International Journal of Molecular Sciences

23 pages, 2342 KiB

Open AccessReview

LncRNA-Mediated Adipogenesis in Different Adipocytes

by Peiwen Zhang, Shuang Wu, Yuxu He, Xinrong Li, Yan Zhu, Xutao Lin, Lei Chen, Ye Zhao, Lili Niu, Shunhua Zhang, Xuewei Li, Li Zhu and Linyuan Shen

Int. J. Mol. Sci. 2022, 23(13), 7488; https://doi.org/10.3390/ijms23137488 - 5 Jul 2022

Cited by 31 | Viewed by 6114

Abstract

Long-chain noncoding RNAs (lncRNAs) are RNAs that do not code for proteins, widely present in eukaryotes. They regulate gene expression at multiple levels through different mechanisms at epigenetic, transcription, translation, and the maturation of mRNA transcripts or regulation of the chromatin structure, and [...] Read more.

Long-chain noncoding RNAs (lncRNAs) are RNAs that do not code for proteins, widely present in eukaryotes. They regulate gene expression at multiple levels through different mechanisms at epigenetic, transcription, translation, and the maturation of mRNA transcripts or regulation of the chromatin structure, and compete with microRNAs for binding to endogenous RNA. Adipose tissue is a large and endocrine-rich functional tissue in mammals. Excessive accumulation of white adipose tissue in mammals can cause metabolic diseases. However, unlike white fat, brown and beige fats release energy as heat. In recent years, many lncRNAs associated with adipogenesis have been reported. The molecular mechanisms of how lncRNAs regulate adipogenesis are continually investigated. In this review, we discuss the classification of lncRNAs according to their transcriptional location. lncRNAs that participate in the adipogenesis of white or brown fats are also discussed. The function of lncRNAs as decoy molecules and RNA double-stranded complexes, among other functions, is also discussed. Full article

(This article belongs to the Collection Regulation by Non-coding RNAs)

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13 pages, 695 KiB

Open AccessReview

The Biochemical Assessment of Mitochondrial Respiratory Chain Disorders

by Nadia Turton, Neve Cufflin, Mollie Dewsbury, Olivia Fitzpatrick, Rahida Islam, Lowidka Linares Watler, Cara McPartland, Sophie Whitelaw, Caitlin Connor, Charlotte Morris, Jason Fang, Ollie Gartland, Liv Holt and Iain P. Hargreaves

Int. J. Mol. Sci. 2022, 23(13), 7487; https://doi.org/10.3390/ijms23137487 - 5 Jul 2022

Cited by 8 | Viewed by 7880

Abstract

Mitochondrial respiratory chain (MRC) disorders are a complex group of diseases whose diagnosis requires a multidisciplinary approach in which the biochemical investigations play an important role. Initial investigations include metabolite analysis in both blood and urine and the measurement of lactate, pyruvate and [...] Read more.

Mitochondrial respiratory chain (MRC) disorders are a complex group of diseases whose diagnosis requires a multidisciplinary approach in which the biochemical investigations play an important role. Initial investigations include metabolite analysis in both blood and urine and the measurement of lactate, pyruvate and amino acid levels, as well as urine organic acids. Recently, hormone-like cytokines, such as fibroblast growth factor-21 (FGF-21), have also been used as a means of assessing evidence of MRC dysfunction, although work is still required to confirm their diagnostic utility and reliability. The assessment of evidence of oxidative stress may also be an important parameter to consider in the diagnosis of MRC function in view of its association with mitochondrial dysfunction. At present, due to the lack of reliable biomarkers available for assessing evidence of MRC dysfunction, the spectrophotometric determination of MRC enzyme activities in skeletal muscle or tissue from the disease-presenting organ is considered the ‘Gold Standard’ biochemical method to provide evidence of MRC dysfunction. The purpose of this review is to outline a number of biochemical methods that may provide diagnostic evidence of MRC dysfunction in patients. Full article

(This article belongs to the Special Issue Disorders of Mitochondrial Metabolism)

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17 pages, 3024 KiB

Open AccessArticle

The Fate of Epidermal Tight Junctions in the stratum corneum: Their Involvement in the Regulation of Desquamation and Phenotypic Expression of Certain Skin Conditions

by Marek Haftek, Vinzenz Oji, Laurence Feldmeyer, Daniel Hohl, Smaïl Hadj-Rabia and Rawad Abdayem

Int. J. Mol. Sci. 2022, 23(13), 7486; https://doi.org/10.3390/ijms23137486 - 5 Jul 2022

Cited by 5 | Viewed by 2955

Abstract

We evaluated the presence of tight junction (TJ) remnants in the stratum corneum (SC) of in vitro reconstructed human epidermis and human skin explants subjected or not to an aggressive topical treatment with beta-lipohydroxy salicylic acid (LSA) for 24 h. LSA-treated samples showed [...] Read more.

We evaluated the presence of tight junction (TJ) remnants in the stratum corneum (SC) of in vitro reconstructed human epidermis and human skin explants subjected or not to an aggressive topical treatment with beta-lipohydroxy salicylic acid (LSA) for 24 h. LSA-treated samples showed an increased presence of TJ remnants in the two lowermost layers of the SC, as quantified with standard electron microscopy. The topical aggression-induced overexpression of TJ-like cell–cell envelope fusions may influence SC functions: (1) directly, through an enhanced cohesion, and (2) indirectly, by impeding accessibility of peripheral corneodesmosomes to extracellular hydrolytic enzymes and, thus, slowing down desquamation. Observations of ichthyotic epidermis in peeling skin disease (PSD; corneodesmosin deficiency; two cases) and ichthyosis hypotrichosis sclerosing cholangitis syndrome (IHSC/NISCH; absence of claudin-1; two cases) also demonstrated increased persistence of TJ-like intercellular fusions in pathological SC and contributed to the interpretation of the diseases’ pathological mechanisms. Full article

(This article belongs to the Special Issue Barrier Function of Skin and Oral Mucosa 2.0)

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13 pages, 663 KiB

Open AccessReview

The Specific Role of Dermatan Sulfate as an Instructive Glycosaminoglycan in Tissue Development

by Shuji Mizumoto and Shuhei Yamada

Int. J. Mol. Sci. 2022, 23(13), 7485; https://doi.org/10.3390/ijms23137485 - 5 Jul 2022

Cited by 17 | Viewed by 6130

Abstract

The crucial roles of dermatan sulfate (DS) have been demonstrated in tissue development of the cutis, blood vessels, and bone through construction of the extracellular matrix and cell signaling. Although DS classically exerts physiological functions via interaction with collagens, growth factors, and heparin [...] Read more.

