bluuebunny/crossref_metadata_2025 huggingface dataset:
Impulsivity and Compulsivity and Their Relationship with Non-Adherence to Treatment in the Prison Population
Authors: López-Torrecillas Francisca , Castillo-Fernández Eva , Ramírez-Uclés Isabel , Martín Ignacio
Published: August 2021

The main challenge of interventions in penitentiary institutions is the re-education and reintegration of inmates, i.e., that inmates have the intention and ability to live law-abiding lives. Therefore, an increase in self-control or, on the contrary, the decrease or elimination of impulsive versus compulsive behaviors becomes necessary. This study aimed to evaluate the role of impulsivity versus compulsivity in treatment adherence in the prison population. The study included 134 men from the Penitentiary Center of Granada who were divided into two groups. Group 1 was considered treatment adherent, and Group 2 was considered non-adherent to treatment. The following instruments were used: Symptom Inventory (SCL-90-R), Addiction Severity Index (EuropASI), Impulsivity Scale (UPPS-P), and Compulsive Belief Questionnaire (OBQ-44). Statistically significant differences were found in impulsivity in the dimensions of negative urgency, sensation seeking, and positive urgency, with higher scores in all cases for the non-adherent group than for the adherent group. We also found statistically significant differences in responsibility/inhibition, perfectionism/uncertainty, and importance/control, with higher scores for the non-adherent group compared to the adherent group. Treatment adherence is inversely related to impulsive and compulsive behaviors.
Vaping-Related Adverse Events and Perceived Health Improvements: A Cross-Sectional Survey among Daily E-Cigarette Users
Authors: Pénzes Melinda , Bakacs Márta , Brys Zoltán , Vitrai József , Tóth Gergely , Berezvai Zombor , Urbán Róbert
Published: August 2021

Web-based samples of e-cigarette users commonly report significant vaping-related health improvements (HIs) and mild adverse events (AEs). This cross-sectional study with in-person interviewing data collection examined self-reported AEs and perceived HIs among Hungarian adult current daily exclusive e-cigarette (n = 65) and dual users (n = 127), and former daily e-cigarette users (n = 91) in 2018. Logistic regression was used to evaluate associations between reporting any AEs/HIs, vaping status, and covariates. More former users (52.7%) reported AEs than current users (39.6%; p = 0.038). Exclusive and dual daily users reported similar rates of AEs (44.6% and 37.0%, respectively; p = 0.308). More current users (46.9%) experienced HIs than former users (35.2%; p = 0.064). Exclusive daily users were more likely to report HIs than dual users (63.1% versus 38.6%; p = 0.001). Former user status and smoking cessation/reduction reasons increased the odds of reporting AEs, whereas nicotine-containing e-liquid use and older age decreased the odds of reporting AEs. Exclusive vaper status, using advanced generation devices, and smoking cessation/reduction reasons increased the odds of experiencing HIs. This study, which used a traditional data collection methodology, found a higher rate of AEs and a lower rate of HIs compared to web-based surveys. Our results highlight that experiencing AEs and HIs is affected by users’ characteristics, in addition to the device and e-liquid type.
Psychiatry in the Digital Age: A Blessing or a Curse?
Authors: Roth Carl B. , Papassotiropoulos Andreas , Brühl Annette B. , Lang Undine E. , Huber Christian G.
Published: August 2021

Social distancing and the shortage of healthcare professionals during the COVID-19 pandemic, the impact of population aging on the healthcare system, as well as the rapid pace of digital innovation are catalyzing the development and implementation of new technologies and digital services in psychiatry. Is this transformation a blessing or a curse for psychiatry? To answer this question, we conducted a literature review covering a broad range of new technologies and eHealth services, including telepsychiatry; computer-, internet-, and app-based cognitive behavioral therapy; virtual reality; digital applied games; a digital medicine system; omics; neuroimaging; machine learning; precision psychiatry; clinical decision support; electronic health records; physician charting; digital language translators; and online mental health resources for patients. We found that eHealth services provide effective, scalable, and cost-efficient options for the treatment of people with limited or no access to mental health care. This review highlights innovative technologies spearheading the way to more effective and safer treatments. We identified artificially intelligent tools that relieve physicians from routine tasks, allowing them to focus on collaborative doctor–patient relationships. The transformation of traditional clinics into digital ones is outlined, and the challenges associated with the successful deployment of digitalization in psychiatry are highlighted.
Mercury and Antibiotic Resistance Co-Selection in Bacillus sp. Isolates from the Almadén Mining District
Authors: Robas Marina , Probanza Agustín , González Daniel , Jiménez Pedro A.
Published: August 2021

Antibiotic resistance (AR) in the environment is of great global concern and a threat to public health. Soil bacteria, including Bacillus spp., could act as recipients and reservoirs of AR genes of clinical, livestock, or agricultural origin. These genes can be shared between bacteria, some of which could be potentially human pathogens. This process can be favored in conditions of abiotic stress, such as heavy metal contamination. The Almadén mining district (Ciudad Real, Spain) is one of the environments with the highest mercury (Hg) contamination worldwide. The link between heavy metal contamination and increased AR in environmental bacteria seems clear, due to co-resistance and co-selection phenomena. In the present study, 53 strains were isolated from rhizospheric and bulk soil samples in Almadén. AR was tested using Vitek® 2 and minimum inhibitory concentration (MIC) values were obtained and interpreted based on the criteria of the Clinical and Laboratory Standards Institute (CLSI) guidelines. Based on the resistance profiles, five different antibiotypes were established. The Hg minimum bactericidal concentration (MBC) of each strain was obtained using the plating method with increasing concentrations of HgCl2. A total of 72% of Bacillus spp. showed resistance to two or more commonly used antibiotics. A total of 38 isolates expressed AR to cephalosporins. Finally, the environmental co-selection of AR to cephalosporins and tetracyclines by selective pressure of Hg has been statistically demonstrated.
Kurarinone Attenuates BLM-Induced Pulmonary Fibrosis via Inhibiting TGF-β Signaling Pathways
Authors: Park Soo-Jin , Kim Tae-hyoun , Lee Kiram , Kang Min-Ah , Jang Hyun-Jae , Ryu Hyung-Won , Oh Sei-Ryang , Lee Hyun-Jun
Published: August 2021

