA splicing. These problems cannot be solved simply by sequencing the entire coding region using next-generation sequencing (NGS). We recently developed a new strategy, named combined long amplicon sequencing (CoLAS), which is a method for simultaneously analysing the whole genomic DNA region and, also, the full-length cDNA of the disease-causative gene with long-range PCR-based NGS. In this study, CoLAS was specifically arranged for NF1 genetic analysis, then applied to 20 patients (five previously reported and 15 newly recruited patients, including suspicious cases) for optimising the method and to verify its efficacy and benefits. Among new cases, CoLAS detected not only 10 mutations, including three unreported mutations and one mosaic mutation, but also various splicing abnormalities and allelic expression ratios quantitatively. In addition, heterozygous mapping by polymorphisms, including introns, showed copy number monitoring of the entire NF1 gene region was possible in the majority of patients tested. Moreover, it was shown that, when a chromosomal level microdeletion was suspected from heterozygous mapping, it could be detected directly by breakpoint-specific long PCR. In conclusion, CoLAS not simply detect the causative mutation but accurately elucidated the entire structure of the NF1 gene, its mRNA expression, and also the splicing status, which reinforces its high usefulness in the gene analysis of NF1.