The crucial roles of dermatan sulfate (DS) have been demonstrated in tissue development of the cutis, blood vessels, and bone through construction of the extracellular matrix and cell signaling. Although DS classically exerts physiological functions via interaction with collagens, growth factors, and heparin cofactor-II, new functions have been revealed through analyses of human genetic disorders as well as of knockout mice with loss of DS-synthesizing enzymes. Mutations in human genes encoding the epimerase and sulfotransferase responsible for the biosynthesis of DS chains cause connective tissue disorders including spondylodysplastic type Ehlers–Danlos syndrome, characterized by skin hyperextensibility, joint hypermobility, and tissue fragility. DS-deficient mice show perinatal lethality, skin fragility, vascular abnormalities, thoracic kyphosis, myopathy-related phenotypes, acceleration of nerve regeneration, and impairments in self-renewal and proliferation of neural stem cells. These findings suggest that DS is essential for tissue development in addition to the assembly of collagen fibrils in the skin, and that DS-deficient knockout mice can be utilized as models of human genetic disorders that involve impairment of DS biosynthesis. This review highlights a novel role of DS in tissue development studies from the past decade. Full article

(This article belongs to the Special Issue Matrix Embedded Instructional Cues Direct Development and Tissue Repair)

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20 pages, 1812 KiB

Open AccessReview

Probing the Skin–Brain Axis: New Vistas Using Mouse Models

by Aliće Weiglein, Evelyn Gaffal and Anne Albrecht

Int. J. Mol. Sci. 2022, 23(13), 7484; https://doi.org/10.3390/ijms23137484 - 5 Jul 2022

Cited by 8 | Viewed by 5273

Abstract

Inflammatory diseases of the skin, including atopic dermatitis and psoriasis, have gained increasing attention with rising incidences in developed countries over the past decades. While bodily properties, such as immunological responses of the skin, have been described in some detail, interactions with the [...] Read more.

Inflammatory diseases of the skin, including atopic dermatitis and psoriasis, have gained increasing attention with rising incidences in developed countries over the past decades. While bodily properties, such as immunological responses of the skin, have been described in some detail, interactions with the brain via different routes are less well studied. The suggested routes of the skin–brain axis comprise the immune system, HPA axis, and the peripheral and central nervous system, including microglia responses and structural changes. They provide starting points to investigate the molecular mechanisms of neuropsychiatric comorbidities in AD and psoriasis. To this end, mouse models exist for AD and psoriasis that could be tested for relevant behavioral entities. In this review, we provide an overview of the current mouse models and assays. By combining an extensive behavioral characterization and state-of-the-art genetic interventions with the investigation of underlying molecular pathways, insights into the mechanisms of the skin–brain axis in inflammatory cutaneous diseases are examined, which will spark further research in humans and drive the development of novel therapeutic strategies. Full article

(This article belongs to the Collection Feature Papers in Molecular Immunology)

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12 pages, 2369 KiB

Open AccessArticle

Regulation of VEGFA, KRAS, and NFE2L2 Oncogenes by MicroRNAs in Head and Neck Cancer

by Caroline Izak Cuzziol, Ludimila Leite Marzochi, Vitória Scavacini Possebon, Rosa Sayoko Kawasaki-Oyama, Marlon Fraga Mattos, Vilson Serafim Junior, Letícia Antunes Muniz Ferreira, Érika Cristina Pavarino, Márcia Maria Urbanin Castanhole-Nunes and Eny Maria Goloni-Bertollo

Int. J. Mol. Sci. 2022, 23(13), 7483; https://doi.org/10.3390/ijms23137483 - 5 Jul 2022

Cited by 9 | Viewed by 2750

Abstract

Mutations and alterations in the expression of VEGFA, KRAS, and NFE2L2 oncogenes play a key role in cancer initiation and progression. These genes are enrolled not only in cell proliferation control, but also in angiogenesis, drug resistance, metastasis, and survival of [...] Read more.

Mutations and alterations in the expression of VEGFA, KRAS, and NFE2L2 oncogenes play a key role in cancer initiation and progression. These genes are enrolled not only in cell proliferation control, but also in angiogenesis, drug resistance, metastasis, and survival of tumor cells. MicroRNAs (miRNAs) are small, non-coding regulatory RNA molecules that can regulate post-transcriptional expression of multiple target genes. We aimed to investigate if miRNAs hsa-miR-17-5p, hsa-miR-140-5p, and hsa-miR-874-3p could interfere in VEGFA, KRAS, and NFE2L2 expression in cell lines derived from head and neck cancer (HNC). FADU (pharyngeal cancer) and HN13 (oral cavity cancer) cell lines were transfected with miR-17-5p, miR-140-5p, and miR-874-3p microRNA mimics. RNA and protein expression analyses revealed that miR-17-5p, miR-140-5p and miR-874-3p overexpression led to a downregulation of VEGFA, KRAS, and NFE2L2 gene expression in both cell lines analyzed. Taken together, our results provide evidence for the establishment of new biomarkers in the diagnosis and treatment of HNC. Full article

(This article belongs to the Special Issue State-of-the-Art Molecular Oncology in Brazil)

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17 pages, 23982 KiB

Open AccessReview

Staphylococcus aureus Infection-Related Glomerulonephritis with Dominant IgA Deposition

by Mamiko Takayasu, Kouichi Hirayama, Homare Shimohata, Masaki Kobayashi and Akio Koyama

Int. J. Mol. Sci. 2022, 23(13), 7482; https://doi.org/10.3390/ijms23137482 - 5 Jul 2022

Cited by 11 | Viewed by 5141

Abstract

Since 1995, when we reported the case of a patient with glomerulonephritis with IgA deposition that occurred after a methicillin-resistant Staphylococcus aureus (MRSA) infection, many reports of MRSA infection-associated glomerulonephritis have accumulated. This disease is being systematized as Staphylococcus infection-associated glomerulonephritis (SAGN) in [...] Read more.

