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Chinmedomics strategy for elucidating the effects and effective constituents of Danggui Buxue Decoction in treating blood deficiency syndrome Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-15 Ye Zhang, Yu Yang, Junling Ren, Guangli Yan, Le Yang, Xiuhong Wu, Ling Kong, Hui Sun, Ying Han, Xiwu Zhang, Xijun Wang
Introduction:Danggui Buxue Decoction (DBD) is a clinically proven, effective, classical traditional Chinese medicine (TCM) formula for treating blood deficiency syndrome (BDS). However, its effects and effective constituents in the treatment of BDS remain unclear, limiting precise clinical therapy and quality control. This study aimed to accurately evaluate the effects of DBD and identify its effective
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Kinesin-7 CENP-E in tumorigenesis: Chromosome instability, spindle assembly checkpoint, and applications Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-15 Yu-Hao Yang, Ya-Lan Wei, Zhen-Yu She
Kinesin motors are a large family of molecular motors that walk along microtubules to fulfill many roles in intracellular transport, microtubule organization, and chromosome alignment. Kinesin-7 CENP-E (Centromere protein E) is a chromosome scaffold-associated protein that is located in the corona layer of centromeres, which participates in kinetochore-microtubule attachment, chromosome alignment,
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Membrane-assisted tariquidar access and binding mechanisms of human ATP-binding cassette transporter P-glycoprotein Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-15 Yingjie Gao, Caiyan Wei, Lanxin Luo, Yang Tang, Yongzhen Yu, Yaling Li, Juan Xing, Xianchao Pan
The human multidrug transporter P-glycoprotein (P-gp) is physiologically essential and of key relevance to biomedicine. Recent structural studies have shed light on the mode of inhibition of the third-generation inhibitors for human P-gp, but the molecular mechanism by which these inhibitors enter the transmembrane sites remains poorly understood. In this study, we utilized all-atom molecular dynamics
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Urinary metabolic characterization of advanced tuberculous meningitis cases in a South African paediatric population Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-15 Simon Isaiah, Du Toit Loots, Mari van Reenen, Regan Solomons, Sabine van Elsland, A. Marceline Tutu van Furth, Martijn van der Kuip, Shayne Mason
Tuberculous meningitis (TBM) is a severe form of tuberculosis with high neuro-morbidity and mortality, especially among the paediatric population (aged ≤12 years). Little is known of the associated metabolic changes. This study aimed to identify characteristic metabolic markers that differentiate severe cases of paediatric TBM from controls, through non-invasive urine collection. Urine samples selected
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An in vitro analysis of an innovative standardized phospholipid carrier-based Melissa officinalis L. extract as a potential neuromodulator for emotional distress and related conditions Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-13 Mehtap Kara, Sumeyye Sahin, Fazle Rabbani, Ezgi Oztas, Gozde Hasbal-Celikok, Ebru Kanımdan, Abdurrahim Kocyigit, Ayesha Kanwal, Ursula Wade, Anastasia Yakunina, Francesco Di Pierro, Amjad Khan
Background:Melissa officinalis L. (MO), commonly known as lemon balm, a member of the mint family, is considered a calming herb. In various traditional medicines, it has been utilized to reduce stress and anxiety and promote sleep. A growing body of clinical evidence suggests that MO leaf extract supplementation possesses considerable neuropharmacological properties. However, its possible mechanism
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Impact of antiplatelet therapy on microvascular thrombosis during ST-elevation myocardial infarction Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-13 Sophia Khattak, Jonathan N. Townend, Mark R. Thomas
During an acute coronary syndrome, atherosclerotic plaque rupture triggers platelet activation and thrombus formation, which may completely occlude a coronary artery leading to ST-elevation myocardial infarction (STEMI). Although emergency percutaneous coronary intervention (PCI) is effective in re-opening the main coronary arteries, the downstream microvasculature can become obstructed by embolised
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An insight into the role of the N-terminal domain of Salmonella CobB in oligomerization and Zn2+ mediated inhibition of the deacetylase activity Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-13 Shibangini Beura, Pulak Pritam, Ajit Kumar Dhal, Arindam Jana, Aiswarya Dash, Pritisundar Mohanty, Alok Kumar Panda, Rahul Modak
Prokaryotic deacetylases are classified into nicotinamide adenine dinucleotide (NAD+)-dependent sirtuins and Zn2+-dependent deacetylases. NAD+ is a coenzyme for redox reactions, thus serving as an essential component for energy metabolism. The NAD+-dependent deacetylase domain is quite conserved and well characterized across bacterial species like CobB in Escherichia coli and Salmonella, Rv1151c in
