bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Localization and Homologous Genes Mining for Barley Grain Size
Authors: Hong Yi , Zhang Mengna , Xu Rugen
Published: March 2023

Grain size is an important agronomic trait determining barley yield and quality. An increasing number of QTLs (quantitative trait loci) for grain size have been reported due to the improvement in genome sequencing and mapping. Elucidating the molecular mechanisms underpinning barley grain size is vital for producing elite cultivars and accelerating breeding processes. In this review, we summarize the achievements in the molecular mapping of barley grain size over the past two decades, highlighting the results of QTL linkage analysis and genome-wide association studies. We discuss the QTL hotspots and predict candidate genes in detail. Moreover, reported homologs that determine the seed size clustered into several signaling pathways in model plants are also listed, providing the theoretical basis for mining genetic resources and regulatory networks of barley grain size.
Vapor-Induced Pore-Forming Atmospheric-Plasma-Sprayed Zinc-, Strontium-, and Magnesium-Doped Hydroxyapatite Coatings on Titanium Implants Enhance New Bone Formation—An In Vivo and In Vitro Investigation
Authors: Hou Hsin-Han , Lee Bor-Shiunn , Liu Yu-Cheng , Wang Yi-Ping , Kuo Wei-Ting , Chen I-Hui , He Ai-Chia , Lai Chern-Hsiung , Tung Kuo-Lun , Chen Yi-Wen
Published: March 2023

Objectives: Titanium implants are regarded as a promising treatment modality for replacing missing teeth. Osteointegration and antibacterial properties are both desirable characteristics for titanium dental implants. The aim of this study was to create zinc (Zn)-, strontium (Sr)-, and magnesium (Mg)-multidoped hydroxyapatite (HAp) porous coatings, including HAp, Zn-doped HAp, and Zn-Sr-Mg-doped HAp, on titanium discs and implants using the vapor-induced pore-forming atmospheric plasma spraying (VIPF-APS) technique. Methods: The mRNA and protein levels of osteogenesis-associated genes such as collagen type I alpha 1 chain (COL1A1), decorin (DCN), osteoprotegerin (TNFRSF11B), and osteopontin (SPP1) were examined in human embryonic palatal mesenchymal cells. The antibacterial effects against periodontal bacteria, including Porphyromonas gingivalis and Prevotella nigrescens, were investigated. In addition, a rat animal model was used to evaluate new bone formation via histologic examination and micro-computed tomography (CT). Results: The ZnSrMg-HAp group was the most effective at inducing mRNA and protein expression of TNFRSF11B and SPP1 after 7 days of incubation, and TNFRSF11B and DCN after 11 days of incubation. In addition, both the ZnSrMg-HAp and Zn-HAp groups were effective against P. gingivalis and P. nigrescens. Furthermore, according to both in vitro studies and histologic findings, the ZnSrMg-HAp group exhibited the most prominent osteogenesis and concentrated bone growth along implant threads. Significance: A porous ZnSrMg-HAp coating using VIPF-APS could serve as a novel technique for coating titanium implant surfaces and preventing further bacterial infection.
Quantitative Analysis of Transcription Termination via Position-Selective Labeling of RNA (PLOR) Method
Authors: Chien Ping-Yi , Gao Lingzhi , Liu Yu
Published: March 2023

T7 RNA polymerase is the most widely used enzyme in RNA synthesis, and it is also used for RNA labeling in position-selective labeling of RNA (PLOR). PLOR is a liquid–solid hybrid phase method that has been developed to introduce labels to specific positions of RNA. Here, we applied PLOR as a single-round transcription method to quantify the terminated and read-through products in transcription for the first time. Various factors, including pausing strategies, Mg2+, ligand and the NTP concentration at the transcriptional termination of adenine riboswitch RNA have been characterized. This helps to understand transcription termination, which is one of the least understood processes in transcription. Additionally, our strategy can potentially be used to study the co-transcription behavior of general RNA, especially when continuous transcription is not desired.
The Role of Histone Modification in DNA Replication-Coupled Nucleosome Assembly and Cancer
Authors: Zhang Yaguang , Zhang Qin , Zhang Yang , Han Junhong
Published: March 2023

Histone modification regulates replication-coupled nucleosome assembly, DNA damage repair, and gene transcription. Changes or mutations in factors involved in nucleosome assembly are closely related to the development and pathogenesis of cancer and other human diseases and are essential for maintaining genomic stability and epigenetic information transmission. In this review, we discuss the role of different types of histone posttranslational modifications in DNA replication-coupled nucleosome assembly and disease. In recent years, histone modification has been found to affect the deposition of newly synthesized histones and the repair of DNA damage, further affecting the assembly process of DNA replication-coupled nucleosomes. We summarize the role of histone modification in the nucleosome assembly process. At the same time, we review the mechanism of histone modification in cancer development and briefly describe the application of histone modification small molecule inhibitors in cancer therapy.
Gardenia jasminoides Extract, with a Melatonin-Like Activity, Protects against Digital Stress and Reverses Signs of Aging
Authors: De Tollenaere Morgane , Chapuis Emilie , Martinez Jessy , Paulus Chantal , Dupont Joran , Don Simoni Eglantine , Robe Patrick , Sennelier-Portet Bénédicte , Auriol Daniel , Scandolera Amandine , Reynaud Romain
Published: March 2023

