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Int. J. Mol. Sci., Volume 24, Issue 7 (April-1 2023) – 860 articles

Cover Story (view full-size image): Schizophrenia is a severe mental disorder with a chronic, progressive course. The etiology of this condition is linked to the interactions of multiple genes and environmental factors. The earlier age of onset of schizophrenia, the higher frequency of negative symptoms in the clinical presentation, and the poorer response to antipsychotic treatment in men compared to women suggest the involvement of sex hormones in these processes. This article aims to draw attention to the possible relationship between testosterone and some clinical features in male schizophrenic patients and discuss the complex nature of these phenomena based on data from the literature. View this paper
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12 pages, 2681 KiB  
Article
Strong Metal Support Effect of Pt/g-C3N4 Photocatalysts for Boosting Photothermal Synergistic Degradation of Benzene
by Zhongcheng Huang, Xiaorong Cai, Shaohong Zang, Yixin Li, Dandan Zheng and Fuying Li
Int. J. Mol. Sci. 2023, 24(7), 6872; https://doi.org/10.3390/ijms24076872 - 06 Apr 2023
Cited by 1 | Viewed by 1676
Abstract
Catalysis is the most efficient and economical method for treating volatile organic pollutants (VOCs). Among the many materials that are used in engineering, platinized carbon nitride (Pt/g-C3N4) is an efficient and multifunctional catalyst which has strong light absorption and [...] Read more.
Catalysis is the most efficient and economical method for treating volatile organic pollutants (VOCs). Among the many materials that are used in engineering, platinized carbon nitride (Pt/g-C3N4) is an efficient and multifunctional catalyst which has strong light absorption and mass transfer capabilities, which enable it to be used in photocatalysis, thermal catalysis and photothermal synergistic catalysis for the degradation of benzene. In this work, Pt/g-C3N4 was prepared by four precursors for the photothermal synergistic catalytic degradation of benzene, which show different activities, and many tests were carried out to explore the possible reasons for the discrepancy. Among them, the Pt/g-C3N4 prepared from dicyanamide showed the highest activity and could convert benzene (300 ppm, 20 mL·min−1) completely at 162 °C under solar light and 173 °C under visible light. The reaction temperature was reduced by nearly half compared to the traditional thermal catalytic degradation of benzene at about 300 °C. Full article
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15 pages, 2348 KiB  
Article
Enhancement of the Antioxidant Effect of Natural Products on the Proliferation of Caco-2 Cells Produced by Fish Protein Hydrolysates and Collagen
by Mercedes Taroncher, Yelko Rodríguez-Carrasco, Francisco J. Barba and María-José Ruiz
Int. J. Mol. Sci. 2023, 24(7), 6871; https://doi.org/10.3390/ijms24076871 - 06 Apr 2023
Cited by 2 | Viewed by 1380
Abstract
A large amount of fish side streams are produced each year, promoting huge economic and environmental problems. In order to address this issue, a potential alternative is to isolate the high-added-value compounds with beneficial properties on human health. The objectives of this study [...] Read more.
A large amount of fish side streams are produced each year, promoting huge economic and environmental problems. In order to address this issue, a potential alternative is to isolate the high-added-value compounds with beneficial properties on human health. The objectives of this study were to determine the effect of hydrolyzed fish protein and collagen samples on cell proliferation, as well as to determine the specific influence of minerals and metals on this effect and whether dietary antioxidants can enhance cell proliferation. The results of hydrolyzed fish protein and collagen samples showed negative effects on Caco-2 cell proliferation at the highest concentrations tested. Moreover, the pre-treatment of these hydrolyzates with vitamin C and E, quercetin and resveratrol increased the proliferation of bioaccessible fractions of hydrolyzated fish protein and collagen samples compared to the bioaccessible fractions without pre-treatment. The highest mineral concentrations were found for P, Ca and Mg. The metals found in the pure hydrolyzates were As, Cd, Hg and Pb; however, they appeared at almost undetectable levels in bioavailable fractions. It can be concluded that the consumption of hydrolyzates of fish by-products is an interesting strategy for complying with EFSA recommendations regarding fish consumption while at the same time reducing fish waste. Full article
(This article belongs to the Special Issue Natural Compounds and Oxidative Stress)
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19 pages, 3207 KiB  
Article
Nonsteroidal Anti-Inflammatory Drug Conjugated with Gadolinium (III) Complex as an Anti-Inflammatory MRI Agent
by Bokyung Sung, Hee-Kyung Kim, Ah-Rum Baek, Byeong-Woo Yang, Yeoun-Hee Kim, Garam Choi, Hyun-Jin Park, Minsup Kim, Jongmin Lee and Yongmin Chang
Int. J. Mol. Sci. 2023, 24(7), 6870; https://doi.org/10.3390/ijms24076870 - 06 Apr 2023
Cited by 1 | Viewed by 1618
Abstract
Studies have been actively conducted to ensure that gadolinium-based contrast agents for magnetic resonance imaging (MRI) are accompanied by various biological functions. A new example is the anti-inflammatory theragnostic MRI agent to target inflammatory mediators for imaging diagnosis and to treat inflammatory diseases [...] Read more.
Studies have been actively conducted to ensure that gadolinium-based contrast agents for magnetic resonance imaging (MRI) are accompanied by various biological functions. A new example is the anti-inflammatory theragnostic MRI agent to target inflammatory mediators for imaging diagnosis and to treat inflammatory diseases simultaneously. We designed, synthesized, and characterized a Gd complex of 1,4,7-tris(carboxymethylaza) cyclododecane-10-azaacetylamide (DO3A) conjugated with a nonsteroidal anti-inflammatory drug (NSAID) that exerts the innate therapeutic effect of NSAIDs and is also applicable in MRI diagnostics. Gd-DO3A-fen (0.1 mmol/kg) was intravenously injected into the turpentine oil-induced mouse model, with Gd-DO3A-BT as a control group. In the in vivo MRI experiment, the contrast-to-noise ratio (CNR) was higher and persisted longer than that with Gd-DO3A-BT; specifically, the CNR difference was almost five times at 2 h after injection. Gd-DO3A-fen had a binding affinity (Ka) of 6.68 × 106 M−1 for the COX-2 enzyme, which was 2.1-fold higher than that of fenbufen, the original NSAID. In vivo evaluation of anti-inflammatory activity was performed in two animal models. In the turpentine oil-induced model, the mRNA expression levels of inflammatory parameters such as COX-2, TNF-α, IL-1β, and IL-6 were reduced, and in the carrageenan-induced edema model, swelling was suppressed by 72% and there was a 2.88-fold inhibition compared with the saline group. Correlation analysis between in vitro, in silico, and in vivo studies revealed that Gd-DO3A-fen acts as an anti-inflammatory theragnostic agent by directly binding to COX-2. Full article
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25 pages, 4413 KiB  
Article
The Role of Tyr-His-Trp Triad and Water Molecule Near the N1-Atom of 2-Hydroperoxycoelenterazine in Bioluminescence of Hydromedusan Photoproteins: Structural and Mutagenesis Study
by Pavel V. Natashin, Ludmila P. Burakova, Margarita I. Kovaleva, Mikhail B. Shevtsov, Daria A. Dmitrieva, Elena V. Eremeeva, Svetlana V. Markova, Alexey V. Mishin, Valentin I. Borshchevskiy and Eugene S. Vysotski
Int. J. Mol. Sci. 2023, 24(7), 6869; https://doi.org/10.3390/ijms24076869 - 06 Apr 2023
Cited by 2 | Viewed by 1732
Abstract
Hydromedusan photoproteins responsible for the bioluminescence of a variety of marine jellyfish and hydroids are a unique biochemical system recognized as a stable enzyme-substrate complex consisting of apoprotein and preoxygenated coelenterazine, which is tightly bound in the protein inner cavity. The binding of [...] Read more.