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The C-terminal selenenylsulfide of extracellular/non-reduced thioredoxin reductase endows this protein with selectivity to small-molecule electrophilic reagents under oxidative conditions Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-08 Huijun Qin, Chenchen Guo, Bozhen Chen, Hui Huang, Yaping Tian, Liangwei Zhong
Mammalian cytosolic thioredoxin reductase (TrxR1) serves as an antioxidant protein by transferring electrons from NADPH to various substrates. The action of TrxR1 is achieved via reversible changes between NADPH-reduced and non-reduced forms, which involves C-terminal selenolthiol/selenenylsulfide exchanges. TrxR1 may be released into extracellular environment, where TrxR1 is present mainly in the
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Illumination of understudied ciliary kinases Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-08 Raymond G. Flax, Peter Rosston, Cecilia Rocha, Brian Anderson, Jacob L. Capener, Thomas M. Durcan, David H. Drewry, Panagiotis Prinos, Alison D. Axtman
Cilia are cellular signaling hubs. Given that human kinases are central regulators of signaling, it is not surprising that kinases are key players in cilia biology. In fact, many kinases modulate ciliogenesis, which is the generation of cilia, and distinct ciliary pathways. Several of these kinases are understudied with few publications dedicated to the interrogation of their function. Recent efforts
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Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson’s disease in an Egyptian cohort Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-08 Nourhan Shebl, Shaimaa El-Jaafary, Ayman A. Saeed, Passent Elkafrawy, Amr El-Sayed, Samir Shamma, Rasha Elnemr, Jaidaa Mekky, Lobna A. Mohamed, Omar Kittaneh, Hassan El-Fawal, Mie Rizig, Mohamed Salama
Introduction: Parkinson’s disease (PD) is the most common motor neurodegenerative disease worldwide. Given the complexity of PD etiology and the different metabolic derangements correlated to the disease, metabolomics profiling of patients is a helpful tool to identify patho-mechanistic pathways for the disease development. Dopamine metabolism has been the target of several previous studies, of which
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Structural insights into the C-terminus of the histone-lysine N-methyltransferase NSD3 by small-angle X-ray scattering Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-07 Benny Danilo Belviso, Yunpeng Shen, Benedetta Carrozzini, Masayo Morishita, Eric di Luccio, Rocco Caliandro
NSD3 is a member of six H3K36-specific histone lysine methyltransferases in metazoans. Its overexpression or mutation is implicated in developmental defects and oncogenesis. Aside from the well-characterized catalytic SET domain, NSD3 has multiple clinically relevant potential chromatin-binding motifs, such as the proline–tryptophan–tryptophan–proline (PWWP), the plant homeodomain (PHD), and the adjacent
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Anion exchange HPLC monitoring of mRNA in vitro transcription reactions to support mRNA manufacturing process development Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-07 Emma N. Welbourne, Kate A. Loveday, Adithya Nair, Ehsan Nourafkan, Jixin Qu, Ken Cook, Zoltán Kis, Mark J. Dickman
mRNA technology has recently demonstrated the ability to significantly change the timeline for developing and delivering a new vaccine from years to months. The potential of mRNA technology for rapid vaccine development has recently been highlighted by the successful development and approval of two mRNA vaccines for COVID-19. Importantly, this RNA-based approach holds promise for treatments beyond
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The underlying mechanisms of arenaviral entry through matriglycan Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-07 Michael Katz, Ron Diskin
Matriglycan, a recently characterized linear polysaccharide, is composed of alternating xylose and glucuronic acid subunits bound to the ubiquitously expressed protein α-dystroglycan (α-DG). Pathogenic arenaviruses, like the Lassa virus (LASV), hijack this long linear polysaccharide to gain cellular entry. Until recently, it was unclear through what mechanisms LASV engages its matriglycan receptor
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Emerging roles of long non-coding RNAs in osteosarcoma Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-07 Xun Liao, Rong Wei, Junxiu Zhou, Ke Wu, Jiao Li
Osteosarcoma (OS) is a highly aggressive and lethal malignant bone tumor that primarily afflicts children, adolescents, and young adults. However, the molecular mechanisms underlying OS pathogenesis remain obscure. Mounting evidence implicates dysregulated long non-coding RNAs (lncRNAs) in tumorigenesis and progression. These lncRNAs play a pivotal role in modulating gene expression at diverse epigenetic
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Proband-independent haplotyping based on NGS-based long-read sequencing for detecting pathogenic variant carrier status in preimplantation genetic testing for monogenic diseases Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-07 Peiyu Zhang, Xiaomei Zhao, Qinshan Li, Yaqiong Xu, Zengmei Cheng, Lu Yang, Houmei Wang, Yang Tao, Guanyou Huang, Rui Wu, Hua Zhou, Shuyun Zhao
