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Int. J. Mol. Sci., Volume 23, Issue 23 (December-1 2022) – 947 articles

Cover Story (view full-size image): 7,7,8,8-Tetracyanoquinodimethane (TCNQ) is utilized for the polyvinylpyrrolidone (PVP)/CuO composite membrane to modify the surface of particles, resulting in the enhancement of CO2 solubility. When the separation performance of the PVP/CuO/TCNQ composite membrane is measured for CO2/N2 gases, the selectivity reached about 174. This improvement in performance is attributed to the fact that TCNQ plays the role of polarizing the surface of CuO and dispersing the particles as a small size in PVP. Furthermore, the intensity of bonds between chains in PVP became weakened and the free volume increased. View this paper
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38 pages, 4509 KiB  
Review
Selenium in Bodily Homeostasis: Hypothalamus, Hormones, and Highways of Communication
by Pamela Toh, Jessica L. Nicholson, Alyssa M. Vetter, Marla J. Berry and Daniel J. Torres
Int. J. Mol. Sci. 2022, 23(23), 15445; https://doi.org/10.3390/ijms232315445 - 06 Dec 2022
Cited by 16 | Viewed by 4772
Abstract
The ability of the body to maintain homeostasis requires constant communication between the brain and peripheral tissues. Different organs produce signals, often in the form of hormones, which are detected by the hypothalamus. In response, the hypothalamus alters its regulation of bodily processes, [...] Read more.
The ability of the body to maintain homeostasis requires constant communication between the brain and peripheral tissues. Different organs produce signals, often in the form of hormones, which are detected by the hypothalamus. In response, the hypothalamus alters its regulation of bodily processes, which is achieved through its own pathways of hormonal communication. The generation and transmission of the molecules involved in these bi-directional axes can be affected by redox balance. The essential trace element selenium is known to influence numerous physiological processes, including energy homeostasis, through its various redox functions. Selenium must be obtained through the diet and is used to synthesize selenoproteins, a family of proteins with mainly antioxidant functions. Alterations in selenium status have been correlated with homeostatic disturbances in humans and studies with animal models of selenoprotein dysfunction indicate a strong influence on energy balance. The relationship between selenium and energy metabolism is complicated, however, as selenium has been shown to participate in multiple levels of homeostatic communication. This review discusses the role of selenium in the various pathways of communication between the body and the brain that are essential for maintaining homeostasis. Full article
(This article belongs to the Special Issue The Role of Magnesium and Other Bio-Elements in Health and Disease)
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16 pages, 5806 KiB  
Article
Effects of β-amyloid (1-42) Administration on the Main Neurogenic Niches of the Adult Brain: Amyloid-Induced Neurodegeneration Influences Neurogenesis
by Konstantin Yenkoyan, Tigran Margaryan, Senik Matinyan, Vergine Chavushyan, Margarita Danielyan, Tigran Davtyan and Michail Aghajanov
Int. J. Mol. Sci. 2022, 23(23), 15444; https://doi.org/10.3390/ijms232315444 - 06 Dec 2022
Cited by 2 | Viewed by 2017
Abstract
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and warrants further study as well as timely treatment. Additionally, the mechanisms of the brain’s intrinsic defense against chronic injury are not yet fully understood. Herein, we examined the response of the main neurogenic [...] Read more.
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and warrants further study as well as timely treatment. Additionally, the mechanisms of the brain’s intrinsic defense against chronic injury are not yet fully understood. Herein, we examined the response of the main neurogenic niches to amyloid exposure and the associated changes in structure and synaptic activity. Flow cytometry of Nestin-, Vimentin-, Nestin/Vimentin-, NeuN-, GFAP-, NeuN/GFAP-, NSE-, BrdU-, Wnt-, BrdU/Wnt-, VEGF-, Sox14-, VEGF/Sox14-, Sox10-, Sox2-, Sox10/Sox2-, Bax-, and Bcl-xL-positive cells was performed in the subventricular zone (SVZ), hippocampus, and cerebral cortex of rat brains on 90th day after intracerebroventricular (i.c.v.) single injection of a fraction of β-amyloid (Aβ) (1-42). The relative structural changes in these areas and disruptions to synaptic activity in the entorhinal cortex–hippocampus circuit were also evaluated. Our flow analyses revealed a reduction in the numbers of Nestin-, Vimentin-, and Nestin/Vimentin-positive cells in neurogenic niches and the olfactory bulb. These changes were accompanied by an increased number of BrdU-positive cells in the hippocampus and SVZ. The latter changes were strongly correlated with changes in the numbers of VEGF- and VEGF/Sox14-positive cells. The morphological changes were characterized by significant neural loss, a characteristic shift in entorhinal cortex–hippocampus circuit activity, and decreased spontaneous alternation in a behavioral test. We conclude that although an injection of Aβ (1-42) induced stem cell proliferation and triggered neurogenesis at a certain stage, this process was incomplete and led to neural stem cell immaturity. We propose the idea of enhancing adult neurogenesis as a promising strategy for preventing dementia at healthy elderly people andpeople at high risk for developing AD, or treating patients diagnosed with AD. Full article
(This article belongs to the Special Issue Molecular Biomarkers in Neurodevelopmental and Neurodegenerative Disorders)
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19 pages, 2728 KiB  
Article
Distinct Changes in Calpain and Calpastatin during PNS Myelination and Demyelination in Rodent Models
by John A. Miller, Domenica E. Drouet, Leonid M. Yermakov, Mahmoud S. Elbasiouny, Fatima Z. Bensabeur, Michael Bottomley and Keiichiro Susuki
Int. J. Mol. Sci. 2022, 23(23), 15443; https://doi.org/10.3390/ijms232315443 - 06 Dec 2022
Viewed by 1813
Abstract
Myelin forming around axons provides electrical insulation and ensures rapid and efficient transmission of electrical impulses. Disruptions to myelinated nerves often result in nerve conduction failure along with neurological symptoms and long-term disability. In the central nervous system, calpains, a family of calcium [...] Read more.
Myelin forming around axons provides electrical insulation and ensures rapid and efficient transmission of electrical impulses. Disruptions to myelinated nerves often result in nerve conduction failure along with neurological symptoms and long-term disability. In the central nervous system, calpains, a family of calcium dependent cysteine proteases, have been shown to have a role in developmental myelination and in demyelinating diseases. The roles of calpains in myelination and demyelination in the peripheral nervous system remain unclear. Here, we show a transient increase of activated CAPN1, a major calpain isoform, in postnatal rat sciatic nerves when myelin is actively formed. Expression of the endogenous calpain inhibitor, calpastatin, showed a steady decrease throughout the period of peripheral nerve development. In the sciatic nerves of Trembler-J mice characterized by dysmyelination, expression levels of CAPN1 and calpastatin and calpain activity were significantly increased. In lysolecithin-induced acute demyelination in adult rat sciatic nerves, we show an increase of CAPN1 and decrease of calpastatin expression. These changes in the calpain-calpastatin system are distinct from those during central nervous system development or in acute axonal degeneration in peripheral nerves. Our results suggest that the calpain-calpastatin system has putative roles in myelination and demyelinating diseases of peripheral nerves. Full article
(This article belongs to the Special Issue Molecular Aspects of Degeneration and Regeneration in the Peripheral Nervous System)
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16 pages, 1595 KiB  
Review
Glycosphingolipids in Diabetes, Oxidative Stress, and Cardiovascular Disease: Prevention in Experimental Animal Models
by Amrita Balram, Spriha Thapa and Subroto Chatterjee
Int. J. Mol. Sci. 2022, 23(23), 15442; https://doi.org/10.3390/ijms232315442 - 06 Dec 2022
Cited by 6 | Viewed by 2028
Abstract
Diabetes contributes to about 30% morbidity and mortality world-wide and has tidal wave increases in several countries in Asia. Diabetes is a multi-factorial disease compounded by inflammation, dyslipidemia, atherosclerosis, and is sometimes accompanied with gains in body weight. Sphingolipid pathways that interplay in [...] Read more.
