bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolism of Selenium, Selenocysteine, and Selenoproteins in Ferroptosis in Solid Tumor Cancers
Authors: Shimada Briana K. , Swanson Sydonie , Toh Pamela , Seale Lucia A.
Published: October 2022

A potential target of precision nutrition in cancer therapeutics is the micronutrient selenium (Se). Se is metabolized and incorporated as the amino acid selenocysteine (Sec) into 25 human selenoproteins, including glutathione peroxidases (GPXs) and thioredoxin reductases (TXNRDs), among others. Both the processes of Se and Sec metabolism for the production of selenoproteins and the action of selenoproteins are utilized by cancer cells from solid tumors as a protective mechanism against oxidative damage and to resist ferroptosis, an iron-dependent cell death mechanism. Protection against ferroptosis in cancer cells requires sustained production of the selenoprotein GPX4, which involves increasing the uptake of Se, potentially activating Se metabolic pathways such as the trans-selenation pathway and the TXNRD1-dependent decomposition of inorganic selenocompounds to sustain GPX4 synthesis. Additionally, endoplasmic reticulum-resident selenoproteins also affect apoptotic responses in the presence of selenocompounds. Selenoproteins may also help cancer cells adapting against increased oxidative damage and the challenges of a modified nutrient metabolism that result from the Warburg switch. Finally, cancer cells may also rewire the selenoprotein hierarchy and use Se-related machinery to prioritize selenoproteins that are essential to the adaptations against ferroptosis and oxidative damage. In this review, we discuss both the evidence and the gaps in knowledge on how cancer cells from solid tumors use Se, Sec, selenoproteins, and the Se-related machinery to promote their survival particularly via resistance to ferroptosis.
Precise Design of Alginate Hydrogels Crosslinked with Microgels for Diabetic Wound Healing
Authors: Yan Yishu , Ren Panpan , Wu Qingqing , Zhang Tianmeng
Published: October 2022

Alginate hydrogel has received great attention in diabetic wound healing. However, the limited tunability of the ionic crosslinking method prevents the delicate management of physical properties in response to diverse wound conditions. We addressed this issue by using a microgel particle (fabricated by zinc ions and coordinated through the complex of carboxymethyl chitosan and aldehyde hyaluronic acid) as a novel crosslinker. Then the cation was introduced as a second crosslinker to create a double crosslinked network. The method leads to the precise regulation of the hydrogel characters, including the biodegradation rate and the controlled release rate of the drug. As a result, the optimized hydrogels facilitated the live-cell infiltration in vitro and boosted the tissue regeneration of diabetic wounds in vivo. The results indicated that the addition of the microgel as a new crosslinker created flexibility during the construction of the alginate hydrogel, adapting for diverse applications during diabetic-induced wound therapy.
Essential Role of Histidine for Rapid Copper(II)-Mediated Disassembly of Neurokinin B Amyloid
Authors: Jayawardena Bhawantha M. , Peacey Lorraine , Gamsjaeger Roland , Jones Christopher E.
Published: October 2022

Neurokinin B is a tachykinin peptide involved in a diverse range of neuronal functions. It rapidly forms an amyloid, which is considered physiologically important for efficient packing into dense core secretory vesicles within hypothalamic neurons. Disassembly of the amyloid is thought to require the presence of copper ions, which interact with histidine at the third position in the peptide sequence. However, it is unclear how the histidine is involved in the amyloid structure and why copper coordination can trigger disassembly. In this work, we demonstrate that histidine contributes to the amyloid structure via π-stacking interactions with nearby phenylalanine residues. The ability of neurokinin B to form an amyloid is dependent on any aromatic residue at the third position in the sequence; however, only the presence of histidine leads to both amyloid formation and rapid copper-induced disassembly.
Druggable Metabolic Vulnerabilities Are Exposed and Masked during Progression to Castration Resistant Prostate Cancer
Authors: Choi Stephen Y. C. , Ribeiro Caroline Fidalgo , Wang Yuzhuo , Loda Massimo , Plymate Stephen R. , Uo Takuma
Published: October 2022

There is an urgent need for exploring new actionable targets other than androgen receptor to improve outcome from lethal castration-resistant prostate cancer. Tumor metabolism has reemerged as a hallmark of cancer that drives and supports oncogenesis. In this regard, it is important to understand the relationship between distinctive metabolic features, androgen receptor signaling, genetic drivers in prostate cancer, and the tumor microenvironment (symbiotic and competitive metabolic interactions) to identify metabolic vulnerabilities. We explore the links between metabolism and gene regulation, and thus the unique metabolic signatures that define the malignant phenotypes at given stages of prostate tumor progression. We also provide an overview of current metabolism-based pharmacological strategies to be developed or repurposed for metabolism-based therapeutics for castration-resistant prostate cancer.
Small-Angle Neutron Scattering for Studying Lipid Bilayer Membranes
Authors: Heller William T.
Published: October 2022