Digital stress is a newly identified cosmetic stress that is mainly characterized by blue light exposure. The effects of this stress have become increasingly important with the emergence of personal digital devices, and its deleterious effects on the body are now well-known. Blue light has been observed to cause perturbation of the natural melatonin cycle and skin damage similar to that from UVA exposure, thus leading to premature aging. “A melatonin-like ingredient” was discovered in the extract of Gardenia jasminoides, which acts as a filter against blue light and as a melatonin-like ingredient to prevent and stop premature aging. The extract showed significant protective effects on the mitochondrial network of primary fibroblasts, a significant decrease of −86% in oxidized proteins on skin explants, and preservation of the natural melatonin cycle in the co-cultures of sensory neurons and keratinocytes. Upon analysis using in silico methods, only the crocetin form, released through skin microbiota activation, was found to act as a melatonin-like molecule by interacting with the MT1-receptor, thus confirming its melatonin-like properties. Finally, clinical studies revealed a significant decrease in wrinkle number of −21% in comparison to the placebo. The extract showed strong protection against blue light damage and the prevention of premature aging through its melatonin-like properties.
Silk Sericin Protein Materials: Characteristics and Applications in Food-Sector Industries
Authors: Seo Su-Jin , Das Gitishree , Shin Han-Seung , Patra Jayanta Kumar
Published: March 2023

There is growing concern about the use of plastic in packaging for food materials, as this results in increased plastic waste materials in the environment. To counter this, alternative sources of packaging materials that are natural and based on eco-friendly materials and proteins have been widely investigated for their potential application in food packaging and other industries of the food sector. Sericin, a silk protein that is usually discarded in large quantities by the sericulture and textile industries during the degumming process of manufacturing silk from silk cocoons, can be explored for its application in food packaging and in other food sectors as a functional food and component of food items. Hence, its repurposing can result in reduced economic costs and environmental waste. Sericin extracted from silk cocoon possesses several useful amino acids, such as aspartic acid, glycine, and serine. Likewise, sericin is strongly hydrophilic, a property that confers effective biological and biocompatible characteristics, including antibacterial, antioxidant, anticancer, and anti-tyrosinase properties. When used in combination with other biomaterials, sericin has proved to be effective in the manufacture of films or coating or packaging materials. In this review, the characteristics of sericin materials and their potential application in food-sector industries are discussed in detail.
Effects of Single and Combined Ciprofloxacin and Lead Treatments on Zebrafish Behavior, Oxidative Stress, and Elements Content
Authors: Jijie Roxana , Paduraru Emanuela , Simionov Ira-Adeline , Faggio Caterina , Ciobica Alin , Nicoara Mircea
Published: March 2023

Even though the toxic effects of antibiotics and heavy metals have been extensively studied in the last decades, their combined adverse impact on aquatic organisms is poorly understood. Therefore, the objective of this study was to assess the acute effects of a ciprofloxacin (Cipro) and lead (Pb) mixture on the 3D swimming behavior, acetylcholinesterase (AChE) activity, lipid peroxidation level (MDA—malondialdehyde), activity of some oxidative stress markers (SOD—superoxide dismutase and GPx—glutathione peroxidase), and the essential elements content (Cu—copper, Zn—zinc, Fe—iron, Ca—calcium, Mg—magnesium, Na—sodium and K—potassium) in the body of zebrafish (Danio rerio). For this purpose, zebrafish were exposed to environmentally relevant concentrations of Cipro, Pb, and a mixture for 96 h. The results revealed that acute exposure to Pb alone and in mixture with Cipro impaired zebrafish exploratory behavior by decreasing swimming activity and elevating freezing duration. Moreover, significant deficiencies of Ca, K, Mg, and Na contents, as well as an excess of Zn level, were observed in fish tissues after exposure to the binary mixture. Likewise, the combined treatment with Pb and Cipro inhibited the activity of AChE and increased the GPx activity and MDA level. The mixture produced more damage in all studied endpoints, while Cipro had no significant effect. The findings highlight that the simultaneous presence of antibiotics and heavy metals in the environment can pose a threat to the health of living organisms.
Targeting Mitochondrial Metabolic Reprogramming as a Potential Approach for Cancer Therapy
Authors: Zhang Liufeng , Wei Yuancheng , Yuan Shengtao , Sun Li
Published: March 2023

Abnormal energy metabolism is a characteristic of tumor cells, and mitochondria are important components of tumor metabolic reprogramming. Mitochondria have gradually received the attention of scientists due to their important functions, such as providing chemical energy, producing substrates for tumor anabolism, controlling REDOX and calcium homeostasis, participating in the regulation of transcription, and controlling cell death. Based on the concept of reprogramming mitochondrial metabolism, a range of drugs have been developed to target the mitochondria. In this review, we discuss the current progress in mitochondrial metabolic reprogramming and summarized the corresponding treatment options. Finally, we propose mitochondrial inner membrane transporters as new and feasible therapeutic targets.
miRNome and Proteome Profiling of Human Keratinocytes and Adipose Derived Stem Cells Proposed miRNA-Mediated Regulations of Epidermal Growth Factor and Interleukin 1-Alpha
Authors: Shahin Hady , Abdallah Sallam , Das Jyotirmoy , He Weihai , El-Serafi Ibrahim , Steinvall Ingrid , Sjöberg Folke , Elmasry Moustafa , El-Serafi Ahmed T.
Published: March 2023