Idiopathic pulmonary fibrosis (IPF) is a refractory interstitial lung disease for which there is no effective treatment. Although the pathogenesis of IPF is not fully understood, TGF-β and epithelial–mesenchymal transition (EMT) have been shown to be involved in the fibrotic changes of lung tissues. Kurarinone is a prenylated flavonoid isolated from Sophora Flavescens with antioxidant and anti-inflammatory properties. In this study, we investigated the effect of kurarinone on pulmonary fibrosis. Kurarinone suppressed the TGF-β-induced EMT of lung epithelial cells. To assess the therapeutic effects of kurarinone in bleomycin (BLM)-induced pulmonary fibrosis, mice were treated with kurarinone daily for 2 weeks starting 7 days after BLM instillation. Oral administration of kurarinone attenuated the fibrotic changes of lung tissues, including accumulation of collagen and improved mechanical pulmonary functions. Mechanistically, kurarinone suppressed phosphorylation of Smad2/3 and AKT induced by TGF-β1 in lung epithelial cells, as well as in lung tissues treated with BLM. Taken together, these results suggest that kurarinone has a therapeutic effect on pulmonary fibrosis via suppressing TGF-β signaling pathways and may be a novel drug candidate for pulmonary fibrosis.
CDK4, CDK6/cyclin-D1 Complex Inhibition and Radiotherapy for Cancer Control: A Role for Autophagy
Authors: Nardone Valerio , Barbarino Marcella , Angrisani Antonio , Correale Pierpaolo , Pastina Pierpaolo , Cappabianca Salvatore , Reginelli Alfonso , Mutti Luciano , Miracco Clelia , Giannicola Rocco , Giordano Antonio , Pirtoli Luigi
Published: August 2021

The expanding clinical application of CDK4- and CDK6-inhibiting drugs in the managements of breast cancer has raised a great interest in testing these drugs in other neoplasms. The potential of combining these drugs with other therapeutic approaches seems to be an interesting work-ground to explore. Even though a potential integration of CDK4 and CDK6 inhibitors with radiotherapy (RT) has been hypothesized, this kind of approach has not been sufficiently pursued, neither in preclinical nor in clinical studies. Similarly, the most recent discoveries focusing on autophagy, as a possible target pathway able to enhance the antitumor efficacy of CDK4 and CDK6 inhibitors is promising but needs more investigations. The aim of this review is to discuss the recent literature on the field in order to infer a rational combination strategy including cyclin-D1/CDK4-CDK6 inhibitors, RT, and/or other anticancer agents targeting G1-S phase cell cycle transition.
The Role of Glycemic Variability in Cardiovascular Disorders
Authors: Alfieri Valentina , Myasoedova Veronika A. , Vinci Maria Cristina , Rondinelli Maurizio , Songia Paola , Massaiu Ilaria , Cosentino Nicola , Moschetta Donato , Valerio Vincenza , Ciccarelli Michele , Marenzi Giancarlo , Genovese Stefano , Poggio Paolo
Published: August 2021

Diabetes mellitus (DM) is one of the most common and costly disorders that affect humans around the world. Recently, clinicians and scientists have focused their studies on the effects of glycemic variability (GV), which is especially associated with cardiovascular diseases. In healthy subjects, glycemia is a very stable parameter, while in poorly controlled DM patients, it oscillates greatly throughout the day and between days. Clinically, GV could be measured by different parameters, but there are no guidelines on standardized assessment. Nonetheless, DM patients with high GV experience worse cardiovascular disease outcomes. In vitro and in vivo studies showed that high GV causes several detrimental effects, such as increased oxidative stress, inflammation, and apoptosis linked to endothelial dysfunction. However, the evidence that treating GV is beneficial is still scanty. Clinical trials aiming to improve the diagnostic and prognostic accuracy of GV measurements correlated with cardiovascular outcomes are needed. The present review aims to evaluate the clinical link between high GV and cardiovascular diseases, taking into account the underlined biological mechanisms. A clear view of this challenge may be useful to standardize the clinical evaluation and to better identify treatments and strategies to counteract this DM aspect.
Expression of Low Level of VPS35-mCherry Fusion Protein Diminishes Vps35 Depletion Induced Neuron Terminal Differentiation Deficits and Neurodegenerative Pathology, and Prevents Neonatal Death
Authors: Zhao Yang , Tang Fulei , Lee Daehoon , Xiong Wen-Cheng
Published: August 2021