Preimplantation genetic testing for monogenic diseases (PGT-M) can be used to select embryos that do not develop disease phenotypes or carry disease-causing genes for implantation into the mother’s uterus, to block disease transmission to the offspring, and to increase the birth rate of healthy newborns. However, the traditional PGT-M technique has some limitations, such as its time consumption, experimental
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A GC–MS-based untargeted metabolomics approach for comprehensive metabolic profiling of mycophenolate mofetil-induced toxicity in mice Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-07 Tongfeng Zhao, Yaxin Zhao, Haotian Chen, Wenxue Sun, Yun Guan
Background: Mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid, is widely used for maintenance immunosuppression in transplantation. The gastrointestinal toxicity of MMF has been widely uncovered. However, the comprehensive metabolic analysis of MMF-induced toxicity is lacking. This study is aimed to ascertain the metabolic changes after MMF administration in mice.Methods:
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Genetic ablation of Lmp2 increases the susceptibility for impaired cardiac function Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-07 Felix A. Trogisch, Franziska Koser, Synje Michel, David A. Liem, Bogdan I. Florea, Markus Hecker, Oliver Drews
Proteasome degradation is an integral part of cellular growth and function. Proteasomal intervention may mitigate adverse myocardial remodeling, but is associated with the onset of heart failure. Previously, we have demonstrated that increasing abundance of cardiac Lmp2 and its incorporation into proteasome complexes is an endogenous mechanism for proteasome regulation during hypertrophic remodeling
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Transfer of membrane(s) matter(s)—non-genetic inheritance of (metabolic) phenotypes? Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-07 Günter A. Müller, Timo D. Müller
Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are anchored at the outer phospholipid layer of eukaryotic plasma membranes exclusively by a glycolipid. GPI-APs are not only released into extracellular compartments by lipolytic cleavage. In addition, certain GPI-APs with the glycosylphosphatidylinositol anchor including their fatty acids remaining coupled to the carboxy-terminus of their protein
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The structural properties of full-length annexin A11 Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-07 Erika F. Dudas, Mark D. Tully, Tamas Foldes, Geoff Kelly, Gian Gaetano Tartaglia, Annalisa Pastore
Annexin A11 (ANXA11) is a calcium-dependent phospholipid-binding protein belonging to the annexin protein family and implicated in the neurodegenerative amyotrophic lateral sclerosis. Structurally, ANXA11 contains a conserved calcium-binding C-terminal domain common to all annexins and a putative intrinsically unfolded N-terminus specific for ANXA11. Little is known about the structure and functions
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Revealing innovative JAK1 and JAK3 inhibitors: a comprehensive study utilizing QSAR, 3D-Pharmacophore screening, molecular docking, molecular dynamics, and MM/GBSA analyses Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-07 Abdelmoujoud Faris, Ivana Cacciatore, Radwan Alnajjar, Hadni Hanine, Adnane Aouidate, Ramzi A. Mothana, Abdullah R. Alanzi, Menana Elhallaoui
The heterocycle compounds, with their diverse functionalities, are particularly effective in inhibiting Janus kinases (JAKs). Therefore, it is crucial to identify the correlation between their complex structures and biological activities for the development of new drugs for the treatment of rheumatoid arthritis (RA) and cancer. In this study, a diverse set of 28 heterocyclic compounds selective for
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Integrating virtual screening, pharmacoinformatics profiling, and molecular dynamics: identification of promising inhibitors targeting 3CLpro of SARS-CoV-2 Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-07 Abeer Mohammad, Ahmed Zheoat, Amjad Oraibi, Ajay Manaithiya, Khalid S. Almaary, Hiba Allah Nafidi, Mohammed Bourhia, Soumaya Kilani-Jaziri, Yousef A. Bin Jardan
Introduction: The pursuit of effective therapeutic solutions for SARS-CoV-2 infections and COVID-19 necessitates the repurposing of existing compounds. This study focuses on the detailed examination of the central protease, 3-chymotrypsin-like protease (3CLpro), a pivotal player in virus replication. The combined approach of molecular dynamics simulations and virtual screening is employed to identify
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Cryo-electron microscopy-based drug design Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-04 Ecenur Cebi, Joohyun Lee, Vinod Kumar Subramani, Nayeon Bak, Changsuk Oh, Kyeong Kyu Kim
Structure-based drug design (SBDD) has gained popularity owing to its ability to develop more potent drugs compared to conventional drug-discovery methods. The success of SBDD relies heavily on obtaining the three-dimensional structures of drug targets. X-ray crystallography is the primary method used for solving structures and aiding the SBDD workflow; however, it is not suitable for all targets.