Hydromedusan photoproteins responsible for the bioluminescence of a variety of marine jellyfish and hydroids are a unique biochemical system recognized as a stable enzyme-substrate complex consisting of apoprotein and preoxygenated coelenterazine, which is tightly bound in the protein inner cavity. The binding of calcium ions to the photoprotein molecule is only required to initiate the light emission reaction. Although numerous experimental and theoretical studies on the bioluminescence of these photoproteins were performed, many features of their functioning are yet unclear. In particular, which ionic state of dioxetanone intermediate decomposes to yield a coelenteramide in an excited state and the role of the water molecule residing in a proximity to the N1 atom of 2-hydroperoxycoelenterazine in the bioluminescence reaction are still under discussion. With the aim to elucidate the function of this water molecule as well as to pinpoint the amino acid residues presumably involved in the protonation of the primarily formed dioxetanone anion, we constructed a set of single and double obelin and aequorin mutants with substitutions of His, Trp, Tyr, and Ser to residues with different properties of side chains and investigated their bioluminescence properties (specific activity, bioluminescence spectra, stopped-flow kinetics, and fluorescence spectra of Ca2+-discharged photoproteins). Moreover, we determined the spatial structure of the obelin mutant with a substitution of His64, the key residue of the presumable proton transfer, to Phe. On the ground of the bioluminescence properties of the obelin and aequorin mutants as well as the spatial structures of the obelin mutants with the replacements of His64 and Tyr138, the conclusion was made that, in fact, His residue of the Tyr-His-Trp triad and the water molecule perform the “catalytic function” by transferring the proton from solvent to the dioxetanone anion to generate its neutral ionic state in complex with water, as only the decomposition of this form of dioxetanone can provide the highest light output in the light-emitting reaction of the hydromedusan photoproteins. Full article
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11 pages, 3087 KiB  
Article
Germination and Growth of Plasma-Treated Maize Seeds Planted in Fields and Exposed to Realistic Environmental Conditions
by Nina Recek, Rok Zaplotnik, Alenka Vesel, Gregor Primc, Peter Gselman, Miran Mozetič and Matej Holc
Int. J. Mol. Sci. 2023, 24(7), 6868; https://doi.org/10.3390/ijms24076868 - 06 Apr 2023
Viewed by 1168
Abstract
In this study, we applied an inductively coupled, radio frequency oxygen plasma to maize seeds and investigated its effects on seedling emergence, plant number at tasseling, and crop yield of maize in realistic field conditions. Maize seeds of seven different hybrids were treated [...] Read more.
In this study, we applied an inductively coupled, radio frequency oxygen plasma to maize seeds and investigated its effects on seedling emergence, plant number at tasseling, and crop yield of maize in realistic field conditions. Maize seeds of seven different hybrids were treated over two harvest years. In addition to plasma-treated seeds, a control sample, fungicide-treated seeds, an eco-layer, and a plasma and eco-layer combination, were planted. Seedling emergence, plant number at tasseling (plants/m2), and yield (kg/ha), were recorded. In the first harvest year, results were negatively affected by the presence of an insect pest. In the second harvest year, plant number and yield results were more uniform. In both years, for two and three hybrids, respectively, the highest yield arose from plants from plasma-treated seeds, but the differences were only partially significant. Considering our results, plasma treatment of maize seeds appears to have a positive effect on the yield of the plant. Full article
(This article belongs to the Special Issue Advances in Molecular Plant Sciences)
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22 pages, 1529 KiB  
Review
Imbalance of Essential Metals in Traumatic Brain Injury and Its Possible Link with Disorders of Consciousness
by Rosanna Squitti, Giuseppe Reale, Vincenzo Tondolo, Daniela Crescenti, Sonia Bellini, Marco Moci, Pietro Caliandro, Luca Padua and Mauro Rongioletti
Int. J. Mol. Sci. 2023, 24(7), 6867; https://doi.org/10.3390/ijms24076867 - 06 Apr 2023
Cited by 4 | Viewed by 2123
Abstract
Dysfunction of the complex cerebral networks underlying wakefulness and awareness is responsible for Disorders of Consciousness (DoC). Traumatic Brain Injury (TBI) is a common cause of DoC, and it is responsible for a multi-dimensional pathological cascade that affects the proper functioning of the [...] Read more.
Dysfunction of the complex cerebral networks underlying wakefulness and awareness is responsible for Disorders of Consciousness (DoC). Traumatic Brain Injury (TBI) is a common cause of DoC, and it is responsible for a multi-dimensional pathological cascade that affects the proper functioning of the brainstem and brain consciousness pathways. Iron (Fe), Zinc (Zn), and Copper (Cu) have a role in the neurophysiology of both the ascending reticular activating system, a multi-neurotransmitter network located in the brainstem that is crucial for consciousness, and several brain regions. We aimed to summarize the role of these essential metals in TBI and its possible link with consciousness alterations. We found that TBI alters many neuronal molecular mechanisms involving essential metals, causing neurodegeneration, neural apoptosis, synaptic dysfunction, oxidative stress, and inflammation. This final pattern resembles that described for Alzheimer’s disease (AD) and other neurological and psychiatric diseases. Furthermore, we found that amantadine, zolpidem, and transcranial direct current stimulation (tDCS)—the most used treatments for DoC recovery—seem to have an effect on essential metals-related pathways and that Zn might be a promising new therapeutic approach. This review summarizes the neurophysiology of essential metals in the brain structures of consciousness and focuses on the mechanisms underlying their imbalance following TBI, suggesting their possible role in DoC. The scenario supports further studies aimed at getting a deeper insight into metals’ role in DoC, in order to evaluate metal-based drugs, such as metal complexes and metal chelating agents, as potential therapeutic options. Full article
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16 pages, 1234 KiB  
Article
The Nitric Oxide (NO) Donor Molsidomine Counteract Social Withdrawal and Cognition Deficits Induced by Blockade of the NMDA Receptor in the Rat
by Lamprini Katsanou, Evangelia Fragkiadaki, Sotirios Kampouris, Anastasia Konstanta, Aikaterini Vontzou and Nikolaos Pitsikas
Int. J. Mol. Sci. 2023, 24(7), 6866; https://doi.org/10.3390/ijms24076866 - 06 Apr 2023
Cited by 2 | Viewed by 1545
Abstract
The deficiency of the gaseous molecule nitric oxide (NO) seems to be critically involved in the pathogenesis of schizophrenia. Thus, molecules that can normalize NO levels, as are NO donors, might be of utility for the medication of this psychiatric disease. The aim [...] Read more.
The deficiency of the gaseous molecule nitric oxide (NO) seems to be critically involved in the pathogenesis of schizophrenia. Thus, molecules that can normalize NO levels, as are NO donors, might be of utility for the medication of this psychiatric disease. The aim of the present study was to detect the ability of the NO donor molsidomine to reduce schizophrenia-like impairments produced by the blockade of the N-methyl-D-aspartate (NMDA) receptor in rats. Molsidomine’s ability to attenuate social withdrawal and spatial recognition memory deficits induced by the NMDA receptor antagonist ketamine were assessed using the social interaction and the object location test, respectively. Further, the efficacy of the combination of sub-effective doses of molsidomine with sub-effective doses of the atypical antipsychotic clozapine in alleviating non-spatial recognition memory deficits was evaluated utilizing the object recognition task. Molsidomine (2 and 4 mg/kg) attenuated social withdrawal and spatial recognition memory deficits induced by ketamine. Co-administration of inactive doses of molsidomine (1 mg/kg) and clozapine (0.1 mg/kg) counteracted delay-dependent and ketamine-induced non-spatial recognition memory deficits. The current findings suggest that molsidomine is sensitive to glutamate hypofunction since it attenuated behavioral impairments in animal models mimicking the negative symptoms and cognitive deficits of schizophrenia. Additionally, the present results support the potential of molsidomine as an adjunctive drug for the therapy of schizophrenia. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Schizophrenia and Novel Targets 2.0)
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26 pages, 6225 KiB  
Article
Novel Insights into circRNA Saga Coming from Spermatozoa and Epididymis of HFD Mice
by Francesco Manfrevola, Teresa Chioccarelli, Vincenza Grazia Mele, Veronica Porreca, Monica Mattia, Donatella Cimini, Antonella D’Agostino, Gilda Cobellis, Silvia Fasano, Chiara Schiraldi, Rosanna Chianese and Riccardo Pierantoni
Int. J. Mol. Sci. 2023, 24(7), 6865; https://doi.org/10.3390/ijms24076865 - 06 Apr 2023
Cited by 2 | Viewed by 1735
Abstract
Obesity is a pathophysiological disorder associated with adiposity accumulation, oxidative stress, and chronic inflammation state that is progressively increasing in younger population worldwide, negatively affecting male reproductive skills. An emerging topic in the field of male reproduction is circRNAs, covalently closed RNA molecules [...] Read more.