Vps35 (vacuolar protein sorting 35) is a key component of retromer that consists of Vps35, Vps26, and Vps29 trimers, and sortin nexin dimers. Dysfunctional Vps35/retromer is believed to be a risk factor for development of various neurodegenerative diseases. Vps35Neurod6 mice, which selectively knock out Vps35 in Neurod6-Cre+ pyramidal neurons, exhibit age-dependent impairments in terminal differentiation of dendrites and axons of cortical and hippocampal neurons, neuro-degenerative pathology (i.e., increases in P62 and Tdp43 (TAR DNA-binding protein 43) proteins, cell death, and reactive gliosis), and neonatal death. The relationships among these phenotypes and the underlying mechanisms remain largely unclear. Here, we provide evidence that expression of low level of VPS35-mCherry fusion protein in Vps35Neurod6 mice could diminish the phenotypes in an age-dependent manner. Specifically, we have generated a conditional transgenic mouse line, LSL-Vps35-mCherry, which expresses VPS35-mCherry fusion protein in a Cre-dependent manner. Crossing LSL-Vps35-mCherry with Vps35Neurod6 to obtain TgVPS35-mCherry, Vps35Neurod6 mice prevent the neonatal death and diminish the dendritic morphogenesis deficit and gliosis at the neonatal, but not the adult age. Further studies revealed that the Vps35-mCherry transgene expression was low, and the level of Vps35 mRNA comprised only ~5–7% of the Vps35 mRNA of control mice. Such low level of VPS35-mCherry could restore the amount of other retromer components (Vps26a and Vps29) at the neonatal age (P14). Importantly, the neurodegenerative pathology presented in the survived adult TgVps35-mCherry; Vps35Neurod6 mice. These results demonstrate the sufficiency of low level of VPS35-mCherry fusion protein to diminish the phenotypes in Vps35Neurod6 mice at the neonatal age, verifying a key role of neuronal Vps35 in stabilizing retromer complex proteins, and supporting the view for Vps35 as a potential therapeutic target for neurodegenerative diseases.
Development of a Novel Nanoarchitecture of the Robust Photosystem I from a Volcanic Microalga Cyanidioschyzon merolae on Single Layer Graphene for Improved Photocurrent Generation
Authors: Izzo Miriam , Jacquet Margot , Fujiwara Takayuki , Harputlu Ersan , Mazur Radosław , Wróbel Piotr , Góral Tomasz , Unlu C. Gokhan , Ocakoglu Kasim , Miyagishima Shinya , Kargul Joanna
Published: August 2021

Here, we report the development of a novel photoactive biomolecular nanoarchitecture based on the genetically engineered extremophilic photosystem I (PSI) biophotocatalyst interfaced with a single layer graphene via pyrene-nitrilotriacetic acid self-assembled monolayer (SAM). For the oriented and stable immobilization of the PSI biophotocatalyst, an His6-tag was genetically engineered at the N-terminus of the stromal PsaD subunit of PSI, allowing for the preferential binding of this photoactive complex with its reducing side towards the graphene monolayer. This approach yielded a novel robust and ordered nanoarchitecture designed to generate an efficient direct electron transfer pathway between graphene, the metal redox center in the organic SAM and the photo-oxidized PSI biocatalyst. The nanosystem yielded an overall current output of 16.5 µA·cm−2 for the nickel- and 17.3 µA·cm−2 for the cobalt-based nanoassemblies, and was stable for at least 1 h of continuous standard illumination. The novel green nanosystem described in this work carries the high potential for future applications due to its robustness, highly ordered and simple architecture characterized by the high biophotocatalyst loading as well as simplicity of manufacturing.
Image-Based Method to Quantify Decellularization of Tissue Sections
Authors: Narciso Maria , Otero Jorge , Navajas Daniel , Farré Ramon , Almendros Isaac , Gavara Núria
Published: August 2021

Tissue decellularization is typically assessed through absorbance-based DNA quantification after tissue digestion. This method has several disadvantages, namely its destructive nature and inadequacy in experimental situations where tissue is scarce. Here, we present an image processing algorithm for quantitative analysis of DNA content in (de)cellularized tissues as a faster, simpler and more comprehensive alternative. Our method uses local entropy measurements of a phase contrast image to create a mask, which is then applied to corresponding nuclei labelled (UV) images to extract average fluorescence intensities as an estimate of DNA content. The method can be used on native or decellularized tissue to quantify DNA content, thus allowing quantitative assessment of decellularization procedures. We confirm that our new method yields results in line with those obtained using the standard DNA quantification method and that it is successful for both lung and heart tissues. We are also able to accurately obtain a timeline of decreasing DNA content with increased incubation time with a decellularizing agent. Finally, the identified masks can also be applied to additional fluorescence images of immunostained proteins such as collagen or elastin, thus allowing further image-based tissue characterization.
Optimal Brassinosteroid Levels Are Required for Soybean Growth and Mineral Nutrient Homeostasis
Authors: Cheng Ling , Li Man , Min Wanling , Wang Mengke , Chen Rongqing , Wang Wenfei
Published: August 2021

Brassinosteroids (BRs) are steroid phytohormones that are known to regulate plant growth and nutrient uptake and distribution. However, how BRs regulate nutrient uptake and balance in legume species is not fully understood. Here, we show that optimal BR levels are required for soybean (Glycine max L.) seedling growth, as treatments with both 24-epicastasterone (24-epiCS) and the BR biosynthesis inhibitor propiconazole (PPZ) inhibit root growth, including primary root elongation and lateral root formation and elongation. Specifically, 24-epiCS and PPZ reduced the total phosphorus and potassium levels in the shoot and affected several minor nutrients, such as magnesium, iron, manganese, and molybdenum. A genome-wide transcriptome analysis identified 3774 and 4273 differentially expressed genes in the root tip after brassinolide and PPZ treatments, respectively. The gene ontology (GO) analysis suggested that genes related to “DNA-replication”, “microtubule-based movement”, and “plant-type cell wall organization” were highly responsive to the brassinolide and PPZ treatments. Furthermore, consistent with the effects on the nutrient concentrations, corresponding mineral transporters were found to be regulated by BR levels, including the GmPHT1s, GmKTs, GmVIT2, GmZIPs, and GmMOT1 genes. Our study demonstrates that optimal BR levels are important for growth and mineral nutrient homeostasis in soybean seedlings.
The Influence of Microbiome Dysbiosis and Bacterial Biofilms on Epidermal Barrier Function in Atopic Dermatitis—An Update
Authors: Blicharz Leszek , Rudnicka Lidia , Czuwara Joanna , Waśkiel-Burnat Anna , Goldust Mohamad , Olszewska Małgorzata , Samochocki Zbigniew
Published: August 2021