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Unveiling the affinity–stability relationship in anti-measles virus antibodies: a computational approach for hotspots prediction Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-03-01 Rimpa Paul, Keisuke Kasahara, Jiei Sasaki, Jorge Fernández Pérez, Ryo Matsunaga, Takao Hashiguchi, Daisuke Kuroda, Kouhei Tsumoto
Recent years have seen an uptick in the use of computational applications in antibody engineering. These tools have enhanced our ability to predict interactions with antigens and immunogenicity, facilitate humanization, and serve other critical functions. However, several studies highlight the concern of potential trade-offs between antibody affinity and stability in antibody engineering. In this study
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Serum ferritin and neutrophil-to-lymphocyte ratio predict all-cause mortality in patients receiving maintenance hemodialysis: a prospective study Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-29 Jiamin He, Changyan Li, Jie Ge, Zhen Li, Lingyan Cao, Wenxing Fan, Yunzhu Peng, Qiongfang Li
Introduction: Maintenance hemodialysis is an effective treatment for end-stage renal disease patients. A critical factor contributing to the deterioration and death of maintenance hemodialysis patients is inflammation. Therefore, we focused on two inflammatory markers, serum ferritin and neutrophil-to-lymphocyte ratio, to speculate whether they could predict the prognosis of maintenance hemodialysis
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Distinguishing two distinct types of salivary extracellular vesicles: a potential tool for understanding their pathophysiological roles Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-28 Yuko Ogawa, Yuri Miura, Mamoru Ikemoto, Atsushi Ohnishi, Yoshikuni Goto, Kazuma Aoki, Yuki Motokurumada, Yoshihiro Akimoto, Tamao Endo, Masafumi Tsujimoto, Ryohei Yanoshita
Extracellular vesicles (EVs), which are found in almost all cells and human body fluids, are currently being studied as a source of pathophysiological information. Previously, we demonstrated that at least two types of EVs can be isolated from human whole saliva (WS) using enzymatic activity of dipeptidyl peptidase IV (DPP IV) as a marker for differentiating the EV subsets. In the present study, EV
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Urtica pilulifera leaves extract mitigates cadmium induced hepatotoxicity via modulation of antioxidants, inflammatory markers and Nrf-2 signaling in mice Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-26 Shaimaa Hussein, Abir Ben Bacha, Mona Alonazi, Maha Abdullah Alwaili, Maysa A. Mobasher, Najla Ali Alburae, Abeer A. Banjabi, Karim Samy El-Said
Introduction: Cadmium (Cd) is a harmful heavy metal that results in many toxic issues. Urtica pilulifera showed potential pharmaceutical applications. This study investigated the possible ameliorative mechanism of Urtica pilulifera leaves extract (UPLE) against hepatotoxicity induced by cadmium chloride (CdCl2) in mice.Methods:In vitro phytochemical screening and the metal-chelating activity of UPLE
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Serpin peptidase inhibitor, clade E, member 2 in physiology and pathology: recent advancements Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-26 Shutong Wu, Yuchao Yang, Meiling Zhang, Asmat Ullah Khan, Jingxing Dai, Jun Ouyang
Serine protease inhibitors (serpins) are the most numerous and widespread multifunctional protease inhibitor superfamily and are expressed by all eukaryotes. Serpin E2 (serpin peptidase inhibitor, clade E, member 2), a member of the serine protease inhibitor superfamily is a potent endogenous thrombin inhibitor, mainly found in the extracellular matrix and platelets, and expressed in numerous organs
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Diosgenin alleviates D-galactose-induced oxidative stress in rats’ brain and liver targeting aging and apoptotic marker genes Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-23 Ali H. El-Far, Mona M. Elghaity, Shymaa A. Mohamed, Ahmed E. Noreldin, Yaser H. A. Elewa, Soad Khalil Al Jaouni, Abdelwahab A. Alsenosy
The theory of aging is primarily concerned with oxidative stress caused by an imbalance in reactive oxygen species generation and cellular antioxidants. To alleviate the oxidative stress, we investigated the protective effect of diosgenin (DSG) for D-galactose (D-gal) using 20 and 40 mg of DSG/kg/day/orally for 42 days. The findings showed that D-gal caused brain and liver oxidative injuries by upregulating
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Integrating clinical and cross-cohort metagenomic features: a stable and non-invasive colorectal cancer and adenoma diagnostic model Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-22 Dan Zhou, Youli Chen, Zehao Wang, Siran Zhu, Lei Zhang, Jun Song, Tao Bai, Xiaohua Hou
Background: Dysbiosis is associated with colorectal cancer (CRC) and adenomas (CRA). However, the robustness of diagnostic models based on microbial signatures in multiple cohorts remains unsatisfactory.Materials and Methods: In this study, we used machine learning models to screen metagenomic signatures from the respective cross-cohort datasets of CRC and CRA (selected from CuratedMetagenomicData
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Dynamic interactions in the tumor niche: how the cross-talk between CAFs and the tumor microenvironment impacts resistance to therapy Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-22 Oliwia Piwocka, Igor Piotrowski, Wiktoria M. Suchorska, Katarzyna Kulcenty
The tumor microenvironment (TME) is a complex ecosystem of cells, signaling molecules, and extracellular matrix components that profoundly influence cancer progression. Among the key players in the TME, cancer-associated fibroblasts (CAFs) have gained increasing attention for their diverse and influential roles. CAFs are activated fibroblasts found abundantly within the TME of various cancer types
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In the moonlight: non-catalytic functions of ubiquitin and ubiquitin-like proteases Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-22 Marta Campos Alonso, Klaus-Peter Knobeloch
Proteases that cleave ubiquitin or ubiquitin-like proteins (UBLs) are critical players in maintaining the homeostasis of the organism. Concordantly, their dysregulation has been directly linked to various diseases, including cancer, neurodegeneration, developmental aberrations, cardiac disorders and inflammation. Given their potential as novel therapeutic targets, it is essential to fully understand