Small-angle neutron scattering (SANS) is a powerful tool for studying biological membranes and model lipid bilayer membranes. The length scales probed by SANS, being from 1 nm to over 100 nm, are well-matched to the relevant length scales of the bilayer, particularly when it is in the form of a vesicle. However, it is the ability of SANS to differentiate between isotopes of hydrogen as well as the availability of deuterium labeled lipids that truly enable SANS to reveal details of membranes that are not accessible with the use of other techniques, such as small-angle X-ray scattering. In this work, an overview of the use of SANS for studying unilamellar lipid bilayer vesicles is presented. The technique is briefly presented, and the power of selective deuteration and contrast variation methods is discussed. Approaches to modeling SANS data from unilamellar lipid bilayer vesicles are presented. Finally, recent examples are discussed. While the emphasis is on studies of unilamellar vesicles, examples of the use of SANS to study intact cells are also presented.
Blood Transcript Biomarkers Selected by Machine Learning Algorithm Classify Neurodegenerative Diseases including Alzheimer’s Disease
Authors: Huseby Carol J. , Delvaux Elaine , Brokaw Danielle L. , Coleman Paul D.
Published: October 2022

The clinical diagnosis of neurodegenerative diseases is notoriously inaccurate and current methods are often expensive, time-consuming, or invasive. Simple inexpensive and noninvasive methods of diagnosis could provide valuable support for clinicians when combined with cognitive assessment scores. Biological processes leading to neuropathology progress silently for years and are reflected in both the central nervous system and vascular peripheral system. A blood-based screen to distinguish and classify neurodegenerative diseases is especially interesting having low cost, minimal invasiveness, and accessibility to almost any world clinic. In this study, we set out to discover a small set of blood transcripts that can be used to distinguish healthy individuals from those with Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, Friedreich’s ataxia, or frontotemporal dementia. Using existing public datasets, we developed a machine learning algorithm for application on transcripts present in blood and discovered small sets of transcripts that distinguish a number of neurodegenerative diseases with high sensitivity and specificity. We validated the usefulness of blood RNA transcriptomics for the classification of neurodegenerative diseases. Information about features selected for the classification can direct the development of possible treatment strategies.
Serum Metabolomic Profiling in Aging Mice Using Liquid Chromatography—Mass Spectrometry
Authors: Yue Tong , Tan Huiling , Shi Yu , Xu Mengyun , Luo Sihui , Weng Jianping , Xu Suowen
Published: October 2022

Background: The process of aging and metabolism are intricately linked, thus rendering the identification of reliable biomarkers related to metabolism crucial for delaying the aging process. However, research of reliable markers that reflect aging profiles based on machine learning is scarce. Methods: Serum samples were obtained from aged mice (18-month-old) and young mice (3-month-old). LC-MS was used to perform a comprehensive analysis of the serum metabolome and machine learning was used to screen potential aging-related biomarkers. Results: In total, aging mice were characterized by 54 different metabolites when compared to control mice with criteria: VIP ≥ 1, q-value < 0.05, and Fold-Change ≥ 1.2 or ≤0.83. These metabolites were mostly involved in fatty acid biosynthesis, cysteine and methionine metabolism, D-glutamine and D-glutamate metabolism, and the citrate cycle (TCA cycle). We merged the comprehensive analysis and four algorithms (LR, GNB, SVM, and RF) to screen aging-related biomarkers, leading to the recognition of oleic acid. In addition, five metabolites were identified as novel aging-related indicators, including oleic acid, citric acid, D-glutamine, trypophol, and L-methionine. Conclusions: Changes in the metabolism of fatty acids and conjugates, organic acids, and amino acids were identified as metabolic dysregulation related to aging. This study revealed the metabolic profile of aging and provided insights into novel potential therapeutic targets for delaying the effects of aging.
Metabolic Regulation of Mitochondrial Protein Biogenesis from a Neuronal Perspective
Authors: Hees Jara Tabitha , Harbauer Angelika Bettina
Published: October 2022

Neurons critically depend on mitochondria for ATP production and Ca2+ buffering. They are highly compartmentalized cells and therefore a finely tuned mitochondrial network constantly adapting to the local requirements is necessary. For neuronal maintenance, old or damaged mitochondria need to be degraded, while the functional mitochondrial pool needs to be replenished with freshly synthesized components. Mitochondrial biogenesis is known to be primarily regulated via the PGC-1α-NRF1/2-TFAM pathway at the transcriptional level. However, while transcriptional regulation of mitochondrial genes can change the global mitochondrial content in neurons, it does not explain how a morphologically complex cell such as a neuron adapts to local differences in mitochondrial demand. In this review, we discuss regulatory mechanisms controlling mitochondrial biogenesis thereby making a case for differential regulation at the transcriptional and translational level. In neurons, additional regulation can occur due to the axonal localization of mRNAs encoding mitochondrial proteins. Hitchhiking of mRNAs on organelles including mitochondria as well as contact site formation between mitochondria and endolysosomes are required for local mitochondrial biogenesis in axons linking defects in any of these organelles to the mitochondrial dysfunction seen in various neurological disorders.
The Potential Role of Polyamines in Epilepsy and Epilepsy-Related Pathophysiological Changes
Authors: Liu Jiayu , Yu Zhi , Maimaiti Buajieerguli , Meng Qian , Meng Hongmei
Published: October 2022

Epilepsy is one of the most common neurological disorders and severely impacts the life quality of patients. Polyamines are ubiquitous, positively charged aliphatic amines that are present at a relatively high level and help regulate the maintenance of cell membrane excitability and neuronal physiological functions in the central nervous system. Studies have shown abnormalities in the synthesis and catabolism of polyamines in patients with epilepsy and in animal models of epilepsy. The polyamine system seems to involve in the pathophysiological processes of epilepsy via several mechanisms such as the regulation of ion permeability via interaction with ion channels, involvement in antioxidation as hydroperoxide scavengers, and the induction of cell damage via the production of toxic metabolites. In this review, we try to describe the possible associations between polyamines and epilepsy and speculate that the polyamine system is a potential target for the development of novel strategies for epilepsy treatment.
LRRK2 and Lipid Pathways: Implications for Parkinson’s Disease
Authors: Galper Jasmin , Kim Woojin S. , Dzamko Nicolas
Published: October 2022