Wound healing is regulated by complex crosstalk between keratinocytes and other cell types, including stem cells. In this study, a 7-day direct co-culture model of human keratinocytes and adipose-derived stem cells (ADSCs) was proposed to study the interaction between the two cell types, in order to identify regulators of ADSCs differentiation toward the epidermal lineage. As major mediators of cell communication, miRNome and proteome profiles in cell lysates of cultured human keratinocytes and ADSCs were explored through experimental and computational analyses. GeneChip® miRNA microarray, identified 378 differentially expressed miRNAs; of these, 114 miRNAs were upregulated and 264 miRNAs were downregulated in keratinocytes. According to miRNA target prediction databases and the Expression Atlas database, 109 skin-related genes were obtained. Pathway enrichment analysis revealed 14 pathways including vesicle-mediated transport, signaling by interleukin, and others. Proteome profiling showed a significant upregulation of the epidermal growth factor (EGF) and Interleukin 1-alpha (IL-1α) compared to ADSCs. Integrated analysis through cross-matching the differentially expressed miRNA and proteins suggested two potential pathways for regulations of epidermal differentiation; the first is EGF-based through the downregulation of miR-485-5p and miR-6765-5p and/or the upregulation of miR-4459. The second is mediated by IL-1α overexpression through four isomers of miR-30-5p and miR-181a-5p.
In Situ Formation of Injectable Gelatin Methacryloyl (GelMA) Hydrogels for Effective Intraocular Delivery of Triamcinolone Acetonide
Authors: Shen Chaolan , Zhao Xuan , Ren Zewen , Yang Bing , Wang Xiaohui , Hu Andina , Hu Jie
Published: March 2023

A novel drug delivery system designed for intraocular injection, gelatin methacryloyl (GelMA), has attracted much attention due to its sustained-release character and low cytotoxicity. We aimed to explore the sustained drug effect of GelMA hydrogels coupled with triamcinolone acetonide (TA) after injection into the vitreous cavity. The GelMA hydrogel formulations were characterized using scanning electron microscopy, swelling measurements, biodegradation, and release studies. The biological safety effect of GelMA on human retinal pigment epithelial cells and retinal conditions was verified by in vitro and in vivo experiments. The hydrogel exhibited a low swelling ratio, resistance to enzymatic degradation, and excellent biocompatibility. The swelling properties and in vitro biodegradation characteristics were related to the gel concentration. Rapid gel formation was observed after injection, and the in vitro release study confirmed that TA-hydrogels have slower and more prolonged release kinetics than TA suspensions. In vivo fundus imaging, optical coherence tomography measurements of retinal and choroid thickness, and immunohistochemistry did not reveal any apparent abnormalities of retinal or anterior chamber angle, and ERG indicated that the hydrogel had no impact on retinal function. The GelMA hydrogel implantable intraocular device exhibited an extended duration, in situ polymerization, and support cell viability, making it an attractive, safe, and well-controlled platform for treating the posterior segment diseases of the eye.
Status of Metabolomic Measurement for Insights in Alzheimer’s Disease Progression—What Is Missing?
Authors: Yin Chunyuan , Harms Amy C. , Hankemeier Thomas , Kindt Alida , de Lange Elizabeth C. M.
Published: March 2023

Alzheimer’s disease (AD) is an aging-related neurodegenerative disease, leading to the progressive loss of memory and other cognitive functions. As there is still no cure for AD, the growth in the number of susceptible individuals represents a major emerging threat to public health. Currently, the pathogenesis and etiology of AD remain poorly understood, while no efficient treatments are available to slow down the degenerative effects of AD. Metabolomics allows the study of biochemical alterations in pathological processes which may be involved in AD progression and to discover new therapeutic targets. In this review, we summarized and analyzed the results from studies on metabolomics analysis performed in biological samples of AD subjects and AD animal models. Then this information was analyzed by using MetaboAnalyst to find the disturbed pathways among different sample types in human and animal models at different disease stages. We discuss the underlying biochemical mechanisms involved, and the extent to which they could impact the specific hallmarks of AD. Then we identify gaps and challenges and provide recommendations for future metabolomics approaches to better understand AD pathogenesis.
Preclinical Ultrasonography in Rodent Models of Neuromuscular Disorders: The State of the Art for Diagnostic and Therapeutic Applications
Authors: Mele Antonietta , Mantuano Paola , Boccanegra Brigida , Conte Elena , Liantonio Antonella , De Luca Annamaria
Published: March 2023

Ultrasonography is a safe, non-invasive imaging technique used in several fields of medicine, offering the possibility to longitudinally monitor disease progression and treatment efficacy over time. This is particularly useful when a close follow-up is required, or in patients with pacemakers (not suitable for magnetic resonance imaging). By virtue of these advantages, ultrasonography is commonly used to detect multiple skeletal muscle structural and functional parameters in sports medicine, as well as in neuromuscular disorders, e.g., myotonic dystrophy and Duchenne muscular dystrophy (DMD). The recent development of high-resolution ultrasound devices allowed the use of this technique in preclinical settings, particularly for echocardiographic assessments that make use of specific guidelines, currently lacking for skeletal muscle measurements. In this review, we describe the state of the art for ultrasound skeletal muscle applications in preclinical studies conducted in small rodents, aiming to provide the scientific community with necessary information to support an independent validation of these procedures for the achievement of standard protocols and reference values useful in translational research on neuromuscular disorders.
Targeting Cellular Retinoic Acid Binding Protein 1 with Retinoic Acid-like Compounds to Mitigate Motor Neuron Degeneration
Authors: Nhieu Jennifer , Milbauer Liming , Lerdall Thomas , Najjar Fatimah , Wei Chin-Wen , Ishida Ryosuke , Ma Yue , Kagechika Hiroyuki , Wei Li-Na
Published: March 2023