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Circulating serum miR-362-3p and miR-6721-5p as potential biomarkers for classification patients with adult-type diffuse glioma Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-22 Magdalena Niemira, Agnieszka Bielska, Karolina Chwialkowska, Justyna Raczkowska, Anna Skwarska, Anna Erol, Anna Zeller, Gabriela Sokolowska, Damian Toczydlowski, Iwona Sidorkiewicz, Zenon Mariak, Joanna Reszec, Tomasz Lyson, Marcin Moniuszko, Adam Kretowski
According to the fifth edition of the WHO Classification of Tumours of the Central Nervous System (CNS) published in 2021, grade 4 gliomas classification includes IDH-mutant astrocytomas and wild-type IDH glioblastomas. Unfortunately, despite precision oncology development, the prognosis for patients with grade 4 glioma remains poor, indicating an urgent need for better diagnostic and therapeutic strategies
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Exosomal microRNAs in breast cancer: towards theranostic applications Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-22 Richa Gulati, Tridip Mitra, Rohan Rajiv, Emilda Judith Ezhil Rajan, Chris Pierret, Elizabeth Ann L. Enninga, Rajiv Janardhanan
Breast cancer is one of the top two reproductive cancers responsible for high rates of morbidity and mortality among women globally. Despite the advancements in the treatment of breast cancer, its early diagnosis remains a challenge. Recent evidence indicates that despite the adroit use of numerous strategies to facilitate rapid and precision-oriented screening of breast cancer at the community level
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Targeting host-specific metabolic pathways—opportunities and challenges for anti-infective therapy Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-22 Monika I. Konaklieva, Balbina J. Plotkin
Microorganisms can takeover critical metabolic pathways in host cells to fuel their replication. This interaction provides an opportunity to target host metabolic pathways, in addition to the pathogen-specific ones, in the development of antimicrobials. Host-directed therapy (HDT) is an emerging strategy of anti-infective therapy, which targets host cell metabolism utilized by facultative and obligate
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Carbonic anhydrases in the cell wall and plasma membrane of Arabidopsis thaliana are required for optimal plant growth on low CO2 Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-22 Hiruni N. Weerasooriya, David J. Longstreth, Robert J. DiMario, Viviana C. Rosati, Brittany A. Cassel, James V. Moroney
Introduction: Plants have many genes encoding both alpha and beta type carbonic anhydrases. Arabidopsis has eight alpha type and six beta type carbonic anhydrase genes. Individual carbonic anhydrases are localized to specific compartments within the plant cell. In this study, we investigate the roles of αCA2 and βCA4.1 in the growth of the plant Arabidopsis thaliana under different CO2 regimes.Methods:
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Transposable elements as scaffold/matrix attachment regions: shaping organization and functions in genomes Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-22 Rashmi Upadhyay Pathak, Kundurthi Phanindhar, Rakesh K. Mishra
The hierarchical structure of eukaryotic genomes has regulatory layers, one of them being epigenetic “indexing” of the genome that leads to cell-type-specific patterns of gene expression. By establishing loops and defining chromatin domains, cells can achieve coordinated control over multi-locus segments of the genome. This is thought to be achieved using scaffold/matrix attachment regions (S/MARs)
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Tumor cell stemness in gastrointestinal cancer: regulation and targeted therapy Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-22 Kangqi Yang, Tuo Yi
The cancer stem cells are a rare group of self-renewable cancer cells capable of the initiation, progression, metastasis and recurrence of tumors, and also a key contributor to the therapeutic resistance. Thus, understanding the molecular mechanism of tumor stemness regulation, especially in the gastrointestinal (GI) cancers, is of great importance for targeting CSC and designing novel therapeutic
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Harnessing microRNA-enriched extracellular vesicles for liquid biopsy Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-21 Song Yi Ko, WonJae Lee, Honami Naora
Extracellular microRNAs (miRNAs) can be detected in body fluids and hold great potential as cancer biomarkers. Extracellular miRNAs are protected from degradation by binding various proteins and through their packaging into extracellular vesicles (EVs). There is evidence that the diagnostic performance of cancer-associated extracellular miRNAs can be improved by assaying EV-miRNA instead of total cell-free
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Iron-induced kidney cell damage: insights into molecular mechanisms and potential diagnostic significance of urinary FTL Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-21 Soraya Punchai, Nachayada Chaiyagot, Nadthanicha Artkaew, Apinya Jusakul, Ubon Cha’on, Raynoo Thanan, Kulthida Vaeteewoottacharn, Worachart Lert-Itthiporn
Background: Iron overload can lead to organ and cell injuries. Although the mechanisms of iron-induced cell damage have been extensively studied using various cells, little is known about these processes in kidney cells.Methods: In this study, we first examined the correlation between serum iron levels and kidney function. Subsequently, we investigated the molecular impact of excess iron on kidney
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Gene expression in metastatic breast cancer—patterns in primary tumors and metastatic tissue with prognostic potential Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-21 Julia Tutzauer, Anna-Maria Larsson, Kristina Aaltonen, Caroline Bergenfelz, Pär-Ola Bendahl, Lisa Rydén
Background: Metastatic breast cancer (MBC) is the main cause of breast cancer-related death. The outcome of MBC varies, and there is a lack of biomarkers to aid in prognostication. The primary aim of this study was to evaluate the prognostic value of gene expression (GEX) signatures in the primary tumor (PT) and distant metastasis (DM) for progression-free survival (PFS) and overall survival (OS).
