bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurobiological Highlights of Cognitive Impairment in Psychiatric Disorders
Authors: Morozova Anna , Zorkina Yana , Abramova Olga , Pavlova Olga , Pavlov Konstantin , Soloveva Kristina , Volkova Maria , Alekseeva Polina , Andryshchenko Alisa , Kostyuk Georgiy , Gurina Olga , Chekhonin Vladimir
Published: January 2022

This review is focused on several psychiatric disorders in which cognitive impairment is a major component of the disease, influencing life quality. There are plenty of data proving that cognitive impairment accompanies and even underlies some psychiatric disorders. In addition, sources provide information on the biological background of cognitive problems associated with mental illness. This scientific review aims to summarize the current knowledge about neurobiological mechanisms of cognitive impairment in people with schizophrenia, depression, mild cognitive impairment and dementia (including Alzheimer’s disease).The review provides data about the prevalence of cognitive impairment in people with mental illness and associated biological markers.
A Review of Sensors and Biosensors Modified with Conducting Polymers and Molecularly Imprinted Polymers Used in Electrochemical Detection of Amino Acids: Phenylalanine, Tyrosine, and Tryptophan
Authors: Dinu Ancuța , Apetrei Constantin
Published: January 2022

Recently, the studies on developing sensors and biosensors—with an obvious interdisciplinary character—have drawn the attention of many researchers specializing in various fundamental, but also complex domains such as chemistry, biochemistry, physics, biophysics, biology, bio-pharma-medicine, and bioengineering. Along these lines, the present paper is structured into three parts, and is aimed at synthesizing the most relevant studies on the construction and functioning of versatile devices, of electrochemical sensors and biosensors, respectively. The first part presents examples of the most representative scientific research focusing on the role and the importance of the phenylalanine, tyrosine, and tryptophan amino acids, selected depending on their chemical structure and their impact on the central nervous system. The second part is dedicated to presenting and exemplifying conductor polymers and molecularly imprinted polymers used as sensitive materials in achieving electrochemical sensors and biosensors. The last part of the review analyzes the sensors and biosensors developed so far to detect amino acids with the aid of conductor polymers and molecularly imprinted polymers from the point of view of the performances obtained, with emphasis on the detection methods, on the electrochemical reactions that take place upon detection, and on the electroanalytical performances. The present study was carried out with a view to highlighting, for the benefit of specialists in medicine and pharmacy, the possibility of achieving and purchasing efficient devices that might be used in the quality control of medicines, as well as in studying and monitoring diseases associated with these amino acids.
Deep Resequencing of 9 Candidate Genes Identifies a Role for ARAP1 and IGF2BP2 in Modulating Insulin Secretion Adjusted for Insulin Resistance in Obese Southern Europeans
Authors: Bailetti Diego , Sentinelli Federica , Prudente Sabrina , Cimini Flavia Agata , Barchetta Ilaria , Totaro Maria , Di Costanzo Alessia , Barbonetti Arcangelo , Leonetti Frida , Cavallo Maria Gisella , Baroni Marco Giorgio
Published: January 2022

Type 2 diabetes is characterized by impairment in insulin secretion, with an established genetic contribution. We aimed to evaluate common and low-frequency (1–5%) variants in nine genes strongly associated with insulin secretion by targeted sequencing in subjects selected from the extremes of insulin release measured by the disposition index. Collapsing data by gene and/or function, the association between disposition index and nonsense variants were significant, also after adjustment for confounding factors (OR = 0.25, 95% CI = 0.11–0.59, p = 0.001). Evaluating variants individually, three novel variants in ARAP1, IGF2BP2 and GCK, out of eight reaching significance singularly, remained associated after adjustment. Constructing a genetic risk model combining the effects of the three variants, only carriers of the ARAP1 and IGF2BP2 variants were significantly associated with a reduced probability to be in the lower, worst, extreme of insulin secretion (OR = 0.223, 95% CI = 0.105–0.473, p < 0.001). Observing a high number of normal glucose tolerance between carriers, a regression posthoc analysis was performed. Carriers of genetic risk model variants had higher probability to be normoglycemic, also after adjustment (OR = 2.411, 95% CI = 1.136–5.116, p = 0.022). Thus, in our southern European cohort, nonsense variants in all nine candidate genes showed association with better insulin secretion adjusted for insulin resistance, and we established the role of ARAP1 and IGF2BP2 in modulating insulin secretion.
Thyroid Hormone Receptor α Controls the Hind Limb Metamorphosis by Regulating Cell Proliferation and Wnt Signaling Pathways in Xenopus tropicalis
Authors: Tanizaki Yuta , Shibata Yuki , Zhang Hongen , Shi Yun-Bo
Published: January 2022

Thyroid hormone (T3) receptors (TRs) mediate T3 effects on vertebrate development. We have studied Xenopus tropicalis metamorphosis as a model for postembryonic human development and demonstrated that TRα knockout induces precocious hind limb development. To reveal the molecular pathways regulated by TRα during limb development, we performed chromatin immunoprecipitation- and RNA-sequencing on the hind limb of premetamorphic wild type and TRα knockout tadpoles, and identified over 700 TR-bound genes upregulated by T3 treatment in wild type but not TRα knockout tadpoles. Interestingly, most of these genes were expressed at higher levels in the hind limb of premetamorphic TRα knockout tadpoles than stage-matched wild-type tadpoles, suggesting their derepression upon TRα knockout. Bioinformatic analyses revealed that these genes were highly enriched with cell cycle and Wingless/Integrated (Wnt) signaling-related genes. Furthermore, cell cycle and Wnt signaling pathways were also highly enriched among genes bound by TR in wild type but not TRα knockout hind limb. These findings suggest that direct binding of TRα to target genes related to cell cycle and Wnt pathways is important for limb development: first preventing precocious hind limb formation by repressing these pathways as unliganded TR before metamorphosis and later promoting hind limb development during metamorphosis by mediating T3 activation of these pathways.
Protein Modification with Ribose Generates Nδ-(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine
Authors: Ban Ikuho , Sugawa Hikari , Nagai Ryoji
Published: January 2022