Atopic dermatitis (AD) is a common inflammatory dermatosis affecting up to 30% of children and 10% of adults worldwide. AD is primarily driven by an epidermal barrier defect which triggers immune dysregulation within the skin. According to recent research such phenomena are closely related to the microbial dysbiosis of the skin. There is growing evidence that cutaneous microbiota and bacterial biofilms negatively affect skin barrier function, contributing to the onset and exacerbation of AD. This review summarizes the latest data on the mechanisms leading to microbiome dysbiosis and biofilm formation in AD, and the influence of these phenomena on skin barrier function.
Astroglial and Microglial Purinergic P2X7 Receptor as a Major Contributor to Neuroinflammation during the Course of Multiple Sclerosis
Authors: Sidoryk-Węgrzynowicz Marta , Strużyńska Lidia
Published: August 2021

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system that leads to the progressive disability of patients. A characteristic feature of the disease is the presence of focal demyelinating lesions accompanied by an inflammatory reaction. Interactions between autoreactive immune cells and glia cells are considered as a central mechanism underlying the pathology of MS. A glia-mediated inflammatory reaction followed by overproduction of free radicals and generation of glutamate-induced excitotoxicity promotes oligodendrocyte injury, contributing to demyelination and subsequent neurodegeneration. Activation of purinergic signaling, in particular P2X7 receptor-mediated signaling, in astrocytes and microglia is an important causative factor in these pathological processes. This review discusses the role of astroglial and microglial cells, and in particular glial P2X7 receptors, in inducing MS-related neuroinflammatory events, highlighting the importance of P2X7R-mediated molecular pathways in MS pathology and identifying these receptors as a potential therapeutic target.
Synergistic Antitumor Activity of SH003 and Docetaxel via EGFR Signaling Inhibition in Non-Small Cell Lung Cancer
Authors: Jeong Mi-So , Lee Kang-Wook , Choi Yu-Jeong , Kim Yun-Gyeong , Hwang Hyun-Ha , Lee Seo-Yeon , Jung Se-Eun , Park Sun-Ah , Lee Jin-Hee , Joo Yong-Joon , Cho Sung-Gook , Ko Seong-Gyu
Published: August 2021

Epidermal growth factor receptor (EGFR) is overexpressed in lung cancer patients. Despite treatment with various EGFR tyrosine kinase inhibitors, recurrence and metastasis of lung cancer are inevitable. Docetaxel (DTX) is an effective conventional drug that is used to treat various cancers. Several researchers have studied the use of traditional herbal medicine in combination with docetaxel, to improve lung cancer treatment. SH003, a novel herbal mixture, exerts anticancer effects in different cancer cell types. Here, we aimed to investigate the apoptotic and anticancer effects of SH003 in combination with DTX, in human non-small-cell lung cancer (NSCLC). SH003, with DTX, induced apoptotic cell death, with increased expression of cleaved caspases and cleaved poly (ADP-ribose) polymerase in NSCLC cells. Moreover, SH003 and DTX induced the apoptosis of H460 cells via the suppression of the EGFR and signal transducer and activator of transcription 3 (STAT3) signaling pathways. In H460 tumor xenograft models, the administration of SH003 or docetaxel alone diminished tumor growth, and their combination effectively killed cancer cells, with increased expression of apoptotic markers and decreased expression of p-EGFR and p-STAT3. Collectively, the combination of SH003 and DTX may be a novel anticancer strategy to overcome the challenges that are associated with conventional lung cancer therapy.
An Update on the Role of Nrf2 in Respiratory Disease: Molecular Mechanisms and Therapeutic Approaches
Authors: Lee Jooyeon , Jang Jimin , Park Sung-Min , Yang Se-Ran
Published: August 2021

Nuclear factor erythroid 2-related factor (Nrf2) is a transcriptional activator of the cell protection gene that binds to the antioxidant response element (ARE). Therefore, Nrf2 protects cells and tissues from oxidative stress. Normally, Kelch-like ECH-associated protein 1 (Keap1) inhibits the activation of Nrf2 by binding to Nrf2 and contributes to Nrf2 break down by ubiquitin proteasomes. In moderate oxidative stress, Keap1 is inhibited, allowing Nrf2 to be translocated to the nucleus, which acts as an antioxidant. However, under unusually severe oxidative stress, the Keap1-Nrf2 mechanism becomes disrupted and results in cell and tissue damage. Oxide-containing atmospheric environment generally contributes to the development of respiratory diseases, possibly leading to the failure of the Keap1-Nrf2 pathway. Until now, several studies have identified changes in Keap1-Nrf2 signaling in models of respiratory diseases, such as acute respiratory distress syndrome (ARDS)/acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and asthma. These studies have confirmed that several Nrf2 activators can alleviate symptoms of respiratory diseases. Thus, this review describes how the expression of Keap1-Nrf2 functions in different respiratory diseases and explains the protective effects of reversing this expression.
Integrin αv and Vitronectin Prime Macrophage-Related Inflammation and Contribute the Development of Dry Eye Disease
Authors: Ho Tsung-Chuan , Yeh Shu-I , Chen Show-Li , Tsao Yeou-Ping
Published: August 2021