Obesity is a pathophysiological disorder associated with adiposity accumulation, oxidative stress, and chronic inflammation state that is progressively increasing in younger population worldwide, negatively affecting male reproductive skills. An emerging topic in the field of male reproduction is circRNAs, covalently closed RNA molecules produced by backsplicing, actively involved in a successful spermatogenesis and in establishing high-quality sperm parameters. However, a direct correlation between obesity and impaired circRNA cargo in spermatozoa (SPZ) remains unclear. In the current work, using C57BL6/J male mice fed with a high-fat diet (HFD, 60% fat) as experimental model of oxidative stress, we investigated the impact of HFD on sperm morphology and motility as well as on spermatic circRNAs. We performed a complete dataset of spermatic circRNA content by a microarray strategy, and differentially expressed (DE)-circRNAs were identified. Using a circRNA/miRNA/target network (ceRNET) analysis, we identified circRNAs potentially involved in oxidative stress and sperm motility pathways. Interestingly, we demonstrated an enhanced skill of HFD sperm in backsplicing activity together with an inefficient epididymal circRNA biogenesis. Fused protein in sarcoma (FUS) and its ability to recruit quaking (QKI) could be involved in orchestrating such mechanism. Full article
(This article belongs to the Special Issue Novel Insights into the Biology of Spermatozoa 2.0)
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12 pages, 1994 KiB  
Article
Conformational Changes of Acyl Carrier Protein Switch the Chain Length Preference of Acyl-ACP Thioesterase ChFatB2
by Tianxiang Yang, Yunlong Yang, Ming Yang, Jiangang Ren, Changying Xue, Yanbin Feng and Song Xue
Int. J. Mol. Sci. 2023, 24(7), 6864; https://doi.org/10.3390/ijms24076864 - 06 Apr 2023
Viewed by 1616
Abstract
Microbial fatty acids are synthesized by Type II fatty acid synthase and could be tailored by acyl-ACP thioesterase. With the prospects of medium-chain fatty-acid-derivative biofuels, the selectivity of thioesterase has been studied to control the fatty acid product chain length. Here, we report [...] Read more.
Microbial fatty acids are synthesized by Type II fatty acid synthase and could be tailored by acyl-ACP thioesterase. With the prospects of medium-chain fatty-acid-derivative biofuels, the selectivity of thioesterase has been studied to control the fatty acid product chain length. Here, we report an alternative approach by manipulating the acyl carrier protein portion of acyl-ACP to switch the chain length propensity of the thioesterase. It was demonstrated that ChFatB2 from Cuphea hookeriana preferred C10-ACP to C8-ACP with ACP from E. coli, while converting preference to C8-ACP with ACP from Cuphea lanceolate. Circular dichroism (CD) results indicated that the C8-EcACP encountered a 34.4% α-helix increment compared to C10-EcACP, which resulted in an approximate binding affinity decrease in ChFatB2 compared to C10-EcACP. Similarly, the C10-ClACP2 suffered a 45% decrease in helix content compared to C8–ClACP2, and the conformational changes resulted in an 18% binding affinity decline with ChFatB2 compared with C10-ClACP2. In brief, the study demonstrates that the ACP portion of acyl-ACP contributes to the selectivity of acyl-ACP thioesterase, and the conformational changes of EcACP and ClACP2 switch the chain length preference of ChFatB2 between C8 and C10. The result provides fundamentals for the directed synthesis of medium-chain fatty acids based on regulating the conformational changes of ACPs. Full article
(This article belongs to the Section Biochemistry)
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13 pages, 982 KiB  
Communication
Redox Proteomic Profile of Tirapazamine-Resistant Murine Hepatoma Cells
by Aušra Nemeikaitė-Čėnienė, Per Haberkant, Dalius Kučiauskas, Frank Stein and Narimantas Čėnas
Int. J. Mol. Sci. 2023, 24(7), 6863; https://doi.org/10.3390/ijms24076863 - 06 Apr 2023
Viewed by 1718
Abstract
3-Amino-1,2,4-benzotriazine-1,4-dioxide (tirapazamine, TPZ) and other heteroaromatic N-oxides (ArN→O) exhibit tumoricidal, antibacterial, and antiprotozoal activities. Their action is attributed to the enzymatic single-electron reduction to free radicals that initiate the prooxidant processes. In order to clarify the mechanisms of aerobic mammalian cytotoxicity of [...] Read more.
3-Amino-1,2,4-benzotriazine-1,4-dioxide (tirapazamine, TPZ) and other heteroaromatic N-oxides (ArN→O) exhibit tumoricidal, antibacterial, and antiprotozoal activities. Their action is attributed to the enzymatic single-electron reduction to free radicals that initiate the prooxidant processes. In order to clarify the mechanisms of aerobic mammalian cytotoxicity of ArN→O, we derived a TPZ-resistant subline of murine hepatoma MH22a cells (resistance index, 5.64). The quantitative proteomic of wild-type and TPZ-resistant cells revealed 5818 proteins, of which 237 were up- and 184 down-regulated. The expression of the antioxidant enzymes aldehyde- and alcohol dehydrogenases, carbonyl reductases, catalase, and glutathione reductase was increased 1.6–5.2 times, whereas the changes in the expression of glutathione peroxidase, superoxide dismutase, thioredoxin reductase, and peroxiredoxins were less pronounced. The expression of xenobiotics conjugating glutathione-S-transferases was increased by 1.6–2.6 times. On the other hand, the expression of NADPH:cytochrome P450 reductase was responsible for the single-electron reduction in TPZ and for the 2.1-fold decrease. These data support the fact that the main mechanism of action of TPZ under aerobic conditions is oxidative stress. The unchanged expression of intranuclear antioxidant proteins peroxiredoxin, glutaredoxin, and glutathione peroxidase, and a modest increase in the expression of DNA damage repair proteins, tend to support non-site-specific but not intranuclear oxidative stress as a main factor of TPZ aerobic cytotoxicity. Full article
(This article belongs to the Section Biochemistry)
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13 pages, 2000 KiB  
Brief Report
Doxorubicin–Mediated miR–433 Expression on Exosomes Promotes Bystander Senescence in Multiple Myeloma Cells in a DDR–Independent Manner
by Elisabetta Vulpis, Lorenzo Cuollo, Cristiana Borrelli, Fabrizio Antonangeli, Laura Masuelli, Marco Cippitelli, Cinzia Fionda, Giulio Caracciolo, Maria Teresa Petrucci, Angela Santoni, Alessandra Zingoni and Alessandra Soriani
Int. J. Mol. Sci. 2023, 24(7), 6862; https://doi.org/10.3390/ijms24076862 - 06 Apr 2023
Cited by 3 | Viewed by 1753
Abstract
The success of senescence-based anticancer therapies relies on their anti-proliferative power and on their ability to trigger anti-tumor immune responses. Indeed, genotoxic drug-induced senescence increases the expression of NK cell-activating ligands on multiple myeloma (MM) cells, boosting NK cell recognition and effector functions. [...] Read more.