Advanced glycation end products (AGEs) are associated with diabetes and its complications. AGEs are formed by the non-enzymatic reactions of proteins and reducing sugars, such as glucose and ribose. Ribose is widely used in glycation research as it generates AGEs more rapidly than glucose. This study analyzed the AGE structures generated from ribose-modified protein by liquid chromatography–quadrupole time-of-flight mass spectrometry. Among these AGEs, Nδ-(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine (MG-H1) was the most abundant in ribose-glycated bovine serum albumin (ribated-BSA) among others, such as Nε-(carboxymethyl) lysine, Nε-(carboxyethyl) lysine, and Nω-(carboxymethyl) arginine. Surprisingly, MG-H1 was produced by ribated-BSA in a time-dependent manner, whereas methylglyoxal levels (MG) were under the detectable level. In addition, Trapa bispinosa Roxb. hot water extract (TBE) possesses several anti-oxidative compounds, such as ellagic acid, and has been reported to inhibit the formation of MG-H1 in vivo. Thus, we evaluated the inhibitory effects of TBE on MG-H1 formation using ribose- or MG-modified proteins. TBE inhibited MG-H1 formation in gelatin incubated with ribose and ribated-BSA, but not in MG-modified gelatin. Furthermore, MG-H1 formation was inhibited by diethylenetriaminepentaacetic acid. These results demonstrated that ribose reacts with proteins to generate Amadori compounds and form MG-H1 via oxidation.
Effect of Porcine Whole Blood Protein Hydrolysate on Slow-Twitch Muscle Fiber Expression and Mitochondrial Biogenesis via the AMPK/SIRT1 Pathway
Authors: Jin Sun Woo , Lee Gi Ho , Kim Ji Yeon , Kim Chae Yeon , Choo Young Moo , Cho Whajung , Han Eun Hee , Hwang Yong Pil , Kim Yong An , Jeong Hye Gwang
Published: January 2022

Skeletal muscle is a heterogeneous tissue composed of a variety of functionally different fiber types. Slow-twitch type I muscle fibers are rich with mitochondria, and mitochondrial biogenesis promotes a shift towards more slow fibers. Leucine, a branched-chain amino acid (BCAA), regulates slow-twitch muscle fiber expression and mitochondrial function. The BCAA content is increased in porcine whole-blood protein hydrolysates (PWBPH) but the effect of PWBPH on muscle fiber type conversion is unknown. Supplementation with PWBPH (250 and 500 mg/kg for 5 weeks) increased time to exhaustion in the forced swimming test and the mass of the quadriceps femoris muscle but decreased the levels of blood markers of exercise-induced fatigue. PWBPH also promoted fast-twitch to slow-twitch muscle fiber conversion, elevated the levels of mitochondrial biogenesis markers (SIRT1, p-AMPK, PGC-1α, NRF1 and TFAM) and increased succinate dehydrogenase and malate dehydrogenase activities in ICR mice. Similarly, PWBPH induced markers of slow-twitch muscle fibers and mitochondrial biogenesis in C2C12 myotubes. Moreover, AMPK and SIRT1 inhibition blocked the PWBPH-induced muscle fiber type conversion in C2C12 myotubes. These results indicate that PWBPH enhances exercise performance by promoting slow-twitch muscle fiber expression and mitochondrial function via the AMPK/SIRT1 signaling pathway.
Increased Risky Choice and Reduced CHRNB2 Expression in Adult Male Rats Exposed to Nicotine Vapor
Authors: Giner Priscilla , Maynez-Anchondo Liliana , Liley Anna E. , Uribe Kevin P. , Frietze Gabriel A. , Simon Nicholas W. , Mendez Ian A.
Published: January 2022

While the cognitive enhancing effects of nicotine use have been well documented, it has also been shown to impair decision making. The goal of this study was to determine if exposure to nicotine vapor increases risky decision making. The study also aims to investigate possible long-term effects of nicotine vapor exposure on the expression of genes coding for cholinergic and dopaminergic receptors in brain. Thirty-two adult male Sprague Dawley rats were exposed to 24 mg/mL nicotine vapor or vehicle control, immediately followed by testing in the probability discounting task for 10 consecutive days. Fifty-four days after the 10-day vapor exposure, animals were sacrificed and expression of genes coding for the α4 and β2 cholinergic receptor subunits, and dopamine D1 and D2 receptors, were analyzed using RT-PCR. Exposure to nicotine vapor caused an immediate and transient increase in risky choice. Analyses of gene expression identified significant reductions in CHRNB2 and DRD1 in the nucleus accumbens core and CHRNB2 and DRD2 in the medial prefrontal cortex of rats previously exposed to nicotine vapor, relative to vehicle controls. Results provide data on the negative cognitive effects of nicotine vapor exposure and identify cholinergic and dopaminergic mechanisms that may affected with repeated use.
Prion Protein: The Molecule of Many Forms and Faces
Authors: Kovač Valerija , Čurin Šerbec Vladka
Published: January 2022