Cell signaling mediated by the αv integrin plays a pivotal role in macrophage activation in various inflammatory processes, but its involvement in the pathogenesis of dry eye disease (DED) remains unclear. In a murine model of DED, we found increased αv integrin expression in ocular surface macrophages. The αv integrins inhibitor c(RGDfK) ameliorated the corneal damage caused by DED, suggesting a pathogenic role for αv integrin. Because tear hyperosmolarity induces ocular inflammation in DED, a hyperosmolar culture of murine bone marrow-derived macrophages (BMDMs) is used to reproduce inflammation in vitro. However, the expression of proinflammatory cytokine mRNA was minimal, even though αv integrin was induced. In searching for components that are involved in αv integrin-mediated inflammation but that are missing from the culture model, we showed that the levels of vitronectin (VTN), a binding ligand of αv integrins, were increased in the tear fluid and conjunctival stroma of DED animals. The addition of VTN prominently enhanced hyperosmolarity-induced inflammation in BMDMs. Mechanistically, we showed that VTN/αv integrins mediated NF-κB activation to induce inflammatory gene expression in the BMDMs. Our findings indicate that interaction the of VTN with αv integrins is a crucial step in the inflammatory process in DED and suggests a novel therapeutic target.
Structural and Biochemical Features of Human Serum Albumin Essential for Eukaryotic Cell Culture
Authors: Mishra Vibhor , Heath Richard J.
Published: August 2021

Serum albumin physically interacts with fatty acids, small molecules, metal ions, and several other proteins. Binding with a plethora of bioactive substances makes it a critical transport molecule. Albumin also scavenges the reactive oxygen species that are harmful to cell survival. These properties make albumin an excellent choice to promote cell growth and maintain a variety of eukaryotic cells under in vitro culture environment. Furthermore, purified recombinant human serum albumin is mostly free from impurities and modifications, providing a perfect choice as an additive in cell and tissue culture media while avoiding any regulatory constraints. This review discusses key features of human serum albumin implicated in cell growth and survival under in vitro conditions.
Inorganic Salts of N-phenylbiguanidium(1+)—Novel Family with Promising Representatives for Nonlinear Optics
Authors: Matulková Irena , Císařová Ivana , Fridrichová Michaela , Gyepes Róbert , Němec Petr , Kroupa Jan , Němec Ivan
Published: August 2021

Seven inorganic salts containing N-phenylbiguanide as a prospective organic molecular carrier of nonlinear optical properties were prepared and studied within our research of novel hydrogen-bonded materials for nonlinear optics (NLO). All seven salts, namely N-phenylbiguanidium(1+) nitrate (C2/c), N-phenylbiguanidium(1+) perchlorate (P-1), N-phenylbiguanidium(1+) hydrogen carbonate (P21/c), bis(N-phenylbiguanidium(1+)) sulfate (C2), bis(N-phenylbiguanidium(1+)) hydrogen phosphate sesquihydrate (P-1), bis(N-phenylbiguanidium(1+)) phosphite (P21), and bis(N-phenylbiguanidium(1+)) phosphite dihydrate (P21/n), were characterised by X-ray diffraction (powder and single-crystal X-ray diffraction) and by vibrational spectroscopy (FTIR and Raman). Two salts with non-centrosymmetric crystal structures—bis(N-phenylbiguanidium(1+)) sulfate and bis(N-phenylbiguanidium(1+)) phosphite—were further studied to examine their linear and nonlinear optical properties using experimental and computational methods. As a highly SHG-efficient and phase-matchable material transparent down to 320 nm and thermally stable to 483 K, bis(N-phenylbiguanidium(1+)) sulfate is a promising novel candidate for NLO.
Stimulating GABAergic Neurons in the Nucleus Accumbens Core Alters the Trigeminal Neuropathic Pain Responses in a Rat Model of Infraorbital Nerve Injury
Authors: Islam Jaisan , KC Elina , Kim Soochong , Kim Hyong Kyu , Park Young Seok
Published: August 2021

The nucleus accumbens core (NAcc) is an important component of brain reward circuitry, but studies have revealed its involvement in pain circuitry also. However, its effect on trigeminal neuralgia (TN) and the mechanism underlying it are yet to be fully understood. Therefore, this study aimed to examine the outcomes of optogenetic stimulation of NAcc GABAergic neurons in an animal model of TN. Animals were allocated into TN, sham, and control groups. TN was generated by infraorbital nerve constriction and the optogenetic virus was injected into the NAcc. In vivo extracellular recordings were acquired from the ventral posteromedial nucleus of the thalamus. Alterations of behavioral responses during stimulation “ON” and “OFF” conditions were evaluated. In vivo microdialysis was performed in the NAcc of TN and sham animals. During optogenetic stimulation, electrophysiological recordings revealed a reduction of both tonic and burst firing activity in TN animals, and significantly improved behavioral responses were observed as well. Microdialysis coupled with liquid chromatography/tandem mass spectrometry analysis revealed significant alterations in extracellular concentration levels of GABA, glutamate, acetylcholine, dopamine, and citrulline in NAcc upon optic stimulation. In fine, our results suggested that NAcc stimulation could modulate the transmission of trigeminal pain signals in the TN animal model.
miR-302 Attenuates Mutant Huntingtin-Induced Cytotoxicity through Restoration of Autophagy and Insulin Sensitivity
Authors: Chang Ching-Chi , Tsou Sing-Hua , Chen Wei-Jen , Ho Ying-Jui , Hung Hui-Chih , Liu Guang-Yaw , Singh Sandeep Kumar , Li Hsin-Hua , Lin Chih-Li
Published: August 2021