Genetic alterations in the LRRK2 gene, encoding leucine-rich repeat kinase 2, are a common risk factor for Parkinson’s disease. How LRRK2 alterations lead to cell pathology is an area of ongoing investigation, however, multiple lines of evidence suggest a role for LRRK2 in lipid pathways. It is increasingly recognized that in addition to being energy reservoirs and structural entities, some lipids, including neural lipids, participate in signaling cascades. Early investigations revealed that LRRK2 localized to membranous and vesicular structures, suggesting an interaction of LRRK2 and lipids or lipid-associated proteins. LRRK2 substrates from the Rab GTPase family play a critical role in vesicle trafficking, lipid metabolism and lipid storage, all processes which rely on lipid dynamics. In addition, LRRK2 is associated with the phosphorylation and activity of enzymes that catabolize plasma membrane and lysosomal lipids. Furthermore, LRRK2 knockout studies have revealed that blood, brain and urine exhibit lipid level changes, including alterations to sterols, sphingolipids and phospholipids, respectively. In human LRRK2 mutation carriers, changes to sterols, sphingolipids, phospholipids, fatty acyls and glycerolipids are reported in multiple tissues. This review summarizes the evidence regarding associations between LRRK2 and lipids, and the functional consequences of LRRK2-associated lipid changes are discussed.
The Executive Functioning Paradox in Substance Use Disorders
Authors: Jakubiec Louise , Chirokoff Valentine , Abdallah Majd , Sanz-Arigita Ernesto , Dupuy Maud , Swendsen Joel , Berthoz Sylvie , Gierski Fabien , Guionnet Sarah , Misdrahi David , Serre Fuschia , Auriacombe Marc , Fatseas Melina
Published: October 2022

Deficits in neurocognitive functioning are trait-like vulnerabilities that have been widely studied in persons with substance use disorders (SUD), but their role in the craving–use association and relapse vulnerability remains poorly understood. The main objectives of this study were to examine whether executive capacities moderate the magnitude of the craving–substance use relationship, and if this influence is correlated with the functional connectivity of cerebral networks, combining rsfMRI examinations and ecological momentary assessment (EMA). Eighty-six patients beginning outpatient treatment for alcohol, tobacco or cannabis addiction and 40 healthy controls completed neuropsychological tests followed by EMA to collect real-time data on craving. Fifty-four patients and 30 healthy controls also completed a resting-state fMRI before the EMA. Among the patients with SUD, better verbal fluency and resistance to interference capacities were associated with a greater propensity to use substances when the individual was experiencing craving. Preliminary rsfMRI results identified specific networks that interacted with executive performance capacities to influence the magnitude of the craving–use association. Individuals with better executive functioning may be more prone to relapse after craving episodes. Specifically, better resistance to interference and cognitive flexibility skills may reduce attention to distracting stimuli, leading to a greater awareness of craving and susceptibility to use substances.
SOD3 Expression in Tumor Stroma Provides the Tumor Vessel Maturity in Oral Squamous Cell Carcinoma
Authors: Oo May Wathone , Kawai Hotaka , Eain Htoo Shwe , Soe Yamin , Takabatake Kiyofumi , Sanou Sho , Shan Qiusheng , Inada Yasunori , Fujii Masae , Fukuhara Yoko , Wang Ziyi , Sukegawa Shintaro , Ono Mitsuaki , Nakano Keisuke , Nagatsuka Hitoshi
Published: October 2022

Tumor angiogenesis is one of the hallmarks of solid tumor development. The progressive tumor cells produce the angiogenic factors and promote tumor angiogenesis. However, how the tumor stromal cells influence tumor vascularization is still unclear. In the present study, we evaluated the effects of oral squamous cell carcinoma (OSCC) stromal cells on tumor vascularization. The tumor stromal cells were isolated from two OSCC patients with different subtypes: low invasive verrucous squamous carcinoma (VSCC) and highly invasive squamous cell carcinoma (SCC) and co-xenografted with the human OSCC cell line (HSC-2) on nude mice. In comparison, the CD34+ vessels in HSC-2+VSCC were larger than in HSC-2+SCC. Interestingly, the vessels in the HSC-2+VSCC expressed vascular endothelial cadherin (VE-cadherin), indicating well-formed vascularization. Our microarray data revealed that the expression of extracellular superoxide dismutase, SOD3 mRNA is higher in VSCC stromal cells than in SCC stromal cells. Moreover, we observed that SOD3 colocalized with VE-cadherin on endothelial cells of low invasive stroma xenograft. These data suggested that SOD3 expression in stromal cells may potentially regulate tumor vascularization in OSCC. Thus, our study suggests the potential interest in SOD3-related vascular integrity for a better OSCC therapeutic strategy.
Experimental Static Cold Storage of the Rat Uterus: Protective Effects of Relaxin- or Erythropoietin-Supplemented HTK-N Solutions
Authors: Jakubauskiene Lina , Jakubauskas Matas , Razanskiene Gintare , Leber Bettina , Ramasauskaite Diana , Strupas Kestutis , Stiegler Philipp , Schemmer Peter
Published: October 2022

