bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell Penetrating Peptide-Based Self-Assembly for PD-L1 Targeted Tumor Regression
Authors: Guo Feng , Ke Junfeng , Fu Zhengdong , Han Wenzhao , Wang Liping
Published: December 2021

Cell penetrating peptides (CPPs) are peptides that can directly adapt to cell membranes and then permeate into cells. CPPs are usually covalently linked to the surface of nanocarriers to endow their permeability to the whole system. However, hybrids with lipids or polymers make the metabolism much more sophisticated and even more difficult to determine. In this study, we present a continuous sequence of 18 amino acids (FFAARTMIWY(d-P)GAWYKRI). It forms nanospheres around 170 nm, which increase slightly after loading with siRNA and DOX. Notably, it can be internalized by cancer cells mainly through electronic interactions and PD-L1-mediated endocytosis. Compared with poly-l-lysine and polyethyleneimine, it has a much higher efficiency (about four times) of gene transduction while lowering toxicity. In the treatment of cancer, it causes apoptosis (21%) and inhibits the expression of SURVIVIN protein in vitro. In vivo, it shows good biocompatibility as there are no changes in mice’s body weight. When administering peptide-siRNA-DOX, tumor growth is inhibited the most (about three times). These results above prove the sequence to be a good candidate for gene therapy and drug delivery.
Crosstalk between Neuron and Glial Cells in Oxidative Injury and Neuroprotection
Authors: Lee Kyung Hee , Cha Myeounghoon , Lee Bae Hwan
Published: December 2021

To counteract oxidative stress and associated brain diseases, antioxidant systems rescue neuronal cells from oxidative stress by neutralizing reactive oxygen species and preserving gene regulation. It is necessary to understand the communication and interactions between brain cells, including neurons, astrocytes and microglia, to understand oxidative stress and antioxidant mechanisms. Here, the role of glia in the protection of neurons against oxidative injury and glia–neuron crosstalk to maintain antioxidant defense mechanisms and brain protection are reviewed. The first part of this review focuses on the role of glia in the morphological and physiological changes required for brain homeostasis under oxidative stress and antioxidant defense mechanisms. The second part focuses on the essential crosstalk between neurons and glia for redox balance in the brain for protection against oxidative stress.
Targeting Non-Replicating Mycobacterium tuberculosis and Latent Infection: Alternatives and Perspectives (Mini-Review)
Authors: Egorova Anna , Salina Elena G. , Makarov Vadim
Published: December 2021

Latent tuberculosis infection (LTBI) represents a major challenge to curing TB disease. Current guidelines for LTBI management include only three older drugs and their combinations—isoniazid and rifamycins (rifampicin and rifapentine). These available control strategies have little impact on latent TB elimination, and new specific therapeutics are urgently needed. In the present mini-review, we highlight some of the alternatives that may potentially be included in LTBI treatment recommendations and a list of early-stage prospective small molecules that act on drug targets specific for Mycobacterium tuberculosis latency.
Effects of a Cc2d1a/Freud-1 Knockdown in the Hippocampus on Behavior, the Serotonin System, and BDNF
Authors: Kondaurova Elena M. , Plyusnina Alexandra V. , Ilchibaeva Tatiana V. , Eremin Dmitry V. , Rodnyy Alexander Ya. , Grygoreva Yulia D. , Naumenko Vladimir S.
Published: December 2021

The serotonin 5-HT1A receptor is one of the most abundant and widely distributed brain serotonin (5-HT) receptors that play a major role in the modulation of emotions and behavior. The 5-HT1A receptor gene (Htr1a) is under the control of transcription factor Freud-1 (also known as Cc2d1a/Freud-1). Here, using adeno-associated virus (AAV) constructs in vivo, we investigated effects of a Cc2d1a/Freud-1 knockdown in the hippocampus of C57BL/6J mice on behavior, the brain 5-HT system, and brain-derived neurotrophic factor (BDNF). AAV particles carrying the pAAV_H1-2_shRNA-Freud-1_Syn_EGFP plasmid encoding a short-hairpin RNA targeting mouse Cc2d1a/Freud-1 mRNA had an antidepressant effect in the forced swim test 5 weeks after virus injection. The knockdown impaired spatiotemporal memory as assessed in the Morris water maze. pAAV_H1-2_shRNA-Freud-1_Syn_EGFP decreased Cc2d1a/Freud-1 mRNA and protein levels. Furthermore, the Cc2d1a/Freud-1 knockdown upregulated 5-HT and its metabolite 5-hydroxyindoleacetic acid but not their ratio. The Cc2d1a/Freud-1 knockdown failed to increase mRNA and protein levels of Htr1a but diminished a 5-HT1A receptor functional response. Meanwhile, the Cc2d1a/Freud-1 knockdown reduced Creb mRNA expression and CREB phosphorylation and upregulated cFos mRNA. The knockdown enhanced the expression of a BDNF precursor (proBDNF protein), which is known to play a crucial part in neuroplasticity. Our data indicate that transcription factor Cc2d1a/Freud-1 is implicated in the pathogenesis of depressive disorders not only via the 5-HT1A receptor and transcription factor CREB but also through an influence on BDNF.
Adult-Onset Still’s Disease: Novel Biomarkers of Specific Subsets, Disease Activity, and Relapsing Forms
Authors: Maranini Beatrice , Ciancio Giovanni , Govoni Marcello
Published: December 2021