Huntington’s disease (HD) is an autosomal-dominant brain disorder caused by mutant huntingtin (mHtt). Although the detailed mechanisms remain unclear, the mutational expansion of polyglutamine in mHtt is proposed to induce protein aggregates and neuronal toxicity. Previous studies have shown that the decreased insulin sensitivity is closely related to mHtt-associated impairments in HD patients. However, how mHtt interferes with insulin signaling in neurons is still unknown. In the present study, we used a HD cell model to demonstrate that the miR-302 cluster, an embryonic stem cell-specific polycistronic miRNA, is significantly downregulated in mHtt-Q74-overexpressing neuronal cells. On the contrary, restoration of miR-302 cluster was shown to attenuate mHtt-induced cytotoxicity by improving insulin sensitivity, leading to a reduction of mHtt aggregates through the enhancement of autophagy. In addition, miR-302 also promoted mitophagy and stimulated Sirt1/AMPK-PGC1α pathway thereby preserving mitochondrial function. Taken together, these results highlight the potential role of miR-302 cluster in neuronal cells, and provide a novel mechanism for mHtt-impaired insulin signaling in the pathogenesis of HD.
MAO-A Inhibition by Metaxalone Reverts IL-1β-Induced Inflammatory Phenotype in Microglial Cells
Authors: Pallio Giovanni , D’Ascola Angela , Cardia Luigi , Mannino Federica , Bitto Alessandra , Minutoli Letteria , Picciolo Giacomo , Squadrito Violetta , Irrera Natasha , Squadrito Francesco , Altavilla Domenica
Published: August 2021

Experimental and clinical studies have suggested that several neurological disorders are associated with the occurrence of central nervous system neuroinflammation. Metaxalone is an FDA-approved muscle relaxant that has been reported to inhibit monoamine oxidase A (MAO-A). The aim of this study was to investigate whether metaxalone might exert antioxidant and anti-inflammatory effects in HMC3 microglial cells. An inflammatory phenotype was induced in HMC3 microglial cells through stimulation with interleukin-1β (IL-1β). Control cells and IL-1β-stimulated cells were subsequently treated with metaxalone (10, 20, and 40 µM) for six hours. IL-1β stimulated the release of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), but reduced the anti-inflammatory cytokine interleukin-13 (IL-13). The upstream signal consisted of an increased priming of nuclear factor-kB (NF-kB), blunted peroxisome proliferator-activated receptor gamma (PPARγ), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression. IL-1β also augmented MAO-A expression/activity and malondialdehyde levels and decreased Nrf2 mRNA expression and protein levels. Metaxalone decreased MAO-A activity and expression, reduced NF-kB, TNF-α, and IL-6, enhanced IL-13, and also increased PPARγ, PGC-1α, and Nrf2 expression. The present experimental study suggests that metaxalone has potential for the treatment of several neurological disorders associated with neuroinflammation.
At the Edges of Photosynthetic Metabolic Plasticity—On the Rapidity and Extent of Changes Accompanying Salinity Stress-Induced CAM Photosynthesis Withdrawal
Authors: Nosek Michał , Gawrońska Katarzyna , Rozpądek Piotr , Sujkowska-Rybkowska Marzena , Miszalski Zbigniew , Kornaś Andrzej
Published: August 2021

The common ice plant (Mesembryanthemum crystallinum L.) is a facultative crassulacean acid metabolism (CAM) plant, and its ability to recover from stress-induced CAM has been confirmed. We analysed the photosynthetic metabolism of this plant during the 72-h response period following salinity stress removal from three perspectives. In plants under salinity stress (CAM) we found a decline of the quantum efficiencies of PSII (Y(II)) and PSI (Y(I)) by 17% and 15%, respectively, and an increase in nonphotochemical quenching (NPQ) by almost 25% in comparison to untreated control. However, 48 h after salinity stress removal, the PSII and PSI efficiencies, specifically Y(II) and Y(I), elevated nonphotochemical quenching (NPQ) and donor side limitation of PSI (YND), were restored to the level observed in control (C3 plants). Swelling of the thylakoid membranes, as well as changes in starch grain quantity and size, have been found to be components of the salinity stress response in CAM plants. Salinity stress induced an over 3-fold increase in average starch area and over 50% decline of average seed number in comparison to untreated control. However, in plants withdrawn from salinity stress, during the first 24 h of recovery, we observed chloroplast ultrastructures closely resembling those found in intact (control) ice plants. Rapid changes in photosystem functionality and chloroplast ultrastructure were accompanied by the induction of the expression (within 24 h) of structural genes related to the PSI and PSII reaction centres, including PSAA, PSAB, PSBA (D1), PSBD (D2) and cp43. Our findings describe one of the most flexible photosynthetic metabolic pathways among facultative CAM plants and reveal the extent of the plasticity of the photosynthetic metabolism and related structures in the common ice plant.
The Role of lncRNA in the Development of Tumors, including Breast Cancer
Authors: Smolarz Beata , Zadrożna-Nowak Anna , Romanowicz Hanna
Published: August 2021