Since 1995, when we reported the case of a patient with glomerulonephritis with IgA deposition that occurred after a methicillin-resistant Staphylococcus aureus (MRSA) infection, many reports of MRSA infection-associated glomerulonephritis have accumulated. This disease is being systematized as Staphylococcus infection-associated glomerulonephritis (SAGN) in light of the apparent cause of infection, and as immunoglobulin A-dominant deposition infection-related glomerulonephritis (IgA-IRGN) in light of its histopathology. This glomerulonephritis usually presents as rapidly progressive glomerulonephritis or acute kidney injury with various degrees of proteinuria and microscopic hematuria along with an ongoing infection. Its renal pathology has shown several types of mesangial and/or endocapillary proliferative glomerulonephritis with various degrees of crescent formation and tubulointerstitial nephritis. IgA, IgG, and C₃ staining in the mesangium and along the glomerular capillary walls have been observed on immunofluorescence examinations. A marked activation of T cells, an increase in specific variable regions of the T-cell receptor β-chain-positive cells, hypercytokinemia, and increased polyclonal immune complexes have also been observed in this glomerulonephritis. In the development of this disease, staphylococcal enterotoxin may be involved as a superantigen, but further investigations are needed to clarify the mechanisms underlying this disease. Here, we review 336 cases of IgA-IRGN and 218 cases of SAGN. Full article

(This article belongs to the Special Issue Infection and the Kidney)

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27 pages, 3195 KiB

Open AccessReview

Functions of Breast Cancer Predisposition Genes: Implications for Clinical Management

by Akiyo Yoshimura, Issei Imoto and Hiroji Iwata

Int. J. Mol. Sci. 2022, 23(13), 7481; https://doi.org/10.3390/ijms23137481 - 5 Jul 2022

Cited by 24 | Viewed by 4785

Abstract

Approximately 5–10% of all breast cancer (BC) cases are caused by germline pathogenic variants (GPVs) in various cancer predisposition genes (CPGs). The most common contributors to hereditary BC are BRCA1 and BRCA2, which are associated with hereditary breast and ovarian cancer (HBOC). [...] Read more.

Approximately 5–10% of all breast cancer (BC) cases are caused by germline pathogenic variants (GPVs) in various cancer predisposition genes (CPGs). The most common contributors to hereditary BC are BRCA1 and BRCA2, which are associated with hereditary breast and ovarian cancer (HBOC). ATM, BARD1, CHEK2, PALB2, RAD51C, and RAD51D have also been recognized as CPGs with a high to moderate risk of BC. Primary and secondary cancer prevention strategies have been established for HBOC patients; however, optimal preventive strategies for most hereditary BCs have not yet been established. Most BC-associated CPGs participate in DNA damage repair pathways and cell cycle checkpoint mechanisms, and function jointly in such cascades; therefore, a fundamental understanding of the disease drivers in such cascades can facilitate the accurate estimation of the genetic risk of developing BC and the selection of appropriate preventive and therapeutic strategies to manage hereditary BCs. Herein, we review the functions of key BC-associated CPGs and strategies for the clinical management in individuals harboring the GPVs of such genes. Full article

(This article belongs to the Special Issue Molecular Biology of Hereditary Tumors)

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11 pages, 2335 KiB

Open AccessArticle

Soybean Meal-Dependent Acute Intestinal Inflammation Delays Osteogenesis in Zebrafish Larvae

by Marta Carnovali, Giuseppe Banfi, Giovanni Porta and Massimo Mariotti

Int. J. Mol. Sci. 2022, 23(13), 7480; https://doi.org/10.3390/ijms23137480 - 5 Jul 2022

Cited by 2 | Viewed by 2470

Abstract

Foods are known to be modulators of inflammation and skeletal development. The intestine plays an essential role in the regulation of bone health mainly through the regulation of the absorption of vitamin D and calcium; in fact, inflammatory bowel diseases are often related [...] Read more.

Foods are known to be modulators of inflammation and skeletal development. The intestine plays an essential role in the regulation of bone health mainly through the regulation of the absorption of vitamin D and calcium; in fact, inflammatory bowel diseases are often related to bone health issues such as low bone mineral density, high fracture risk, osteoporosis and osteopenia. Considering the complexity of the pathways involved, the use of a simple animal model can be highly useful to better elucidate the pathogenic mechanisms. Soybean flour with a high saponin content has been used in many studies to induce intestinal inflammation in zebrafish larvae. Using a 50% soybean meal (SBM), we analyzed the effects of this soy-induced inflammatory bowel disease on zebrafish larval osteogenesis. Soybean meal induces intestinal functional alterations and an inflammatory state, highlighted by neutral red staining, without altering the general development of the larvae. Our data show that the chondrogenesis as well as endochondral ossification of the head of zebrafish larvae are not affected by an SBM-diet, whereas intramembranous ossification was delayed both in the head, where the length of the ethmoid plate reduced by 17%, and in the trunk with a delayed vertebral mineralization of 47% of SBM larvae. These data highlight that diet-dependent bowel inflammation can differently modulate the different mechanisms of bone development in different zones of the skeleton of zebrafish larvae. Full article

(This article belongs to the Special Issue Diet and Lifestyle: Impact on the Molecular and Cellular Mechanism of NCDs)

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19 pages, 5165 KiB

Open AccessArticle

Far-Red Light Coordinates the Diurnal Changes in the Transcripts Related to Nitrate Reduction, Glutathione Metabolism and Antioxidant Enzymes in Barley

by Eszter Balogh, Balázs Kalapos, Mohamed Ahres, Ákos Boldizsár, Krisztián Gierczik, Zsolt Gulyás, Mónika Gyugos, Gabriella Szalai, Aliz Novák and Gábor Kocsy

Int. J. Mol. Sci. 2022, 23(13), 7479; https://doi.org/10.3390/ijms23137479 - 5 Jul 2022

Cited by 4 | Viewed by 2237

Abstract

Spectral quality, intensity and period of light modify many regulatory and stress signaling pathways in plants. Both nitrate and sulfate assimilations must be synchronized with photosynthesis, which ensures energy and reductants for these pathways. However, photosynthesis is also a source of reactive oxygen [...] Read more.