Cellular prion protein (PrPC) is a glycosylphosphatidylinositol (GPI)-anchored protein most abundantly found in the outer membrane of neurons. Due to structural characteristics (a flexible tail and structured core), PrPC interacts with a wide range of partners. Although PrPC has been proposed to be involved in many physiological functions, only peripheral nerve myelination homeostasis has been confirmed as a bona fide function thus far. PrPC misfolding causes prion diseases and PrPC has been shown to mediate β-rich oligomer-induced neurotoxicity in Alzheimer’s and Parkinson’s disease as well as neuroprotection in ischemia. Upon proteolytic cleavage, PrPC is transformed into released and attached forms of PrP that can, depending on the contained structural characteristics of PrPC, display protective or toxic properties. In this review, we will outline prion protein and prion protein fragment properties as well as overview their involvement with interacting partners and signal pathways in myelination, neuroprotection and neurodegenerative diseases.
Fetal Undernutrition Modifies Vascular RAS Balance Enhancing Oxidative Damage and Contributing to Remodeling
Authors: Vieira-Rocha Maria Sofia , Rodriguez-Rodriguez Pilar , Ferreira-Duarte Mariana , Faria Miguel , Sousa Joana Beatriz , Morato Manuela , Arribas Silvia Magdalena , Diniz Carmen
Published: January 2022

Fetal stress is known to increase susceptibility to cardiometabolic diseases and hypertension in adult age in a process known as fetal programming. This study investigated the relationship between vascular RAS, oxidative damage and remodeling in fetal programming. Six-month old Sprague-Dawley offspring from mothers that were fed ad libitum (CONTROL) or with 50% intake during the second half of gestation (maternal undernutrition, MUN) were used. qPCR or immunohistochemistry were used to obtain the expression of receptors and enzymes. Plasma levels of carbonyls were measured by spectrophotometry. In mesenteric arteries from MUN rats we detected an upregulation of ACE, ACE2, AT1 receptors and NADPH oxidase, and lower expression of AT2, Mas and MrgD receptors compared to CONTROL. Systolic and diastolic blood pressure and plasma levels of carbonyls were higher in MUN than in CONTROL. Vascular morphology evidenced an increased media/lumen ratio and adventitia/lumen ratio, and more connective tissue in MUN compared to CONTROL. In conclusion, fetal undernutrition indices RAS alterations and oxidative damage which may contribute to the remodeling of mesenteric arteries, and increase the risk of adverse cardiovascular events and hypertension.
An Insight into miR-1290: An Oncogenic miRNA with Diagnostic Potential
Authors: Guz Małgorzata , Jeleniewicz Witold , Cybulski Marek
Published: January 2022

For more than two decades, the view of the roles of non-coding RNAs (ncRNAs) has been radically changing. These RNA molecules that are transcribed from our genome do not have the capacity to encode proteins, but are critical regulators of gene expression at different levels. Our knowledge is constantly enriched by new reports revealing the role of these new molecular players in the development of many pathological conditions, including cancer. One of the ncRNA classes includes short RNA molecules called microRNAs (miRNAs), which are involved in the post-transcriptional control of gene expression affecting various cellular processes. The aberrant expression of miRNAs with oncogenic and tumor-suppressive function is associated with cancer initiation, promotion, malignant transformation, progression and metastasis. Oncogenic miRNAs, also known as oncomirs, mediate the downregulation of tumor-suppressor genes and their expression is upregulated in cancer. Nowadays, miRNAs show promising application in diagnosis, prediction, disease monitoring and therapy response. Our review presents a current view of the oncogenic role of miR-1290 with emphasis on its properties as a cancer biomarker in clinical medicine.
Transcription Factor RrANT1 of Rosa rugosa Positively Regulates Flower Organ Size in Petunia hybrida
Authors: Xu Yong , Xing Yongxiang , Wei Tiantian , Wang Pengqing , Liang Yue , Xu Mengmeng , Ding Haiquan , Wang Jianwen , Feng Liguo
Published: January 2022

The flower is the main organ that produces essential oils in many plants. The yield of raw flowers and the number of secretory epidermal cells are the main factors for essential oil production. The cultivated rose species “Pingyin 1” in China was used to study the effect of RrANT1 on floral organ development. Eighteen AP2 transcription factors with dual AP2 domains were identified from Rosa rugosa genome. RrANT1 belonged to euANT. The subcellular localization results showed that RrANT1 protein is localized in the nucleus. The relative expression level of RrANT1 in the receptacle is higher than that in petals in the developmental stages, and both decreased from the initial phase to senescence. Compared with the RrANT1 expression level in petals in the blooming stage, RrANT1 expression level was significant in petals (~48.8) and highest in the receptacle (~102.5) in the large bud stage. It was only highly expressed in the receptacle (~39.4) in the blooming period. RrANT1 overexpression significantly increased petunia flower and leaf sizes (~1.2), as well as flower fresh weight (~30%). The total number of epidermis cells in the petals of overexpressing plants significantly increased (>40%). This study concluded that RrANT1 overexpression can increase the size and weight of flowers by promoting cell proliferation, providing a basis for creating new rose germplasm to increase rose and essential oil yield.
Protective Role of Melatonin and Its Metabolites in Skin Aging
Authors: Bocheva Georgeta , Slominski Radomir M. , Janjetovic Zorica , Kim Tae-Kang , Böhm Markus , Steinbrink Kerstin , Reiter Russel J. , Kleszczyński Konrad , Slominski Andrzej T.
Published: January 2022