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Extracellular vesicles in the treatment of oxidative stress injury: global research status and trends Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-15 Wenwen Zhang, Bin Gan, Tingyu Wang, Xiangjie Yang, Yuanye Xue, Yuanqing Zhong, Xintong He, Xinsheng Peng, Yanfang Zhou, Xiaoyan Cheng
Objective: The aim of this study was to conduct a bibliometric analysis of the literature on “Extracellular Vesicles in the Treatment of Oxidative Stress Injury” and to reveal its current status, hot spots and trends.Methods: The relevant literature was obtained from the Web of Science Core Collection (WoSCC) on 29 April 2023. We performed clustering and partnership analysis of authors, institutions
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2′-19F labelling of ribose in RNAs: a tool to analyse RNA/protein interactions by NMR in physiological conditions Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-14 Hesna Kara, Alexander Axer, Frederick W. Muskett, Carlos J. Bueno-Alejo, Vasileios Paschalis, Andrea Taladriz-Sender, Sumera Tubasum, Marina Santana Vega, Zhengyun Zhao, Alasdair W. Clark, Andrew J. Hudson, Ian C. Eperon, Glenn A. Burley, Cyril Dominguez
Protein-RNA interactions are central to numerous cellular processes. In this work, we present an easy and straightforward NMR-based approach to determine the RNA binding site of RNA binding proteins and to evaluate the binding of pairs of proteins to a single-stranded RNA (ssRNA) under physiological conditions, in this case in nuclear extracts. By incorporation of a 19F atom on the ribose of different
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Pyrazinoic acid, the active form of the anti-tuberculosis drug pyrazinamide, and aromatic carboxylic acid analogs are protonophores Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-13 Fabio L. Fontes, Steven A. Rooker, Jamie K. Lynn-Barbe, Michael A. Lyons, Debbie C. Crans, Dean C. Crick
Pyrazinoic acid is the active form of pyrazinamide, a first-line antibiotic used to treat Mycobacterium tuberculosis infections. However, the mechanism of action of pyrazinoic acid remains a subject of debate, and alternatives to pyrazinamide in cases of resistance are not available. The work presented here demonstrates that pyrazinoic acid and known protonophores including salicylic acid, benzoic
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Deciphering non-canonical ubiquitin signaling: biology and methodology Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-13 Nila K. van Overbeek, Tim Aguirre, Gerbrand J. van der Heden van Noort, Blagoy Blagoev, Alfred C. O. Vertegaal
Ubiquitination is a dynamic post-translational modification that regulates virtually all cellular processes by modulating function, localization, interactions and turnover of thousands of substrates. Canonical ubiquitination involves the enzymatic cascade of E1, E2 and E3 enzymes that conjugate ubiquitin to lysine residues giving rise to monomeric ubiquitination and polymeric ubiquitination. Emerging
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Identification of the KIF18A alpha-4 helix as a therapeutic target for chromosomally unstable tumor cells Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-12 Katherine L. Schutt, Katelyn A. Queen, Kira Fisher, Olivia Budington, Weifeng Mao, Wei Liu, Xiaohui Gu, Yisong Xiao, Fred Aswad, James Joseph, Jason Stumpff
Background: The mitotic kinesin, KIF18A, is required for proliferation of cancer cells that exhibit chromosome instability (CIN), implicating it as a promising target for treatment of a subset of aggressive tumor types. Determining regions of the KIF18A protein to target for inhibition will be important for the design and optimization of effective small molecule inhibitors.Methods: In this study, we
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Analytical validation and clinical utilization of K-4CARE™: a comprehensive genomic profiling assay with personalized MRD detection Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-09 Thien-Phuc Nguyen Hoang, Tien Anh Nguyen, Nam H. B. Tran, Van-Anh Nguyen Hoang, Hong Thuy Thi Dao, Vu-Uyen Tran, Yen Nhi Nguyen, Anh Tuan Nguyen, Cam Tu Nguyen Thi, Thanh Thuy Do Thi, Duy Sinh Nguyen, Hoai-Nghia Nguyen, Hoa Giang, Lan N. Tu
Background: Biomarker testing has gradually become standard of care in precision oncology to help physicians select optimal treatment for patients. Compared to single-gene or small gene panel testing, comprehensive genomic profiling (CGP) has emerged as a more time- and tissue-efficient method. This study demonstrated in-depth analytical validation of K-4CARE, a CGP assay that integrates circulating
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Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-09 Alejandra María Rivera Nieves, Brian Michael Wauford, Accalia Fu