Diabetes contributes to about 30% morbidity and mortality world-wide and has tidal wave increases in several countries in Asia. Diabetes is a multi-factorial disease compounded by inflammation, dyslipidemia, atherosclerosis, and is sometimes accompanied with gains in body weight. Sphingolipid pathways that interplay in the enhancement of the pathology of this disease may be potential therapeutic targets. Thus, the application of advanced sphingolipidomics may help predict the progression of this disease and therapeutic outcomes in man. Pre-clinical studies using various experimental animal models of diabetes provide valuable information on the role of sphingolipid signaling networks in diabetes and the efficacy of drugs to determine the translatability of innovative discoveries to man. In this review, we discuss three major concepts regarding sphingolipids and diabetes. First, we discuss a possible involvement of a monosialodihexosylceramide (GM3) in insulin–insulin receptor interactions. Second, a potential role for ceramide (Cer) and lactosylceramide (LacCer) in apoptosis and mitochondrial dysfunction is proposed. Third, a larger role of LacCer in antioxidant status and inflammation is discussed. We also discuss how inhibitors of glycosphingolipid synthesis can ameliorate diabetes in experimental animal models. Full article
(This article belongs to the Special Issue Molecular Pharmacology in Diabetes)
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10 pages, 2565 KiB  
Article
Systematic Comparison of Plant Promoters in Nicotiana spp. Expression Systems
by Ekaterina S. Shakhova, Nadezhda M. Markina, Tatiana Mitiouchkina, Evgenia N. Bugaeva, Tatiana A. Karataeva, Kseniia A. Palkina, Liliia I. Fakhranurova, Ilia V. Yampolsky, Karen S. Sarkisyan and Alexander S. Mishin
Int. J. Mol. Sci. 2022, 23(23), 15441; https://doi.org/10.3390/ijms232315441 - 06 Dec 2022
Cited by 3 | Viewed by 1818
Abstract
We report a systematic comparison of 19 plant promoters and 20 promoter-terminator combinations in two expression systems: agroinfiltration in Nicotiana benthamiana leaves, and Nicotiana tabacum BY-2 plant cell packs. The set of promoters tested comprised those not present in previously published work, including [...] Read more.
We report a systematic comparison of 19 plant promoters and 20 promoter-terminator combinations in two expression systems: agroinfiltration in Nicotiana benthamiana leaves, and Nicotiana tabacum BY-2 plant cell packs. The set of promoters tested comprised those not present in previously published work, including several computationally predicted synthetic promoters validated here for the first time. The expression of EGFP driven by different promoters varied by more than two orders of magnitude and was largely consistent between two tested Nicotiana systems. We confirmed previous reports of significant modulation of expression by terminators, as well as synergistic effects of promoters and terminators. Additionally, we observed non-linear effects of gene dosage on expression level. The dataset presented here can inform the design of genetic constructs for plant engineering and transient expression assays. Full article
(This article belongs to the Special Issue Advanced Research in Fluorescent Proteins)
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50 pages, 7226 KiB  
Review
Targeted Protein Degradation: Clinical Advances in the Field of Oncology
by Abdelrahman K. A. A. Salama, Marija V. Trkulja, Emilio Casanova and Iris Z. Uras
Int. J. Mol. Sci. 2022, 23(23), 15440; https://doi.org/10.3390/ijms232315440 - 06 Dec 2022
Cited by 10 | Viewed by 6586
Abstract
The field of targeted protein degradation (TPD) is a rapidly developing therapeutic modality with the promise to tame disease-relevant proteins in ways that are difficult or impossible to tackle with other strategies. While we move into the third decade of TPD, multiple degrader [...] Read more.
The field of targeted protein degradation (TPD) is a rapidly developing therapeutic modality with the promise to tame disease-relevant proteins in ways that are difficult or impossible to tackle with other strategies. While we move into the third decade of TPD, multiple degrader drugs have entered the stage of the clinic and many more are expected to follow. In this review, we provide an update on the most recent advances in the field of targeted degradation with insights into possible clinical implications for cancer prevention and treatment. Full article
(This article belongs to the Special Issue Molecular Target and Action Mechanism of Anti-cancer Agents 2.0)
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16 pages, 3214 KiB  
Article
Role of Monovalent Ions in the NKCC1 Inhibition Mechanism Revealed through Molecular Simulations
by Pavel Janoš and Alessandra Magistrato
Int. J. Mol. Sci. 2022, 23(23), 15439; https://doi.org/10.3390/ijms232315439 - 06 Dec 2022
Cited by 1 | Viewed by 1435
Abstract
The secondary active Na-K-Cl cotransporter 1 (NKCC1) promotes electroneutral uptake of two chloride ions, one sodium ion and one potassium ion. NKCC1 regulates Cl− homeostasis, thus being implicated in transepithelial water transport and in neuronal excitability. Aberrant NKCC1 transport is linked to [...] Read more.
The secondary active Na-K-Cl cotransporter 1 (NKCC1) promotes electroneutral uptake of two chloride ions, one sodium ion and one potassium ion. NKCC1 regulates Cl− homeostasis, thus being implicated in transepithelial water transport and in neuronal excitability. Aberrant NKCC1 transport is linked to a variety of human diseases. The loop diuretic drugs bumetanide, furosemide, azosemide and ethacrynic acid target NKCC1, but are characterized by poor selectivity leading to severe side effects. Despite its therapeutic importance, the molecular details of the NKCC1 inhibition mechanism remain unclear. Using all-atom simulations, we predict a putative binding mode of these drugs to the zebrafish (z) and human (h) NKCC1 orthologs. Although differing in their specific interactions with NKCC1 and/or monovalent ions, all drugs can fit within the same cavity and engage in hydrophobic interactions with M304/M382 in z/hNKCC1, a proposed ion gating residue demonstrated to be key for bumetanide binding. Consistent with experimental evidence, all drugs take advantage of the K+/Na+ ions, which plastically respond to their binding. This study not only provides atomic-level insights useful for drug discovery campaigns of more selective/potent NKCC1 inhibitors aimed to tackle diseases related to deregulated Cl− homeostasis, but it also supplies a paradigmatic example of the key importance of dynamical effects when drug binding is mediated by monovalent ions. Full article
(This article belongs to the Special Issue Computational Design of Materials for Applications (Drugs, Photonics))
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10 pages, 561 KiB  
Review
Potential Roles of Exosomes in the Development and Detection of Malignant Mesothelioma: An Update
by Phillip Munson and Arti Shukla
Int. J. Mol. Sci. 2022, 23(23), 15438; https://doi.org/10.3390/ijms232315438 - 06 Dec 2022
Cited by 1 | Viewed by 1539
Abstract
Malignant mesothelioma (MM) is a devastating cancer of mesothelial cells, caused by asbestos exposure. Limited knowledge regarding the detection of asbestos exposure and the early diagnosis of MM, as well as a lack of successful treatment options for this deadly cancer, project an [...] Read more.