All-trans-retinoic Acid (atRA) is the principal active metabolite of Vitamin A, essential for various biological processes. The activities of atRA are mediated by nuclear RA receptors (RARs) to alter gene expression (canonical activities) or by cellular retinoic acid binding protein 1 (CRABP1) to rapidly (minutes) modulate cytosolic kinase signaling, including calcium calmodulin-activated kinase 2 (CaMKII) (non-canonical activities). Clinically, atRA-like compounds have been extensively studied for therapeutic applications; however, RAR-mediated toxicity severely hindered the progress. It is highly desirable to identify CRABP1-binding ligands that lack RAR activity. Studies of CRABP1 knockout (CKO) mice revealed CRABP1 to be a new therapeutic target, especially for motor neuron (MN) degenerative diseases where CaMKII signaling in MN is critical. This study reports a P19-MN differentiation system, enabling studies of CRABP1 ligands in various stages of MN differentiation, and identifies a new CRABP1-binding ligand C32. Using the P19-MN differentiation system, the study establishes C32 and previously reported C4 as CRABP1 ligands that can modulate CaMKII activation in the P19-MN differentiation process. Further, in committed MN cells, elevating CRABP1 reduces excitotoxicity-triggered MN death, supporting a protective role for CRABP1 signaling in MN survival. C32 and C4 CRABP1 ligands were also protective against excitotoxicity-triggered MN death. The results provide insight into the potential of signaling pathway-selective, CRABP1-binding, atRA-like ligands in mitigating MN degenerative diseases.
BRCA Mutations—The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers
Authors: Loboda Anna P. , Adonin Leonid S. , Zvereva Svetlana D. , Guschin Dmitri Y. , Korneenko Tatyana V. , Telegina Alexandra V. , Kondratieva Olga K. , Frolova Sofia E. , Pestov Nikolay B. , Barlev Nick A.
Published: March 2023

Two related tumor suppressor genes, BRCA1 and BRCA2, attract a lot of attention from both fundamental and clinical points of view. Oncogenic hereditary mutations in these genes are firmly linked to the early onset of breast and ovarian cancers. However, the molecular mechanisms that drive extensive mutagenesis in these genes are not known. In this review, we hypothesize that one of the potential mechanisms behind this phenomenon can be mediated by Alu mobile genomic elements. Linking mutations in the BRCA1 and BRCA2 genes to the general mechanisms of genome stability and DNA repair is critical to ensure the rationalized choice of anti-cancer therapy. Accordingly, we review the literature available on the mechanisms of DNA damage repair where these proteins are involved, and how the inactivating mutations in these genes (BRCAness) can be exploited in anti-cancer therapy. We also discuss a hypothesis explaining why breast and ovarian epithelial tissues are preferentially susceptible to mutations in BRCA genes. Finally, we discuss prospective novel therapeutic approaches for treating BRCAness cancers.
Approaches to Reduce Rice Blast Disease Using Knowledge from Host Resistance and Pathogen Pathogenicity
Authors: Younas Muhammad Usama , Wang Guanda , Du Haibo , Zhang Yi , Ahmad Irshad , Rajput Nimra , Li Mingyou , Feng Zhiming , Hu Keming , Khan Nasr Ullah , Xie Wenya , Qasim Muhammad , Chen Zongxiang , Zuo Shimin
Published: March 2023

Rice is one of the staple foods for the majority of the global population that depends directly or indirectly on it. The yield of this important crop is constantly challenged by various biotic stresses. Rice blast, caused by Magnaporthe oryzae (M. oryzae), is a devastating rice disease causing severe yield losses annually and threatening rice production globally. The development of a resistant variety is one of the most effective and economical approaches to control rice blast. Researchers in the past few decades have witnessed the characterization of several qualitative resistance (R) and quantitative resistance (qR) genes to blast disease as well as several avirulence (Avr) genes from the pathogen. These provide great help for either breeders to develop a resistant variety or pathologists to monitor the dynamics of pathogenic isolates, and ultimately to control the disease. Here, we summarize the current status of the isolation of R, qR and Avr genes in the rice–M. oryzae interaction system, and review the progresses and problems of these genes utilized in practice for reducing rice blast disease. Research perspectives towards better managing blast disease by developing a broad-spectrum and durable blast resistance variety and new fungicides are also discussed.
In Vitro Characteristics of Canine Primary Tracheal Epithelial Cells Maintained at an Air–Liquid Interface Compared to In Vivo Morphology
Authors: Runft Sandra , Färber Iris , Krüger Johannes , Schöne Kerstin , Lehmbecker Annika , Baumgärtner Wolfgang
Published: March 2023