In Type 1 and Type 2 diabetes, pancreatic β-cell survival and function are impaired. Additional etiologies of diabetes include dysfunction in insulin-sensing hepatic, muscle, and adipose tissues as well as immune cells. An important determinant of metabolic health across these various tissues is mitochondria function and structure. This review focuses on the role of mitochondria in diabetes pathogenesis
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Sex-specific nociceptor modulation of the apical periodontitis transcriptome Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-09 Katherine V. Lillis, Ruta Grinceviciute, Anibal Diogenes
Introduction: Apical periodontitis (AP) is a painful disease that develops quickly following dental infections and is primarily characterized by robust inflammation surrounding the tissues of the affected tooth, resulting in disruption of bone homeostasis and periradicular bone loss. Moreover, there are distinct clinical presentations, symptoms, and responses to AP treatment between male and female
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Dysfunction in atox-1 and ceruloplasmin alters labile Cu levels and consequently Cu homeostasis in C. elegans Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-08 Ann-Kathrin Weishaupt, Karsten Lamann, Elke Tallarek, Aidan T. Pezacki, Carson D. Matier, Tanja Schwerdtle, Michael Aschner, Christopher J. Chang, Stephen R. Stürzenbaum, Julia Bornhorst
Copper (Cu) is an essential trace element, however an excess is toxic due to its redox properties. Cu homeostasis therefore needs to be tightly regulated via cellular transporters, storage proteins and exporters. An imbalance in Cu homeostasis has been associated with neurodegenerative disorders such as Wilson’s disease, but also Alzheimer’s or Parkinson’s disease. In our current study, we explored
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Insights into Hsp90 mechanism and in vivo functions learned from studies in the yeast, Saccharomyces cerevisiae Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-08 Erick I. Rios, Isabel L. Hunsberger, Jill L. Johnson
The molecular chaperone Hsp90 (Heat shock protein, 90 kDa) is an abundant and essential cytosolic protein required for the stability and/or folding of hundreds of client proteins. Hsp90, along with helper cochaperone proteins, assists client protein folding in an ATP-dependent pathway. The laboratory of Susan Lindquist, in collaboration with other researchers, was the first to establish the yeast Saccharomyces
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Comprehensive proteomics of monocytes indicates oxidative imbalance functionally related to inflammatory response in chronic kidney disease-related atherosclerosis Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-08 Joanna Watral, Dorota Formanowicz, Bartłomiej Perek, Katarzyna Kostka-Jeziorny, Alina Podkowińska, Andrzej Tykarski, Magdalena Luczak
Atherosclerosis-induced cardiovascular events are the leading cause of mortality in chronic kidney disease (CKD) patients. Monocytes are involved in the formation of atherosclerotic plaques and mediate in the overproduction of ROS, promoting inflammation and oxidative stress. However, the relationship between monocytes, inflammation, and oxidative status in CKD-associated atherosclerosis has not been
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Metabolomics unveils the exacerbating role of arachidonic acid metabolism in atherosclerosis Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-07 Sai Ma, Songqing He, Jing Liu, Wei Zhuang, Hanqing Li, Chen Lin, Lijun Wang, Jing Feng, Lei Wang
Atherosclerosis is a complex vascular disorder characterized by the deposition of lipids, inflammatory cascades, and plaque formation in arterial walls. A thorough understanding of its causes and progression is necessary to develop effective diagnostic and therapeutic strategies. Recent breakthroughs in metabolomics have provided valuable insights into the molecular mechanisms and genetic factors involved
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Transcriptomic and metabolic analysis unveils the mechanism behind leaf color development in Disanthus cercidifolius var. longipes Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-06 Xiaoming Tian, Guangfeng Xiang, Hao Lv, Lu Zhu, Jing Peng, Gaofei Li, Cun Mou
Introduction: Leaf coloration in Disanthus cercidifolius var. longipes results from the interplay of various pigments undergoing complex catalytic reactions.Methods: We aimed to elucidate the mechanisms of pigment biosynthesis affecting leaf color transition in D. cercidifolius var. longipes by analyzing variations in pigment accumulation and levels of gene expression.Results: We identified 468, 577
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Alternative polyadenylation and dynamic 3′ UTR length is associated with polysome recruitment throughout the cardiomyogenic differentiation of hESCs Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-06 Aruana F. F. Hansel-Frose, Jens Allmer, Marcel Friedrichs, Hellen Geremias dos Santos, Bruno Dallagiovanna, Lucía Spangenberg