Long noncoding RNAs (lncRNAs) are the largest groups of ribonucleic acids, but, despite the increasing amount of literature data, the least understood. Given the involvement of lncRNA in basic cellular processes, especially in the regulation of transcription, the role of these noncoding molecules seems to be of great importance for the proper functioning of the organism. Studies have shown a relationship between disturbed lncRNA expression and the pathogenesis of many diseases, including cancer. The present article presents a detailed review of the latest reports and data regarding the importance of lncRNA in the development of cancers, including breast carcinoma.
WNT Signaling as a Therapeutic Target for Glioblastoma
Authors: Latour Michael , Her Nam-Gu , Kesari Santosh , Nurmemmedov Elmar
Published: August 2021

The WNT (Wingless/Integrated) signaling pathway is implicated in various stages of glioblastoma, which is an aggressive brain tumor for which therapeutic options are limited. WNT has been recognized as a hallmark of therapeutic challenge due to its context-dependent role and critical function in healthy tissue homeostasis. In this review, we deeply scrutinize the WNT signaling pathway and its involvement in the genesis of glioblastoma as well as its acquired therapy resistance. We also provide an analysis of the WNT pathway in terms of its therapeutic importance in addition to an overview of the current targeted therapies under clinical investigation.
Immunometabolic Modulatory Role of Naltrexone in BV-2 Microglia Cells
Authors: Kučić Natalia , Rački Valentino , Šverko Roberta , Vidović Toni , Grahovac Irena , Mršić-Pelčić Jasenka
Published: August 2021

Background: Naltrexone is an opioid receptor antagonist commonly used to treat opioid and alcohol dependence. The use of low dose naltrexone (LDN) was found to have anti-inflammatory properties for treatment of diseases such as fibromyalgia, Crohn’s disease, multiple sclerosis and regional pain syndromes. Related to its anti-neuroinflammatory properties, the mechanism of action is possibly mediated via Toll-like receptor 4 antagonism, which is widely expressed on microglial cells. The aim of the present study was to assess the immunometabolic effects of naltrexone on microglia cells in in vitro conditions. Methods: All experiments were performed in the BV-2 microglial cell line. The cells were treated with naltrexone at 100 μM concentrations corresponding to low dose for 24 h. Cell viability was assessed for every drug dose. To induce additional activation, the cells were pretreated with LPS and IFN-γ. Immunofluorescence was used to analyse the classical microglial activation markers iNOS and CD206, while Seahorse was used for real-time cellular metabolic assessments. mTOR activity measured over the expression of a major direct downstream target S6K was assessed using western blot. Results: LDN induced a shift from highly activated pro-inflammatory phenotype (iNOShighCD206low) to quiescent anti-inflammatory M2 phenotype (iNOSlowCD206high) in BV-2 microglia cells. Changes in the inflammatory profile were accompanied by cellular metabolic switching based on the transition from high glycolysis to mitochondrial oxidative phosphorylation (OXPHOS). LDN-treated cells were able to maintain a metabolically suppressive phenotype by supporting OXPHOS with high oxygen consumption, and also maintain a lower energetic state due to lower lactate production. The metabolic shift induced by transition from glycolysis to mitochondrial oxidative metabolism was more prominent in cells pretreated with immunometabolic modulators such as LPS and IFN-γ. In a dose-dependent manner, naltrexone also modulated mTOR/S6K expression, which underlies the cell metabolic phenotype regulating microglia immune properties and adaptation. Conclusion: By modulating the phenotypic features by metabolic switching of activated microglia, naltrexone was found to be an effective and powerful tool for immunometabolic reprogramming and could be a promising novel treatment for various neuroinflammatory conditions.
Extracellular Vesicles: New Tools for Early Diagnosis of Breast and Genitourinary Cancers
Authors: Testa Anna , Venturelli Emilio , Brizzi Maria Felice
Published: August 2021

Breast cancers and cancers of the genitourinary tract are the most common malignancies among men and women and are still characterized by high mortality rates. In order to improve the outcomes, early diagnosis is crucial, ideally by applying non-invasive and specific biomarkers. A key role in this field is played by extracellular vesicles (EVs), lipid bilayer-delimited structures shed from the surface of almost all cell types, including cancer cells. Subcellular structures contained in EVs such as nucleic acids, proteins, and lipids can be isolated and exploited as biomarkers, since they directly stem from parental cells. Furthermore, it is becoming even more evident that different body fluids can also serve as sources of EVs for diagnostic purposes. In this review, EV isolation and characterization methods are described. Moreover, the potential contribution of EV cargo for diagnostic discovery purposes is described for each tumor.
Compost Functions as Effective Replacement for Peat-Based Potting Media in Organic Greenhouse Transplant Production
Authors: Isaka Tsuzuchi , Clark Sean , Meyer Janet
Published: August 2021

Commercial horticulture in many regions of the world depends upon Sphagnum peat as a potting-media substrate, but extracting peat has serious environmental consequences. Composts may be able to serve as effective substitutes for peat and offer potential environmental advantages. The suitability of compost as potting media depends upon the raw materials as well as processing methods used. This study includes two related experiments—one with beet (Beta vulgaris L.) and the other with tomato (Solanum lycopersicum L.)—aimed at assessing the potential viability of farm-produced, food-residuals compost as a replacement for peat-based potting media in the production of organic vegetable transplants. The experiments were conducted in 2021 on the Berea College Farm in Kentucky, USA, a USDA certified organic farm. The results indicated that potting media composed of 75% to 100% compost performed as well as fertilized, peat-based growing media for plant growth. Further, although weeds were present in the compost, weed pressure was not severe enough to adversely affect crop growth. Thus, sterilization of compost, which did eliminate weeds in the compost, was not deemed necessary for using the compost as a partial or complete potting medium. Compost pasteurization was also assessed but was ineffective in destroying weed seeds.
Subjective Quality Assessment for Cloud Gaming
Authors: Wahab Abdul , Ahmad Nafi , Martini Maria G. , Schormans John
Published: August 2021