The skin, being the largest organ in the human body, is exposed to the environment and suffers from both intrinsic and extrinsic aging factors. The skin aging process is characterized by several clinical features such as wrinkling, loss of elasticity, and rough-textured appearance. This complex process is accompanied with phenotypic and functional changes in cutaneous and immune cells, as well as structural and functional disturbances in extracellular matrix components such as collagens and elastin. Because skin health is considered one of the principal factors representing overall “well-being” and the perception of “health” in humans, several anti-aging strategies have recently been developed. Thus, while the fundamental mechanisms regarding skin aging are known, new substances should be considered for introduction into dermatological treatments. Herein, we describe melatonin and its metabolites as potential “aging neutralizers”. Melatonin, an evolutionarily ancient derivative of serotonin with hormonal properties, is the main neuroendocrine secretory product of the pineal gland. It regulates circadian rhythmicity and also exerts anti-oxidative, anti-inflammatory, immunomodulatory, and anti-tumor capacities. The intention of this review is to summarize changes within skin aging, research advances on the molecular mechanisms leading to these changes, and the impact of the melatoninergic anti-oxidative system controlled by melatonin and its metabolites, targeting the prevention or reversal of skin aging.
Dehydrogenation of Betacyanins in Heated Betalain-Rich Extracts of Red Beet (Beta vulgaris L.)
Authors: Sutor-Świeży Katarzyna , Antonik Michał , Proszek Justyna , Nemzer Boris , Pietrzkowski Zbigniew , Popenda Łukasz , Świergosz Tomasz , Wybraniec Sławomir
Published: January 2022

Betacyanins are a group of water-soluble red-violet compounds containing nitrogen in their structure. These are biosynthesized in red beetroot (Beta vulgaris L.), a widely consumed vegetable that contains significant amounts of nutritious and bioactive compounds which are also found in dietary supplements. This contribution presents results of betacyanin thermal oxidation (resulting in dehydrogenation) interrelated with decarboxylation in selected acetate/phosphate buffers at pH 3–8 and at 85 °C, which may be of particular significance for formulation and performance of foods. Most of the reaction products were detected at the highest concentrations in the acidic solutions (pH 3–4). The main dehydrogenation reaction pathways were monitored by LC-DAD-MS/MS and were associated with decarboxylation of the principal extract pigments, betanin/isobetanin and neobetanin, at carbon positions C-2 and C-17. Additional reactions are accompanied by the 2,15-decarboxylation processes at different dehydrogenation levels with 15-decarboxy-betanin and 2,15-bidecarboxy-betanin, structurally elucidated by NMR analysis, as the distinct indicators of this route type. For other novel pigments detected, 2,15-bidecarboxy-xanbetanin, 2,15-bidecarboxy-xanneobetanin and 2,15,17-tridecarboxy-neobetanin, additional high resolution mass spectrometric analyses were performed and confirmed their molecular formulas.
Chitosan/Alginate Hydrogel Dressing Loaded FGF/VE-Cadherin to Accelerate Full-Thickness Skin Regeneration and More Normal Skin Repairs
Authors: Wei Lai , Tan Jianying , Li Li , Wang Huanran , Liu Sainan , Chen Junying , Weng Yajun , Liu Tao
Published: January 2022

The process of full-thickness skin regeneration is complex and has many parameters involved, which makes it difficult to use a single dressing to meet the various requirements of the complete regeneration at the same time. Therefore, developing hydrogel dressings with multifunction, including tunable rheological properties and aperture, hemostatic, antibacterial and super cytocompatibility, is a desirable candidate in wound healing. In this study, a series of complex hydrogels were developed via the hydrogen bond and covalent bond between chitosan (CS) and alginate (SA). These hydrogels exhibited suitable pore size and tunable rheological properties for cell adhesion. Chitosan endowed hemostatic, antibacterial properties and great cytocompatibility and thus solved two primary problems in the early stage of the wound healing process. Moreover, the sustained cytocompatibility of the hydrogels was further investigated after adding FGF and VE-cadherin via the co-culture of L929 and EC for 12 days. The confocal 3D fluorescent images showed that the cells were spherical and tended to form multicellular spheroids, which distributed in about 40–60 μm thick hydrogels. Furthermore, the hydrogel dressings significantly accelerate defected skin turn to normal skin with proper epithelial thickness and new blood vessels and hair follicles through the histological analysis of in vivo wound healing. The findings mentioned above demonstrated that the CS/SA hydrogels with growth factors have great potential as multifunctional hydrogel dressings for full-thickness skin regeneration incorporated with hemostatic, antibacterial, sustained cytocompatibility for 3D cell culture and normal skin repairing.
Triptolide Suppresses NF-κB-Mediated Inflammatory Responses and Activates Expression of Nrf2-Mediated Antioxidant Genes to Alleviate Caerulein-Induced Acute Pancreatitis
Authors: Yang Jing , Tang Xujiao , Ke Xue , Dai Yutong , Shi Jinsong
Published: January 2022