Alternative polyadenylation (APA) increases transcript diversity through the generation of isoforms with varying 3′ untranslated region (3′ UTR) lengths. As the 3′ UTR harbors regulatory element target sites, such as miRNAs or RNA-binding proteins, changes in this region can impact post-transcriptional regulation and translation. Moreover, the APA landscape can change based on the cell type, cell state
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Effect of TraN key residues involved in DNA binding on pIP501 transfer rates in Enterococcus faecalis Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-06 Claudia Michaelis, Tamara M. I. Berger, Kirill Kuhlmann, Rangina Ghulam, Lukas Petrowitsch, Maria Besora Vecino, Bernd Gesslbauer, Tea Pavkov-Keller, Walter Keller, Elisabeth Grohmann
Conjugation is a major mechanism that facilitates the exchange of antibiotic resistance genes among bacteria. The broad-host-range Inc18 plasmid pIP501 harbors 15 genes that encode for a type IV secretion system (T4SS). It is a membrane-spanning multiprotein complex formed between conjugating donor and recipient cells. The penultimate gene of the pIP501 operon encodes for the cytosolic monomeric protein
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The potential of N2-modified cap analogues for precise genetic manipulation through mRNA engineering Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-06 Karol Kurpiejewski, Anna Stankiewicz-Drogon, Karolina Piecyk, Eliza Rajkowska, Paulina Skrzypczyk, Jingping Geng, Edward Darzynkiewicz, Renata Grzela, Marzena Jankowska-Anyszka
The technology of mRNA-based drugs is currently being intensively developed and implemented. Medical products of this type are already being used as viral vaccines and could potentially find application in a wide range of diseases. The tremendous interest in mRNA is due to the relatively easy production process, which can be quickly adapted to meet societal needs. The properties of this molecule depend
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CCN3, POSTN, and PTHLH as potential key regulators of genomic integrity and cellular survival in iPSCs Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-05 Nuha T. Swaidan, Nada H. Soliman, Ahmed T. Aboughalia, Toqa Darwish, Ruba O. Almeshal, Azhar A. Al-Khulaifi, Rowaida Z. Taha, Rania Alanany, Ahmed Y. Hussein, Salam Salloum-Asfar, Sara A. Abdulla, Abdallah M. Abdallah, Mohamed M. Emara
Reprogramming human somatic cells into a pluripotent state, achieved through the activation of well-defined transcriptional factors known as OSKM factors, offers significant potential for regenerative medicine. While OSKM factors are a robust reprogramming method, efficiency remains a challenge, with only a fraction of cells undergoing successful reprogramming. To address this, we explored genes related
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14-3-3 proteins—a moonlight protein complex with therapeutic potential in neurological disorder: in-depth review with Alzheimer’s disease Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-05 Gholamareza Abdi, Mukul Jain, Nil Patil, Bindiya Upadhyay, Nigam Vyas, Manish Dwivedi, Radhey Shyam Kaushal
Alzheimer’s disease (AD) affects millions of people worldwide and is a gradually worsening neurodegenerative condition. The accumulation of abnormal proteins, such as tau and beta-amyloid, in the brain is a hallmark of AD pathology. 14-3-3 proteins have been implicated in AD pathology in several ways. One proposed mechanism is that 14-3-3 proteins interact with tau protein and modulate its phosphorylation
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Virus sequencing performance during the SARS-CoV-2 pandemic: a retrospective analysis of data from multiple rounds of external quality assessment in Austria Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-05 Jeremy V. Camp, Elisabeth Puchhammer-Stöckl, Stephan W. Aberle, Christoph Buchta
Introduction: A notable feature of the 2019 coronavirus disease (COVID-19) pandemic was the widespread use of whole genome sequencing (WGS) to monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Countries around the world relied on sequencing and other forms of variant detection to perform contact tracing and monitor changes in the virus genome, in the hopes that epidemic
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Comprehensive detection of CRLF2 alterations in acute lymphoblastic leukemia: a rapid and accurate novel approach Front. Mol. Biosci. (IF 5.0) Pub Date : 2024-02-02 José Vicente Gil, Alberto Miralles, Sandra de las Heras, Esperanza Such, Gayane Avetisyan, Álvaro Díaz-González, Marta Santiago, Carolina Fuentes, José María Fernández, Pilar Lloret, Irene Navarro, Pau Montesinos, Marta Llop, Eva Barragán
Introduction: Acute lymphoblastic leukemia (ALL) is a prevalent childhood cancer with high cure rate, but poses a significant medical challenge in adults and relapsed patients. Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype, with approximately half of cases characterized by CRLF2 overexpression and frequent concomitant IKZF1 deletions.Methods: To address the need