Using subjective testing, we study the effect of the network parameters, delay and packet loss ratio, on the QoE of cloud gaming. We studied three different games, selected based on genre, popularity, content complexity and pace, and tested them in a controlled network environment, using a novel emulator to create realistic lognormal delay distributions instead of relying on a static mean delay, as used previously; we also used Parsec as a good representative of the state of the art. We captured user ratings on an ordinal Absolute Category Rating scale for three quality dimensions: Video QoE, Game-Playability QoE, and Overall QoE. We show that Mean Opinion Scores (MOS) for the game with the highest levels of content complexity and pace are most severely affected by network impairments. We also show that the QoE of interactive cloud applications rely more on the game playability than the video quality of the game. Unlike earlier studies, the differences in MOS are validated using the distributions of the underlying dimensions. A Wilcoxon Signed-Rank test showed that the distributions of Video QoE and Game Playability QoE are not significantly different.
Assessment of Subclinical Psychotic Symptoms in Patients with Rheumatoid Arthritis and Spondyloarthritis
Authors: Prados-Ojeda Juan L. , Luque-Luque Rogelio , Gordillo-Urbano Rafael M. , Guler Ipek , López-Medina Clementina , Collantes-Estévez Eduardo , Escudero-Contreras Alejandro
Published: August 2021

Inflammatory and autoimmune processes have been associated with the onset of depressive and psychotic symptoms. Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are rheumatic diseases with an inflammatory etiology. A high prevalence of depressive and anxiety-related comorbidity has been reported for both diseases, with no evidence of a greater prevalence of psychosis. The objective of the present study was to evaluate for the first time subclinical psychotic symptoms in patients with RA and SpA. This is a cross-sectional, single-center study including RA and SpA patients, as well as healthy controls. Abnormal psychotic experiences (positive, negative, and depressive symptoms) were evaluated using the Community Assessment of Psychic Experiences (CAPE-42). Functional capacity was evaluated using the Short-Form Health Survey SF-12. We compared the CAPE and SF-12 scores between the three groups. We recruited 385 individuals: 218 with RA, 100 with SpA, and 67 healthy controls. According to the CAPE scale, the frequency of subclinical psychotic symptoms was greater in patients than in healthy controls (RA, 1.90 vs. 1.63, p < 0.001; SpA, 1.88 vs. 1.63, p = 0.001). Distress was also greater in patients than in controls owing to the presence of symptoms. No differences were observed between the three groups for the mental dimension scores in the SF-12 Health Survey (43.75 in RA, 45.54 in SpA, and 43.19 in healthy controls). Our findings point to a greater prevalence of subclinical psychotic symptoms in patients with RA and patients with SpA than in the general population. The results suggest an association between inflammation and depression/subclinical psychotic symptoms.
Changes in Corneal Epithelial Thickness Induced by Topical Antiglaucoma Medications
Authors: Nam Myungsik , Kim Sun Woong
Published: August 2021

Corneal thickness measurement is important for assessing intraocular pressure in patients with glaucoma. This study investigated the changes in corneal epithelial thickness (CET) induced by antiglaucoma medications and explored the factors affecting CET measurement. CET was measured over a 9.0 mm diameter area by using Fourier domain optical coherence tomography in 125 patients with primary open-angle glaucoma and 125 age-matched controls without glaucoma. The influence of sex, age, benzalkonium chloride (BAK)-containing instillations, disease severity, and types and numbers of medications was analyzed using simple and multiple regression analyses. CET over 25 sectors was smaller in the glaucoma group than in the control group (mean difference of 4.2 µm in the central 2.0 mm zone; 52.8 ± 3.6 vs. 48.5 ± 3.9, p < 0.001). Simple regression analysis revealed age, use of β-blockers, prostaglandin, carbonic anhydrase inhibitors, total number of medications, and number of daily BAK-containing instillations were associated with a thinner epithelium. Multiple regression analysis revealed β-blockers, prostaglandin, and number of BAK-containing instillations were significant factors. Use of β-blockers and number of BAK-containing instillations were also associated with a thinner epithelium in the monotherapy subgroup analysis. CET was significantly smaller in patients with glaucoma receiving topical medications and was affected by the use of β-blockers, prostaglandin, and BAK.
CNN-Based Multi-Modal Camera Model Identification on Video Sequences
Authors: Dal Cortivo Davide , Mandelli Sara , Bestagini Paolo , Tubaro Stefano
Published: August 2021

Identifying the source camera of images and videos has gained significant importance in multimedia forensics. It allows tracing back data to their creator, thus enabling to solve copyright infringement cases and expose the authors of hideous crimes. In this paper, we focus on the problem of camera model identification for video sequences, that is, given a video under analysis, detecting the camera model used for its acquisition. To this purpose, we develop two different CNN-based camera model identification methods, working in a novel multi-modal scenario. Differently from mono-modal methods, which use only the visual or audio information from the investigated video to tackle the identification task, the proposed multi-modal methods jointly exploit audio and visual information. We test our proposed methodologies on the well-known Vision dataset, which collects almost 2000 video sequences belonging to different devices. Experiments are performed, considering native videos directly acquired by their acquisition devices and videos uploaded on social media platforms, such as YouTube and WhatsApp. The achieved results show that the proposed multi-modal approaches significantly outperform their mono-modal counterparts, representing a valuable strategy for the tackled problem and opening future research to even more challenging scenarios.