Malignant mesothelioma (MM) is a devastating cancer of mesothelial cells, caused by asbestos exposure. Limited knowledge regarding the detection of asbestos exposure and the early diagnosis of MM, as well as a lack of successful treatment options for this deadly cancer, project an immediate need to understand the mechanism(s) of MM development. With the recent discovery of nano-vesicles, namely exosomes, and their enormous potential to contain signature molecules representative of different diseases, as well as to communicate with distant targets, we were encouraged to explore their role(s) in MM biology. In this review, we summarize what we know so far about exosomes and MM based on our own studies and on published literature from other groups in the field. We expect that the information contained in this review will help advance the field of MM forward by revealing the mechanisms of MM development and survival. Based on this knowledge, future therapeutic strategies for MM can potentially be developed. We also hope that the outcome of our studies presented here may help in the detection of MM. Full article
(This article belongs to the Special Issue The Role of Exosomes in Cancer Diagnosis and Therapy)
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17 pages, 935 KiB  
Review
Biologically Active Peptides from Venoms: Applications in Antibiotic Resistance, Cancer, and Beyond
by Lucía Ageitos, Marcelo D. T. Torres and Cesar de la Fuente-Nunez
Int. J. Mol. Sci. 2022, 23(23), 15437; https://doi.org/10.3390/ijms232315437 - 06 Dec 2022
Cited by 6 | Viewed by 2853
Abstract
Peptides are potential therapeutic alternatives against global diseases, such as antimicrobial-resistant infections and cancer. Venoms are a rich source of bioactive peptides that have evolved over time to act on specific targets of the prey. Peptides are one of the main components responsible [...] Read more.
Peptides are potential therapeutic alternatives against global diseases, such as antimicrobial-resistant infections and cancer. Venoms are a rich source of bioactive peptides that have evolved over time to act on specific targets of the prey. Peptides are one of the main components responsible for the biological activity and toxicity of venoms. South American organisms such as scorpions, snakes, and spiders are important producers of a myriad of peptides with different biological activities. In this review, we report the main venom-derived peptide families produced from South American organisms and their corresponding activities and biological targets. Full article
(This article belongs to the Special Issue Antimicrobial Peptides: Structure and Mechanism of Biological Activity 2.0)
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16 pages, 3836 KiB  
Article
Arabidopsis Cys2/His2 Zinc Finger Transcription Factor ZAT18 Modulates the Plant Growth-Defense Tradeoff
by Weiwei Li, Min Zhang, Tingyu Zhang, Yueyan Liu and Lijing Liu
Int. J. Mol. Sci. 2022, 23(23), 15436; https://doi.org/10.3390/ijms232315436 - 06 Dec 2022
Cited by 1 | Viewed by 1903
Abstract
Plant defense responses under unfavorable conditions are often associated with reduced growth. However, the mechanisms underlying the growth-defense tradeoff remain to be fully elucidated, especially at the transcriptional level. Here, we revealed a Cys2/His2-type zinc finger transcription factor, namely, ZAT18, which played dual [...] Read more.
Plant defense responses under unfavorable conditions are often associated with reduced growth. However, the mechanisms underlying the growth-defense tradeoff remain to be fully elucidated, especially at the transcriptional level. Here, we revealed a Cys2/His2-type zinc finger transcription factor, namely, ZAT18, which played dual roles in plant immunity and growth by oppositely regulating the signaling of defense- and growth-related hormones. ZAT18 was first identified as a salicylic acid (SA)-inducible gene and was required for plant responses to SA in this study. In addition, we observed that ZAT18 enhanced the plant immunity with growth penalties that may have been achieved by activating SA signaling and repressing auxin signaling. Further transcriptome analysis of the zat18 mutant showed that the biological pathways of defense-related hormones, including SA, ethylene and abscisic acid, were repressed and that the biological pathways of auxin and cytokinin, which are growth-related hormones, were activated by abolishing the function of ZAT18. The ZAT18-mediated regulation of hormone signaling was further confirmed using qRT-PCR. Our results explored a mechanism by which plants handle defense and growth at the transcriptional level under stress conditions. Full article
(This article belongs to the Special Issue Phytohormones and the Regulation of Stress Tolerance in Plants)
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16 pages, 515 KiB  
Review
Structural and Functional Changes in Aging Kidneys
by Jill Dybiec, Magdalena Szlagor, Ewelina Młynarska, Jacek Rysz and Beata Franczyk
Int. J. Mol. Sci. 2022, 23(23), 15435; https://doi.org/10.3390/ijms232315435 - 06 Dec 2022
Cited by 13 | Viewed by 4908
Abstract
The renal condition is one of the crucial predictors of longevity; therefore, early diagnosis of any dysfunction plays an important role. Kidneys are highly susceptible to the aging process. Unfavorable conditions may lead to a significant disturbance of the body’s homeostasis. Apart from [...] Read more.
The renal condition is one of the crucial predictors of longevity; therefore, early diagnosis of any dysfunction plays an important role. Kidneys are highly susceptible to the aging process. Unfavorable conditions may lead to a significant disturbance of the body’s homeostasis. Apart from physiological changes, there are some conditions such as hypertension, diabetes or obesity which contribute to the acceleration of the aging process. A determination of macroscopic and microscopic changes is essential for assessing the progression of aging. With age, we observe a decrease in the volume of renal parenchyma and an increase in adipose tissue in the renal sinuses. Senescence may also be manifested by the roughness of the kidney surface or simple renal cysts. The main microscopic changes are a thickening of the glomerular basement membrane, nephrosclerosis, an accumulation of extracellular matrix, and mesangial widening. The principal aspect of stopping unfavorable changes is to maintain health. Studies have shown many useful ways to mitigate renal aging. This review is focused especially on medications such as renin-angiotensin-aldosterone system blockers or resveratrol, but even eating habits and lifestyle. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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25 pages, 826 KiB  
Review
Experimental Chemotherapy-Induced Mucositis: A Scoping Review Guiding the Design of Suitable Preclinical Models
by Junhua Huang, Alan Yaw Min Hwang, Yuting Jia, Brian Kim, Melania Iskandar, Ali Ibrahim Mohammed and Nicola Cirillo
Int. J. Mol. Sci. 2022, 23(23), 15434; https://doi.org/10.3390/ijms232315434 - 06 Dec 2022
Cited by 10 | Viewed by 3402
Abstract
Mucositis is a common and most debilitating complication associated with the cytotoxicity of chemotherapy. The condition affects the entire alimentary canal from the mouth to the anus and has a significant clinical and economic impact. Although oral and intestinal mucositis can occur concurrently [...] Read more.