Adult-onset Still’s disease (AOSD) is a systemic inflammatory disease of unknown etiology. Recent studies have demonstrated that the hallmark of AOSD is a cytokine storm, which is characterized by the excessive production of interleukin (IL)-1, IL-6, IL-18, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), suggesting how pro-inflammatory cytokines play an important role in the pathogenesis of this disease. Actually, a certain proportion of patients (around 17–32%) with severe clinical symptoms achieves only partial remission or is resistant to both first-line corticosteroids and second-line DMARDs. These patients are defined as refractory AOSD patients, requiring higher dosage glucocorticoids, longer treatment duration, or the simultaneous introduction of immunosuppressive drugs, further leading to AOSD relapses. In this narrative review, we will analyze the latest literature data to unravel potential pathogenetic factors associated with specific patterns of AOSD disease or relapses in order to identify biomarkers that may guide clinical decisions, eventually leading to new therapeutic options.
B Cell Involvement in the Pathogenesis of Ankylosing Spondylitis
Authors: Wilbrink Rick , Spoorenberg Anneke , Verstappen Gwenny M. P. J. , Kroese Frans G. M.
Published: December 2021

Extensive research into ankylosing spondylitis (AS) has suggested the major role of genetics, immune reactions, and the joint–gut axis in its etiology, although an ultimate consensus does not yet exist. The available evidence indicates that both autoinflammation and T-cell-mediated autoimmune processes are actively involved in the disease process of AS. So far, B cells have received relatively little attention in AS pathogenesis; this is largely due to a lack of conventional disease-defining autoantibodies. However, against prevailing dogma, there is a growing body of evidence suggestive of B cell involvement. This is illustrated by disturbances in circulating B cell populations and the formation of auto-reactive and non-autoreactive antibodies, along with B cell infiltrates within the axial skeleton of AS patients. Furthermore, the depletion of B cells, using rituximab, displayed beneficial results in a subgroup of patients with AS. This review provides an overview of our current knowledge of B cells in AS, and discusses their potential role in its pathogenesis. An overarching picture portrays increased B cell activation in AS, although it is unclear whether B cells directly affect pathogenesis, or are merely bystanders in the disease process.
Recent Discoveries in Epigenetic Modifications of Polycystic Kidney Disease
Authors: Bowden Sarah A. , Rodger Euan J. , Chatterjee Aniruddha , Eccles Michael R. , Stayner Cherie
Published: December 2021

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a heritable renal disease that results in end-stage kidney disease, due to the uncontrolled bilateral growth of cysts throughout the kidneys. While it is known that a mutation within a PKD-causing gene is required for the development of ADPKD, the underlying mechanism(s) causing cystogenesis and progression of the disease are not well understood. Limited therapeutic options are currently available to slow the rate of cystic growth. Epigenetic modifications, including DNA methylation, are known to be altered in neoplasia, and several FDA-approved therapeutics target these disease-specific changes. As there are many similarities between ADPKD and neoplasia, we (and others) have postulated that ADPKD kidneys contain alterations to their epigenetic landscape that could be exploited for future therapeutic discovery. Here we summarise the current understanding of epigenetic changes that are associated with ADPKD, with a particular focus on the burgeoning field of ADPKD-specific alterations in DNA methylation.
Main and Minor Types of Collagens in the Articular Cartilage: The Role of Collagens in Repair Tissue Evaluation in Chondral Defects
Authors: Alcaide-Ruggiero Lourdes , Molina-Hernández Verónica , Granados María M. , Domínguez Juan M.
Published: December 2021

Several collagen subtypes have been identified in hyaline articular cartilage. The main and most abundant collagens are type II, IX and XI collagens. The minor and less abundant collagens are type III, IV, V, VI, X, XII, XIV, XVI, XXII, and XXVII collagens. All these collagens have been found to play a key role in healthy cartilage, regardless of whether they are more or less abundant. Additionally, an exhaustive evaluation of collagen fibrils in a repaired cartilage tissue after a chondral lesion is necessary to determine the quality of the repaired tissue and even whether or not this repaired tissue is considered hyaline cartilage. Therefore, this review aims to describe in depth all the collagen types found in the normal articular cartilage structure, and based on this, establish the parameters that allow one to consider a repaired cartilage tissue as a hyaline cartilage.
The HDAC Inhibitor Butyrate Impairs β Cell Function and Activates the Disallowed Gene Hexokinase I
Authors: Bridgeman Stephanie , Ellison Gaewyn , Newsholme Philip , Mamotte Cyril
Published: December 2021

Histone deacetylase (HDAC) inhibitors such as butyrate have been reported to reduce diabetes risk and protect insulin-secreting pancreatic β cells in animal models. However, studies on insulin-secreting cells in vitro have found that butyrate treatment resulted in impaired or inappropriate insulin secretion. Our study explores the effects of butyrate on insulin secretion by BRIN BD-11 rat pancreatic β cells and examined effects on the expression of genes implicated in β cell function. Robust HDAC inhibition with 5 mM butyrate or trichostatin A for 24 h in β cells decreased basal insulin secretion and content, as well as insulin secretion in response to acute stimulation. Treatment with butyrate also increased expression of the disallowed gene hexokinase I, possibly explaining the impairment to insulin secretion, and of TXNIP, which may increase oxidative stress and β cell apoptosis. In contrast to robust HDAC inhibition (>70% after 24 h), low-dose and acute high-dose treatment with butyrate enhanced nutrient-stimulated insulin secretion. In conclusion, although protective effects of HDAC inhibition have been observed in vivo, potent HDAC inhibition impairs β cell function in vitro. The chronic low dose and acute high dose butyrate treatments may be more reflective of in vivo effects.
Biochemical Mapping of Pyrodinium bahamense Unveils Molecular Underpinnings behind Organismal Processes
Authors: Subong Bryan John J. , Malto Zabrina Bernice L. , Lluisma Arturo O. , Azanza Rhodora V. , Salvador-Reyes Lilibeth A.
Published: December 2021