Uterus transplantation (UTx) is the only treatment method for women with absolute uterine infertility. Currently, the number of grafts retrieved from deceased donors is increasing; hence, prolonged cold ischemia time is inevitable. Thus, this study was designed to assess the effect of the novel relaxin (RLN)- or erythropoietin (EPO)-supplemented Custodiol-N (HTK-N) solutions in an experimental uterus static cold storage (SCS) model. A total of 15 Sprague Dawley rats were used. Uterus horns were randomly assigned into three groups (n = 10/group). SCS was performed by keeping samples at 4 °C in HTK-N solution without or with different additives: 10 IU/mL EPO or 20 nM RLN. Tissue samples were taken after 8 and 24 h of preservation. Uterine tissue histology, and biochemical and immunohistochemical markers were analyzed. No significant differences in SCS-induced tissue damage were observed between groups after 8 h of preservation. Uterine tissue histology, MDA, SOD levels and the TUNEL-positive cell number showed severe damage in HTK-N without additives after 24 h of preservation. This damage was significantly attenuated by adding RLN to the preservation solution. EPO showed no favorable effect. Our study shows that RLN as an additive to an HTK-N solution can serve as an effective uterine tissue preservative in the uterus SCS setting.
Editorials for ‘Advances in Cold Plasma in Biomedicines’
Authors: Kim Gyoo-Cheon
Published: October 2022

Research in the field of plasma medicine has provided many explanations for various phenomena, as well as the involvement of the chemical elements of plasma; however, it still lacks in biological mechanism analyses [...]
Genomic and Immune Approach in Platinum Refractory HPV-Negative Head and Neck Squamous Cell Carcinoma Patients Treated with Immunotherapy: A Novel Combined Profile
Authors: Mezi Silvia , Pomati Giulia , Zizzari Ilaria Grazia , Di Filippo Alessandra , Cerbelli Bruna , Cirillo Alessio , Fiscon Giulia , Amirhassankhani Sasan , Valentini Valentino , De Vincentiis Marco , Corsi Alessandro , Di Gioia Cira , Tombolini Vincenzo , Della Rocca Carlo , Polimeni Antonella , Nuti Marianna , Marchetti Paolo , Botticelli Andrea
Published: October 2022

Introduction: Only a minority of patients with platinum refractory head and neck squamous cell carcinoma (PR/HNSCC) gain some lasting benefit from immunotherapy. Methods: The combined role of the comprehensive genomic (through the FoundationOne Cdx test) and immune profiles of 10 PR/HNSCC patients treated with the anti-PD-1 nivolumab was evaluated. The immune profiles were studied both at baseline and at the second cycle of immunotherapy, weighing 20 circulating cytokines/chemokines, adhesion molecules, and 14 soluble immune checkpoints dosed through a multiplex assay. A connectivity map was obtained by calculating the Spearman correlation between the expression profiles of circulating molecules. Results: Early progression occurred in five patients, each of them showing TP53 alteration and three of them showing a mutation/loss/amplification of genes involved in the cyclin-dependent kinase pathway. In addition, ERB2 amplification (1 patient), BRCA1 mutation (1 patient), and NOTCH1 genes alteration (3 patients) occurred. Five patients achieved either stable disease or partial response. Four of them carried mutations in PI3K/AKT/PTEN pathways. In the only two patients, with a long response to immunotherapy, the tumor mutational burden (TMB) was high. Moreover, a distinct signature, in terms of network connectivity of the circulating soluble molecules, characterizing responder and non-responder patients, was evidenced. Moreover, a strong negative and statistically significant (p-value ≤ 0.05) correlation with alive status was evidenced for sE-selectin at T1. Conclusions: Our results highlighted the complexity and heterogeneity of HNSCCs, even though it was in a small cohort. Molecular and immune approaches, combined in a single profile, could represent a promising strategy, in the context of precision immunotherapy.
Cumulative Effect Assessment of Common Genetic Variants on Prostate Cancer: Preliminary Studies
Authors: Pavel Anca Gabriela , Stambouli Danae , Anton Gabriela , Gener Ismail , Preda Adrian , Baston Catalin , Gingu Constantin
Published: October 2022

Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation among people. Genome Wide Association studies (GWASs) have generated multiple genetic variants associated with prostate cancer (PC) risk. Taking into account previously identified genetic susceptibility variants, the purpose of our study was to determine the cumulative association between four common SNPs and the overall PC risk. A total of 78 specimens from both PC and benign prostate hyperplasia (BPH) patients were included in the study. Genotyping of all selected SNPs was performed using the TaqMan assay. The association between each SNP and the PC risk was assessed individually and collectively. Analysis of the association between individual SNPs and PC risk revealed that only the rs4054823 polymorphism was significantly associated with PC, and not with BPH (p < 0.001). Statistical analysis also showed that the heterozygous genotype of the rs2735839 polymorphism is more common within the BPH group than in the PC group (p = 0.042). The cumulative effect of high-risk alleles on PC was analyzed using a logistic regression model. As a result, the carriers of at least one risk allele copy in each particular region had a cumulative odd ratio (OR) of 1.42 times, compared to subjects who did not have any of these factors. In addition, the combination of these four genetic variants increased the overall risk of PC by 52%. Our study provides further evidence of the cumulative effects of genetic risk factors on overall PC risk. These results should encourage future research to explain the interactions between known susceptibility variants and their contribution to the development and progression of PC disease.
Distribution of Viral Respiratory Infections during the COVID-19 Pandemic Using the FilmArray Respiratory Panel
Authors: Chen Ying-Ju , Er Tze-Kiong
Published: October 2022