Culturing respiratory epithelial cells at an air–liquid interface (ALI) represents an established method for studies on infection or toxicology by the generation of an in vivo-like respiratory tract epithelial cellular layer. Although primary respiratory cells from a variety of animals have been cultured, an in-depth characterization of canine tracheal ALI cultures is lacking despite the fact that canines are a highly relevant animal species susceptible to various respiratory agents, including zoonotic pathogens such as severe acute respiratory coronavirus 2 (SARS-CoV-2). In this study, canine primary tracheal epithelial cells were cultured under ALI conditions for four weeks, and their development was characterized during the entire culture period. Light and electron microscopy were performed to evaluate cell morphology in correlation with the immunohistological expression profile. The formation of tight junctions was confirmed using transepithelial electrical resistance (TEER) measurements and immunofluorescence staining for the junctional protein ZO-1. After 21 days of culture at the ALI, a columnar epithelium containing basal, ciliated and goblet cells was seen, resembling native canine tracheal samples. However, cilia formation, goblet cell distribution and epithelial thickness differed significantly from the native tissue. Despite this limitation, tracheal ALI cultures could be used to investigate the pathomorphological interactions of canine respiratory diseases and zoonotic agents.
Extracellular Calcium-Induced Calcium Transient Regulating the Proliferation of Osteoblasts through Glycolysis Metabolism Pathways
Authors: Gao Xiaohang , Di Xiaohui , Li Jingjing , Kang Yiting , Xie Wenjun , Sun Lijun , Zhang Jianbao
Published: March 2023

During bone remodeling, high extracellular calcium levels accumulated around the resorbing bone tissue as soon as the activation of osteoclasts. However, if and how calcium is involved in the regulation of bone remodeling remains unclear. In this study, the effect of high extracellular calcium concentrations on osteoblast proliferation and differentiation, intracellular calcium ([Ca2+]i) levels, metabolomics, and the expression of proteins related to energy metabolism were investigated. Our results showed that high extracellular calcium levels initiated a [Ca2+]i transient via the calcium-sensing receptor (CaSR) and promoted the proliferation of MC3T3-E1 cells. Metabolomics analysis showed that the proliferation of MC3T3-E1 cells was dependent on aerobic glycolysis, but not the tricarboxylic acid cycle. Moreover, the proliferation and glycolysis of MC3T3-E1 cells were suppressed following the inhibition of AKT. These results indicate that calcium transient triggered by high extracellular calcium levels activated glycolysis via AKT-related signaling pathways and ultimately promoted the proliferation of osteoblasts.
PPARβ/δ Ligands Regulate Oxidative Status and Inflammatory Response in Inflamed Corpus Luteum—An In Vitro Study
Authors: Mierzejewski Karol , Kurzyńska Aleksandra , Gerwel Zuzanna , Golubska Monika , Stryiński Robert , Bogacka Iwona
Published: March 2023

Inflammation in the female reproductive system causes serious health problems including infertility. The aim of this study was to determine the in vitro effects of peroxisome proliferator-activated receptor-beta/delta (PPARβ/δ) ligands on the transcriptomic profile of the lipopolysaccharide (LPS)-stimulated pig corpus luteum (CL) in the mid-luteal phase of the estrous cycle using RNA-seq technology. The CL slices were incubated in the presence of LPS or in combination with LPS and the PPARβ/δ agonist—GW0724 (1 μmol/L or 10 μmol/L) or the antagonist—GSK3787 (25 μmol/L). We identified 117 differentially expressed genes after treatment with LPS; 102 and 97 differentially expressed genes after treatment, respectively, with the PPARβ/δ agonist at a concentration of 1 μmol/L or 10 μmol/L, as well as 88 after the treatment with the PPARβ/δ antagonist. In addition, biochemical analyses of oxidative status were performed (total antioxidant capacity and activity of peroxidase, catalase, superoxide dismutase, and glutathione S-transferase). This study revealed that PPARβ/δ agonists regulate genes involved in the inflammatory response in a dose-dependent manner. The results indicate that the lower dose of GW0724 showed an anti-inflammatory character, while the higher dose seems to be pro-inflammatory. We propose that GW0724 should be considered for further research to alleviate chronic inflammation (at the lower dose) or to support the natural immune response against pathogens (at the higher dose) in the inflamed corpus luteum.
SPRED2: A Novel Regulator of Epithelial-Mesenchymal Transition and Stemness in Hepatocellular Carcinoma Cells
Authors: Gao Tong , Yang Xu , Fujisawa Masayoshi , Ohara Toshiaki , Wang Tianyi , Tomonobu Nahoko , Sakaguchi Masakiyo , Yoshimura Teizo , Matsukawa Akihiro
Published: March 2023

The downregulation of SPRED2, a negative regulator of the ERK1/2 pathway, was previously detected in human cancers; however, the biological consequence remains unknown. Here, we investigated the effects of SPRED2 loss on hepatocellular carcinoma (HCC) cell function. Human HCC cell lines, expressing various levels of SPRED2 and SPRED2 knockdown, increased ERK1/2 activation. SPRED2-knockout (KO)-HepG2 cells displayed an elongated spindle shape with increased cell migration/invasion and cadherin switching, with features of epithelial–mesenchymal transition (EMT). SPRED2-KO cells demonstrated a higher ability to form spheres and colonies, expressed higher levels of stemness markers and were more resistant to cisplatin. Interestingly, SPRED2-KO cells also expressed higher levels of the stem cell surface markers CD44 and CD90. When CD44+CD90+ and CD44−CD90− populations from WT cells were analyzed, a lower level of SPRED2 and higher levels of stem cell markers were detected in CD44+CD90+ cells. Further, endogenous SPRED2 expression decreased when WT cells were cultured in 3D, but was restored in 2D culture. Finally, the levels of SPRED2 in clinical HCC tissues were significantly lower than those in adjacent non-HCC tissues and were negatively associated with progression-free survival. Thus, the downregulation of SPRED2 in HCC promotes EMT and stemness through the activation of the ERK1/2 pathway, and leads to more malignant phenotypes.
Genome-Wide Identification of Homeodomain Leucine Zipper (HD-ZIP) Transcription Factor, Expression Analysis, and Protein Interaction of HD-ZIP IV in Oil Palm Somatic Embryogenesis
Authors: Khianchaikhan Kamolwan , Aroonluk Suvichark , Vuttipongchaikij Supachai , Jantasuriyarat Chatchawan
Published: March 2023