Proteins, lipids, and carbohydrates from the harmful algal bloom (HAB)-causing organism Pyrodinium bahamense were characterized to obtain insights into the biochemical processes in this environmentally relevant dinoflagellate. Shotgun proteomics using label-free quantitation followed by proteome mapping using the P. bahamense transcriptome and translated protein databases of Marinovum algicola, Alexandrium sp., Cylindrospermopsis raciborskii, and Symbiodinium kawagutii for annotation enabled the characterization of the proteins in P. bahamense. The highest number of annotated hits were obtained from M. algicola and highlighted the contribution of microorganisms associated with P. bahamense. Proteins involved in dimethylsulfoniopropionate (DMSP) degradation such as propionyl CoA synthethase and acryloyl-CoA reductase were identified, suggesting the DMSP cleavage pathway as the preferred route in this dinoflagellate. Most of the annotated proteins were involved in amino acid biosynthesis and carbohydrate degradation and metabolism, indicating the active roles of these molecules in the vegetative stage of P. bahamense. This characterization provides baseline information on the cellular machinery and the molecular basis of the ecophysiology of P. bahamense.
Comparative Mitogenomics of Fungal Species in Stachybotryaceae Provides Evolutionary Insights into Hypocreales
Authors: Ren Li-Yuan , Zhang Shu , Zhang Yong-Jie
Published: December 2021

Stachybotrys chartarum is one of the world’s ten most feared fungi within the family Stachybotryaceae, although to date, not a single mitogenome has been documented for Stachybotryaceae. Herein, six mitogenomes of four different species in Stachybotryaceae are newly reported. The S. chartarum mitogenome was 30.7 kb in length and contained two introns (one each in rnl and cox1). A comparison of the mitogenomes of three different individuals of S. chartarum showed few nucleotide variations and conservation of gene content/order and intron insertion. A comparison of the mitogenomes of four different Stachybotryaceae species (Memnoniella echinata, Myrothecium inundatum, S. chartarum, and S. chlorohalonata), however, revealed variations in intron insertion, gene order/content, and nad2/nad3 joining pattern. Further investigations on all Hypocreales species with available mitogenomes showed greater variabilities in gene order (six patterns) and nad2/nad3 joining pattern (five patterns) although a dominant pattern always existed in each case. Ancestral state estimation showed that in each case the dominant pattern was always more ancestral than those rare patterns. Phylogenetic analyses based on mitochondrion-encoded genes supported the placement of Stachybotryaceae in Hypocreales. The crown age of Stachybotryaceae was estimated to be approximately the Early Cretaceous (141–142 Mya). This study greatly promotes our understanding of the evolution of fungal species in Hypocreales.
The Role of ATRA, Natural Ligand of Retinoic Acid Receptors, on EMT-Related Proteins in Breast Cancer: Minireview
Authors: Bobal Pavel , Lastovickova Marketa , Bobalova Janette
Published: December 2021

The knowledge of the structure, function, and abundance of specific proteins related to the EMT process is essential for developing effective diagnostic approaches to cancer with the perspective of diagnosis and therapy of malignancies. The success of all-trans retinoic acid (ATRA) differentiation therapy in acute promyelocytic leukemia has stimulated studies in the treatment of other tumors with ATRA. This review will discuss the impact of ATRA use, emphasizing epithelial-mesenchymal transition (EMT) proteins in breast cancer, of which metastasis and recurrence are major causes of death.
Bio-Scaffolds as Cell or Exosome Carriers for Nerve Injury Repair
Authors: Poongodi Raju , Chen Ying-Lun , Yang Tao-Hsiang , Huang Ya-Hsien , Yang Kuender D. , Lin Hsin-Chieh , Cheng Jen-Kun
Published: December 2021

Central and peripheral nerve injuries can lead to permanent paralysis and organ dysfunction. In recent years, many cell and exosome implantation techniques have been developed in an attempt to restore function after nerve injury with promising but generally unsatisfactory clinical results. Clinical outcome may be enhanced by bio-scaffolds specifically fabricated to provide the appropriate three-dimensional (3D) conduit, growth-permissive substrate, and trophic factor support required for cell survival and regeneration. In rodents, these scaffolds have been shown to promote axonal regrowth and restore limb motor function following experimental spinal cord or sciatic nerve injury. Combining the appropriate cell/exosome and scaffold type may thus achieve tissue repair and regeneration with safety and efficacy sufficient for routine clinical application. In this review, we describe the efficacies of bio-scaffolds composed of various natural polysaccharides (alginate, chitin, chitosan, and hyaluronic acid), protein polymers (gelatin, collagen, silk fibroin, fibrin, and keratin), and self-assembling peptides for repair of nerve injury. In addition, we review the capacities of these constructs for supporting in vitro cell-adhesion, mechano-transduction, proliferation, and differentiation as well as the in vivo properties critical for a successful clinical outcome, including controlled degradation and re-absorption. Finally, we describe recent advances in 3D bio-printing for nerve regeneration.
6-Benzylaminopurine Alleviates the Impact of Cu2+ Toxicity on Photosynthetic Performance of Ricinus communis L. Seedlings
Authors: Sameena Puthukkolli P. , Kalaji Hazem M. , Żuk-Gołaszewska Krystyna , Horaczek Tomasz , Sierka Edyta , Puthur Jos T.
Published: December 2021