This study was conducted to evaluate the distribution of respiratory viral pathogens in the emergency department during the coronavirus disease 2019 (COVID-19) pandemic. Between May 2020 and September 2022, patients aged between 0.1 and 98 years arrived at the emergency department of Asia University Hospital, and samples from nasopharyngeal swabs were tested by the FilmArrayTM Respiratory Panel (RP). SARS-CoV-2 positivity was subsequently retested by the cobas Liat system. There were 804 patients for whom the FilmArrayTM RP was tested, and 225 (27.9%) of them had positive results for respiratory viruses. Rhinovirus/enterovirus was the most commonly detected pathogen, with 170 (61.8%) cases, followed by adenovirus with 38 (13.8%), SARS-CoV-2 with 16 (5.8%) cases, and coronavirus 229E, with 16 (5.8%) cases. SARS-CoV-2 PCR results were positive in 16 (5.8%) cases, and there were two coinfections of SARS-CoV-2 with adenovirus and rhinovirus/enterovirus. A total of 43 (5.3%) patients were coinfected; the most coinfection was adenovirus plus rhinovirus/enterovirus, which was detectable in 18 (41.9%) cases. No atypical pathogens were found in this study. Intriguingly, our results showed that there was prefect agreement between the detection of SARS-CoV-2 conducted with the cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test and the FilmArrayTM RP. Therefore, the FilmArrayTM RP assay is a reliable and feasible method for the detection of SARS-CoV-2. In summary, FilmArrayTM RP significantly broadens our capability to detect multiple respiratory infections due to viruses and atypical bacteria. It provides a prompt evaluation of pathogens to enhance patient care and clinical selection strategies in emergency departments during the COVID-19 pandemic.
Implications for Self-Management among African Caribbean Adults with Noncommunicable Diseases and Mental Health Disorders: A Systematic Review
Authors: Magny-Normilus Cherlie , Hassan Saria , Sanders Julie , Longhurst Catrina , Lee Christopher S. , Jurgens Corrine Y.
Published: October 2022

Mental health problems are common among individuals suffering from chronic noncommunicable diseases (NCDs) such as type 2 diabetes mellitus and hypertension. Self-management is essential in preventing NCD progression. Mental health problems can impede the ability to self-manage one’s NCDs. The African Caribbean population in the United States suffers from a high burden of NCDs and has unique societal factors that alter disease management. This systematic review aimed to better understand the burden of mental health problems among African Caribbean adults with one or more NCDs and explore the association between mental health disorders and the level of control of NCDs. A literature search was conducted for original research documenting the prevalence of mental illnesses in individuals with NCDs. Data were descriptively summarized. Fourteen studies met inclusion criteria. Three themes emerged: (1) prevalence of comorbid mental health problems and chronic NCDs; (2) factors that mitigate or mediate the association between mental health problems and chronic NCDs—(a) factors influencing self-management; (b) association between mental health and NCD outcome studies focused on (b1) risk factors and (b2) protective factors; and (3) varied results. Chronic disease self-management and disease outcomes are influenced by mental problems and the association is mitigated by complex factors in the African Caribbean population.
A Strategy for Magnetic and Electric Stimulation to Enhance Proliferation and Differentiation of NPCs Seeded over PLA Electrospun Membranes
Authors: Cuenca-Ortolá Irene , Martínez-Rojas Beatriz , Moreno-Manzano Victoria , García Castelló Marcos , Monleón Pradas Manuel , Martínez-Ramos Cristina , Más Estellés Jorge
Published: October 2022

Neural progenitor cells (NPCs) have been shown to serve as an efficient therapeutic strategy in different cell therapy approaches, including spinal cord injury treatment. Despite the reported beneficial effects of NPC transplantation, the low survival and differentiation rates constrain important limitations. Herein, a new methodology has been developed to overcome both limitations by applying a combination of wireless electrical and magnetic stimulation to NPCs seeded on aligned poly(lactic acid) nanofibrous scaffolds for in vitro cell conditioning prior transplantation. Two stimulation patterns were tested and compared, continuous (long stimulus applied once a day) and intermittent (short stimulus applied three times a day). The results show that applied continuous stimulation promotes NPC proliferation and preferential differentiation into oligodendrocytic and neuronal lineages. A neural-like phenotypic induction was observed when compared to unstimulated NPCs. In contrast, intermittent stimulation patterns did not affect NPC proliferation and differentiation to oligodendrocytes or astrocytes morphology with a detrimental effect on neuronal differentiation. This study provides a new approach of using a combination of electric and magnetic stimulation to induce proliferation and further neuronal differentiation, which would improve therapy outcomes in disorders such as spinal cord injury.
Tissue Factor, Thrombosis, and Chronic Kidney Disease
Authors: Oe Yuji , Takahashi Nobuyuki
Published: October 2022