Triptolide (TP), the main active ingredient of Tripterygium wilfordii Hook.f., displays potent anti-inflammatory, antioxidant, and antiproliferative activities. In the present study, the effect of TP on acute pancreatitis and the underlying mechanisms of the disease were investigated using a caerulein-induced animal model of acute pancreatitis (AP) and an in vitro cell model. In vivo, pretreatment with TP notably ameliorated pancreatic damage, shown as the improvement in serum amylase and lipase levels and pancreatic morphology. Meanwhile, TP modulated the infiltration of neutrophils and macrophages (Ly6G staining and CD68 staining) and decreased the levels of proinflammatory factors (TNF-α and IL-6) through inhibiting the transactivation of nuclear factor-κB (NF-κB) in caerulein-treated mice. Furthermore, TP reverted changes in oxidative stress markers, including pancreatic glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA), in acute pancreatitis mice. Additionally, TP pretreatment inhibited intracellular reactive oxygen species (ROS) levels via upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and Nrf2-regulated redox genes expression (HO-1, SOD1, GPx1 and NQO1) in vitro. Taken together, our data suggest that TP exert protection against pancreatic inflammation and tissue damage by inhibiting NF-κB transactivation, modulating immune cell responses and activating the Nrf2-mediated antioxidative system, thereby alleviating acute pancreatitis.
The Role of Sphingolipid Signaling in Oxidative Lung Injury and Pathogenesis of Bronchopulmonary Dysplasia
Authors: Thomas Jaya M. , Sudhadevi Tara , Basa Prathima , Ha Alison W. , Natarajan Viswanathan , Harijith Anantha
Published: January 2022

Premature infants are born with developing lungs burdened by surfactant deficiency and a dearth of antioxidant defense systems. Survival rate of such infants has significantly improved due to advances in care involving mechanical ventilation and oxygen supplementation. However, a significant subset of such survivors develops the chronic lung disease, Bronchopulmonary dysplasia (BPD), characterized by enlarged, simplified alveoli and deformed airways. Among a host of factors contributing to the pathogenesis is oxidative damage induced by exposure of the developing lungs to hyperoxia. Recent data indicate that hyperoxia induces aberrant sphingolipid signaling, leading to mitochondrial dysfunction and abnormal reactive oxygen species (ROS) formation (ROS). The role of sphingolipids such as ceramides and sphingosine 1-phosphate (S1P), in the development of BPD emerged in the last decade. Both ceramide and S1P are elevated in tracheal aspirates of premature infants of <32 weeks gestational age developing BPD. This was faithfully reflected in the murine models of hyperoxia and BPD, where there is an increased expression of sphingolipid metabolites both in lung tissue and bronchoalveolar lavage. Treatment of neonatal pups with a sphingosine kinase1 specific inhibitor, PF543, resulted in protection against BPD as neonates, accompanied by improved lung function and reduced airway remodeling as adults. This was accompanied by reduced mitochondrial ROS formation. S1P receptor1 induced by hyperoxia also aggravates BPD, revealing another potential druggable target in this pathway for BPD. In this review we aim to provide a detailed description on the role played by sphingolipid signaling in hyperoxia induced lung injury and BPD.
The Pathomechanism, Antioxidant Biomarkers, and Treatment of Oxidative Stress-Related Eye Diseases
Authors: Hsueh Yi-Jen , Chen Yen-Ning , Tsao Yu-Ting , Cheng Chao-Min , Wu Wei-Chi , Chen Hung-Chi
Published: January 2022

Oxidative stress is an important pathomechanism found in numerous ocular degenerative diseases. To provide a better understanding of the mechanism and treatment of oxidant/antioxidant imbalance-induced ocular diseases, this article summarizes and provides updates on the relevant research. We review the oxidative damage (e.g., lipid peroxidation, DNA lesions, autophagy, and apoptosis) that occurs in different areas of the eye (e.g., cornea, anterior chamber, lens, retina, and optic nerve). We then introduce the antioxidant mechanisms present in the eye, as well as the ocular diseases that occur as a result of antioxidant imbalances (e.g., keratoconus, cataracts, age-related macular degeneration, and glaucoma), the relevant antioxidant biomarkers, and the potential of predictive diagnostics. Finally, we discuss natural antioxidant therapies for oxidative stress-related ocular diseases.
The Potential Role of Spermine and Its Acetylated Derivative in Human Malignancies
Authors: Tse Ryan Tsz-Hei , Wong Christine Yim-Ping , Chiu Peter Ka-Fung , Ng Chi-Fai
Published: January 2022

Polyamines are essential biomolecules for normal cellular metabolism in humans. The roles of polyamines in cancer development have been widely discussed in recent years. Among all, spermine alongside with its acetylated derivative, N1, N12-Diacetylspermine, demonstrate a relationship with the diagnosis and staging of various cancers, including lung, breast, liver, colorectal and urogenital. Numerous studies have reported the level of spermine in different body fluids and organ tissues in patients with different types of cancers. Currently, the role and the underlying mechanisms of spermine in cancer development and progression are still under investigation. This review summarized the roles of spermine in cancer development and as a diagnostic, prognostic and therapeutic tool in various cancers.
9-Aminoacridine Inhibits Ribosome Biogenesis by Targeting Both Transcription and Processing of Ribosomal RNA
Authors: Anikin Leonid , Pestov Dimitri G.
Published: January 2022