Understanding the molecular mechanisms underlying somatic embryogenesis is essential for resolving the problems related to the long duration of the process and a low rate of somatic embryo induction in oil palm tissue culture. In this study, we conducted genome-wide identification of the oil palm homeodomain leucine zipper (EgHD-ZIP) family, which is one of the plant-specific transcription factors reported to be involved in embryogenesis. EgHD-ZIP proteins can be divided into four subfamilies, which have similarities in gene structure and protein-conserved motifs within a group. In silico expression analysis showed that the expression of EgHD-ZIP gene members in the EgHD-ZIP I and II families, as well as most members in the EgHD-ZIP IV family, were up-regulated during the zygotic and somatic embryo developmental stages. In contrast, the expression of EgHD-ZIP gene members in the EgHD-ZIP III family was down-regulated during zygotic embryo development. Moreover, the expression of EgHD-ZIP IV genes was validated in the oil palm callus and at the somatic embryo stages (globular, torpedo, and cotyledon). The results revealed that EgHD-ZIP IV genes were up-regulated at the late stages of somatic embryogenesis (torpedo and cotyledon). While BABY BOOM (BBM) gene was up-regulated at the early stage of somatic embryogenesis (globular). In addition, the Yeast-two hybrid assay revealed the direct binding between all members of the oil palm HD-ZIP IV subfamily (EgROC2, EgROC3, EgROC5, EgROC8, and EgBBM). Our findings suggested that the EgHD-ZIP IV subfamily and EgBBM work together to regulate somatic embryogenesis in oil palms. This process is important because it is widely used in plant biotechnology to produce large quantities of genetically identical plants, which can be used for oil palm tissue culture improvement.
In Silico Screening and Molecular Dynamics Simulation Studies in the Identification of Natural Compound Inhibitors Targeting the Human Norovirus RdRp Protein to Fight Gastroenteritis
Authors: Obaid Rami J. , Shafie Alaa , Malik M. Shaheer , Al-Rooqi Munirah M. , Moussa Ziad , Abdulaziz Osama , Aljuaid Abdulelah , Allahyani Mamdouh , Almehmadi Mazen , Anjum Farah , Ahmed Saleh A.
Published: March 2023

Norovirus (HNoV) is a leading cause of gastroenteritis globally, and there are currently no treatment options or vaccines available to combat it. RNA-dependent RNA polymerase (RdRp), one of the viral proteins that direct viral replication, is a feasible target for therapeutic development. Despite the discovery of a small number of HNoV RdRp inhibitors, the majority of them have been found to possess a little effect on viral replication, owing to low cell penetrability and drug-likeness. Therefore, antiviral agents that target RdRp are in high demand. For this purpose, we used in silico screening of a library of 473 natural compounds targeting the RdRp active site. The top two compounds, ZINC66112069 and ZINC69481850, were chosen based on their binding energy (BE), physicochemical and drug-likeness properties, and molecular interactions. ZINC66112069 and ZINC69481850 interacted with key residues of RdRp with BEs of −9.7, and −9.4 kcal/mol, respectively, while the positive control had a BE of −9.0 kcal/mol with RdRp. In addition, hits interacted with key residues of RdRp and shared several residues with the PPNDS, the positive control. Furthermore, the docked complexes showed good stability during the molecular dynamic simulation of 100 ns. ZINC66112069 and ZINC69481850 could be proven as potential inhibitors of the HNoV RdRp in future antiviral medication development investigations.
Evaluation of the Synovial Effects of Biological and Targeted Synthetic DMARDs in Patients with Psoriatic Arthritis: A Systematic Literature Review and Meta-Analysis
Authors: Ciliento Maria Sofia , Venturelli Veronica , Schettini Natale , Bertola Riccardo , Garaffoni Carlo , Lanza Giovanni , Gafà Roberta , Borghi Alessandro , Corazza Monica , Zabotti Alen , Missiroli Sonia , Boncompagni Caterina , Patergnani Simone , Perrone Mariasole , Giorgi Carlotta , Pinton Paolo , Govoni Marcello , Scirè Carlo Alberto , Bortoluzzi Alessandra , Silvagni Ettore
Published: March 2023

The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD −0.85 [95% CI −1.23; −0.47]) and CD68+ macrophages (sublining, sl) (SMD −0.74 [−1.16; −0.32]) in synovial biopsies from patients treated for 4–12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature.
Revisiting Host-Pathogen Interactions in Cystic Fibrosis Lungs in the Era of CFTR Modulators
Authors: Ribeiro Carla M. P. , Higgs Matthew G. , Muhlebach Marianne S. , Wolfgang Matthew C. , Borgatti Monica , Lampronti Ilaria , Cabrini Giulio
Published: March 2023