Mucositis is a common and most debilitating complication associated with the cytotoxicity of chemotherapy. The condition affects the entire alimentary canal from the mouth to the anus and has a significant clinical and economic impact. Although oral and intestinal mucositis can occur concurrently in the same individual, these conditions are often studied independently using organ-specific models that do not mimic human disease. Hence, the purpose of this scoping review was to provide a comprehensive yet systematic overview of the animal models that are utilised in the study of chemotherapy-induced mucositis. A search of PubMed/MEDLINE and Scopus databases was conducted to identify all relevant studies. Multiple phases of filtering were conducted, including deduplication, title/abstract screening, full-text screening, and data extraction. Studies were reported according to the updated Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. An inter-rater reliability test was conducted using Cohen’s Kappa score. After title, abstract, and full-text screening, 251 articles met the inclusion criteria. Seven articles investigated both chemotherapy-induced intestinal and oral mucositis, 198 articles investigated chemotherapy-induced intestinal mucositis, and 46 studies investigated chemotherapy-induced oral mucositis. Among a total of 205 articles on chemotherapy-induced intestinal mucositis, 103 utilised 5-fluorouracil, 34 irinotecan, 16 platinum-based drugs, 33 methotrexate, and 32 other chemotherapeutic agents. Thirteen articles reported the use of a combination of 5-fluorouracil, irinotecan, platinum-based drugs, or methotrexate to induce intestinal mucositis. Among a total of 53 articles on chemotherapy-induced oral mucositis, 50 utilised 5-fluorouracil, 2 irinotecan, 2 methotrexate, 1 topotecan and 1 with other chemotherapeutic drugs. Three articles used a combination of these drugs to induce oral mucositis. Various animal models such as mice, rats, hamsters, piglets, rabbits, and zebrafish were used. The chemotherapeutic agents were introduced at various dosages via three routes of administration. Animals were mainly mice and rats. Unlike intestinal mucositis, most oral mucositis models combined mechanical or chemical irritation with chemotherapy. In conclusion, this extensive assessment of the literature revealed that there was a large variation among studies that reproduce oral and intestinal mucositis in animals. To assist with the design of a suitable preclinical model of chemotherapy-induced alimentary tract mucositis, animal types, routes of administration, dosages, and types of drugs were reported in this study. Further research is required to define an optimal protocol that improves the translatability of findings to humans. Full article
(This article belongs to the Collection State-of-the-Art Molecular Mechanisms and Pathophysiology of Head and Neck Diseases in Australia)
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17 pages, 6500 KiB  
Article
GOLM1 and FAM49B: Potential Biomarkers in HNSCC Based on Bioinformatics and Immunohistochemical Analysis
by Yue Xi, Tiange Zhang, Wei Sun, Ruobing Liang, Sridha Ganesh and Honglei Chen
Int. J. Mol. Sci. 2022, 23(23), 15433; https://doi.org/10.3390/ijms232315433 - 06 Dec 2022
Cited by 3 | Viewed by 1612
Abstract
Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide. We aimed to identify potential genetic markers that could predict the prognosis of HNSCC. A total of 44 samples of GSE83519 from Gene Expression Omnibus (GEO) datasets and [...] Read more.
Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide. We aimed to identify potential genetic markers that could predict the prognosis of HNSCC. A total of 44 samples of GSE83519 from Gene Expression Omnibus (GEO) datasets and 546 samples of HNSCC from The Cancer Genome Atlas (TCGA) were adopted. The differently expressed genes (DEGs) of the samples were screened by GEO2R. We integrated the expression information of DEGs with clinical data from GES42743 using the weighted gene co-expression network analysis (WGCNA). A total of 17 hub genes were selected by the module membership (|MM| > 0.8), and the gene significance (|GS| > 0.3) was selected from the turquoise module. GOLM1 and FAM49B genes were chosen based on single-gene analysis results. Survival analysis showed that the higher expression of GOLM1 and FAM49B genes was correlated with a worse prognosis of HNSCC patients. Immunohistochemistry and multiplex immunofluorescence techniques verified that GOLM1 and FAM49B genes were highly expressed in HNSCC cells, and high expressions of GOLM1 were associated with the pathological grades of HNSCC. In conclusion, our study illustrated a new insight that GOLM1 and FAM49B genes might be used as potential biomarkers to determine the development of HNSCC, while GOLM1 and FAM49B have the possibility to be prognostic indicators for HNSCC. Full article
(This article belongs to the Section Molecular Informatics)
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17 pages, 3730 KiB  
Article
Comparative Transcriptome Analysis Unravels the Response Mechanisms of Fusarium oxysporum f.sp. cubense to a Biocontrol Agent, Pseudomonas aeruginosa Gxun-2
by Shuyan Li, Junpeng Ma, Shiyong Li, Fuhui Chen, Chaodong Song, Hongyan Zhang, Mingguo Jiang and Naikun Shen
Int. J. Mol. Sci. 2022, 23(23), 15432; https://doi.org/10.3390/ijms232315432 - 06 Dec 2022
Cited by 2 | Viewed by 1780
Abstract
Banana Fusarium wilt, which is caused by Fusarium oxysporum f.sp. cubense Tropical Race 4 (FOC TR4), is one of the most serious fungal diseases in the banana-producing regions in east Asia. Pseudomonas aeruginosa Gxun-2 could significantly inhibit the growth of FOC TR4. Strain [...] Read more.
Banana Fusarium wilt, which is caused by Fusarium oxysporum f.sp. cubense Tropical Race 4 (FOC TR4), is one of the most serious fungal diseases in the banana-producing regions in east Asia. Pseudomonas aeruginosa Gxun-2 could significantly inhibit the growth of FOC TR4. Strain Gxun-2 strongly inhibited the mycelial growth of FOC TR4 on dual culture plates and caused hyphal wrinkles, ruptures, and deformities on in vitro cultures. Banana seedlings under pot experiment treatment with Gxun-2 in a greenhouse resulted in an 84.21% reduction in the disease. Comparative transcriptome analysis was applied to reveal the response and resistance of FOC TR4 to Gxun-2 stress. The RNA-seq analysis of FOC TR4 during dual-culture with P. aeruginosa Gxun-2 revealed 3075 differentially expressed genes (DEGs) compared with the control. Among the genes, 1158 genes were up-regulated, and 1917 genes were down-regulated. Further analysis of gene function and the pathway of DEGs revealed that genes related to the cell membrane, cell wall formation, peroxidase, ABC transporter, and autophagy were up-regulated, while down-regulated DEGs were enriched in the sphingolipid metabolism and chitinase. These results indicated that FOC TR4 upregulates a large number of genes in order to maintain cell functions. The results of qRT-PCR conducted on a subset of 13 genes were consistent with the results of RNA-seq data. Thus, this study serves as a valuable resource regarding the mechanisms of fungal pathogen resistance to biocontrol agents. Full article
(This article belongs to the Section Molecular Plant Sciences)
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20 pages, 2689 KiB  
Review
Cis-Regulation by NACs: A Promising Frontier in Wheat Crop Improvement
by Adnan Iqbal, Joanna Bocian, Amir Hameed, Waclaw Orczyk and Anna Nadolska-Orczyk
Int. J. Mol. Sci. 2022, 23(23), 15431; https://doi.org/10.3390/ijms232315431 - 06 Dec 2022
Cited by 6 | Viewed by 1839
Abstract
Crop traits are controlled by multiple genes; however, the complex spatio-temporal transcriptional behavior of genes cannot be fully understood without comprehending the role of transcription factors (TFs) and the underlying mechanisms of the binding interactions of their cis-regulatory elements. NAC belongs to [...] Read more.
Crop traits are controlled by multiple genes; however, the complex spatio-temporal transcriptional behavior of genes cannot be fully understood without comprehending the role of transcription factors (TFs) and the underlying mechanisms of the binding interactions of their cis-regulatory elements. NAC belongs to one of the largest families of plant-specific TFs and has been associated with the regulation of many traits. This review provides insight into the cis-regulation of genes by wheat NACs (TaNACs) for the improvement in yield-related traits, including phytohormonal homeostasis, leaf senescence, seed traits improvement, root modulation, and biotic and abiotic stresses in wheat and other cereals. We also discussed the current potential, knowledge gaps, and prospects of TaNACs. Full article
(This article belongs to the Collection Feature Papers in Molecular Plant Sciences)
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17 pages, 2766 KiB  
Article
Evaluation of a Novel Oncolytic Adenovirus Silencing SYVN1
by Christie Vermeulen, Tereza Brachtlova, Nikki Tol, Ida H. van der Meulen-Muileman, Jasmina Hodzic, Henri J. van de Vrugt and Victor W. van Beusechem
Int. J. Mol. Sci. 2022, 23(23), 15430; https://doi.org/10.3390/ijms232315430 - 06 Dec 2022
Viewed by 1800
Abstract
Oncolytic adenoviruses are promising new anticancer agents. To realize their full anticancer potential, they are being engineered to express therapeutic payloads. Tumor suppressor p53 function contributes to oncolytic adenovirus activity. Many cancer cells carry an intact TP53 gene but express p53 inhibitors that [...] Read more.