Copper (Cu) is an essential element involved in various metabolic processes in plants, but at concentrations above the threshold level, it becomes a potential stress factor. The effects of two different cytokinins, kinetin (KIN) and 6-benzylaminopurine (BAP), on chlorophyll a fluorescence parameters, stomatal responses and antioxidation mechanisms in castor (Ricinus communis L.) under Cu2+ toxicity was investigated. Ricinus communis plants were exposed to 80 and 160 μM CuSO4 added to the growth medium. Foliar spraying of 15 μM KIN and BAP was carried out on these seedlings. The application of these cytokinins enhanced the tissue water status, chlorophyll contents, stomatal opening and photosynthetic efficiency in the castor plants subjected to Cu2+ stress. The fluorescence parameters, such as Fm, Fv/Fo, Sm, photochemical and non-photochemical quantum yields, energy absorbed, energy trapped and electron transport per cross-sections, were more efficiently modulated by BAP application than KIN under Cu2+ toxicity. There was also effective alleviation of reactive oxygen species by enzymatic and non-enzymatic antioxidation systems, reducing the membrane lipid peroxidation, which brought about a relative enhancement in the membrane stability index. Of the various treatments, 80 µM CuSO4 + BAP recorded the highest increase in photosynthetic efficiency compared to other cytokinin treatments. Therefore, it can be concluded that BAP could effectively alleviate the detrimental effects of Cu2+toxicity in cotyledonary leaves of R. communis by effectively modulating stomatal responses and antioxidation mechanisms, thereby enhancing the photosynthetic apparatus’ functioning.
Multiple Irradiation Affects Cellular and Extracellular Components of the Mouse Brain Tissue and Adhesion and Proliferation of Glioblastoma Cells in Experimental System In Vivo
Authors: Politko Maxim O. , Tsidulko Alexandra Y. , Pashkovskaya Oxana A. , Kuper Konstantin E. , Suhovskih Anastasia V. , Kazanskaya Galina M. , Klyushova Lyubov S. , Sokolov Dmitry K. , Volkov Alexander M. , Kliver Evgenii E. , Zheravin Alexander A. , Aidagulova Svetlana V. , Grigorieva Elvira V.
Published: December 2021

Intensive adjuvant radiotherapy (RT) is a standard treatment for glioblastoma multiforme (GBM) patients; however, its effect on the normal brain tissue remains unclear. Here, we investigated the short-term effects of multiple irradiation on the cellular and extracellular glycosylated components of normal brain tissue and their functional significance. Triple irradiation (7 Gy*3 days) of C57Bl/6 mouse brain inhibited the viability, proliferation and biosynthetic activity of normal glial cells, resulting in a fast brain-zone-dependent deregulation of the expression of proteoglycans (PGs) (decorin, biglycan, versican, brevican and CD44). Complex time-point-specific (24–72 h) changes in decorin and brevican protein and chondroitin sulfate (CS) and heparan sulfate (HS) content suggested deterioration of the PGs glycosylation in irradiated brain tissue, while the transcriptional activity of HS-biosynthetic system remained unchanged. The primary glial cultures and organotypic slices from triple-irradiated brain tissue were more susceptible to GBM U87 cells’ adhesion and proliferation in co-culture systems in vitro and ex vivo. In summary, multiple irradiation affects glycosylated components of normal brain extracellular matrix (ECM) through inhibition of the functional activity of normal glial cells. The changed content and pattern of PGs and GAGs in irradiated brain tissues are accompanied by the increased adhesion and proliferation of GBM cells, suggesting a novel molecular mechanism of negative side-effects of anti-GBM radiotherapy.
The Current State of Knowledge about Essential Oil Fumigation for Quality of Crops during Postharvest
Authors: Namiota Małgorzata , Bonikowski Radosław
Published: December 2021

Prolonging crops’ shelf-life while retaining their high quality is a major issue related to postharvest management. During storage, fruits and vegetables are exposed to microbial attacks, which may cause spoilage. Crop deterioration causes the loss of physical properties and drops in quality and nutritional value. Hence, new techniques to improve the resistance of food products are being explored. One promising technique is fumigation. Essential oils and their constituents, due to their antimicrobial properties, are likely to be used as fumigants, as they are highly volatile, effective in low concentrations, biodegradable, and safe. Papers indicate that some of them can improve their quality by increasing the content of antioxidants. This comprehensive review aims to present the current state of knowledge about the influence of essential oil fumigation on crop quality. It covers antioxidant capacity, the content of some bioactive compounds, physicochemical properties, decay properties, and sensory attributes of fruits and vegetables treated with essential oil vapors. The review indicates that this technique might be an interesting field for further exploration due to the promising results presented in the studies. Moreover, the review presents major objectives for current studies and indicates a lack of recent papers in this field.
VEGFB Promotes Myoblasts Proliferation and Differentiation through VEGFR1-PI3K/Akt Signaling Pathway
Authors: Ling Mingfa , Quan Lulu , Lai Xumin , Lang Limin , Li Fan , Yang Xiaohua , Fu Yiming , Feng Shengchun , Yi Xin , Zhu Canjun , Gao Ping , Zhu Xiaotong , Wang Lina , Shu Gang , Jiang Qingyan , Wang Songbo
Published: December 2021