Spectral quality, intensity and period of light modify many regulatory and stress signaling pathways in plants. Both nitrate and sulfate assimilations must be synchronized with photosynthesis, which ensures energy and reductants for these pathways. However, photosynthesis is also a source of reactive oxygen species, whose levels are controlled by glutathione and other antioxidants. In this study, we investigated the effect of supplemental far-red (735 nm) and blue (450 nm) lights on the diurnal expression of the genes related to photoreceptors, the circadian clock, nitrate reduction, glutathione metabolism and various antioxidants in barley. The maximum expression of the investigated four photoreceptor and three clock-associated genes during the light period was followed by the peaking of the transcripts of the three redox-responsive transcription factors during the dark phase, while most of the nitrate and sulfate reduction, glutathione metabolism and antioxidant-enzyme-related genes exhibited high expression during light exposure in plants grown in light/dark cycles for two days. These oscillations changed or disappeared in constant white light during the subsequent two days. Supplemental far-red light induced the activation of most of the studied genes, while supplemental blue light did not affect or inhibited them during light/dark cycles. However, in constant light, several genes exhibited greater expression in blue light than in white and far-red lights. Based on a correlation analysis of the gene expression data, we propose a major role of far-red light in the coordinated transcriptional adjustment of nitrate reduction, glutathione metabolism and antioxidant enzymes to changes of the light spectrum. Full article

(This article belongs to the Special Issue Light-Dependent Control of Metabolism in Plants)

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16 pages, 6204 KiB

Open AccessArticle

Lactoferrin Deficiency Impairs Proliferation of Satellite Cells via Downregulating the ERK1/2 Signaling Pathway

by Xiong Wang, Fan Liu, Qin An, Wenli Wang, Zhimei Cheng, Yunping Dai, Qingyong Meng and Yali Zhang

Int. J. Mol. Sci. 2022, 23(13), 7478; https://doi.org/10.3390/ijms23137478 - 5 Jul 2022

Cited by 3 | Viewed by 2520

Abstract

Lactoferrin (Ltf), a naturally active glycoprotein, possesses anti-inflammatory, anti-microbial, anti-tumor, and immunomodulatory activities. Many published studies have indicated that Ltf modulates the proliferation of stem cells. However, the role of Ltf in the proliferation of satellite cells, an important cell type [...] Read more.

Lactoferrin (Ltf), a naturally active glycoprotein, possesses anti-inflammatory, anti-microbial, anti-tumor, and immunomodulatory activities. Many published studies have indicated that Ltf modulates the proliferation of stem cells. However, the role of Ltf in the proliferation of satellite cells, an important cell type in muscle regeneration, has not yet been reported. Here, by using Ltf systemic knockout mice, we illustrate the role of Ltf in skeletal muscle. Results shows that Ltf deficiency impaired proliferation of satellite cells (SCs) and the regenerative capability of skeletal muscle. Mechanistic studies showed that ERK1/2 phosphorylation was significantly downregulated after Ltf deletion in SCs. Simultaneously, the cell cycle-related proteins cyclin D and CDK4 were significantly downregulated. Intervention with exogenous recombinant lactoferrin (R-Ltf) at a concentration of 1000 μg/mL promoted proliferation of SCs. In addition, intraperitoneal injection of Ltf effectively ameliorated the skeletal muscle of mice injured by 1.2% BaCl₂ solution. Our results suggest a protective effect of Ltf in the repair of skeletal muscle damage. Ltf holds promise as a novel therapeutic agent for skeletal muscle injuries. Full article

(This article belongs to the Section Biochemistry)

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14 pages, 4648 KiB

Open AccessArticle

Laser Shock Fabrication of Nitrogen Doped Inverse Spinel Fe₃O₄/Carbon Nanosheet Film Electrodes towards Hydrogen Evolution Reactions in Alkaline Media

by Dun Wu, Jiaming Zhao, Junfeng Cheng, Chunlin Liu and Qiang Wang

Int. J. Mol. Sci. 2022, 23(13), 7477; https://doi.org/10.3390/ijms23137477 - 5 Jul 2022

Cited by 5 | Viewed by 2082

Abstract

The reliable and cost-effective production of high-performance film electrodes for hydrogen evolution reactions remains a challenge for the laser surface modification community. In this study, prior to a thermal imidization reaction, a small number of Fe₃O₄ nanoparticles were vortexed into [...] Read more.

The reliable and cost-effective production of high-performance film electrodes for hydrogen evolution reactions remains a challenge for the laser surface modification community. In this study, prior to a thermal imidization reaction, a small number of Fe₃O₄ nanoparticles were vortexed into a poly(amic acid) (PAA) prepolymer, and the achieved flat composite film was then ablated by a 1064 nm fiber laser. After laser irradiation, the hierarchical architectures of carbon nanosheets decorated with Fe₃O₄ nanoparticles were generated. Although pure polyimide (PI) film and laser carbonized PI film, as well as bare Fe₃O₄, showcase poor intrinsic catalytic activity toward alkaline hydrogen evolution reactions, our laser-derived Fe₃O₄/carbon nanosheet hybrid film demonstrated enhanced electrocatalytic activity and stability in 1 M KOH electrolyte; the overpotential(η₁₀) reached 247 mV when the current density was 10 mA cm⁻² with a slight current decay in the chronoamperometric examination of 12 h. Finally, we proposed that the substitution of N to O in Fe−O sites of trans spinel structured magnetite would be able to modulate the free energy of hydrogen adsorption (ΔG_H*) and accelerate water dissociation. Full article

(This article belongs to the Special Issue Materials for Energy Applications 2.0)

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18 pages, 5070 KiB

Open AccessArticle

Complete Reaction Phenotyping of Propranolol and 4-Hydroxypropranolol with the 19 Enzymes of the Human UGT1 and UGT2 Families

by Fan Yang, Sijie Liu, Gerhard Wolber, Matthias Bureik and Maria Kristina Parr

Int. J. Mol. Sci. 2022, 23(13), 7476; https://doi.org/10.3390/ijms23137476 - 5 Jul 2022

Cited by 4 | Viewed by 2663

Abstract

Propranolol is a competitive non-selective beta-receptor antagonist that is available on the market as a racemic mixture. In the present study, glucuronidation of propranolol and its equipotent phase I metabolite 4-hydroxypropranolol by all 19 members of the human UGT1 and UGT2 families was [...] Read more.