Coagulation abnormalities are common in chronic kidney disease (CKD). Tissue factor (TF, factor III) is a master regulator of the extrinsic coagulation system, activating downstream coagulation proteases, such as factor Xa and thrombin, and promoting fibrin formation. TF and coagulation proteases also activate protease-activated receptors (PARs) and are implicated in various organ injuries. Recent studies have shown the mechanisms by which thrombotic tendency is increased under CKD-specific conditions. Uremic toxins, such as indoxyl sulfate and kynurenine, are accumulated in CKD and activate TF and coagulation; in addition, the TF–coagulation protease–PAR pathway enhances inflammation and fibrosis, thereby exacerbating renal injury. Herein, we review the recent research studies to understand the role of TF in increasing the thrombotic risk and CKD progression.
Quantitative Proteomics Indicate Radical Removal of Non-Small Cell Lung Cancer and Predict Outcome
Authors: Bodén Embla , Andreasson Jesper , Hirdman Gabriel , Malmsjö Malin , Lindstedt Sandra
Published: October 2022

Non-small cell lung cancer (NSCLC) is associated with low survival rates, often due to late diagnosis and lack of personalized medicine. Diagnosing and monitoring NSCLC using blood samples has lately gained interest due to its less invasive nature. In the present study, plasma was collected at three timepoints and analyzed using proximity extension assay technology and quantitative real-time polymerase chain reaction in patients with primary NSCLC stages IA–IIIA undergoing surgery. Results were adjusted for patient demographics, tumor, node, metastasis (TNM) stage, and multiple testing. Major histocompatibility (MHC) class 1 polypeptide-related sequence A/B (MIC-A/B) and tumor necrosis factor ligand superfamily member 6 (FASLG) were significantly increased post-surgery, suggesting radical removal of cancerous cells. Levels of hepatocyte growth factor (HGF) initially increased postoperatively but were later lowered, potentially indicating radical removal of malignant cells. The levels of FASLG in patients who later died or had a relapse of NSCLC were lower at all three timepoints compared to surviving patients without relapse, indicating that FASLG may be used as a prognostic biomarker. The biomarkers were confirmed using microarray data. In conclusion, quantitative proteomics could be used for NSCLC identification but may also provide information on radical surgical removal of NSCLC and post-surgical prognosis.
MicroRNA Profiling Shows a Time-Dependent Regulation within the First 2 Months Post-Birth and after Mild Neonatal Hypoxia in the Hippocampus from Mice
Authors: Leavy Aisling , Brennan Gary P. , Jimenez-Mateos Eva M.
Published: October 2022

Brain development occurs until adulthood, with time-sensitive processes happening during embryo development, childhood, and puberty. During early life and childhood, dynamic changes in the brain are critical for physiological brain maturation, and these changes are tightly regulated by the expression of specific regulatory genetic elements. Early life insults, such as hypoxia, can alter the course of brain maturation, resulting in lifelong neurodevelopmental conditions. MicroRNAs are small non-coding RNAs, which regulate and coordinate gene expression. It is estimated that one single microRNA can regulate the expression of hundreds of protein-coding genes.. Uncovering the miRNome and microRNA-regulated transcriptomes may help to understand the patterns of genes regulating brain maturation, and their contribution to neurodevelopmental pathologies following hypoxia at Postnatal day 7. Here, using a PCR-based platform, we analyzed the microRNA profile postnatally in the hippocampus of control mice at postnatal day 8, 14, and 42 and after hypoxia at postnatal day 7, to elucidate the set of microRNAs which may be key for postnatal hippocampus maturation. We observed that microRNAs can be divided in four groups based on their temporal expression. Further after an early life insult, hypoxia at P7, 15 microRNAs showed a misregulation over time, including Let7a. We speculated that the transcriptional regulator c-myc is a contributor to this process. In conclusion, here, we observed that microRNAs are regulated postnatally in the hippocampus and alteration of their expression after hypoxia at birth may be regulated by the transcriptional regulator c-myc.
Current Trends and Challenges of Fecal Microbiota Transplantation—An Easy Method That Works for All?
Authors: Almeida Cátia , Oliveira Rita , Baylina Pilar , Fernandes Rúben , Teixeira Fábio G. , Barata Pedro
Published: October 2022

The gut microbiota refers to bacteria lodges in the gastrointestinal tract (GIT) that interact through various complex mechanisms. The disturbance of this ecosystem has been correlated with several diseases, such as neurologic, respiratory, cardiovascular, and metabolic diseases and cancer. Therefore, the modulation of the gut microbiota has emerged as a potential therapeutic tool; of the various forms of gut microbiota modulation, fecal microbiota transplantation (FMT) is the most approached. This recent technique involves introducing fecal material from a healthy donor into the patient’s gastrointestinal tract, aiming to restore the gut microbiota and lead to the resolution of symptoms. This procedure implies a careful donor choice, fine collection and handling of fecal material, and a balanced preparation of the recipient and consequent administration of the prepared content. Although FMT is considered a biological therapy with promising effects, side effects such as diarrhea and abdominal pain have also been claimed, making this a significant challenge in the application of FMT. Bearing this in mind, the present review aims to summarize the recent advances in understanding FMT mechanisms, their impact across different pathological conditions, and the associated side effects, emphasizing the most recent published data.
Synaptic Plasticity in the Pain-Related Cingulate and Insular Cortex
Authors: Lee Jung-Hyun Alex , Chen Qiyu , Zhuo Min
Published: October 2022

Cumulative animal and human studies have consistently demonstrated that two major cortical regions in the brain, namely the anterior cingulate cortex (ACC) and insular cortex (IC), play critical roles in pain perception and chronic pain. Neuronal synapses in these cortical regions of adult animals are highly plastic and can undergo long-term potentiation (LTP), a phenomenon that is also reported in brain areas for learning and memory (such as the hippocampus). Genetic and pharmacological studies show that inhibiting such cortical LTP can help to reduce behavioral sensitization caused by injury as well as injury-induced emotional changes. In this review, we will summarize recent progress related to synaptic mechanisms for different forms of cortical LTP and their possible contribution to behavioral pain and emotional changes.
Liquid Biopsies in Cancer Diagnosis, Monitoring and Prognosis
Authors: Ulivi Paola , Indraccolo Stefano
Published: October 2022