It has been demonstrated that vascular endothelial growth factor B (VEGFB) plays a vital role in regulating vascular biological function. However, the role of VEGFB in regulating skeletal muscle cell proliferation and differentiation remains unclear. Thus, this study aimed to investigate the effects of VEGFB on C2C12 myoblast proliferation and differentiation and to explore the underlying mechanism. For proliferation, VEGFB significantly promoted the proliferation of C2C12 myoblasts with the upregulating expression of cyclin D1 and PCNA. Meanwhile, VEGFB enhanced vascular endothelial growth factor receptor 1 (VEGFR1) expression and activated the PI3K/Akt signaling pathway in a VEGFR1-dependent manner. In addition, the knockdown of VEGFR1 and inhibition of PI3K/Akt totally abolished the promotion of C2C12 proliferation induced by VEGFB, suggesting that VEGFB promoted C2C12 myoblast proliferation through the VEGFR1-PI3K/Akt signaling pathway. Regarding differentiation, VEGFB significantly stimulated the differentiation of C2C12 myoblasts via VEGFR, with elevated expressions of MyoG and MyHC. Furthermore, the knockdown of VEGFR1 rather than NRP1 eliminated the VEGFB-stimulated C2C12 differentiation. Moreover, VEGFB activated the PI3K/Akt/mTOR signaling pathway in a VEGFR1-dependent manner. However, the inhibition of PI3K/Akt/mTOR blocked the promotion of C2C12 myoblasts differentiation induced by VEGFB, indicating the involvement of the PI3K/Akt pathway. To conclude, these findings showed that VEGFB promoted C2C12 myoblast proliferation and differentiation via the VEGFR1-PI3K/Akt signaling pathway, providing new insights into the regulation of skeletal muscle development.
Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-β1/SMAD Signaling and Autophagy in Hepatic Stellate Cells
Authors: Kataoka Seita , Umemura Atsushi , Okuda Keiichiro , Taketani Hiroyoshi , Seko Yuya , Nishikawa Taichiro , Yamaguchi Kanji , Moriguchi Michihisa , Kanbara Yoshihiro , Arbiser Jack L. , Shima Toshihide , Okanoue Takeshi , Itoh Yoshito
Published: December 2021

Chronic liver injury may result in hepatic fibrosis, which can progress to cirrhosis and eventually liver failure. There are no drugs that are specifically approved for treating hepatic fibrosis. The natural product honokiol (HNK), a bioactive compound extracted from Magnolia grandiflora, represents a potential tool in the management of hepatic fibrosis. Though HNK has been reported to exhibit suppressive effects in a rat fibrosis model, the mechanisms accounting for this suppression remain unclear. In the present study, the anti-fibrotic effects of HNK on the liver were evaluated in vivo and in vitro. In vivo studies utilized a murine liver fibrosis model, in which fibrosis is induced by treatment with carbon tetrachloride (CCl4). For in vitro studies, LX-2 human hepatic stellate cells (HSCs) were treated with HNK, and expression of markers of fibrosis, cell viability, the transforming growth factor-β (TGF-β1)/SMAD signaling pathway, and autophagy were analyzed. HNK was well tolerated and significantly attenuated CCl4-induced liver fibrosis in vivo. Moreover, HNK decreased HSC activation and collagen expression by downregulating the TGF-β1/SMAD signaling pathway and autophagy. These results suggest that HNK is a new potential candidate for the treatment of hepatic fibrosis through suppressing both TGF-β1/SMAD signaling and autophagy in HSCs.
Impairments of Long-Term Synaptic Plasticity in the Hippocampus of Young Rats during the Latent Phase of the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy
Authors: Postnikova Tatyana Y. , Diespirov Georgy P. , Amakhin Dmitry V. , Vylekzhanina Elizaveta N. , Soboleva Elena B. , Zaitsev Aleksey V.
Published: December 2021

Status epilepticus (SE) causes persistent abnormalities in the functioning of neuronal networks, often resulting in worsening epileptic seizures. Many details of cellular and molecular mechanisms of seizure-induced changes are still unknown. The lithium–pilocarpine model of epilepsy in rats reproduces many features of human temporal lobe epilepsy. In this work, using the lithium–pilocarpine model in three-week-old rats, we examined the morphological and electrophysiological changes in the hippocampus within a week following pilocarpine-induced seizures. We found that almost a third of the neurons in the hippocampus and dentate gyrus died on the first day, but this was not accompanied by impaired synaptic plasticity at that time. A diminished long-term potentiation (LTP) was observed following three days, and the negative effect of SE on plasticity increased one week later, being accompanied by astrogliosis. The attenuation of LTP was caused by the weakening of N-methyl-D-aspartate receptor (NMDAR)-dependent signaling. NMDAR-current was more than two-fold weaker during high-frequency stimulation in the post-SE rats than in the control group. Application of glial transmitter D-serine, a coagonist of NMDARs, allows the enhancement of the NMDAR-dependent current and the restoration of LTP. These results suggest that the disorder of neuron–astrocyte interactions plays a critical role in the impairment of synaptic plasticity.
Cadherin Signaling in Cancer and Autoimmune Diseases
Authors: Sisto Margherita , Ribatti Domenico , Lisi Sabrina
Published: December 2021