Propranolol is a competitive non-selective beta-receptor antagonist that is available on the market as a racemic mixture. In the present study, glucuronidation of propranolol and its equipotent phase I metabolite 4-hydroxypropranolol by all 19 members of the human UGT1 and UGT2 families was monitored. UGT1A7, UGT1A9, UGT1A10 and UGT2A1 were found to glucuronidate propranolol, with UGT1A7, UGT1A9 and UGT2A1 mainly acting on (S)-propranolol, while UGT1A10 displays the opposite stereoselectivity. UGT1A7, UGT1A9 and UGT2A1 were also found to glucuronidate 4-hydroxypropranolol. In contrast to propranolol, 4-hydroxypropranolol was found to be glucuronidated by UGT1A8 but not by UGT1A10. Additional biotransformations with 4-methoxypropanolol demonstrated different regioselectivities of these UGTs with respect to the aliphatic and aromatic hydroxy groups of the substrate. Modeling and molecular docking studies were performed to explain the stereoselective glucuronidation of the substrates under study. Full article

(This article belongs to the Special Issue Small Molecules, Influence of Molecular Pathways 2.0)

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16 pages, 5568 KiB

Open AccessArticle

Loss of TRIM67 Attenuates the Progress of Obesity-Induced Non-Alcoholic Fatty Liver Disease

by Chao Huang, Xiaoli Wei, Qihui Luo, Yu Xia, Ting Pan, Junbo He, Asad Jahangir, Lanlan Jia, Wentao Liu, Yuanfeng Zou, Lixia Li, Hongrui Guo, Yi Geng and Zhengli Chen

Int. J. Mol. Sci. 2022, 23(13), 7475; https://doi.org/10.3390/ijms23137475 - 5 Jul 2022

Cited by 13 | Viewed by 3036

Abstract

Obesity is considered as a major cause for the development and progress of non-alcoholic fatty liver disease (NAFLD), which is one of the most prevalent chronic liver diseases worldwide. However, molecular mechanisms that implicate in obesity-driven pathophysiology of NAFLD are not well defined. [...] Read more.

Obesity is considered as a major cause for the development and progress of non-alcoholic fatty liver disease (NAFLD), which is one of the most prevalent chronic liver diseases worldwide. However, molecular mechanisms that implicate in obesity-driven pathophysiology of NAFLD are not well defined. Here, we report a tripartite motif (TRIM) protein family member—TRIM67—that is hardly expressed in liver but is inducible on obese conditions. Enhanced expression of TRIM67 activates hepatic inflammation to disturb lipid metabolic homeostasis and promote the progress of NAFLD induced by obesity, while the deficiency in TRIM67 is protective against these pathophysiological processes. Finally, we show that the important transcription coactivator PGC-1α implicates in the response of hepatic TRIM67 to obesity. Full article

(This article belongs to the Special Issue Molecular Advances in MAFLD)

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30 pages, 861 KiB

Open AccessReview

Molecular and Circulating Biomarkers in Patients with Glioblastoma

by Nadia Senhaji, Asmae Squalli Houssaini, Salma Lamrabet, Sara Louati and Sanae Bennis

Int. J. Mol. Sci. 2022, 23(13), 7474; https://doi.org/10.3390/ijms23137474 - 5 Jul 2022

Cited by 30 | Viewed by 4306

Abstract

Glioblastoma is the most aggressive malignant tumor of the central nervous system with a low survival rate. The difficulty of obtaining this tumor material represents a major limitation, making the real-time monitoring of tumor progression difficult, especially in the events of recurrence or [...] Read more.

Glioblastoma is the most aggressive malignant tumor of the central nervous system with a low survival rate. The difficulty of obtaining this tumor material represents a major limitation, making the real-time monitoring of tumor progression difficult, especially in the events of recurrence or resistance to treatment. The identification of characteristic biomarkers is indispensable for an accurate diagnosis, the rigorous follow-up of patients, and the development of new personalized treatments. Liquid biopsy, as a minimally invasive procedure, holds promise in this regard. The purpose of this paper is to summarize the current literature regarding the identification of molecular and circulating glioblastoma biomarkers and the importance of their integration as a valuable tool to improve patient care. Full article

(This article belongs to the Special Issue Glioblastoma: Recapitulating the Key Breakthroughs and Future Perspective)

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16 pages, 1007 KiB

Open AccessReview

Polyphenol-Enriched Composite Bone Regeneration Materials: A Systematic Review of In Vitro Studies

by Kamila Checinska, Maciej Checinski, Katarzyna Cholewa-Kowalska, Maciej Sikora and Dariusz Chlubek

Int. J. Mol. Sci. 2022, 23(13), 7473; https://doi.org/10.3390/ijms23137473 - 5 Jul 2022

Cited by 8 | Viewed by 2668

Abstract

One of the possible alternatives for creating materials for the regeneration of bone tissue supporting comprehensive reconstruction is the incorporation of active substances whose controlled release will improve this process. This systematic review aimed to identify and synthesize in vitro studies that assess [...] Read more.

One of the possible alternatives for creating materials for the regeneration of bone tissue supporting comprehensive reconstruction is the incorporation of active substances whose controlled release will improve this process. This systematic review aimed to identify and synthesize in vitro studies that assess the suitability of polyphenolics as additives to polymer-ceramic composite bone regeneration materials. Data on experimental studies in terms of the difference in mechanical, wettability, cytocompatibility, antioxidant and anti-inflammatory properties of materials were synthesized. The obtained numerical data were compiled and analyzed in search of percentage changes of these parameters. The results of the systematic review were based on data from forty-six studies presented in nineteen articles. The addition of polyphenolic compounds to composite materials for bone regeneration improved the cytocompatibility and increased the activity of early markers of osteoblast differentiation, indicating a high osteoinductive potential of the materials. Polyphenolic compounds incorporated into the materials presumably give them high antioxidant properties and reduce the production of reactive oxygen species in macrophage cells, implying anti-inflammatory activity. The evidence was limited by the number of missing data and the heterogeneity of the data. Full article

(This article belongs to the Special Issue Biomaterials and Antimicrobial Materials for Orthopaedic Application)

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12 pages, 1762 KiB

Open AccessArticle

Electrochemical Detection and Analysis of Various Current Responses of a Single Ag Nanoparticle Collision in an Alkaline Electrolyte Solution

by Ki Jun Kim and Seong Jung Kwon

Int. J. Mol. Sci. 2022, 23(13), 7472; https://doi.org/10.3390/ijms23137472 - 5 Jul 2022

Cited by 2 | Viewed by 2200

Abstract

A single silver (Ag) nanoparticle (NP) collision was observed and analyzed in an alkaline solution using the electrocatalytic amplification (EA) method. Previously, the observation of a single Ag NP collision was only possible through limited methods based on a self-oxidation of Ag NPs [...] Read more.