Oncolytic adenoviruses are promising new anticancer agents. To realize their full anticancer potential, they are being engineered to express therapeutic payloads. Tumor suppressor p53 function contributes to oncolytic adenovirus activity. Many cancer cells carry an intact TP53 gene but express p53 inhibitors that compromise p53 function. Therefore, we hypothesized that oncolytic adenoviruses could be made more effective by suppressing p53 inhibitors in selected cancer cells. To investigate this concept, we attenuated the expression of the established p53 inhibitor synoviolin (SYVN1) in A549 lung cancer cells by RNA interference. Silencing SYVN1 inhibited p53 degradation, thereby increasing p53 activity, and promoted adenovirus-induced A549 cell death. Based on these observations, we constructed a new oncolytic adenovirus that expresses a short hairpin RNA against SYVN1. This virus killed A549 cells more effectively in vitro and inhibited A549 xenograft tumor growth in vivo. Surprisingly, increased susceptibility to adenovirus-mediated cell killing by SYVN1 silencing was also observed in A549 TP53 knockout cells. Hence, while the mechanism of SYVN1-mediated inhibition of adenovirus replication is not fully understood, our results clearly show that RNA interference technology can be exploited to design more potent oncolytic adenoviruses. Full article
(This article belongs to the Section Molecular Oncology)
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14 pages, 1701 KiB  
Article
Analysis of Intrinsic Breast Cancer Subtypes: The Clinical Utility of Epigenetic Biomarkers and TP53 Mutation Status in Triple-Negative Cases
by Ieva Sadzeviciene, Kristina Snipaitiene, Asta Scesnaite-Jerdiakova, Kristina Daniunaite, Rasa Sabaliauskaite, Aida Laurinaviciene, Monika Drobniene, Valerijus Ostapenko and Sonata Jarmalaite
Int. J. Mol. Sci. 2022, 23(23), 15429; https://doi.org/10.3390/ijms232315429 - 06 Dec 2022
Cited by 1 | Viewed by 1563
Abstract
This study aimed at analyzing the DNA methylation pattern and TP53 mutation status of intrinsic breast cancer (BC) subtypes for improved characterization and survival prediction. DNA methylation of 17 genes was tested by methylation-specific PCR in 116 non-familial BRCA mutation-negative BC and 29 [...] Read more.
This study aimed at analyzing the DNA methylation pattern and TP53 mutation status of intrinsic breast cancer (BC) subtypes for improved characterization and survival prediction. DNA methylation of 17 genes was tested by methylation-specific PCR in 116 non-familial BRCA mutation-negative BC and 29 control noncancerous cases. At least one gene methylation was detected in all BC specimens and a 10-gene panel statistically significantly separated tumors from noncancerous breast tissues. Methylation of FILIP1L and MT1E was predominant in triple-negative (TN) BC, while other BC subtypes were characterized by RASSF1, PRKCB, MT1G, APC, and RUNX3 hypermethylation. TP53 mutation (TP53-mut) was found in 38% of sequenced samples and mainly affected TN BC cases (87%). Cox analysis revealed that TN status, age at diagnosis, and RUNX3 methylation are independent prognostic factors for overall survival (OS) in BC. The combinations of methylated biomarkers, RUNX3 with MT1E or FILIP1L, were also predictive for shorter OS, whereas methylated FILIP1L was predictive of a poor outcome in the TP53-mut subgroup. Therefore, DNA methylation patterns of specific genes significantly separate BC from noncancerous breast tissues and distinguishes TN cases from non-TN BC, whereas the combination of two-to-three epigenetic biomarkers can be an informative tool for BC outcome predictions. Full article
(This article belongs to the Special Issue Molecular Biology of Breast Cancer)
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24 pages, 6996 KiB  
Article
Comparative Transcriptome Analysis Unveils the Molecular Mechanism Underlying Sepal Colour Changes under Acidic pH Substratum in Hydrangea macrophylla
by Razieh Rahmati, Rasmieh Hamid, Zahra Ghorbanzadeh, Feba Jacob, Pezhman Azadi, Mehrshad Zeinalabedini, Laleh Karimi Farsad, Mehrbano Kazemi, Mohammad Ali Ebrahimi, Fahimeh Shahinnia, Ghasem Hosseini Salekdeh, Mohammad Reza Ghaffari and Mohammad Reza Hajirezaei
Int. J. Mol. Sci. 2022, 23(23), 15428; https://doi.org/10.3390/ijms232315428 - 06 Dec 2022
Cited by 4 | Viewed by 2426
Abstract
The hydrangea (Hydrangea macrophylla (Thunb). Ser.), an ornamental plant, has good marketing potential and is known for its capacity to change the colour of its inflorescence depending on the pH of the cultivation media. The molecular mechanisms causing these changes are still [...] Read more.
The hydrangea (Hydrangea macrophylla (Thunb). Ser.), an ornamental plant, has good marketing potential and is known for its capacity to change the colour of its inflorescence depending on the pH of the cultivation media. The molecular mechanisms causing these changes are still uncertain. In the present study, transcriptome and targeted metabolic profiling were used to identify molecular changes in the RNAome of hydrangea plants cultured at two different pH levels. De novo assembly yielded 186,477 unigenes. Transcriptomic datasets provided a comprehensive and systemic overview of the dynamic networks of the gene expression underlying flower colour formation in hydrangeas. Weighted analyses of gene co-expression network identified candidate genes and hub genes from the modules linked closely to the hyper accumulation of Al3+ during different stages of flower development. F3′5′H, ANS, FLS, CHS, UA3GT, CHI, DFR, and F3H were enhanced significantly in the modules. In addition, MYB, bHLH, PAL6, PAL9, and WD40 were identified as hub genes. Thus, a hypothesis elucidating the colour change in the flowers of Al3+-treated plants was established. This study identified many potential key regulators of flower pigmentation, providing novel insights into the molecular networks in hydrangea flowers. Full article
(This article belongs to the Section Molecular Plant Sciences)
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10 pages, 589 KiB  
Review
A Review of Genetic Polymorphisms and Susceptibilities to Complications after Aneurysmal Subarachnoid Hemorrhage
by Jose Medina-Suárez, Francisco Rodríguez-Esparragón, Coralia Sosa-Pérez, Sara Cazorla-Rivero, Laura B. Torres-Mata, Aruma Jiménez-O’Shanahan, Bernardino Clavo and Jesús Morera-Molina
Int. J. Mol. Sci. 2022, 23(23), 15427; https://doi.org/10.3390/ijms232315427 - 06 Dec 2022
Cited by 3 | Viewed by 1822
Abstract
Delayed cerebral ischemia (DCI) and vasospasm are two complications of subarachnoid hemorrhages (SAHs) which entail high risks of morbidity and mortality. However, it is unknown why only some patients who suffer SAHs will experience DCI and vasospasm. The purpose of this review is [...] Read more.