Aminoacridines, used for decades as antiseptic and antiparasitic agents, are prospective candidates for therapeutic repurposing and new drug development. Although the mechanisms behind their biological effects are not fully elucidated, they are most often attributed to the acridines’ ability to intercalate into DNA. Here, we characterized the effects of 9-aminoacridine (9AA) on pre-rRNA metabolism in cultured mammalian cells. Our results demonstrate that 9AA inhibits both transcription of the ribosomal RNA precursors (pre-rRNA) and processing of the already synthesized pre-rRNAs, thereby rapidly abolishing ribosome biogenesis. Using a fluorescent intercalator displacement assay, we further show that 9AA can bind to RNA in vitro, which likely contributes to its ability to inhibit post-transcriptional steps in pre-rRNA maturation. These findings extend the arsenal of small-molecule compounds that can be used to block ribosome biogenesis in mammalian cells and have implications for the pharmacological development of new ribosome biogenesis inhibitors.
Identification and Characterization of a Mutant PV-PUR Gene Responsible for the Purple Phenotype of Snap Bean (Phaseolus vulgaris L.)
Authors: Liu Chang , Yang Xiaoxu , Yan Zhishan , Liu Dajun , Feng Guojun
Published: January 2022

Pod color is a major economic trait of snap beans (Phaseolus vulgaris L.), among which the pod with a purple stripe is more attractive to people. A stable purple mutant with purple stripes on the pods was obtained by artificial mutagenesis with the high generation snap bean inbred line ‘A18-1’. In order to reveal the genetic factors and pathways responsible for the purple appearance in snap bean, we performed transcriptome and metabolome analyses using the green stem and yellow pod cultivar ‘A18-1’ and its purple mutant ‘pv-pur’ via 60Co-γ radiation. Transcriptome analysis showed that three genes in the anthocyanin biosynthetic pathway were differentially expressed, among which the expression level of F3′5′H (Phvul.006G018800) was increased in the mutant ‘pv-pur’, while expression of F3′H (Phvul.004G021200) and ANS (Phvul.002G152700) was downregulated. Anthocyanin-targeted metabonomics analysis showed significant differences in the contents of 10 metabolites between the wild type and mutant plants. Combined analysis of transcriptome and metabolomics showed that one differential metabolite, delphinidin, was related to the differential expression of Phvul.006G024700, Phvul.002G152700, and Phvul.006G018800. Based on the levels of six anthocyanins in wild type and mutant plants, we speculative that the purple appearance of the mutant ‘pv-pur’ is caused by the increased expression of F3′5′H (Phvul.006G018800), the key enzyme in the transformation from dihydroflavanol (DHK) to dihydromyricetone (DHM) in the anthocyanin biosynthetic pathway. The results lay a foundation for further studies on the molecular mechanism of anthocyanin synthesis in snap bean, and provide a framework for breeding different colors of snap bean.
Epigenomic and Transcriptomic Prioritization of Candidate Obesity-Risk Regulatory GWAS SNPs
Authors: Zhang Xiao , Li Tian-Ying , Xiao Hong-Mei , Ehrlich Kenneth C. , Shen Hui , Deng Hong-Wen , Ehrlich Melanie
Published: January 2022

Concern about rising rates of obesity has prompted searches for obesity-related single nucleotide polymorphisms (SNPs) in genome-wide association studies (GWAS). Identifying plausible regulatory SNPs is very difficult partially because of linkage disequilibrium. We used an unusual epigenomic and transcriptomic analysis of obesity GWAS-derived SNPs in adipose versus heterologous tissues. From 50 GWAS and 121,064 expanded SNPs, we prioritized 47 potential causal regulatory SNPs (Tier-1 SNPs) for 14 gene loci. A detailed examination of seven loci revealed that four (CABLES1, PC, PEMT, and FAM13A) had Tier-1 SNPs positioned so that they could regulate use of alternative transcription start sites, resulting in different polypeptides being generated or different amounts of an intronic microRNA gene being expressed. HOXA11 and long noncoding RNA gene RP11-392O17.1 had Tier-1 SNPs in their 3′ or promoter region, respectively, and strong preferences for expression in subcutaneous versus visceral adipose tissue. ZBED3-AS1 had two intragenic Tier-1 SNPs, each of which could contribute to mediating obesity risk through modulating long-distance chromatin interactions. Our approach not only revealed especially credible novel regulatory SNPs, but also helped evaluate previously highlighted obesity GWAS SNPs that were candidates for transcription regulation.
Evaluation of Two Methods for Quantification of Glycosaminoglycan Biomarkers in Newborn Dried Blood Spots from Patients with Severe and Attenuated Mucopolysaccharidosis Type II
Authors: Herbst Zackary M. , Urdaneta Leslie , Klein Terri , Burton Barbara K. , Basheeruddin Khaja , Liao Hsuan-Chieh , Fuller Maria , Gelb Michael H.
Published: January 2022

All newborn screening (NBS) for mucopolysaccharidosis-I and -II (MPS-I and MPS-II) is carried out via the measurement of α-iduronidase (IDUA) and iduronate-2-sulfatase (IDS) enzymatic activity, respectively, in dried blood spots (DBS). The majority of low enzyme results are due to pseudodeficiencies, and data from recent MPS-II population screenings and studies from the Mayo Clinic show that the false positive rate can be dramatically reduced by the inclusion of a second-tier analysis of glycosaminoglycans (GAGs) in DBS as part of NBS. In the present study, which focused on MPS-II, we obtained newborn DBS from 17 patients with severe MPS-II, 1 with attenuated MPS-II, and 6 patients with various IDS pseudodeficiencies. These samples were submitted to two different GAG mass spectrometry analyses in a comparative study: (1) internal disaccharide biomarkers and (2) endogenous biomarkers. For both of these methods, the biomarker levels in six patients with pseudodeficiencies were below the range measured in MPS-II patients. One patient with attenuated MPS-II was not distinguishable from severe disease patients, but all MPS-II patients were distinguishable from the reference range using both methods. The minimal differential factor (lowest GAG marker level in MPS-II samples divided by highest level in the reference range of 60 random newborns) was 3.01-fold for the internal disaccharide method. The endogenous biomarker method demonstrated an improved minimum differential of 5.41-fold. The minimum differential factors between MPS-II patients and patients with pseudodeficiencies for the internal disaccharide and endogenous biomarker methods were 3.77-fold and 2.06-fold, respectively. This study supports use of the second-tier GAG analysis of newborn DBS, especially the endogenous disaccharide method, as part of NBS to reduce the false positive rate.
AR-Sanad 280K: A Novel 280K Artificial Sanads Dataset for Hadith Narrator Disambiguation
Authors: Mahmoud Somaia , Saif Omar , Nabil Emad , Abdeen Mohammad , ElNainay Mustafa , Torki Marwan
Published: January 2022