A single silver (Ag) nanoparticle (NP) collision was observed and analyzed in an alkaline solution using the electrocatalytic amplification (EA) method. Previously, the observation of a single Ag NP collision was only possible through limited methods based on a self-oxidation of Ag NPs or a blocking strategy. However, it is difficult to characterize the electrocatalytic activity of Ag NPs at a single NP level using a method based on the self-oxidation of Ag NPs. When using a blocking strategy, size analysis is difficult owing to the edge effect in the current signal. The fast oxidative dissolution of Ag NPs has been a problem for observing the staircase response of a single Ag NP collision signal using the EA method. In alkaline electrolyte conditions, Ag oxides are stable, and the oxidative dissolution of Ag NPs is sluggish. Therefore, in this study, the enhanced magnitude and frequency of the current response for single Ag NP collisions were obtained using the EA method in an alkaline electrolyte solution. The peak height and frequency of single Ag NP collisions were analyzed and compared with the theoretical estimation. Full article

(This article belongs to the Special Issue Recent Advances in Nanomaterials Science)

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17 pages, 1397 KiB

Open AccessReview

Next RNA Therapeutics: The Mine of Non-Coding

by Sabrina Garbo, Rossella Maione, Marco Tripodi and Cecilia Battistelli

Int. J. Mol. Sci. 2022, 23(13), 7471; https://doi.org/10.3390/ijms23137471 - 5 Jul 2022

Cited by 40 | Viewed by 3867

Abstract

The growing knowledge on several classes of non-coding RNAs (ncRNAs) and their different functional roles has aroused great interest in the scientific community. Beyond the Central Dogma of Biology, it is clearly known that not all RNAs code for protein products, and they [...] Read more.

The growing knowledge on several classes of non-coding RNAs (ncRNAs) and their different functional roles has aroused great interest in the scientific community. Beyond the Central Dogma of Biology, it is clearly known that not all RNAs code for protein products, and they exert a broader repertoire of biological functions. As described in this review, ncRNAs participate in gene expression regulation both at transcriptional and post-transcriptional levels and represent critical elements driving and controlling pathophysiological processes in multicellular organisms. For this reason, in recent years, a great boost was given to ncRNA-based strategies with potential therapeutic abilities, and nowadays, the use of RNA molecules is experimentally validated and actually exploited in clinics to counteract several diseases. In this review, we summarize the principal classes of therapeutic ncRNA molecules that are potentially implied in disease onset and progression, which are already used in clinics or under clinical trials, highlighting the advantages and the need for a targeted therapeutic strategy design. Furthermore, we discuss the benefits and the limits of RNA therapeutics and the ongoing development of delivery strategies to limit the off-target effects and to increase the translational application. Full article

(This article belongs to the Special Issue The Emerging Role of RNA in Diseases and Cancers)

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9 pages, 701 KiB

Open AccessArticle

Limited Accuracy of Pan-Trk Immunohistochemistry Screening for NTRK Rearrangements in Follicular-Derived Thyroid Carcinoma

by Elisabetta Macerola, Agnese Proietti, Anello Marcello Poma, Paola Vignali, Rebecca Sparavelli, Alessandro Ginori, Alessio Basolo, Rossella Elisei, Ferruccio Santini and Fulvio Basolo

Int. J. Mol. Sci. 2022, 23(13), 7470; https://doi.org/10.3390/ijms23137470 - 5 Jul 2022

Cited by 7 | Viewed by 2131

Abstract

Patients with advanced thyroid cancer harboring NTRK rearrangements can be treated with highly effective selective inhibitors. Immunohistochemistry (IHC) analysis, to detect Trk protein expression, represents an appealing screening strategy for NTRK rearrangements, but its efficacy has been poorly explored in thyroid cancer. The [...] Read more.

Patients with advanced thyroid cancer harboring NTRK rearrangements can be treated with highly effective selective inhibitors. Immunohistochemistry (IHC) analysis, to detect Trk protein expression, represents an appealing screening strategy for NTRK rearrangements, but its efficacy has been poorly explored in thyroid cancer. The aim of this study is to investigate the diagnostic utility of Trk IHC in the identification of NTRK rearrangements. A series of 26 follicular-derived thyroid tumors, positive for NTRK rearrangements, and 28 NTRK fusion-negative controls were retrospectively analyzed by IHC using the pan-Trk monoclonal antibody (clone EPR17341) on the Ventana system. Area under the curve (AUC), sensitivity and specificity were calculated by ROC analysis. Trk expression was detected in 25 samples, including 22 out of the 26 NTRK-rearranged (84.6%) and three out of 28 NTRK-negative samples (10.7%). Four out of twenty-six NTRK-rearranged thyroid tumors were negative for Trk expression (15.4%), all carrying the ETV6/NTRK3 fusion. The AUC, sensitivity and specificity were 0.87, 0.85 and 0.89, respectively. A screening based on IHC analysis showed limited sensitivity and specificity in the identification of NTRK-rearranged tumors. Since falsely negative results could preclude the administration of effective targeted drugs, alternative detection strategies should be considered for thyroid cancer. Full article

(This article belongs to the Special Issue Advances in Metabolism, Immunology, Genetics in Thyroid Cancer and Thyroid Disease: From Bench to Therapy)

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26 pages, 9771 KiB

Open AccessArticle

Directed Evolution of Phi Class Glutathione Transferases Involved in Multiple-Herbicide Resistance of Grass Weeds and Crops

by Elisavet Ioannou, Anastassios C. Papageorgiou and Nikolaos E. Labrou

Int. J. Mol. Sci. 2022, 23(13), 7469; https://doi.org/10.3390/ijms23137469 - 5 Jul 2022

Cited by 10 | Viewed by 2828

Abstract

The extensive application of herbicides in crop cultivation has indisputably led to the emergence of weed populations characterized by multiple herbicide resistance (MHR). This phenomenon is associated with the enhanced metabolism and detoxifying ability of endogenous enzymes, such as phi class glutathione transferases [...] Read more.