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, a new series of therapeutics that correct and potentiate some classes of mutations of the CFTR, have provided a great therapeutic advantage to people with cystic fibrosis (pwCF). The main hindrances of the present CFTR modulators are related to their limitations in reducing chronic lung bacterial infection and inflammation, the main causes of pulmonary tissue damage and progressive respiratory insufficiency, particularly in adults with CF. Here, the most debated issues of the pulmonary bacterial infection and inflammatory processes in pwCF are revisited. Special attention is given to the mechanisms favoring the bacterial infection of pwCF, the progressive adaptation of Pseudomonas aeruginosa and its interplay with Staphylococcus aureus, the cross-talk among bacteria, the bronchial epithelial cells and the phagocytes of the host immune defenses. The most recent findings of the effect of CFTR modulators on bacterial infection and the inflammatory process are also presented to provide critical hints towards the identification of relevant therapeutic targets to overcome the respiratory pathology of pwCF.
Variant Landscape of 15 Genes Involved in Corneal Dystrophies: Report of 30 Families and Comprehensive Analysis of the Literature
Authors: Zhu Di , Wang Junwen , Wang Yingwei , Jiang Yi , Li Shiqiang , Xiao Xueshan , Wang Panfeng , Zhang Qingjiong
Published: March 2023

Corneal dystrophies (CDs) represent a group of inherited diseases characterized by the progressive deposit of abnormal materials in the cornea. This study aimed to describe the variant landscape of 15 genes responsible for CDs based on a cohort of Chinese families and a comparative analysis of literature reports. Families with CDs were recruited from our eye clinic. Their genomic DNA was analyzed using exome sequencing. The detected variants were filtered using multi-step bioinformatics and confirmed using Sanger sequencing. Previously reported variants in the literature were summarized and evaluated based on the gnomAD database and in-house exome data. In 30 of 37 families with CDs, 17 pathogenic or likely pathogenic variants were detected in 4 of the 15 genes, including TGFBI, CHST6, SLC4A11, and ZEB1. A comparative analysis of large datasets revealed that 12 of the 586 reported variants are unlikely causative of CDs in monogenic mode, accounting for 61 of 2933 families in the literature. Of the 15 genes, the gene most frequently implicated in CDs was TGFBI (1823/2902, 62.82% of families), followed by CHST6 (483/2902, 16.64%) and SLC4A11 (201/2902, 6.93%). This study presents, for the first time, the landscape of pathogenic and likely pathogenic variants in the 15 genes responsible for CDs. Awareness of frequently misinterpreted variants, such as c.1501C>A, p.(Pro501Thr) in TGFBI, is crucial in the era of genomic medicine.
Aurora B Kinase Inhibition by AZD1152 Concomitant with Tumor Treating Fields Is Effective in the Treatment of Cultures from Primary and Recurrent Glioblastomas
Authors: Krex Dietmar , Bartmann Paula , Lachmann Doris , Hagstotz Alexander , Jugel Willi , Schneiderman Rosa , Gotlib Karnit , Porat Yaara , Robel Katja , Temme Achim , Giladi Moshe , Michen Susanne
Published: March 2023

Tumor Treating Fields (TTFields) were incorporated into the treatment of glioblastoma, the most malignant brain tumor, after showing an effect on progression-free and overall survival in a phase III clinical trial. The combination of TTFields and an antimitotic drug might further improve this approach. Here, we tested the combination of TTFields with AZD1152, an Aurora B kinase inhibitor, in primary cultures of newly diagnosed (ndGBM) and recurrent glioblastoma (rGBM). AZD1152 concentration was titrated for each cell line and 5–30 nM were used alone or in addition to TTFields (1.6 V/cm RMS; 200 kHz) applied for 72 h using the inovitro™ system. Cell morphological changes were visualized by conventional and confocal laser microscopy. The cytotoxic effects were determined by cell viability assays. Primary cultures of ndGBM and rGBM varied in p53 mutational status; ploidy; EGFR expression and MGMT-promoter methylation status. Nevertheless; in all primary cultures; a significant cytotoxic effect was found following TTFields treatment alone and in all but one, a significant effect after treatment with AZD1152 alone was also observed. Moreover, in all primary cultures the combined treatment had the most pronounced cytotoxic effect in parallel with morphological changes. The combined treatment of TTFields and AZD1152 led to a significant reduction in the number of ndGBM and rGBM cells compared to each treatment alone. Further evaluation of this approach, which has to be considered as a proof of concept, is warranted, before entering into early clinical trials.
Current Practice in Pediatric Cow’s Milk Protein Allergy–Immunological Features and Beyond
Authors: Emmert Vanessza , Lendvai-Emmert Dominika , Eklics Kata , Prémusz Viktória , Tóth Gergely Péter
Published: March 2023

Cow’s milk protein allergy is one of the most common pediatric food allergies. It poses a significant socioeconomic burden in industrialized countries and has a profound effect on the quality of life of affected individuals and their families. Diverse immunologic pathways can lead to the clinical symptoms of cow’s milk protein allergy; some of the pathomechanisms are known in detail, but others need further elucidation. A comprehensive understanding of the development of food allergies and the features of oral tolerance could have the potential to unlock more precise diagnostic tools and novel therapeutic approaches for patients with cow’s milk protein allergy.
Effects of Hydrostatic-Pressure on Muscle Contraction: A Look Back on Some Experimental Findings
Authors: Ranatunga K. W. , Geeves M. A.
Published: March 2023