Liquid biopsy has emerged as new tool for detecting clinically relevant genetic alterations in cancer patients [...]
Recent Developments in Mycobacteria-Based Live Attenuated Vaccine Candidates for Tuberculosis
Authors: Flores-Valdez Mario Alberto , Kupz Andreas , Subbian Selvakumar
Published: October 2022

Vaccination is an excellent approach to stimulating the host immune response and reducing human morbidity and mortality against microbial infections, such as tuberculosis (TB). Bacillus Calmette–Guerin (BCG) is the most widely administered vaccine in the world and the only vaccine approved by the World Health Organization (WHO) to protect against TB. Although BCG confers “protective” immunity in children against the progression of Mycobacterium tuberculosis (Mtb) infection into active TB, this vaccine is ineffective in protecting adults with active TB manifestations, such as multiple-, extensive-, and total-drug-resistant (MDR/XDR/TDR) cases and the co-existence of TB with immune-compromising health conditions, such as HIV infection or diabetes. Moreover, BCG can cause disease in individuals with HIV infection or other immune compromises. Due to these limitations of BCG, novel strategies are urgently needed to improve global TB control measures. Since live vaccines elicit a broader immune response and do not require an adjuvant, developing recombinant BCG (rBCG) vaccine candidates have received significant attention as a potential replacement for the currently approved BCG vaccine for TB prevention. In this report, we aim to present the latest findings and outstanding questions that we consider worth investigating regarding novel mycobacteria-based live attenuated TB vaccine candidates. We also specifically discuss the important features of two key animal models, mice and rabbits, that are relevant to TB vaccine testing. Our review emphasizes that the development of vaccines that block the reactivation of latent Mtb infection (LTBI) into active TB would have a significant impact in reducing the spread and transmission of Mtb. The results and ideas discussed here are only based on reports from the last five years to keep the focus on recent developments.
Affinity Capture Elution (ACE) ELISA Method Development and Validation for Novel RPH-104 Drug Immunogenicity Evaluation
Authors: Kolganova Maria A. , Melnik Elizaveta V. , Fisher Elizaveta N. , Smirnov Valery V. , Vlasov Alexander M. , Gegechkori Vladimir I. , Shulga Nikolay A. , Shokhin Igor E. , Ramenskaya Galina V.
Published: October 2022

As the number of therapeutic protein products is growing rapidly, there is a strong need for the development of bioanalytical methods that are easy to perform, specific, sensitive, robust, and affordable. Methods for immunogenicity evaluation of therapeutic proteins take an important place in this field of bioanalytics. The aim of the study was to develop a method for immunogenicity testing of the novel RPH-104 drug using the Affinity Capture Elution (ACE) ELISA technique. RPH-104 is a promising Interleukin-1 (IL-1) inhibitor that is currently undergoing a series of clinical studies, including those on socially significant and orphan diseases. The developed method was validated for assay cut-point, sensitivity, selectivity, drug tolerance, hook effect, specificity, precision, and stability. Method sensitivity was established at 114.9 ng/mL, while low and high positive controls were equal to anti-RPH-104 antibody concentrations of 155 ng/mL and 2500 ng/mL, respectively. Method specificity was confirmed in the presence of the interfering compounds, namely IL-1α, IL-1β, and IL1-Ra. The developed and validated ELISA method was successfully applied to subject samples.
Potential Effects of Non-Surgical Periodontal Therapy on Periodontal Parameters, Inflammatory Markers, and Kidney Function Indicators in Chronic Kidney Disease Patients with Chronic Periodontitis
Authors: Chaudhry Ahmed , Kassim Nur Karyatee , Zainuddin Siti Lailatul Akmar , Taib Haslina , Ibrahim Hanim Afzan , Ahmad Basaruddin , Hanafi Muhammad Hafiz , Adnan Azreen Syazril
Published: October 2022

Chronic kidney disease (CKD) and chronic periodontitis (CP) contribute to the increased level of inflammatory biomarkers in the blood. This study hypothesized that successful periodontal treatment would reduce the level of inflammatory biomarkers in CKD patients. This prospective study recruited two groups of CP patients: 33 pre-dialysis CKD patients and 33 non-CKD patients. All patients underwent non-surgical periodontal therapy (NSPT). Their blood samples and periodontal parameters were taken before and after six weeks of NSPT. The serum level of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and periodontal parameters were compared between groups. On the other hand, kidney function indicators such as serum urea and estimated glomerular filtration rate (eGFR) were only measured in CKD patients. Clinical periodontal parameters and inflammatory markers levels at baseline were significantly higher (p < 0.05) in the CKD group than in the non-CKD group and showed significant reduction (p < 0.05) after six weeks of NSPT. CKD patients demonstrated a greater periodontitis severity and higher inflammatory burden than non-CKD patients. Additionally, CKD patients with CP showed a good response to NSPT. Therefore, CKD patients’ periodontal health needs to be screened for early dental interventions and monitored accordingly.
Structural Determinant of β-Amyloid Formation: From Transmembrane Protein Dimerization to β-Amyloid Aggregates
Authors: Papadopoulos Nicolas , Suelves Nuria , Perrin Florian , Vadukul Devkee M. , Vrancx Céline , Constantinescu Stefan N. , Kienlen-Campard Pascal
Published: October 2022