The success of senescence-based anticancer therapies relies on their anti-proliferative power and on their ability to trigger anti-tumor immune responses. Indeed, genotoxic drug-induced senescence increases the expression of NK cell-activating ligands on multiple myeloma (MM) cells, boosting NK cell recognition and effector functions. Senescent cells undergo morphological change and context-dependent functional diversification, acquiring the ability to secrete a vast pool of molecules termed the senescence-associated secretory phenotype (SASP), which affects neighboring cells. Recently, exosomes have been recognized as SASP factors, contributing to modulating a variety of cell functions. In particular, evidence suggests a key role for exosomal microRNAs in influencing many hallmarks of cancer. Herein, we demonstrate that doxorubicin treatment of MM cells leads to the enrichment of miR-433 into exosomes, which in turn induces bystander senescence. Our analysis reveals that the establishment of the senescent phenotype on neighboring MM cells is p53- and p21-independent and is related to CDK-6 down-regulation. Notably, miR-433-dependent senescence does not induce the up-regulation of activating ligands on MM cells. Altogether, our findings highlight the possibility of miR-433-enriched exosomes to reinforce doxorubicin-mediated cellular senescence. Full article
(This article belongs to the Special Issue Cellular Senescence in Physiological and Pathological Processes 2.0)
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19 pages, 5011 KiB  
Review
Recent Advances in Manganese-Based Materials for Electrolytic Water Splitting
by Jing Hu, Yuru Zhou, Yinan Liu, Zhichao Xu and Haijin Li
Int. J. Mol. Sci. 2023, 24(7), 6861; https://doi.org/10.3390/ijms24076861 - 06 Apr 2023
Cited by 3 | Viewed by 2626
Abstract
Developing earth-abundant and highly effective electrocatalysts for electrocatalytic water splitting is a prerequisite for the upcoming hydrogen energy society. Recently, manganese-based materials have been one of the most promising candidates to replace noble metal catalysts due to their natural abundance, low cost, adjustable [...] Read more.
Developing earth-abundant and highly effective electrocatalysts for electrocatalytic water splitting is a prerequisite for the upcoming hydrogen energy society. Recently, manganese-based materials have been one of the most promising candidates to replace noble metal catalysts due to their natural abundance, low cost, adjustable electronic properties, and excellent chemical stability. Although some achievements have been made in the past decades, their performance is still far lower than that of Pt. Therefore, further research is needed to improve the performance of manganese-based catalytic materials. In this review, we summarize the research progress on the application of manganese-based materials as catalysts for electrolytic water splitting. We first introduce the mechanism of electrocatalytic water decomposition using a manganese-based electrocatalyst. We then thoroughly discuss the optimization strategy used to enhance the catalytic activity of manganese-based electrocatalysts, including doping and defect engineering, interface engineering, and phase engineering. Finally, we present several future design opportunities for highly efficient manganese-based electrocatalysts. Full article
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15 pages, 3122 KiB  
Article
Electrochemical Behavior of Reduced Graphene Oxide Supported Germanium Oxide, Germanium Nitride, and Germanium Phosphide as Lithium-Ion Battery Anodes Obtained from Highly Soluble Germanium Oxide
by Alexey A. Mikhaylov, Alexander G. Medvedev, Dmitry A. Grishanov, Timur M. Fazliev, Vasilii Chernyshev, Elena A. Mel’nik, Tatiana A. Tripol’skaya, Ovadia Lev and Petr V. Prikhodchenko
Int. J. Mol. Sci. 2023, 24(7), 6860; https://doi.org/10.3390/ijms24076860 - 06 Apr 2023
Cited by 4 | Viewed by 2045
Abstract
Germanium and germanium-based compounds are widely used in microelectronics, optics, solar cells, and sensors. Recently, germanium and its oxides, nitrides, and phosphides have been studied as active electrode materials in lithium- and sodium-ion battery anodes. Herein, the newly introduced highly soluble germanium oxide [...] Read more.
Germanium and germanium-based compounds are widely used in microelectronics, optics, solar cells, and sensors. Recently, germanium and its oxides, nitrides, and phosphides have been studied as active electrode materials in lithium- and sodium-ion battery anodes. Herein, the newly introduced highly soluble germanium oxide (HSGO) was used as a versatile precursor for germanium-based functional materials. In the first stage, a germanium-dioxide-reduced graphene oxide (rGO) composite was obtained by complete precipitation of GeO2 nanoparticles on the GO from an aqueous solution of HSGO and subsequent thermal treatment in argon at low temperature. The composition of the composite, GeO2-rGO (20 to 80 wt.% of crystalline phase), was able to be accurately determined by the HSGO to GO ratio in the initial solution since complete deposition and precipitation were achieved. The chemical activity of germanium dioxide nanoparticles deposited on reduced graphene oxide was shown by conversion to rGO-supported germanium nitride and phosphide phases. The GeP-rGO and Ge3N4-rGO composites with different morphologies were prepared in this study for the first time. As a test case, composite materials with different loadings of GeO2, GeP, and Ge3N4 were evaluated as lithium-ion battery anodes. Reversible conversion–alloying was demonstrated in all cases, and for the low-germanium loading range (20 wt.%), almost theoretical charge capacity based on the germanium content was attained at 100 mA g−1 (i.e., 2595 vs. 2465 mAh g−1 for Ge3N4 and 1790 vs. 1850 mAh g−1 for GeP). The germanium oxide was less efficiently exploited due to its lower conversion reversibility. Full article
(This article belongs to the Special Issue State-of-the-Art Materials Science in Russia—2nd Edition)
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13 pages, 5244 KiB  
Article
Folic Acid Ameliorates Renal Injury in Experimental Obstructive Nephropathy: Role of Glycine N-Methyltransferase
by Ko-Lin Kuo, Chin-Wei Chiang, Yi-Ming Arthur Chen, Chih-Chin Yu and Tzong-Shyuan Lee
Int. J. Mol. Sci. 2023, 24(7), 6859; https://doi.org/10.3390/ijms24076859 - 06 Apr 2023
Viewed by 1727
Abstract
Folic acid exerts both anti-inflammatory and antifibrotic effects. Glycine N-methyltransferase (GNMT), the major folic acid-binding protein in the liver, is a crucial enzyme that regulates the cellular methylation process by maintaining S-adenosylmethionine levels. However, as yet neither the therapeutic effects of folic acid [...] Read more.
Folic acid exerts both anti-inflammatory and antifibrotic effects. Glycine N-methyltransferase (GNMT), the major folic acid-binding protein in the liver, is a crucial enzyme that regulates the cellular methylation process by maintaining S-adenosylmethionine levels. However, as yet neither the therapeutic effects of folic acid in renal fibrosis nor whether GNMT is involved in these folic acid-associated mechanisms has been investigated. First, the expression of GNMT was examined in human kidneys with or without obstructive nephropathy. Later, wild-type and GNMT knockout (GNMT−/−) mice were subjected to unilateral ureteral obstruction (UUO) and then treated with either folic acid or vehicle for 14 days. Renal tubular injury, inflammation, fibrosis, and autophagy were evaluated by histological analysis and Western blotting. We observed increased expression of GNMT in humans with obstructive nephropathy. Furthermore, UUO significantly increased the expression of GNMT in mice; in addition, it caused renal injury as well as the development of both hydronephrosis and tubular injury. These were all alleviated by folic acid treatment. In contrast, GNMT−/− mice exhibited exacerbated UUO-induced renal injury, but the protective effect of folic acid was not observed in GNMT−/− mice. We propose a novel role for folic acid in the treatment of renal fibrosis, which indicates that GNMT may be a therapeutic target. Full article
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19 pages, 1215 KiB  
Review
Inclisiran—A Revolutionary Addition to a Cholesterol-Lowering Therapy
by Adrianna Dec, Aleksandra Niemiec, Eliza Wojciechowska, Mateusz Maligłówka, Łukasz Bułdak, Aleksandra Bołdys and Bogusław Okopień
Int. J. Mol. Sci. 2023, 24(7), 6858; https://doi.org/10.3390/ijms24076858 - 06 Apr 2023
Cited by 4 | Viewed by 2198
Abstract
Hypercholesterolemia plays a crucial role in the development of atherosclerosis, but it remains an undertreated and underdiagnosed disease. Taking into consideration the high prevalence of lipid disorders, long duration of the asymptomatic course of the disease, life-threatening complications resulting from inaccurate therapy, and [...] Read more.