Findings from experiments that used hydrostatic pressure changes to analyse the process of skeletal muscle contraction are re-examined. The force in resting muscle is insensitive to an increase in hydrostatic pressure from 0.1 MPa (atmospheric) to 10 MPa, as also found for force in rubber-like elastic filaments. The force in rigour muscle rises with increased pressure, as shown experimentally for normal elastic fibres (e.g., glass, collagen, keratin, etc.). In submaximal active contractions, high pressure leads to tension potentiation. The force in maximally activated muscle decreases with increased pressure: the extent of this force decrease in maximal active muscle is sensitive to the concentration of products of ATP hydrolysis (Pi—inorganic phosphate and ADP—adenosine diphosphate) in the medium. When the increased hydrostatic pressure is rapidly decreased, the force recovered to the atmospheric level in all cases. Thus, the resting muscle force remained the same: the force in the rigour muscle decreased in one phase and that in active muscle increased in two phases. The rate of rise of active force on rapid pressure release increased with the concentration of Pi in the medium, indicating that it is coupled to the Pi release step in the ATPase-driven crossbridge cycle in muscle. Pressure experiments on intact muscle illustrate possible underlying mechanisms of tension potentiation and causes of muscle fatigue.
Beyond the Clinic: The Activation of Diverse Cellular and Humoral Factors Shapes the Immunological Status of Patients with Active Tuberculosis
Authors: Tateosian Nancy Liliana , Morelli María Paula , Pellegrini Joaquín Miguel , García Verónica Edith
Published: March 2023

Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), has killed nearly one billion people in the last two centuries. Nowadays, TB remains a major global health problem, ranking among the thirteen leading causes of death worldwide. Human TB infection spans different levels of stages: incipient, subclinical, latent and active TB, all of them with varying symptoms, microbiological characteristics, immune responses and pathologies profiles. After infection, Mtb interacts with diverse cells of both innate and adaptive immune compartments, playing a crucial role in the modulation and development of the pathology. Underlying TB clinical manifestations, individual immunological profiles can be identified in patients with active TB according to the strength of their immune responses to Mtb infection, defining diverse endotypes. Those different endotypes are regulated by a complex interaction of the patient’s cellular metabolism, genetic background, epigenetics, and gene transcriptional regulation. Here, we review immunological categorizations of TB patients based on the activation of different cellular populations (both myeloid and lymphocytic subsets) and humoral mediators (such as cytokines and lipid mediators). The analysis of the participating factors that operate during active Mtb infection shaping the immunological status or immune endotypes of TB patients could contribute to the development of Host Directed Therapy.
Fabrication of Silane-Grafted Cellulose Nanocrystals and Their Effects on the Structural, Thermal, Mechanical, and Hysteretic Behavior of Thermoplastic Polyurethane
Authors: Sun Xuenan , Yang Xinze , Zhang Jiajing , Shang Bin , Lyu Pei , Zhang Chunhua , Liu Xin , Xia Liangjun
Published: March 2023

Reinforcement of polymer nanocomposites can be achieved by the selection of the appropriate fabrication method, surface modification, and orientation of the filler. Herein, we present a nonsolvent-induced phase separation method with ternary solvents to prepare thermoplastic polyurethane (TPU) composite films with excellent mechanical properties using 3-Glycidyloxypropyltrimethoxysilane-modified cellulose nanocrystals (GLCNCs). ATR-IR and SEM analyses of the GLCNCs confirmed that GL was successfully coated on the surface of the nanocrystals. The incorporation of GLCNCs in TPU resulted in the enhancement of the tensile strain and toughness of pure TPU owing to the enhanced interfacial interactions between them. The GLCNC–TPU composite film had tensile strain and toughness values of 1740.42% and 90.01 MJ/m3, respectively. Additionally, GLCNC–TPU exhibited a good elastic recovery rate. CNCs were readily aligned along the fiber axis after the spinning and drawing of the composites into fibers, which further improved the mechanical properties of the composites. The stress, strain, and toughness of the GLCNC–TPU composite fiber increased by 72.60%, 10.25%, and 103.61%, respectively, compared to those of the pure TPU film. This study demonstrates a facile and effective strategy for fabricating mechanically enhanced TPU composites.
Genetic Variation in Transcription Factor Binding Sites
Authors: Santpere Gabriel
Published: March 2023

The interaction between transcription factors (TFs) and DNA is the core process that determines the state of a cell’s transcriptome [...]
A Study of Al2O3/MgO Composite Films Deposited by FCVA for Thin-Film Encapsulation
Authors: Yuan Heng , Zhang Yifan , Li Qian , Yan Weiqing , Zhang Xu , Ouyang Xiao , Ouyang Xiaoping , Chen Lin , Liao Bin
Published: March 2023

Al2O3 and MgO composite (Al2O3/MgO) films were rapidly deposited at low temperatures using filtered cathode vacuum arc (FCVA) technology, aiming to achieve good barrier properties for flexible organic light emitting diodes (OLED) thin-film encapsulation (TFE). As the thickness of the MgO layer decreases, the degree of crystallinity decreases gradually. The 3:2 Al2O3:MgO layer alternation type has the best water vapor shielding performance, and the water vapor transmittance (WVTR) is 3.26 × 10−4 g·m−2·day−1 at 85 °C and 85% R.H, which is about 1/3 of that of a single layer of Al2O3 film. Under the action of ion deposition, too many layers will cause internal defects in the film, resulting in decreased shielding ability. The surface roughness of the composite film is very low, which is about 0.3–0.5 nm depending on its structure. In addition, the visible light transmittance of the composite film is lower than that of a single film and increases with the increase in the number of layers.