Most neurodegenerative diseases have the characteristics of protein folding disorders, i.e., they cause lesions to appear in vulnerable regions of the nervous system, corresponding to protein aggregates that progressively spread through the neuronal network as the symptoms progress. Alzheimer’s disease is one of these diseases. It is characterized by two types of lesions: neurofibrillary tangles (NFTs) composed of tau proteins and senile plaques, formed essentially of amyloid peptides (Aβ). A combination of factors ranging from genetic mutations to age-related changes in the cellular context converge in this disease to accelerate Aβ deposition. Over the last two decades, numerous studies have attempted to elucidate how structural determinants of its precursor (APP) modify Aβ production, and to understand the processes leading to the formation of different Aβ aggregates, e.g., fibrils and oligomers. The synthesis proposed in this review indicates that the same motifs can control APP function and Aβ production essentially by regulating membrane protein dimerization, and subsequently Aβ aggregation processes. The distinct properties of these motifs and the cellular context regulate the APP conformation to trigger the transition to the amyloid pathology. This concept is critical to better decipher the patterns switching APP protein conformation from physiological to pathological and improve our understanding of the mechanisms underpinning the formation of amyloid fibrils that devastate neuronal functions.
Obstructive Sleep Apnoea and Lipid Metabolism: The Summary of Evidence and Future Perspectives in the Pathophysiology of OSA-Associated Dyslipidaemia
Authors: Meszaros Martina , Bikov Andras
Published: October 2022

Obstructive sleep apnoea (OSA) is associated with cardiovascular and metabolic comorbidities, including hypertension, dyslipidaemia, insulin resistance and atherosclerosis. Strong evidence suggests that OSA is associated with an altered lipid profile including elevated levels of triglyceride-rich lipoproteins and decreased levels of high-density lipoprotein (HDL). Intermittent hypoxia; sleep fragmentation; and consequential surges in the sympathetic activity, enhanced oxidative stress and systemic inflammation are the postulated mechanisms leading to metabolic alterations in OSA. Although the exact mechanisms of OSA-associated dyslipidaemia have not been fully elucidated, three main points have been found to be impaired: activated lipolysis in the adipose tissue, decreased lipid clearance from the circulation and accelerated de novo lipid synthesis. This is further complicated by the oxidisation of atherogenic lipoproteins, adipose tissue dysfunction, hormonal changes, and the reduced function of HDL particles in OSA. In this comprehensive review, we summarise and critically evaluate the current evidence about the possible mechanisms involved in OSA-associated dyslipidaemia.
Genetic Variants of the TERT Gene and Telomere Length in Obstructive Sleep Apnea
Authors: Macek Piotr , Poreba Rafal , Gac Pawel , Bogunia-Kubik Katarzyna , Dratwa Marta , Wieckiewicz Mieszko , Wojakowska Anna , Michalek-Zrabkowska Monika , Mazur Grzegorz , Martynowicz Helena
Published: October 2022

Introduction: Obstructive sleep apnea (OSA) is a worldwide breathing disorder that has been diagnosed globally in almost 1 billion individuals aged 30–69 years. It is characterized by repeated upper airway collapses during sleep. Telomerase reverse transcriptase (TERT) is involved in the prevention of telomere shortening. This prospective, observational study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) of TERT and the severity of OSA, taking into account hypertension and diabetes prevalence. Methods: A total of 149 patients with OSA were diagnosed using one-night video-polysomnography based on the American Academy of Sleep Medicine guidelines. The TERT SNPs and telomere length (TL) were detected using real-time quantitative polymerase chain reaction. Results: Statistical analysis showed that there is no relationship between the rs2853669 and rs2736100 polymorphisms of TERT, and the severity of OSA (p > 0.05). Moreover, no relationship between TL and the severity of OSA was observed. The G allele in the locus of rs2736100 TERT was associated with hypertension prevalence and was more prevalent in hypertensives patients (46.00% vs. 24.49%, p = 0.011). The prevalence of hypertension was higher in patients with the C allele in the locus of rs2853669 than in patients without this allele (50.79% vs. 30.23%, p = 0.010). Moreover, a lower prevalence of diabetes was observed in homozygotes of rs2736100 TERT than in heterozygotes (5.63% vs. 15.38%, p = 0.039). Conclusion: This study showed no relationship between OSA and TERT SNPs. However, SNPs of the TERT gene (rs2736100 and rs2853669) were found to affect arterial hypertension and diabetes prevalence.
Biomimetic Research for Applications Addressing Technical Environmental Protection
Authors: Wommer Kirsten , Wanieck Kristina
Published: October 2022

Biomimetic research has increased over the last decades, and the development process has been systemized regarding its methods and tools. The aim of biomimetics is to solve practical problems of real-life scenarios. In this context, biomimetics can also address sustainability. To better understand how biomimetics research and development can achieve more sustainable solutions, five projects of applied research have been monitored and analyzed regarding biological models, abstracted biological principles, and the recognition of the applied efficiency strategies. In this manuscript, the way in which sustainability can be addressed is described, possibly serving as inspiration for other projects and topics. The results indicate that sustainability needs to be considered from the very beginning in biomimetic projects, and it can remain a focus during various phases of the development process.