Hypercholesterolemia plays a crucial role in the development of atherosclerosis, but it remains an undertreated and underdiagnosed disease. Taking into consideration the high prevalence of lipid disorders, long duration of the asymptomatic course of the disease, life-threatening complications resulting from inaccurate therapy, and stringent treatment goals concerning LDL cholesterol level in the prevention of cardiovascular events, novel lipid-lowering therapies have been introduced in the last few years. In this article, a drug belonging to the group of small interfering RNA (siRNA) called inclisiran is described. It is a novel molecule that increases the number of LDL receptors (LDLRs) on the surface of hepatic cells by preventing the formation of proprotein convertase subtilisin/kexin type 9 (PCSK9) responsible for the degradation of LDLRs. With great potential for lowering plasma LDL cholesterol level, high liver specificity, comfortable dosing regimen, and good tolerance without significant adverse effects, it could play an important part in future hypolipemic therapies. Full article
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16 pages, 1142 KiB  
Communication
The Effect of Metformin and Carbohydrate-Controlled Diet on DNA Methylation and Gene Expression in the Endometrium of Women with Polycystic Ovary Syndrome
by Elizabeth García-Gómez, Yadira Inés Gómez-Viais, Martin Mizael Cruz-Aranda, Luis Daniel Martínez-Razo, Christian Reyes-Mayoral, Lizeth Ibarra-González, Araceli Montoya-Estrada, Mauricio Osorio-Caballero, Otilia Perichart-Perera, Ignacio Camacho-Arroyo, Marco Cerbón, Enrique Reyes-Muñoz and Edgar Ricardo Vázquez-Martínez
Int. J. Mol. Sci. 2023, 24(7), 6857; https://doi.org/10.3390/ijms24076857 - 06 Apr 2023
Cited by 2 | Viewed by 2414
Abstract
Polycystic ovary syndrome (PCOS) is an endocrine disease associated with infertility and metabolic disorders in reproductive-aged women. In this study, we evaluated the expression of eight genes related to endometrial function and their DNA methylation levels in the endometrium of PCOS patients and [...] Read more.
Polycystic ovary syndrome (PCOS) is an endocrine disease associated with infertility and metabolic disorders in reproductive-aged women. In this study, we evaluated the expression of eight genes related to endometrial function and their DNA methylation levels in the endometrium of PCOS patients and women without the disease (control group). In addition, eight of the PCOS patients underwent intervention with metformin (1500 mg/day) and a carbohydrate-controlled diet (type and quantity) for three months. Clinical and metabolic parameters were determined, and RT-qPCR and MeDIP-qPCR were used to evaluate gene expression and DNA methylation levels, respectively. Decreased expression levels of HOXA10, GAB1, and SLC2A4 genes and increased DNA methylation levels of the HOXA10 promoter were found in the endometrium of PCOS patients compared to controls. After metformin and nutritional intervention, some metabolic and clinical variables improved in PCOS patients. This intervention was associated with increased expression of HOXA10, ESR1, GAB1, and SLC2A4 genes and reduced DNA methylation levels of the HOXA10 promoter in the endometrium of PCOS women. Our preliminary findings suggest that metformin and a carbohydrate-controlled diet improve endometrial function in PCOS patients, partly by modulating DNA methylation of the HOXA10 gene promoter and the expression of genes implicated in endometrial receptivity and insulin signaling. Full article
(This article belongs to the Special Issue New Insight to Polycystic Ovarian Syndrome)
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18 pages, 5293 KiB  
Review
Computer-Assisted Design of Peptide-Based Radiotracers
by Vincenzo Patamia, Chiara Zagni, Ilaria Brullo, Erika Saccullo, Alessandro Coco, Giuseppe Floresta and Antonio Rescifina
Int. J. Mol. Sci. 2023, 24(7), 6856; https://doi.org/10.3390/ijms24076856 - 06 Apr 2023
Cited by 3 | Viewed by 1717
Abstract
In medical imaging, techniques such as magnetic resonance imaging, contrast-enhanced computerized tomography, positron emission tomography (PET), and single-photon emission computed tomography (SPECT) are extensively available and routinely used for disease diagnosis. PET probes with peptide-based targeting are typically composed of small peptides especially [...] Read more.
In medical imaging, techniques such as magnetic resonance imaging, contrast-enhanced computerized tomography, positron emission tomography (PET), and single-photon emission computed tomography (SPECT) are extensively available and routinely used for disease diagnosis. PET probes with peptide-based targeting are typically composed of small peptides especially developed to have high affinity and specificity for a range of cellular and tissue targets. These probes’ key benefits include being less expensive than traditional antibody-based PET tracers and having an effective chemical modification process that allows them to be radiolabeled with almost any radionuclide, making them highly appealing for clinical usage. Currently, as with every pharmaceutical design, the use of in silico strategies is steadily growing in this field, even though it is not part of the standard toolkit used during radiopharmaceutical design. This review describes the recent applications of computational design approaches in the design of novel peptide-based radiopharmaceuticals. Full article
(This article belongs to the Special Issue Latest Review Papers in Molecular Informatics 2023)
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13 pages, 3282 KiB  
Article
RanBP1: A Potential Therapeutic Target for Cancer Stem Cells in Lung Cancer and Glioma
by Yeon-Jee Kahm, In-Gyu Kim and Rae-Kwon Kim
Int. J. Mol. Sci. 2023, 24(7), 6855; https://doi.org/10.3390/ijms24076855 - 06 Apr 2023
Cited by 2 | Viewed by 1605
Abstract
Cancer stem cells (CSCs) are known to be one of the factors that make cancer treatment difficult. Many researchers are thus conducting research to efficiently destroy CSCs. Therefore, we sought to suggest a new target that can efficiently suppress CSCs. In this study, [...] Read more.
Cancer stem cells (CSCs) are known to be one of the factors that make cancer treatment difficult. Many researchers are thus conducting research to efficiently destroy CSCs. Therefore, we sought to suggest a new target that can efficiently suppress CSCs. In this study, we observed a high expression of Ran-binding protein 1 (RanBP1) in lung cancer stem cells (LCSCs) and glioma stem cells (GSCs). Upregulated RanBP1 expression is strongly associated with the expression of CSC marker proteins and CSC regulators. In addition, an elevated RanBP1 expression is strongly associated with a poor patient prognosis. CSCs have the ability to resist radiation, and RanBP1 regulates this ability. RanBP1 also affects the metastasis-associated epithelial–mesenchymal transition (EMT) phenomenon. EMT marker proteins and regulatory proteins are affected by RanBP1 expression, and cell motility was regulated according to RanBP1 expression. The cancer microenvironment influences cancer growth, metastasis, and cancer treatment. RanBP1 can modulate the cancer microenvironment by regulating the cytokine IL-18. Secreted IL-18 acts on cancer cells and promotes cancer malignancy. Our results reveal, for the first time, that RanBP1 is an important regulator in LCSCs and GSCs, suggesting that it holds potential for use as a potential therapeutic target. Full article
(This article belongs to the Special Issue Novel Biological Molecules for Cancer Treatments 2.0)
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17 pages, 4832 KiB  
Article
Delivery of Doxorubicin by Ferric Ion-Modified Mesoporous Polydopamine Nanoparticles and Anticancer Activity against HCT-116 Cells In Vitro
by Mengwen Guo, Junhong Ling, Xinyi Xu and Xiaokun Ouyang
Int. J. Mol. Sci. 2023, 24(7), 6854; https://doi.org/10.3390/ijms24076854 - 06 Apr 2023
Cited by 4 | Viewed by 1880
Abstract
In clinical cancer research, photothermal therapy is one of the most effective ways to increase sensitivity to chemotherapy. Here, we present a simple and effective method for developing a nanotherapeutic agent for chemotherapy combined with photothermal therapy. The nanotherapeutic agent mesoporous polydopamine-Fe(III)-doxorubicin-hyaluronic acid [...] Read more.