Cadherins mediate cell–cell adhesion through a dynamic process that is strongly dependent on the cellular context and signaling. Cadherin regulation reflects the interplay between fundamental cellular processes, including morphogenesis, proliferation, programmed cell death, surface organization of receptors, cytoskeletal organization, and cell trafficking. The variety of molecular mechanisms and cellular functions regulated by cadherins suggests that we have only scratched the surface in terms of clarifying the functions mediated by these versatile proteins. Altered cadherins expression is closely connected with tumorigenesis, epithelial–mesenchymal transition (EMT)-dependent fibrosis, and autoimmunity. We review the current understanding of how cadherins contribute to human health and disease, considering the mechanisms of cadherin involvement in diseases progression, as well as the clinical significance of cadherins as therapeutic targets.
Wheat Breeding through Genetic and Physical Mapping 2
Authors: Gadaleta Agata
Published: December 2021

Following the success of the first topic, the special issue of “Wheat breeding through genetic and physical mapping 2” has been re-proposed in order to keep current the recent advancement in research on genetic and physical mapping of candidate genes for agronomically important traits, in studies of the regulatory sequence for biotic and abiotic stress resistance [...]
Uptake of Ozenoxacin and Other Quinolones in Gram-Positive Bacteria
Authors: López Yuly , Muñoz Laura , Gargallo-Viola Domingo , Cantón Rafael , Vila Jordi , Zsolt Ilonka
Published: December 2021

The big problem of antimicrobial resistance is that it requires great efforts in the design of improved drugs which can quickly reach their target of action. Studies of antibiotic uptake and interaction with their target it is a key factor in this important challenge. We investigated the accumulation of ozenoxacin (OZN), moxifloxacin (MOX), levofloxacin (LVX), and ciprofloxacin (CIP) into the bacterial cells of 5 species, including Staphylococcus aureus (SA4-149), Staphylococcus epidermidis (SEP7602), Streptococcus pyogenes (SPY165), Streptococcus agalactiae (SAG146), and Enterococcus faecium (EF897) previously characterized.The concentration of quinolone uptake was estimated by agar disc-diffusion bioassay. Furthermore, we determined the inhibitory concentrations 50 (IC50) of OZN, MOX, LVX, and CIP against type II topoisomerases from S. aureus.The accumulation of OZN inside the bacterial cell was superior in comparison to MOX, LVX, and CIP in all tested species. The accumulation of OZN inside the bacterial cell was superior in comparison to MOX, LVX, and CIP in all tested species. The rapid penetration of OZN into the cell was reflected during the first minute of exposure with antibiotic values between 190 and 447 ng/mg (dry weight) of bacteria in all strains. Moreover, OZN showed the greatest inhibitory activity among the quinolones tested for both DNA gyrase and topoisomerase IV isolated from S. aureus with IC50 values of 10 and 0.5 mg/L, respectively. OZN intracellular concentration was significantly higher than that of MOX, LVX and CIP. All of these features may explain the higher in vitro activity of OZN compared to the other tested quinolones.
Spin State Switching in Heptauthrene Nanostructure by Electric Field: Computational Study
Authors: Szałowski Karol
Published: December 2021

Recent experimental studies proved the presence of the triplet spin state in atomically precise heptauthrene nanostructure of nanographene type (composed of two interconnected triangles with zigzag edge). In the paper, we report the computational study predicting the possibility of controlling this spin state with an external in-plane electric field by causing the spin switching. We construct and discuss the ground state magnetic phase diagram involving S=1 (triplet) state, S=0 antiferromagnetic state and non-magnetic state and predict the switching possibility with the critical electric field of the order of 0.1 V/Å. We discuss the spin distribution across the nanostructure, finding its concentration along the longest zigzag edge. To model our system of interest, we use the mean-field Hubbard Hamiltonian, taking into account the in-plane external electric field as well as the in-plane magnetic field (in a form of the exchange field from the substrate). We also assess the effect of uniaxial strain on the magnetic phase diagram.
Systematic Analysis and Biochemical Characterization of the Caffeoyl Shikimate Esterase Gene Family in Poplar
Authors: Wang Xuechun , Chao Nan , Zhang Aijing , Kang Jiaqi , Jiang Xiangning , Gai Ying
Published: December 2021