Delayed cerebral ischemia (DCI) and vasospasm are two complications of subarachnoid hemorrhages (SAHs) which entail high risks of morbidity and mortality. However, it is unknown why only some patients who suffer SAHs will experience DCI and vasospasm. The purpose of this review is to describe the main genetic single nucleotide polymorphisms (SNPs) that have demonstrated a relationship with these complications. The SNP of the nitric oxide endothelial synthase (eNOS) has been related to the size and rupture of an aneurysm, as well as to DCI, vasospasm, and poor neurological outcome. The SNPs responsible for the asymmetric dimetilarginine and the high-mobility group box 1 have also been associated with DCI. An association between vasospasm and the SNPs of the eNOS, the haptoglobin, and the endothelin-1 receptor has been found. The SNPs of the angiotensin-converting enzyme have been related to DCI and poor neurological outcome. Studies on the SNPs of the Ryanodine Receptor yielded varying results regarding their association with vasospasm. Full article
(This article belongs to the Collection Feature Papers in Molecular Genetics and Genomics)
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30 pages, 469 KiB  
Review
Ovarian Reserve Disorders, Can We Prevent Them? A Review
by Limor Man, Nicole Lustgarten Guahmich, Nina Vyas, Shelun Tsai, Laury Arazi, Debra Lilienthal, Glenn Schattman, Zev Rosenwaks and Daylon James
Int. J. Mol. Sci. 2022, 23(23), 15426; https://doi.org/10.3390/ijms232315426 - 06 Dec 2022
Cited by 5 | Viewed by 2737
Abstract
The ovarian reserve is finite and begins declining from its peak at mid-gestation until only residual follicles remain as women approach menopause. Reduced ovarian reserve, or its extreme form, premature ovarian insufficiency, stems from multiple factors, including developmental, genetic, environmental exposures, autoimmune disease, [...] Read more.
The ovarian reserve is finite and begins declining from its peak at mid-gestation until only residual follicles remain as women approach menopause. Reduced ovarian reserve, or its extreme form, premature ovarian insufficiency, stems from multiple factors, including developmental, genetic, environmental exposures, autoimmune disease, or medical/surgical treatment. In many cases, the cause remains unknown and resulting infertility is not ultimately addressed by assisted reproductive technologies. Deciphering the mechanisms that underlie disorders of ovarian reserve could improve the outcomes for patients struggling with infertility, but these disorders are diverse and can be categorized in multiple ways. In this review, we will explore the topic from a perspective that emphasizes the prevention or mitigation of ovarian damage. The most desirable mode of fertoprotection is primary prevention (intervening before ablative influence occurs), as identifying toxic influences and deciphering the mechanisms by which they exert their effect can reduce or eliminate exposure and damage. Secondary prevention in the form of screening is not recommended broadly. Nevertheless, in some instances where a known genetic background exists in discrete families, screening is advised. As part of prenatal care, screening panels include some genetic diseases that can lead to infertility or subfertility. In these patients, early diagnosis could enable fertility preservation or changes in family-building plans. Finally, Tertiary Prevention (managing disease post-diagnosis) is critical. Reduced ovarian reserve has a major influence on physiology beyond fertility, including delayed/absent puberty or premature menopause. In these instances, proper diagnosis and medical therapy can reduce adverse effects. Here, we elaborate on these modes of prevention as well as proposed mechanisms that underlie ovarian reserve disorders. Full article
(This article belongs to the Special Issue Ovarian Reserve Disorders: Molecular Mechanisms and Regulation)
18 pages, 6615 KiB  
Article
Top-Down Preparation of Nanoquartz for Toxicological Investigations
by Chiara Bellomo, Cristina Pavan, Gianluca Fiore, Guillermo Escolano-Casado, Lorenzo Mino and Francesco Turci
Int. J. Mol. Sci. 2022, 23(23), 15425; https://doi.org/10.3390/ijms232315425 - 06 Dec 2022
Cited by 2 | Viewed by 1543
Abstract
Occupational exposure to quartz dust is associated with fatal diseases. Quartz dusts generated by mechanical fracturing are characterized by a broad range of micrometric to nanometric particles. The contribution of this nanometric fraction to the overall toxicity of quartz is still largely unexplored, [...] Read more.
Occupational exposure to quartz dust is associated with fatal diseases. Quartz dusts generated by mechanical fracturing are characterized by a broad range of micrometric to nanometric particles. The contribution of this nanometric fraction to the overall toxicity of quartz is still largely unexplored, primarily because of the strong electrostatic adhesion forces that prevent isolation of the nanofraction. Furthermore, fractured silica dust exhibits special surface features, namely nearly free silanols (NFS), which impart a membranolytic activity to quartz. Nanoquartz can be synthetized via bottom-up methods, but the surface chemistry of such crystals strongly differs from that of nanoparticles resulting from fracturing. Here, we report a top-down milling procedure to obtain a nanometric quartz that shares the key surface properties relevant to toxicity with fractured quartz. The ball milling was optimized by coupling the dry and wet milling steps, using water as a dispersing agent, and varying the milling times and rotational speeds. Nanoquartz with a strong tendency to form submicrometric agglomerates was obtained. The deagglomeration with surfactants or simulated body fluids was negligible. Partial lattice amorphization and a bimodal crystallite domain size were observed. A moderate membranolytic activity, which correlated with the number of NFS, signaled coherence with the previous toxicological data. A membranolytic nanoquartz for toxicological investigations was obtained. Full article
(This article belongs to the Topic Molecular Mechanisms of the Toxicity and Carcinogenicity of Particulates)
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14 pages, 2654 KiB  
Article
Conservation Study of Imprinted Genes in Maize Triparental Heterozygotic Kernels
by Xiaomei Dong, Haishan Luo, Jiabin Yao, Qingfeng Guo, Shuai Yu, Xiaoyu Zhang, Fenghai Li, Yanye Ruan, Weiwei Jin and Dexuan Meng
Int. J. Mol. Sci. 2022, 23(23), 15424; https://doi.org/10.3390/ijms232315424 - 06 Dec 2022
Viewed by 1209
Abstract
Genomic imprinting is a classic epigenetic phenomenon related to the uniparental expression of genes. Imprinting variability exists in seeds and can contribute to observed parent-of-origin effects on seed development. Here, we conducted allelic expression of the embryo and endosperm from four crosses at [...] Read more.
Genomic imprinting is a classic epigenetic phenomenon related to the uniparental expression of genes. Imprinting variability exists in seeds and can contribute to observed parent-of-origin effects on seed development. Here, we conducted allelic expression of the embryo and endosperm from four crosses at 11 days after pollination (DAP). First, the F1 progeny of B73(♀) × Mo17(♂) and the inducer line CAU5 were used as parents to obtain reciprocal crosses of BM-C/C-BM. Additionally, the F1 progeny of Mo17(♀) × B73(♂) and CAU5 were used as parents to obtain reciprocal crosses of MB-C/C-MB. In total, 192 and 181 imprinted genes were identified in the BM-C/C-BM and MB-C/C-MB crosses, respectively. Then, by comparing the allelic expression of these imprinted genes in the reciprocal crosses of B73 and CAU5 (BC/CB), fifty-one Mo17-added non-conserved genes were identified as exhibiting imprinting variability. Fifty-one B73-added non-conserved genes were also identified by comparing the allelic expression of imprinted genes identified in BM-C/C-BM, MB-C/C-MB and MC/CM crosses. Specific Gene Ontology (GO) terms were not enriched in B73-added/Mo17-added non-conserved genes. Interestingly, the imprinting status of these genes was less conserved across other species. The cis-element distribution, tissue expression and subcellular location were similar between the B73-added/Mo17-added conserved and B73-added/Mo17-added non-conserved imprinted genes. Finally, genotypic and phenotypic analysis of one non-conserved gene showed that the mutation and overexpression of this gene may affect embryo and kernel size, which indicates that these non-conserved genes may also play an important role in kernel development. The findings of this study will be helpful for elucidating the imprinting mechanism of genes involved in maize kernel development. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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27 pages, 5066 KiB  
Article
miR−122−5p Regulates Renal Fibrosis In Vivo
by Shohei Kaneko, Katsunori Yanai, Hiroki Ishii, Akinori Aomatsu, Keiji Hirai, Susumu Ookawara, Kenichi Ishibashi and Yoshiyuki Morishita
Int. J. Mol. Sci. 2022, 23(23), 15423; https://doi.org/10.3390/ijms232315423 - 06 Dec 2022
Cited by 1 | Viewed by 2012
Abstract
The role of exogenous microRNAs (miRNAs) in renal fibrosis is poorly understood. Here, the effect of exogenous miRNAs on renal fibrosis was investigated using a renal fibrosis mouse model generated by unilateral ureteral obstruction (UUO). miRNA microarray analysis and quantitative reverse-transcription polymerase chain [...] Read more.