The extensive application of herbicides in crop cultivation has indisputably led to the emergence of weed populations characterized by multiple herbicide resistance (MHR). This phenomenon is associated with the enhanced metabolism and detoxifying ability of endogenous enzymes, such as phi class glutathione transferases (GSTFs). In the present work, a library of mutant GSTFs was created by in vitro directed evolution via DNA shuffling. Selected gstf genes from the weeds Alopecurus myosuroides and Lolium rigidum, and the cereal crops Triticum durum and Hordeum vulgare were recombined to forge a library of novel chimeric GSTFs. The library was activity screened and the best-performing enzyme variants were purified and characterized. The work allowed the identification of enzyme variants that exhibit an eight-fold improvement in their catalytic efficiency, higher thermal stability (8.3 °C) and three-times higher inhibition sensitivity towards the herbicide butachlor. The crystal structures of the best-performing enzyme variants were determined by X-ray crystallography. Structural analysis allowed the identification of specific structural elements that are responsible for k_cat regulation, thermal stability and inhibition potency. These improved novel enzymes hold the potential for utilization in biocatalysis and green biotechnology applications. The results of the present work contribute significantly to our knowledge of the structure and function of phi class plant GSTs and shed light on their involvement in the mechanisms of MHR. Full article

(This article belongs to the Collection Feature Papers in “Molecular Biology”)

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30 pages, 4795 KiB

Open AccessArticle

Hepatic Expression of the Na⁺-Taurocholate Cotransporting Polypeptide Is Independent from Genetic Variation

by Roman Tremmel, Anne T. Nies, Barbara A. C. van Eijck, Niklas Handin, Mathias Haag, Stefan Winter, Florian A. Büttner, Charlotte Kölz, Franziska Klein, Pascale Mazzola, Ute Hofmann, Kathrin Klein, Per Hoffmann, Markus M. Nöthen, Fabienne Z. Gaugaz, Per Artursson, Matthias Schwab and Elke Schaeffeler

Int. J. Mol. Sci. 2022, 23(13), 7468; https://doi.org/10.3390/ijms23137468 - 5 Jul 2022

Cited by 6 | Viewed by 4126

Abstract

The hepatic Na⁺-taurocholate cotransporting polypeptide NTCP/SLC10A1 is important for the uptake of bile salts and selected drugs. Its inhibition results in increased systemic bile salt concentrations. NTCP is also the entry receptor for the hepatitis B/D virus. We investigated interindividual [...] Read more.

The hepatic Na⁺-taurocholate cotransporting polypeptide NTCP/SLC10A1 is important for the uptake of bile salts and selected drugs. Its inhibition results in increased systemic bile salt concentrations. NTCP is also the entry receptor for the hepatitis B/D virus. We investigated interindividual hepatic SLC10A1/NTCP expression using various omics technologies. SLC10A1/NTCP mRNA expression/protein abundance was quantified in well-characterized 143 human livers by real-time PCR and LC-MS/MS-based targeted proteomics. Genome-wide SNP arrays and SLC10A1 next-generation sequencing were used for genomic analyses. SLC10A1 DNA methylation was assessed through MALDI-TOF MS. Transcriptomics and untargeted metabolomics (UHPLC-Q-TOF-MS) were correlated to identify NTCP-related metabolic pathways. SLC10A1 mRNA and NTCP protein levels varied 44-fold and 10.4-fold, respectively. Non-genetic factors (e.g., smoking, alcohol consumption) influenced significantly NTCP expression. Genetic variants in SLC10A1 or other genes do not explain expression variability which was validated in livers (n = 50) from The Cancer Genome Atlas. The identified two missense SLC10A1 variants did not impair transport function in transfectants. Specific CpG sites in SLC10A1 as well as single metabolic alterations and pathways (e.g., peroxisomal and bile acid synthesis) were significantly associated with expression. Inter-individual variability of NTCP expression is multifactorial with the contribution of clinical factors, DNA methylation, transcriptional regulation as well as hepatic metabolism, but not genetic variation. Full article

(This article belongs to the Special Issue Overcoming Biological Barriers: Importance of Membrane Transporters in Homeostasis, Disease, and Disease Treatment)

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19 pages, 21169 KiB

Open AccessReview

New Avenues of Heme Synthesis Regulation

by Amy E. Medlock and Harry A. Dailey

Int. J. Mol. Sci. 2022, 23(13), 7467; https://doi.org/10.3390/ijms23137467 - 5 Jul 2022

Cited by 12 | Viewed by 6745

Abstract

During erythropoiesis, there is an enormous demand for the synthesis of the essential cofactor of hemoglobin, heme. Heme is synthesized de novo via an eight enzyme-catalyzed pathway within each developing erythroid cell. A large body of data exists to explain the transcriptional regulation [...] Read more.

During erythropoiesis, there is an enormous demand for the synthesis of the essential cofactor of hemoglobin, heme. Heme is synthesized de novo via an eight enzyme-catalyzed pathway within each developing erythroid cell. A large body of data exists to explain the transcriptional regulation of the heme biosynthesis enzymes, but until recently much less was known about alternate forms of regulation that would allow the massive production of heme without depleting cellular metabolites. Herein, we review new studies focused on the regulation of heme synthesis via carbon flux for porphyrin synthesis to post-translations modifications (PTMs) that regulate individual enzymes. These PTMs include cofactor regulation, phosphorylation, succinylation, and glutathionylation. Additionally discussed is the role of the immunometabolite itaconate and its connection to heme synthesis and the anemia of chronic disease. These recent studies provide new avenues to regulate heme synthesis for the treatment of diseases including anemias and porphyrias. Full article

(This article belongs to the Special Issue Physiology of Red Cell Lineage: From Erythroblast Progenitors to Mature Red Blood Cell)

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10 pages, 901 KiB

Open AccessReview

Hypercholesterolemia in Cancer and in Anorexia Nervosa: A Hypothesis for a Crosstalk

by Giulia Gizzi, Samuela Cataldi, Claudia Mazzeschi, Elisa Delvecchio, Maria Rachele Ceccarini, Michela Codini and Elisabetta Albi

Int. J. Mol. Sci. 2022, 23(13), 7466; https://doi.org/10.3390/ijms23137466 - 5 Jul 2022

Cited by 4 | Viewed by 3187

Abstract

The relationship between cholesterol and cancer has been widely demonstrated. Clinical studies have shown changes in blood cholesterol levels in cancer patients. In parallel, basic research studies have shown that cholesterol is involved in the mechanisms of onset and progression of the disease. [...] Read more.