In clinical cancer research, photothermal therapy is one of the most effective ways to increase sensitivity to chemotherapy. Here, we present a simple and effective method for developing a nanotherapeutic agent for chemotherapy combined with photothermal therapy. The nanotherapeutic agent mesoporous polydopamine-Fe(III)-doxorubicin-hyaluronic acid (MPDA-Fe(III)-DOX-HA) was composed of mesoporous polydopamine modified by ferric ions and loaded with the anticancer drug doxorubicin (DOX), as well as an outer layer coating of hyaluronic acid. The pore size of the mesoporous polydopamine was larger than that of the common polydopamine nanoparticles, and the particle size of MPDA-Fe(III)-DOX-HA nanoparticles was 179 ± 19 nm. With the presence of ferric ions, the heat generation effect of the MPDA-Fe(III)-DOX-HA nanoparticles in the near-infrared light at 808 nm was enhanced. In addition, the experimental findings revealed that the active targeting of hyaluronic acid to tumor cells mitigated the toxicity of DOX on normal cells. Furthermore, under 808 nm illumination, the MPDA-Fe(III)-DOX-HA nanoparticles demonstrated potent cytotoxicity to HCT-116 cells, indicating a good anti-tumor effect in vitro. Therefore, the system developed in this work merits further investigation as a potential nanotherapeutic platform for photothermal treatment of cancer. Full article
(This article belongs to the Special Issue Functional Nanomaterials for Healthcare)
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17 pages, 768 KiB  
Review
Neuroendocrine Neoplasms of the Gastrointestinal Tract versus Neuroendocrine Neoplasms of the Gynaecological Tract—Comparison of the Risk Factors and Non-Surgical Treatment Efficacy
by Anna Lorenz, Sebastian Lenkiewicz, Mateusz Kozłowski, Sebastian Kwiatkowski and Aneta Cymbaluk-Płoska
Int. J. Mol. Sci. 2023, 24(7), 6853; https://doi.org/10.3390/ijms24076853 - 06 Apr 2023
Viewed by 1334
Abstract
Neuroendocrine tumours of the gastrointestinal tract are rare. The incidence has increased in recent years due to improvements in diagnostic methods for detecting these lesions. These tumours have a poor prognosis, especially when detected at an advanced stage. The basis of the treatment [...] Read more.
Neuroendocrine tumours of the gastrointestinal tract are rare. The incidence has increased in recent years due to improvements in diagnostic methods for detecting these lesions. These tumours have a poor prognosis, especially when detected at an advanced stage. The basis of the treatment is resection, and non-surgical treatments are also standard in the treatment process. The situation is similar in even rarer neuroendocrine tumours of the reproductive tract, which are associated with an equally poor prognosis. In this article, we focus on learning about the risk factors (including genetic mutations) that increase the risk of the disease and comparing the effectiveness of non-surgical treatments—chemotherapy, radiotherapy, peptide receptor radionuclide therapy, somatostatin analogues, and immunotherapy. The efficacy of these treatments varies, and immunotherapy appears to be a promising form of treatment; however, this requires further research. Full article
(This article belongs to the Special Issue Gynecological Cancer 2023)
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4 pages, 182 KiB  
Editorial
The Cellular Response to DNA Damage: From DNA Repair to Polyploidy and Beyond
by Razmik Mirzayans
Int. J. Mol. Sci. 2023, 24(7), 6852; https://doi.org/10.3390/ijms24076852 - 06 Apr 2023
Cited by 1 | Viewed by 1145
Abstract
A major challenge in treating patients with solid tumors is posed by intratumor heterogeneity, with different sub-populations of cancer cells within the same tumor exhibiting therapy resistance through different biological processes [...] Full article
25 pages, 9097 KiB  
Article
Design, Synthesis and Biological Evaluation of 6-(Imidazo[1,2-a]pyridin-6-yl)quinazoline Derivatives as Anticancer Agents via PI3Kα Inhibition
by Mei Li, Daoping Wang, Qing Li, Fang Luo, Ting Zhong, Hongshan Wu, Liang Xiong, Meitao Yuan, Mingzhi Su and Yanhua Fan
Int. J. Mol. Sci. 2023, 24(7), 6851; https://doi.org/10.3390/ijms24076851 - 06 Apr 2023
Cited by 2 | Viewed by 1796
Abstract
Aberrant expression of the phosphatidylinositol 3-kinase (PI3K) signalling pathway is often associated with tumourigenesis, progression and poor prognosis. Hence, PI3K inhibitors have attracted significant interest for the treatment of cancer. In this study, a series of new 6-(imidazo[1,2-a]pyridin-6-yl)quinazoline derivatives were designed, synthesized and [...] Read more.
Aberrant expression of the phosphatidylinositol 3-kinase (PI3K) signalling pathway is often associated with tumourigenesis, progression and poor prognosis. Hence, PI3K inhibitors have attracted significant interest for the treatment of cancer. In this study, a series of new 6-(imidazo[1,2-a]pyridin-6-yl)quinazoline derivatives were designed, synthesized and characterized by 1H NMR, 13C NMR and HRMS spectra analyses. In the in vitro anticancer assay, most of the synthetic compounds showed submicromolar inhibitory activity against various tumour cell lines, among which 13k is the most potent compound with IC50 values ranging from 0.09 μΜ to 0.43 μΜ against all the tested cell lines. Moreover, 13k induced cell cycle arrest at G2/M phase and cell apoptosis of HCC827 cells by inhibition of PI3Kα with an IC50 value of 1.94 nM. These results suggested that compound 13k might serve as a lead compound for the development of PI3Kα inhibitor. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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9 pages, 233 KiB  
Communication
A Method and Formula for the Quantitative Analysis of the Total Bioactivity of Natural Products
by Shintu Mathew, Ritesh Raju, Xian Zhou, Francis Bodkin, Suresh Govindaraghavan and Gerald Münch
Int. J. Mol. Sci. 2023, 24(7), 6850; https://doi.org/10.3390/ijms24076850 - 06 Apr 2023
Cited by 3 | Viewed by 1926
Abstract
Identification of bioactive natural products from plants starts with the screening of extracts for a desired bioactivity such as antimicrobial, antifungal, anti-cancer, anti-inflammatory, or neuroprotective. When the bioactivity shows sufficient potency, the plant material is subjected to bio-activity-guided fractionation, which involves, e.g., sequential [...] Read more.
Identification of bioactive natural products from plants starts with the screening of extracts for a desired bioactivity such as antimicrobial, antifungal, anti-cancer, anti-inflammatory, or neuroprotective. When the bioactivity shows sufficient potency, the plant material is subjected to bio-activity-guided fractionation, which involves, e.g., sequential extraction followed by chromatographic separation, including HPLC. The bioactive compounds are then structurally identified by high-resolution mass spectrometry and nuclear magnetic resonance (NMR). One of the questions that come up during the purification process is how much of the bioactivity originally present in the crude extract is preserved during the purification process. If this is the case, it is interesting to investigate if the loss of total bioactivity is caused by the loss of material during purification or by the degradation or evaporation of potent compounds. A further possibility would be the loss of synergy between compounds present in the mixture, which disappears when the compounds are separated. In this publication, a novel formula is introduced that allows researchers to calculate total bioactivity in biological samples using experimental data from our research into the discovery of anti-inflammatory compounds from Backhousia myrtifolia (Grey Myrtle). The results presented show that a raw ethanolic extract retains slightly more bioactivity than the sum of all sequential extracts per gram of starting material and that—despite a large loss of material during HPLC purification—the total bioactivity in all purified fractions is retained, which is indicative of rather an additive than a synergistic principle. Full article
25 pages, 21045 KiB  
Article
POLD1 as a Prognostic Biomarker Correlated with Cell Proliferation and Immune Infiltration in Clear Cell Renal Cell Carcinoma
by Junjie Tian, Cheng Cheng, Jianguo Gao, Guanghou Fu, Zhijie Xu, Xiaoyi Chen, Yunfei Wu and Baiye Jin
Int. J. Mol. Sci. 2023, 24(7), 6849; https://doi.org/10.3390/ijms24076849 - 06 Apr 2023
Cited by 3 | Viewed by 2071
Abstract
DNA polymerase delta 1 catalytic subunit (POLD1) plays a vital role in genomic copy with high fidelity and DNA damage repair processes. However, the prognostic value of POLD1 and its relationship with tumor immunity in clear cell renal cell carcinoma (ccRCC) remains to [...] Read more.