Caffeoyl shikimate esterase (CSE) hydrolyzes caffeoyl shikimate into caffeate and shikimate in the phenylpropanoid pathway. In this study, we performed a systematic analysis of the CSE gene family and investigated the possible roles of CSE and CSE-like genes in Populus. We conducted a genome-wide analysis of the CSE gene family, including functional and phylogenetic analyses of CSE and CSE-like genes, using the poplar (Populus trichocarpa) genome. Eighteen CSE and CSE-like genes were identified in the Populus genome, and five phylogenetic groups were identified from phylogenetic analysis. CSEs in Group Ia, which were proposed as bona fide CSEs, have probably been lost in most monocots except Oryza sativa. Primary functional classification showed that PoptrCSE1 and PoptrCSE2 had putative function in lignin biosynthesis. In addition, PoptrCSE2, along with PoptrCSE12, might also respond to stress with a function in cell wall biosynthesis. Enzymatic assay of PoptoCSE1 (Populus tomentosa), -2 and -12 showed that PoptoCSE1 and -2 maintained CSE activity. PoptoCSE1 and 2 had similar biochemical properties, tissue expression patterns and subcellular localization. Most of the PoptrCSE-like genes are homologs of AtMAGL (monoacylglycerol lipase) genes in Arabidopsis and may function as MAG lipase in poplar. Our study provides a systematic understanding of this novel gene family and suggests the function of CSE in monolignol biosynthesis in Populus.
Melatonin Protects Tobacco Suspension Cells against Pb-Induced Mitochondrial Dysfunction
Authors: Kobylińska Agnieszka , Posmyk Małgorzata Maria
Published: December 2021

Recent studies have shown that melatonin is an important molecule in plant physiology. It seems that the most important is that melatonin effectively eliminates oxidative stress (direct and indirect antioxidant) and switches on different defence strategies (preventive and interventive actions) during environmental stresses. In the presented report, exogenous melatonin potential to protect Nicotiana tabacum L. line Bright Yellow 2 (BY-2) exposed to lead against death was examined. Analyses of cell proliferation and viability, the level of intracellular calcium, changes in mitochondrial membrane potential (ΔΨm) as well as possible translocation of cytochrome c from mitochondria to cytosol and subsequent caspase-like proteolytic activity were conducted. Our results indicate that pretreatment BY-2 with melatonin protected tobacco cells against mitochondrial dysfunction and caspase-like activation caused by lead. The findings suggest the possible role of this indoleamine in the molecular mechanism of mitochondria, safeguarding against potential collapse and cytochrome c release. Thus, it seems that applied melatonin acted as an effective factor, promoting survival and increasing plant tolerance to lead.
High Molecular Weight Kininogen: A Review of the Structural Literature
Authors: Ponczek Michał B.
Published: December 2021

Kininogens are multidomain glycoproteins found in the blood of most vertebrates. High molecular weight kininogen demonstrate both carrier and co-factor activity as part of the intrinsic pathway of coagulation, leading to thrombin generation. Kininogens are the source of the vasoactive nonapeptide bradykinin. To date, attempts to crystallize kininogen have failed, and very little is known about the shape of kininogen at an atomic level. New advancements in the field of cryo-electron microscopy (cryoEM) have enabled researchers to crack the structure of proteins that has been refractory to traditional crystallography techniques. High molecular weight kininogen is a good candidate for structural investigation by cryoEM. The goal of this review is to summarize the findings of kininogen structural studies.
Evaluation of Risk Factors for Dementia Incidence Based on Previous Questionnaire Results of Specific Health Checkups in Japan
Authors: Tamaki Yoh , Hiratsuka Yoshimune , Kumakawa Toshiro
Published: December 2021

The prevalence of dementia is rapidly increasing worldwide, and its treatment and prevention are a health concern. The prevention of dementia requires the identification of risk factors through longitudinal studies of lifestyle. In this study, we aimed to identify the risk factors for the development of dementia in Japan and to clarify their primary care strategies. We analyzed the relationship between the cognitive ability level determined by the survey of long-term care certification and the past questionnaire results of a specific health examination in Japan 10 years ago. To analyze the risk factors for developing dementia, multivariate analysis was used, which showed that residents who gained more than 10 kg since reaching 20 years of age had a significantly lower risk of developing dementia. Regarding the “start of lifestyle modifications” question, those who answered “already started” had a significantly lower risk than those who answered “no plan to improve”. Conversely, residents receiving insulin injections or oral hypoglycemic agents were at a significantly higher risk of developing dementia based on the results of the questionnaire of the health checkups surveyed 10 years prior.
An Overview of Robotic Capsules for Drug Delivery to the Gastrointestinal Tract
Authors: Cortegoso Valdivia Pablo , Robertson Alexander R. , De Boer Nanne K. H. , Marlicz Wojciech , Koulaouzidis Anastasios
Published: December 2021

The introduction of capsule endoscopy two decades ago marked the beginning of the “small bowel revolution”. Since then, the rapid evolution of microtechnology has allowed the development of drug delivery systems (DDS) designed to address some of the needs that are not met by standard drug delivery. To overcome the complex anatomy and physiology of the gastrointestinal (GI) tract, several DDS have been developed, including many prototypes being designed, built and eventually produced with ingenious drug-release mechanisms and anchoring systems allowing targeted therapy. This review highlights the currently available systems for drug delivery in the GI tract and discusses the needs, limitations, and future considerations of these technologies.
Advances in Diagnostic Imaging for Cardiac Sarcoidosis
Authors: Manabe Osamu , Oyama-Manabe Noriko , Aikawa Tadao , Tsuneta Satonori , Tamaki Nagara
Published: December 2021