Determining hadith authenticity is vitally important in the Islamic religion because hadiths record the sayings and actions of Prophet Muhammad (PBUH), and they are the second source of Islamic teachings following the Quran. When authenticating a hadith, the reliability of the hadith narrators is a big factor that hadith scholars consider. However, many narrators share similar names, and the narrators’ full names are not usually included in the narration chains of hadiths. Thus, first, ambiguous narrators need to be identified. Then, their reliability level can be determined. There are no available datasets that could help address this problem of identifying narrators. Here, we present a new dataset that contains narration chains (sanads) with identified narrators. The AR-Sanad 280K dataset has around 280K artificial sanads and could be used to identify 18,298 narrators. After creating the AR-Sanad 280K dataset, we address the narrator disambiguation in several experimental setups. The hadith narrator disambiguation is modeled as a multiclass classification problem with 18,298 class labels. We test different representations and models in our experiments. The best results were achieved by finetuning BERT-Based deep learning model (AraBERT). We obtained a 92.9 Micro F1 score and 30.2 sanad error rate (SER) on the validation set of our artificial sanads AR-Sanad 280K dataset. Furthermore, we extracted a real test set from the sanads of the famous six books in Islamic hadith. We evaluated the best model on the real test data, and we achieved 83.5 Micro F1 score and 60.6 sanad error rate.
Sustained Improvements in Antimicrobial Therapy and Clinical Outcomes following a Pharmacist-Led Antimicrobial Stewardship Intervention: Uncontrolled Before–After Study
Authors: Uda Atsushi , Ebisawa Kei , Sakon Hitomi , Kusuki Mari , Izuta Rie , Yahata Mariko , Yano Ikuko , Miyara Takayuki
Published: January 2022

Our antimicrobial pharmacist-led intervention included: (a) a structured review of antibiotic prescriptions; (b) educating prescribers on antimicrobial therapy; (c) monthly reporting of department-level rates of blood sampling for culture. Daily review began in May 2018 and was discontinued after 10 months; however, the other interventions were conducted throughout the study period. This study aimed to evaluate the sustained impact of pharmacist’s interventions on antimicrobial therapy and clinical outcomes between the baseline (May–December 2017), intervention (May–December 2018), and post-intervention (May–December 2019) periods. The rate of blood culture collections before starting antipseudomonal agent therapy was significantly increased from the baseline to post-intervention periods (71% vs. 85%, p < 0.001). Antipseudomonal agent therapy was more frequently de-escalated in the post-intervention period than in the baseline period (73% vs. 54%, p = 0.038). Total use of antipseudomonal agents was reduced from the baseline to intervention periods and persisted during the post-intervention period (50.5 vs. 41.8 and 42.6 DDD per 1000 patient-days, p = 0.016 and p = 0.022, respectively). During the study period, there were significant reductions in the incidence of hospital-acquired Clostridioides difficile infection (1.12, 0.54, and 0.51 per 10,000 patient-days, respectively, p = 0.031) and 30-day mortality with bacteremia (19%, 18%, and 12%, respectively, p = 0.005). Our pharmacist-led interventions sustainably achieved appropriate antimicrobial therapy and improved clinical outcomes.
Monte Carlo Characterization of the Trimage Brain PET System
Authors: Masturzo Luigi , Carra Pietro , Erba Paola Anna , Morrocchi Matteo , Pilleri Alessandro , Sportelli Giancarlo , Belcari Nicola
Published: January 2022

The TRIMAGE project aims to develop a brain-dedicated PET/MR/EEG (Positron Emission Tomography/Magnetic Resonance/Electroencephalogram) system that is able to perform simultaneous PET, MR and EEG acquisitions. The PET component consists of a full ring with 18 sectors. Each sector includes three square detector modules based on dual sstaggered LYSO:Ce matrices read out by SiPMs. Using Monte Carlo simulations and following NEMA (National Electrical Manufacturers Association) guidelines, image quality procedures have been applied to evaluate the performance of the PET component of the system. The performance are reported in terms of spatial resolution, uniformity, recovery coefficient, spill over ratio, noise equivalent count rate (NECR) and scatter fraction. The results show that the TRIMAGE system is at the top of the current brain PET technologies.
An Intergenerational Issue: The Equity Issues Due to Public–Private Partnerships; The Critical Aspect of the Social Discount Rate Choice for Future Generations
Authors: Al Yaqoobi Abeer , Ausloos Marcel
Published: January 2022