DNA polymerase delta 1 catalytic subunit (POLD1) plays a vital role in genomic copy with high fidelity and DNA damage repair processes. However, the prognostic value of POLD1 and its relationship with tumor immunity in clear cell renal cell carcinoma (ccRCC) remains to be further explored. Transcriptional data sets and clinical information were obtained from the TCGA, ICGC, and GEO databases. Differentially expressed genes (DEGs) were derived from the comparison between the low and high POLD1 expression groups in the TCGA–KIRC cohort. KEGG and gene ontology (GO) analyses were performed for those DEGs to explore the potential influence of POLD1 on the biological behaviors of ccRCC. The prognostic clinical value and mutational characteristics of patients were described and analyzed according to the POLD1 expression levels. TIMER and TISIDB databases were utilized to comprehensively investigate the potential relevance between the POLD1 levels and the status of the immune cells, as well as the tumor infiltration of immune cells. In addition, RT-qPCR, Western blot, immunohistochemistry and several functional and animal experiments were performed for clinical, in vitro and in vivo validation. POLD1 was highly expressed in a variety of tumors including ccRCC, and further verified in a validation cohort of 60 ccRCC samples and in vitro cell line experiments. POLD1 expression levels in the ccRCC samples were associated with various clinical characteristics including pathologic tumor stage and histologic grade. ccRCC patients with high POLD1 expression have poor clinical outcomes and exhibit a higher rate of somatic mutations than those with low POLD1 expression. Cox regression analysis also showed that POLD1 could act as a potential independent prognostic biomarker. The DEGs associated with POLD1 were significantly enriched in the immunity-related pathways. Moreover, further immune infiltration analysis indicated that high POLD1 expression was associated with high NK CD56bright cells, Treg cells, and myeloid-derived suppressor cells’ (MDSCs) infiltration scores, as well as their marker gene sets of immune cell status. Meanwhile, POLD1 exhibited resistance to various drugs when highly expressed. Finally, the knockdown of POLD1 inhibited the proliferation and migration, and promoted the apoptosis of ccRCC cells in vitro and in vivo, as well as influenced the activation of oncogenic signaling. Our current study demonstrated that POLD1 is a potential prognostic biomarker for ccRCC patients. It might create a tumor immunosuppressive microenvironment and inhibit the susceptibility to ferroptosis leading to a poor prognosis. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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10 pages, 2013 KiB  
Article
Genetic Variation among Heterodera schachtii Populations Coincided with Differences in Invasion and Propagation in Roots of a Set of Cruciferous Plants
by Rasha Haj Nuaima and Holger Heuer
Int. J. Mol. Sci. 2023, 24(7), 6848; https://doi.org/10.3390/ijms24076848 - 06 Apr 2023
Cited by 3 | Viewed by 1104
Abstract
Genes of host plants and parasitic nematodes govern the plant–nematode interaction. The biological receptors and parasitism effectors are variable among plant species and nematode populations, respectively. In the present study, hatch testing and bioassays on cabbage, oilseed radish, and mustard were conducted to [...] Read more.
Genes of host plants and parasitic nematodes govern the plant–nematode interaction. The biological receptors and parasitism effectors are variable among plant species and nematode populations, respectively. In the present study, hatch testing and bioassays on cabbage, oilseed radish, and mustard were conducted to compare the biological characteristics among six populations of the beet cyst nematode Heterodera schachtii. Genetic patterns of the vap1 gene for the studied populations were distinct as shown by denaturing the gradient gel electrophoresis of PCR-amplified gene fragments. Concurrently, significant differences in the hatching rates, number of penetrated J2 in roots, and eggs/cyst ratios among the six nematode populations for the three cruciferous species were observed. In conclusion, analyzing the population genetic structure of H. schachtii plays a pivotal role in illustrating the variability in the plant–nematode interaction among its populations and plant species, which in its role leads to developing nematode management depending on plant resistance. Full article
(This article belongs to the Special Issue Plant–Nematode Interactions)
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19 pages, 4012 KiB  
Article
The Influence of Edaphic Factors on DNA Damage and Repair in Wild Wheat Triticum dicoccoides Körn. (Poaceae, Triticeae)
by Olga Raskina, Boris Shklyar and Eviatar Nevo
Int. J. Mol. Sci. 2023, 24(7), 6847; https://doi.org/10.3390/ijms24076847 - 06 Apr 2023
Viewed by 1673
Abstract
A complex DNA repair network maintains genome integrity and genetic stability. In this study, the influence of edaphic factors on DNA damage and repair in wild wheat Triticum dicoccoides was addressed. Plants inhabiting two abutting microsites with dry terra rossa and humid basalt [...] Read more.
A complex DNA repair network maintains genome integrity and genetic stability. In this study, the influence of edaphic factors on DNA damage and repair in wild wheat Triticum dicoccoides was addressed. Plants inhabiting two abutting microsites with dry terra rossa and humid basalt soils were studied. The relative expression level of seven genes involved in DNA repair pathways—RAD51, BRCA1, LigIV, KU70, MLH1, MSH2, and MRE11—was assessed using quantitative real-time PCR (qPCR). Immunolocalization of RAD51, LigIV, γH2AX, RNA Polymerase II, and DNA-RNA hybrid [S9.6] (R-loops) in somatic interphase nuclei and metaphase chromosomes was carried out in parallel. The results showed a lower expression level of genes involved in DNA repair and a higher number of DNA double-strand breaks (DSBs) in interphase nuclei in plants growing in terra rossa soil compared with plants in basalt soil. Further, the number of DSBs and R-loops in metaphase chromosomes was also greater in plants growing on terra rossa soil. Finally, RAD51 and LigIV foci on chromosomes indicate ongoing DSB repair during the M-phase via the Homologous Recombination and Non-Homologous End Joining pathways. Together, these results show the impact of edaphic factors on DNA damage and repair in the wheat genome adapted to contrasting environments. Full article
(This article belongs to the Collection Advances in Cytomolecular Organisation of the Nuclear Genome)
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15 pages, 1296 KiB  
Review
Uses of Papaya Leaf and Seaweed Supplementations for Controlling Glucose Homeostasis in Diabetes
by Benard B. Nyakundi and Jinzeng Yang
Int. J. Mol. Sci. 2023, 24(7), 6846; https://doi.org/10.3390/ijms24076846 - 06 Apr 2023
Cited by 3 | Viewed by 3742
Abstract
Studies from laboratory animal models and complementary medical practices have implied that nutrients from special plants or herbs contain antidiabetic, antioxidant, anti-obese, anti-hypertensive, and anti-inflammatory properties. Seaweed and tropical papaya, which are widely available in Asian and Pacific countries, have been used as [...] Read more.