Sarcoidosis is a systemic granulomatous disease of unknown etiology, and its clinical presentation depends on the affected organ. Cardiac sarcoidosis (CS) is one of the leading causes of death among patients with sarcoidosis. The clinical manifestations of CS are heterogeneous, and range from asymptomatic to life-threatening arrhythmias and progressive heart failure due to the extent and location of granulomatous inflammation in the myocardium. Advances in imaging techniques have played a pivotal role in the evaluation of CS because histological diagnoses obtained by myocardial biopsy tend to have lower sensitivity. The diagnosis of CS is challenging, and several approaches, notably those using positron emission tomography and cardiac magnetic resonance imaging (MRI), have been reported. Delayed-enhanced computed tomography (CT) may also be used for diagnosing CS in patients with MRI-incompatible devices and allows acceptable evaluation of myocardial hyperenhancement in such patients. This article reviews the advances in imaging techniques for the evaluation of CS.
Predictors of Rehospitalization and Mortality in Diabetes-Related Hospital Admissions
Authors: Kozioł Milena , Towpik Iwona , Żurek Michał , Niemczynowicz Jagoda , Wasążnik Małgorzata , Sanchak Yaroslav , Wierzba Waldemar , Franek Edward , Walicka Magdalena
Published: December 2021

The risk factors of rehospitalization and death post-discharge in diabetes-related hospital admissions are not fully understood. To determine them, a population-based retrospective epidemiological survey was performed on diabetes-related admissions from the Polish national database. Logistic regression models were used, in which the dependent variables were rehospitalization due to diabetes complications and death within 90 days after the index hospitalization. In 2017, there were 74,248 hospitalizations related to diabetes. A total of 11.3% ended with readmission. Risk factors for rehospitalization were as follows: age < 35 years; male sex; prior hospitalization due to acute diabetic complications; weight loss; peripheral artery disease; iron deficiency anemia; kidney failure; alcohol abuse; heart failure; urgent, emergency, or weekend admission; length of hospitalization; and hospitalization in a teaching hospital with an endocrinology/diabetology unit. Furthermore, 7.3% of hospitalizations resulted in death within 90 days following discharge. Risk factors for death were as follows: age; neoplastic disease with/without metastases; weight loss; coagulopathy; alcohol abuse; acute diabetes complications; heart failure; kidney failure; iron deficiency anemia; peripheral artery disease; fluid, electrolytes, and acid–base balance disturbances; urgent or emergency and weekend admission; and length of hospitalization. We concluded that of all investigated factors, only hospitalization within an experienced specialist center may reduce the frequency of the assessed outcomes.
CFD Investigation on Hydrodynamic Resistance of a Novel Subsea Shuttle Tanker
Authors: Xing Yihan , Janocha Marek Jan , Yin Guang , Ong Muk Chen
Published: December 2021

The Subsea Shuttle Tanker (SST) was proposed by Equinor as an alternative to subsea pipelines and surface tankers for the transportation of liquid carbon dioxide (CO2) from existing offshore/land facilities to marginal subsea fields. In contrast to highly weather-dependent surface tanker operations, the SST can operate in any condition underwater. Low resistance is paramount to achieving maximum range. In this paper, the resistance of the SST at an operating forward speed of 6 knots (3.09 m/s) and subject to an incoming current velocity of 1 m/s is computed using Computational Fluid Dynamics (CFD). The Delayed Detached Eddy Simulation (DDES) method is used. This method combines features of Reynolds-Averaged Navier–Stokes Simulation (RANS) in the attached boundary layer parts at the near-wall regions, and Large Eddy Simulation (LES) at the unsteady, separated regions near to the propeller. The force required to overcome forward resistance is calculated to be 222 kN and agrees well with experimental measurements available in the open literature. The corresponding power consumption is calculated to be 927 kW, highlighting the high efficiency of the SST. The method presented in this paper is general and can be used for resistance optimization studies of any underwater vessel.
Phytotoxicity in Seedlings of Rhizophora mangle (L.) Exposed to 2,4-Dichlorophenoxyacetic Acid under Experimental Conditions
Authors: Chan-Keb Carlos A. , Agraz-Hernández Claudia M. , Pérez-Balan Román A. , Gutiérrez-Alcántara Eduardo J. , Muñiz-Salazar Raquel , Reyes-Castellano Jordán E. , Osti-Sáenz Juan
Published: December 2021

Mangroves are considered one of the most productive ecosystems worldwide, providing multiple environmental goods and services; however, in recent years, there have been modifications and deterioration in the structure and function of these ecosystems, caused by various natural events and anthropic activities, such as the construction of roads, wastewater discharge, unsustainable livestock, and agricultural practices, as well as the impact of chemicals, such as heavy metals, oil spills, and the use of herbicides. In this research, phytotoxic effects on seedlings of Rhizophora mangle were evaluated at an exposure of five dilutions w/v (5%, 10%, 25%, 50%, and 100%) of the commercial presentation of 2,4-dichlorophenoxyacetic acid (2,4-D). Propagules grown in a greenhouse under local tidal regimes were used, so the growth of stem diameter, height, biomass production in root, leaves, and stems, as well as the concentration of chlorophyll a of the exposed seedlings were measured. The comparison of these parameters in seedlings with only seawater presented significant differences (p ≤ 0.05) and inhibitory effects on growth (diameter), the stem concentration of chlorophyll a, and the production of biomass of leaves, stems, and roots. The inhibitory effect of exposure to 2,4-D on chlorophyll production and root biomass is highlighted, with an average decrease of 45% relative to the control. The sensitivity of the Rhizophora mangle seedlings to the applied concentrations of herbicide evidence the inhibitory effects on the morphological variables of biomass production and chlorophyll a production in mangrove leaves.