The role of exogenous microRNAs (miRNAs) in renal fibrosis is poorly understood. Here, the effect of exogenous miRNAs on renal fibrosis was investigated using a renal fibrosis mouse model generated by unilateral ureteral obstruction (UUO). miRNA microarray analysis and quantitative reverse-transcription polymerase chain reaction showed that miR−122−5p was the most downregulated (0.28-fold) miRNA in the kidneys of UUO mice. The injection of an miR−122−5p mimic promoted renal fibrosis and upregulated COL1A2 and FN1, whereas an miR−122−5p inhibitor suppressed renal fibrosis and downregulated COL1A2 and FN1. The expression levels of fibrosis-related mRNAs, which were predicted targets of miR−122−5p, were evaluated. The expression level of TGFBR2, a pro-fibrotic mRNA, was upregulated by the miR−122−5p mimic, and the expression level of FOXO3, an anti−fibrotic mRNA, was upregulated by the miR−122−5p inhibitor. The protein expressions of TGFBR2 and FOXO3 were confirmed by immunohistochemistry. Additionally, the expression levels of LC3, downstream anti-fibrotic mRNAs of FOXO3, were upregulated by the miR−122−5p inhibitor. These results suggest that miR−122−5p has critical roles in renal fibrosis. Full article
(This article belongs to the Special Issue Cellular and Molecular Research of Kidney Diseases)
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15 pages, 2772 KiB  
Article
The Binomial “Inflammation-Epigenetics” in Breast Cancer Progression and Bone Metastasis: IL-1β Actions Are Influenced by TET Inhibitor in MCF-7 Cell Line
by Daniele Bellavia, Viviana Costa, Angela De Luca, Aurora Cordaro, Milena Fini, Gianluca Giavaresi, Fabio Caradonna and Lavinia Raimondi
Int. J. Mol. Sci. 2022, 23(23), 15422; https://doi.org/10.3390/ijms232315422 - 06 Dec 2022
Cited by 8 | Viewed by 1715
Abstract
The existence of a tight relationship between inflammation and epigenetics that in primary breast tumor cells can lead to tumor progression and the formation of bone metastases was investigated. It was highlighted how the induction of tumor progression and bone metastasis by Interleukin-1 [...] Read more.
The existence of a tight relationship between inflammation and epigenetics that in primary breast tumor cells can lead to tumor progression and the formation of bone metastases was investigated. It was highlighted how the induction of tumor progression and bone metastasis by Interleukin-1 beta, in a non-metastatic breast cancer cell line, MCF-7, was dependent on the de-methylating actions of ten-eleven translocation proteins (TETs). In fact, the inhibition of their activity by the Bobcat339 molecule, an inhibitor of TET enzymes, determined on the one hand, the modulation of the epithelial-mesenchymal transition process, and on the other hand, the reduction in the expression of markers of bone metastasis, indicating that the epigenetic action of TETs is a prerequisite for IL-1β-dependent tumor progression and bone metastasis formation. Full article
(This article belongs to the Special Issue Breast Cancer, Metastatic Breast Cancer, Therapeutic Approaches)
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18 pages, 907 KiB  
Review
The Role of the Gut Microbiome in Pediatric Obesity and Bariatric Surgery
by Cynthia Omoge Akagbosu, Evan Paul Nadler, Shira Levy and Suchitra Kaveri Hourigan
Int. J. Mol. Sci. 2022, 23(23), 15421; https://doi.org/10.3390/ijms232315421 - 06 Dec 2022
Cited by 2 | Viewed by 2720
Abstract
Obesity affects 42.4% of adults and 19.3% of children in the United States. Childhood obesity drives many comorbidities including hypertension, fatty liver disease, and type 2 diabetes mellitus. Prior research suggests that aberrant compositional development of the gut microbiome, with low-grade inflammation, precedes [...] Read more.
Obesity affects 42.4% of adults and 19.3% of children in the United States. Childhood obesity drives many comorbidities including hypertension, fatty liver disease, and type 2 diabetes mellitus. Prior research suggests that aberrant compositional development of the gut microbiome, with low-grade inflammation, precedes being overweight. Therefore, childhood may provide opportunities for interventions that shape the microbiome to mitigate obesity-related diseases. Children with obesity have gut microbiota compositional and functional differences, including increased proinflammatory bacterial taxa, compared to lean controls. Restoration of the gut microbiota to a healthy state may ameliorate conditions associated with obesity and help maintain a healthy weight. Pediatric bariatric (weight-loss) surgery is an effective treatment for childhood obesity; however, there is limited research into the role of the gut microbiome after weight-loss surgery in children. This review will discuss the magnitude of childhood obesity, the importance of the developing microbiome in establishing metabolic pathways, interventions such as bariatric surgery that may modulate the gut microbiome, and future directions for the potential development of microbiome-based therapeutics to treat obesity. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology)
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20 pages, 3713 KiB  
Article
Osseointegration Properties of Titanium Implants Treated by Nonthermal Atmospheric-Pressure Nitrogen Plasma
by Sifan Yan, Satoshi Komasa, Akinori Agariguchi, Giuseppe Pezzotti, Joji Okazaki and Kenji Maekawa
Int. J. Mol. Sci. 2022, 23(23), 15420; https://doi.org/10.3390/ijms232315420 - 06 Dec 2022
Cited by 3 | Viewed by 1904
Abstract
Pure titanium is used in dental implants owing to its excellent biocompatibility and physical properties. However, the aging of the material during storage is detrimental to the long-term stability of the implant after implantation. Therefore, in this study, we attempted to improve the [...] Read more.