Studies from laboratory animal models and complementary medical practices have implied that nutrients from special plants or herbs contain antidiabetic, antioxidant, anti-obese, anti-hypertensive, and anti-inflammatory properties. Seaweed and tropical papaya, which are widely available in Asian and Pacific countries, have been used as home remedies for centuries. The bioactive extracts from these plants contain vitamins A, C, B and E complexes, as well as polysaccharides, phenolic compounds, essential fatty acids, flavonoids, saponins, fucoidan, and phlorotannin. In this review, the authors examine the pathogenesis of diabetes characterized by hyperglycemia due to the dysregulation of glucose homeostasis, antidiabetic/antihyperglycemic seaweed or/and papaya derived bioactive phytochemicals and their proposed mechanisms of action in the management of Type 2 Diabetes Mellitus (T2DM). The authors also propose combining papaya and seaweed to enhance their antidiabetic effects, leveraging the advantages of herb-to-herb combination. Papaya and seaweed have demonstrated antidiabetic effects through in vitro assays, cellular models, and animal studies despite the limited clinical trials. Nutraceuticals with antidiabetic effects, such as secondary metabolites isolated from seaweed and papaya, could be combined for a synergistic effect on T2DM management. However, the application of these compounds in their purified or mixed forms require further scientific studies to evaluate their efficacy against diabetes-related complications, such as hyperlipidemia, elevated free radicals, pro-inflammatory molecules, insulin insensitivity, and the degeneration of pancreatic beta cells. Full article
(This article belongs to the Special Issue Bioactive Compounds in Metabolic Syndrome)
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31 pages, 11986 KiB  
Article
Identification of Orbivirus Non-Structural Protein 5 (NS5), Its Role and Interaction with RNA/DNA in Infected Cells
by Fauziah Mohd Jaafar, Baptiste Monsion, Peter P. C. Mertens and Houssam Attoui
Int. J. Mol. Sci. 2023, 24(7), 6845; https://doi.org/10.3390/ijms24076845 - 06 Apr 2023
Cited by 5 | Viewed by 1982
Abstract
Bioinformatic analyses have predicted that orbiviruses encode an additional, small non-structural protein (NS5) from a secondary open reading frame on genome segment 10. However, this protein has not previously been detected in infected mammalian or insect cells. NS5-specific antibodies were generated in mice [...] Read more.
Bioinformatic analyses have predicted that orbiviruses encode an additional, small non-structural protein (NS5) from a secondary open reading frame on genome segment 10. However, this protein has not previously been detected in infected mammalian or insect cells. NS5-specific antibodies were generated in mice and were used to identify NS5 synthesised in orbivirus-infected BSR cells or cells transfected with NS5 expression plasmids. Confocal microscopy shows that although NS5 accumulates in the nucleus, particularly in the nucleolus, which becomes disrupted, it also appears in the cell cytoplasm, co-localising with mitochondria. NS5 helps to prevent the degradation of ribosomal RNAs during infection and reduces host-cell protein synthesis However, it helps to extend cell viability by supporting viral protein synthesis and virus replication. Pulldown studies showed that NS5 binds to ssRNAs and supercoiled DNAs and demonstrates interactions with ZBP1, suggesting that it modulates host-cell responses. Full article
(This article belongs to the Collection Feature Papers in “Molecular Biology”)
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18 pages, 5955 KiB  
Article
Salvianolic-Acid-B-Loaded HA Self-Healing Hydrogel Promotes Diabetic Wound Healing through Promotion of Anti-Inflammation and Angiogenesis
by Guoying Zhou, Jiayan Zhu, Liang Jin, Jing Chen, Ruojiao Xu, Yali Zhao, Tingzi Yan and Haitong Wan
Int. J. Mol. Sci. 2023, 24(7), 6844; https://doi.org/10.3390/ijms24076844 - 06 Apr 2023
Cited by 6 | Viewed by 2335
Abstract
Inflammatory dysfunction and angiogenesis inhibition are two main factors leading to the delayed healing of diabetic wounds. Hydrogels with anti-inflammatory and angiogenesis-promoting effects have been considered as promising wound care materials. Herein, a salvianolic acid B (SAB)-loaded hyaluronic acid (HA) self-healing hydrogel (HA/SAB) [...] Read more.
Inflammatory dysfunction and angiogenesis inhibition are two main factors leading to the delayed healing of diabetic wounds. Hydrogels with anti-inflammatory and angiogenesis-promoting effects have been considered as promising wound care materials. Herein, a salvianolic acid B (SAB)-loaded hyaluronic acid (HA) self-healing hydrogel (HA/SAB) with anti-inflammatory and pro-angiogenesis capacities for diabetic wound healing is reported. The HA hydrogel was prepared via the covalent cross-linking of aldehyde groups in oxidized HA (OHA) and hydrazide groups in adipic dihydrazide (ADH)-modified HA (HA-ADH) with the formation of reversible acylhydrazone bonds. The obtained HA hydrogel exhibited multiple favorable properties such as porous structures, excellent self-healing properties, a sustainable release capacity of SAB, as well as excellent cytocompatibility. In addition, the effects of the SAB-loaded HA self-healing hydrogel were investigated via a full-thickness skin defect model using diabetic rats. The HA/SAB hydrogel showed enhanced skin regeneration effects with accelerated wound closure, shorter remaining dermal space length, thicker granulation tissue formation, and more collagen deposition. Furthermore, reduced inflammatory response and enhanced vascularization were found with HA/SAB2.5 hydrogel-treated wounds, indicating that the hydrogel promotes diabetic wound healing through the promotion of anti-inflammation and angiogenesis. Our results suggest that the fabricated SAB-loaded HA self-healing hydrogel is promising as a wound dressing for the treatment of diabetic wounds. Full article
(This article belongs to the Special Issue Advanced Therapies and Functional Materials for Wound Healing)
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17 pages, 9565 KiB  
Article
Engineering a HER2-CAR-NK Cell Secreting Soluble Programmed Cell Death Protein with Superior Antitumor Efficacy
by Wenjiao Xia, Jiaxin Chen, Wenqing Hou, Junsheng Chen, Ying Xiong, Hongyan Li, Xin Qi, Hui Xu, Zuoquan Xie, Mingfeng Li, Xiaomin Zhang and Jing Li
Int. J. Mol. Sci. 2023, 24(7), 6843; https://doi.org/10.3390/ijms24076843 - 06 Apr 2023
Cited by 7 | Viewed by 2635
Abstract
A new therapy strategy for relapsing patients who have received trastuzumab treatment urgently needs to be explored. HER2-specific chimeric antigen receptor (CAR)-expressing NK cells are being rapidly developed for solid tumor therapy, as they have many advantages over HER2-CAR-T cells. Endogenous soluble PD-1 [...] Read more.
A new therapy strategy for relapsing patients who have received trastuzumab treatment urgently needs to be explored. HER2-specific chimeric antigen receptor (CAR)-expressing NK cells are being rapidly developed for solid tumor therapy, as they have many advantages over HER2-CAR-T cells. Endogenous soluble PD-1 (sPD-1) from the PD-1 extracellular domain blocks PD-1/PD-L1 interaction to promote cancer immunology. Herein, we engineered a new HER2-CAR-NK cell that co-expresses sPD-1 (designed as sPD-1-CAR-NK cells) and assessed its cytotoxic activities toward various cancer cells, activation of immunity and sPD-1 release in vitro and in mouse models bearing breast cancer cells with high HER2 expression, with or without trastuzumab resistance. We demonstrated that sPD-1-CAR-NK cells were able to release bioactive sPD-1, thereby enhancing the cytolytic activities of HER2-CAR-NK cells against HER2 and PD-L1 highly expressing target cells accompanied by increases in the secretion of perforin, granzyme B and IFN-γ. In vivo, sPD-1-CAR-NK cells had superior immunological anticancer efficacy compared to HER2-CAR-NK cells, and they had advantages over HER2-CAR-NK cells in the intraperitoneal injection of sPD-1. Moreover, the infiltration and activation of NK and T cells into tumor tissue were increased in mice with sPD-1-CAR-NK cells. There was no significant change in the body temperature, organ tissue and body weight in all groups except for the group with the PD-1 injection. Together, these data indicate that HER2-specific sPD-1-CAR-NK cells can transport sPD-1 into cancer tissues with high HER2 expression, further improving the efficacy of HER-CAR-NK cells without obvious side effects. sPD-1-CAR-NK is a promising cytotherapeutic agent for patients bearing HER2-positive breast cancer, including those with trastuzumab resistance. Full article
(This article belongs to the Special Issue The Discovery, Synthesis and Development of Cancer Therapeutic Agents)
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