This paper investigates the impact of Social Discount Rate (SDR) choice on intergenerational equity issues caused by Public–Private Partnerships (PPPs) projects. Indeed, more PPPs mean more debt being accumulated for future generations leading to a fiscal deficit crisis. The paper draws on how the SDR level taken today distributes societies on the Social Welfare Function (SWF). This is done by answering two sub-questions: (i) What is the risk of PPPs’ debts being off-balance sheet? (ii) How do public policies, based on the envisaged SDR, position society within different ethical perspectives? The answers are obtained from a discussion of the different SDRs (applied in the UK for examples) according to the merits of the pertinent ethical theories, namely libertarian, egalitarian, utilitarian and Rawlsian. We find that public policymakers can manipulate the SDR to make PPPs looking like a better option than the traditional financing form. However, this antagonises the Value for Money principle. We also point out that public policy is not harmonised with ethical theories. We find that at present (in the UK), the SDR is somewhere between weighted utilitarian and Rawlsian societies in the trade-off curve. Alas, our study finds no evidence that the (UK) government is using a sophisticated system to keep pace with the accumulated off-balance sheet debts. Thus, the exact prediction of the final state is hardly made because of the uncertainty factor. We conclude that our study hopefully provides a good analytical framework for policymakers in order to draw on the merits of ethical theories before initiating public policies like PPPs.
Temperature, Time, and Interactions between Them in Relation to Colour Parameters of Black Poplar (Populus nigra L.) Thermally Modified in Nitrogen Atmosphere
Authors: Bytner Olga , Drożdżek Michał , Laskowska Agnieszka , Zawadzki Janusz
Published: January 2022

Thermal modification of wood in nitrogen atmosphere permits its usability value to be improved. The aim of the research was to determine the impact of technological modification parameters at different levels on the colour of black poplar (Populus nigra L.). Black poplar was thermally modified in nitrogen atmosphere at a range of temperatures from 160 °C to 220 °C, at times between 2 h and 8 h. The parameters of wood colour were measured according to the CIE L*a*b* colour space model. The changes in a* and b* had a non-linear profile. The maximum value of a* for black poplar wood was achieved after a modification at the temperature of 200 °C, while the maximum value of the b* parameter was achieved after modification at 190 °C. Colour changes in the ΔE of black poplar after modification at 160 °C and 170 °C were similar, and the dynamics of changes increased after modification at the temperature of 180 °C. The highest value of ΔE, around 40, was observed after modification at the temperature of 220 °C and time of 8 h. There were no statistically significant differences between the ΔE for radial and tangential sections. Statistical analysis showed that modification temperature was responsible for the variability of the L* value in 90%, and in ca. 70% for the changes in parameters a* and b*. The influence of the modification time on the colour parameters was minor—below 4%. The influence of the interaction between modification temperature and time on the colour parameters was below 10%. As a consequence, in the case of ΔE of black poplar wood, the influence of temperature was at a level of ca. 80%. On the other hand, the influence of time and the interaction between temperature and time of modification was low—below 3%.
Effect of Hydroxyapatite Nanoparticles and Nitrogen Plasma Treatment on Osteoblast Biological Behaviors of 3D-Printed HDPE Scaffold for Bone Tissue Regeneration Applications
Authors: Park Hyun-Chul , Ryu Jaeyoung , Jung Seunggon , Park Hong-Ju , Oh Hee-Kyun , Kook Min-Suk
Published: January 2022

The need for the repair of bone defects has been increasing due to various causes of loss of skeletal tissue. High density polyethylenes (HDPE) have been used as bone substitutes due to their excellent biocompatibility and mechanical strength. In the present study, we investigated the preosteoblast cell proliferation and differentiation on the adding nano-hydroxyapatite (n-HAp) particles into HDPE scaffold and treating HDPE/n-HAp scaffolds with nitrogen (N2) plasma. The three-dimensional (3D) HDPE/n-HAp scaffolds were prepared by fused modeling deposition 3D printer. The HDPE/n-HAp was blended with 10 wt% of n-HAp particle. The scaffold surface was reactive ion etched with nitrogen plasma to improve the preosteoblast biological response in vitro. After N2 plasma treatment, surfaces characterizations were investigated using Fourier transform infrared spectroscopy, scanning electron microscopy, and atomic force microscopy. The proliferation and differentiation of preosteoblast (MC3T3-E1) cells were evaluated by MTT assay and alkaline phosphatase (ALP) activity. The incorporation of n-HAp particles and N2 plasma surface treatment showed the improvement of biological responses of MC3T3-E1 cells in the HDPE scaffolds.
Rejuvenation in Deep Thermal Cycling of a Generic Model Glass: A Study of Per-Particle Energy Distribution
Authors: Bruns Marian , Varnik Fathollah
Published: January 2022

We investigate the effect of low temperature (cryogenic) thermal cycling on a generic model glass and observe signature of rejuvenation in terms of per-particle potential energy distributions. Most importantly, these distributions become broader and its average values successively increase when applying consecutive thermal cycles. We show that linear dimension plays a key role for these effects to become visible, since we do only observe a weak effect for a cubic system of roughly one hundred particle diameter but observe strong changes for a rule-type geometry with the longest length being two thousand particle diameters. A consistent interpretation of this new finding is provided in terms of a competition between relaxation processes, which are inherent to glassy systems, and excitation due to thermal treatment. In line with our previous report (Bruns et al., PRR 3, 013234 (2021)), it is shown that, depending on the parameters of thermal cycling, rejuvenation can be either too weak to be detected or strong enough for a clear observation.