Pure titanium is used in dental implants owing to its excellent biocompatibility and physical properties. However, the aging of the material during storage is detrimental to the long-term stability of the implant after implantation. Therefore, in this study, we attempted to improve the surface properties and circumvent the negative effects of material aging on titanium implants by using a portable handheld nonthermal plasma device capable of piezoelectric direct discharge to treat pure titanium discs with nitrogen gas. We evaluated the osteogenic properties of the treated samples by surface morphology and elemental analyses, as well as in vitro and in vivo experiments. The results showed that nonthermal atmospheric-pressure nitrogen plasma can improve the hydrophilicity of pure titanium without damaging its surface morphology while introducing nitrogen-containing functional groups, thereby promoting cell attachment, proliferation, and osseointegration to some extent. Therefore, nitrogen plasma treatment may be a promising method for the rapid surface treatment of titanium implants. Full article
(This article belongs to the Special Issue Advances in Dental Bio-Nanomaterials (II))
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15 pages, 696 KiB  
Article
Longitudinal Analysis of Urinary Cytokines and Biomarkers in COVID-19 Patients with Subclinical Acute Kidney Injury
by Gustavo Casas-Aparicio, Claudia Alvarado-de la Barrera, David Escamilla-Illescas, Isabel León-Rodríguez, Perla Mariana Del Río-Estrada, Mauricio González-Navarro, Natalia Calderón-Dávila, Rossana Olmedo-Ocampo, Manuel Castillejos-López, Liliana Figueroa-Hernández, Amy B. Peralta-Prado, Yara Luna-Villalobos, Elvira Piten-Isidro, Paola Fernández-Campos, Alejandro Juárez-Díaz, Karolina Piekarska and Santiago Ávila-Ríos
Int. J. Mol. Sci. 2022, 23(23), 15419; https://doi.org/10.3390/ijms232315419 - 06 Dec 2022
Cited by 4 | Viewed by 1588
Abstract
In hospitalized COVID-19 patients, disease progression leading to acute kidney injury (AKI) may be driven by immune dysregulation. We explored the role of urinary cytokines and their relationship with kidney stress biomarkers in COVID-19 patients before and after the development of AKI. Of [...] Read more.
In hospitalized COVID-19 patients, disease progression leading to acute kidney injury (AKI) may be driven by immune dysregulation. We explored the role of urinary cytokines and their relationship with kidney stress biomarkers in COVID-19 patients before and after the development of AKI. Of 51 patients, 54.9% developed AKI. The principal component analysis indicated that in subclinical AKI, epidermal growth factor (EGF) and interferon (IFN)-α were associated with a lower risk of AKI, while interleukin-12 (IL-12) and macrophage inflammatory protein (MIP)-1β were associated with a higher risk of AKI. After the manifestation of AKI, EGF and IFN-α remained associated with a lower risk of AKI, while IL-1 receptor (IL-1R), granulocyte-colony stimulating factor (G-CSF), interferon-gamma-inducible protein 10 (IP-10) and IL-5 were associated with a higher risk of AKI. EGF had an inverse correlation with kidney stress biomarkers. Subclinical AKI was characterized by a significant up-regulation of kidney stress biomarkers and proinflammatory cytokines. The lack of EGF regenerative effects and IFN-α antiviral activity seemed crucial for renal disease progression. AKI involved a proinflammatory urinary cytokine storm. Full article
(This article belongs to the Special Issue New Insights into the Molecular Mechanisms of Kidney Injury and Repair)
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17 pages, 2672 KiB  
Article
A Single Variant in Pri-miRNA-155 Associated with Susceptibility to Hereditary Breast Cancer Promotes Aggressiveness in Breast Cancer Cells
by Natalia Landeros, Patricio Gonzalez-Hormazabal, Pablo Pérez-Moreno, Julio C. Tapia and Lilian Jara
Int. J. Mol. Sci. 2022, 23(23), 15418; https://doi.org/10.3390/ijms232315418 - 06 Dec 2022
Cited by 3 | Viewed by 1897
Abstract
Variants in genes encoding for microRNAs have been associated with their deregulation in breast cancer (BC). Sequencing of microRNAs deregulated in BC was performed using DNA from Chilean patients with a strong family history and negative for mutations in BRCA1/BRCA2. Seventeen variants were [...] Read more.
Variants in genes encoding for microRNAs have been associated with their deregulation in breast cancer (BC). Sequencing of microRNAs deregulated in BC was performed using DNA from Chilean patients with a strong family history and negative for mutations in BRCA1/BRCA2. Seventeen variants were identified, three of which were selected for a case-control association study: rs376491654 (miR-335), rs755634302 (miR-497), and rs190708267 (miR-155). For rs190708267 C>T, the heterozygous T allele was detected in four BC cases and absent in controls, while homozygous TT cases were not detected. Variants were modelled in silico, cloned in a plasmid, expressed in BC cell lines, and functional in vitro assays were performed. Overexpression of the miR-155-T allele increased mature miR-155-5p levels in both BC cell lines, suggesting that its presence alters pre-miR-155 processing. Moreover, BC cells overexpressing the miR-155-T allele showed increased proliferation, migration, and resistance to cisplatin-induced death compared to miR-155-C overexpressing cells. Of note, the 3′UTR of APC, GSK3β, and PPP1CA genes, all into the canonical Wnt signaling pathway, were identified as direct targets. APC and GSK3β mRNA levels decreased while PP1 levels increased. These results suggest a pathogenic role of the variant rs190708267 (miR-155) in BRCA 1/2 negative BC, conferring susceptibility and promoting traits of aggressiveness. Full article
(This article belongs to the Special Issue Translational Research in Breast Cancer)
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10 pages, 1135 KiB  
Article
Peculiarities of Scattering of Ultrashort Laser Pulses on DNA and RNA Trinucleotides
by Dmitry Makarov and Anastasia Kharlamova
Int. J. Mol. Sci. 2022, 23(23), 15417; https://doi.org/10.3390/ijms232315417 - 06 Dec 2022
Cited by 2 | Viewed by 940
Abstract
Currently, X-ray diffraction analysis (XRD) with high spatial and time resolution (TR-XRD) is based on the known theory of X-ray scattering, where the main parameter of USP—its duration—is not taken into account. In the present work, it is shown that, for scattering of [...] Read more.
Currently, X-ray diffraction analysis (XRD) with high spatial and time resolution (TR-XRD) is based on the known theory of X-ray scattering, where the main parameter of USP—its duration—is not taken into account. In the present work, it is shown that, for scattering of attosecond USPs on DNA and RNA trinucleotides, the pulse length is the most important scattering parameter. The diffraction pattern changes considerably in comparison with the previously known scattering theory. The obtained results are extremely important in TR-XRD when using attosecond pulses to study trinucleotides of DNA and RNA, because with the previously known scattering theory, which does not take into account the duration of USP, one cannot correctly interpret, and therefore “decode”, DNA and RNA structures. Full article
(This article belongs to the Special Issue Structural Dynamics of Macromolecules)
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16 pages, 1159 KiB  
Review
Role of the Intermediate Filament Protein Peripherin in Health and Disease
by Roberta Romano, Victoria Stefania Del Fiore and Cecilia Bucci
Int. J. Mol. Sci. 2022, 23(23), 15416; https://doi.org/10.3390/ijms232315416 - 06 Dec 2022
Cited by 5 | Viewed by 2441
Abstract
Intermediate filaments are the most heterogeneous class among cytoskeletal elements. While some of them have been well-characterized, little is known about peripherin. Peripherin is a class III intermediate filament protein with a specific expression in the peripheral nervous system. Epigenetic modifications are involved [...] Read more.
Intermediate filaments are the most heterogeneous class among cytoskeletal elements. While some of them have been well-characterized, little is known about peripherin. Peripherin is a class III intermediate filament protein with a specific expression in the peripheral nervous system. Epigenetic modifications are involved in this cell-type-specific expression. Peripherin has important roles in neurite outgrowth and stability, axonal transport, and axonal myelination. Moreover, peripherin interacts with proteins involved in vesicular trafficking, signal transduction, DNA/RNA processing, protein folding, and mitochondrial metabolism, suggesting a role in all these processes. This review collects information regarding peripherin gene regulation, post-translational modifications, and functions and its involvement in the onset of a number of diseases. Full article
(This article belongs to the Special Issue Structure and Function of Intermediate Filaments in Health and Disease)
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