The relationship between cholesterol and cancer has been widely demonstrated. Clinical studies have shown changes in blood cholesterol levels in cancer patients. In parallel, basic research studies have shown that cholesterol is involved in the mechanisms of onset and progression of the disease. On the other hand, anorexic patients have high cholesterol levels and a high susceptibility to cancer. In this review, we first present a brief background on the relations among nutrition, eating disorders and cancer. Using several notable examples, we then illustrate the changes in cholesterol in cancer and in anorexia nervosa, providing evidence for their important relationship. Finally, we show a new possible link between cholesterol disorder in cancer and in anorexia nervosa. Full article

(This article belongs to the Special Issue Lipid as a Cancer Therapeutic Target 2.0)

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31 pages, 771 KiB

Open AccessReview

Extraterrestrial Gynecology: Could Spaceflight Increase the Risk of Developing Cancer in Female Astronauts? An Updated Review

by Rosa Drago-Ferrante, Riccardo Di Fiore, Fathi Karouia, Yashwanth Subbannayya, Saswati Das, Begum Aydogan Mathyk, Shehbeel Arif, Ana Paula Guevara-Cerdán, Allen Seylani, Aman Singh Galsinh, Weronika Kukulska, Joseph Borg, Sherif Suleiman, David Marshall Porterfield, Andrea Camera, Lane K. Christenson, April Elizabeth Ronca, Jonathan G. Steller, Afshin Beheshti and Jean Calleja-Agius

Int. J. Mol. Sci. 2022, 23(13), 7465; https://doi.org/10.3390/ijms23137465 - 5 Jul 2022

Cited by 10 | Viewed by 7494

Abstract

Outer space is an extremely hostile environment for human life, with ionizing radiation from galactic cosmic rays and microgravity posing the most significant hazards to the health of astronauts. Spaceflight has also been shown to have an impact on established cancer hallmarks, possibly [...] Read more.

Outer space is an extremely hostile environment for human life, with ionizing radiation from galactic cosmic rays and microgravity posing the most significant hazards to the health of astronauts. Spaceflight has also been shown to have an impact on established cancer hallmarks, possibly increasing carcinogenic risk. Terrestrially, women have a higher incidence of radiation-induced cancers, largely driven by lung, thyroid, breast, and ovarian cancers, and therefore, historically, they have been permitted to spend significantly less time in space than men. In the present review, we focus on the effects of microgravity and radiation on the female reproductive system, particularly gynecological cancer. The aim is to provide a summary of the research that has been carried out related to the risk of gynecological cancer, highlighting what further studies are needed to pave the way for safer exploration class missions, as well as postflight screening and management of women astronauts following long-duration spaceflight. Full article

(This article belongs to the Special Issue Cellular and Molecular Signaling Meet the Space Environment)

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26 pages, 15564 KiB

Open AccessArticle

Size-Dependent Cytoprotective Effects of Selenium Nanoparticles during Oxygen-Glucose Deprivation in Brain Cortical Cells

by Elena G. Varlamova, Sergey V. Gudkov, Egor Y. Plotnikov and Egor A. Turovsky

Int. J. Mol. Sci. 2022, 23(13), 7464; https://doi.org/10.3390/ijms23137464 - 5 Jul 2022

Cited by 24 | Viewed by 3114

Abstract

It is known that selenium nanoparticles (SeNPs) obtained on their basis have a pleiotropic effect, inducing the process of apoptosis in tumor cells, on the one hand, and protecting healthy tissue cells from death under stress, on the other hand. It has been [...] Read more.

It is known that selenium nanoparticles (SeNPs) obtained on their basis have a pleiotropic effect, inducing the process of apoptosis in tumor cells, on the one hand, and protecting healthy tissue cells from death under stress, on the other hand. It has been established that SeNPs protect brain cells from ischemia/reoxygenation through activation of the Ca²⁺ signaling system of astrocytes and reactive astrogliosis. At the same time, for a number of particles, the limitations of their use, associated with their size, are shown. The use of nanoparticles with a diameter of less than 10 nm leads to their short life-time in the bloodstream and rapid removal by the liver. Nanoparticles larger than 200 nm activate the complement system and are also quickly removed from the blood. The effects of different-sized SeNPs on brain cells have hardly been studied. Using the laser ablation method, we obtained SeNPs of various diameters: 50 nm, 100 nm, and 400 nm. Using fluorescence microscopy, vitality tests, PCR analysis, and immunocytochemistry, it was shown that all three types of the different-sized SeNPs have a cytoprotective effect on brain cortex cells under conditions of oxygen-glucose deprivation (OGD) and reoxygenation (R), suppressing the processes of necrotic death and inhibiting different efficiency processes of apoptosis. All of the studied SeNPs activate the Ca²⁺ signaling system of astrocytes, while simultaneously inducing different types of Ca²⁺ signals. SeNPs sized at 50 nm- induce Ca²⁺ responses of astrocytes in the form of a gradual irreversible increase in the concentration of cytosolic Ca²⁺ ([Ca²⁺]_i), 100 nm-sized SeNPs induce stable Ca²⁺ oscillations without increasing the base level of [Ca²⁺]_i, and 400 nm-sized SeNPs cause mixed patterns of Ca²⁺ signals. Such differences in the level of astrocyte Ca²⁺ signaling can explain the different cytoprotective efficacy of SeNPs, which is expressed in the expression of protective proteins and the activation of reactive astrogliosis. In terms of the cytoprotective efficiency under OGD/R conditions, different-sized SeNPs can be arranged in descending order: 100 nm-sized > 400 nm-sized > 50 nm-sized. Full article

(This article belongs to the Collection Feature Papers in Molecular Nanoscience)

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16 pages, 2297 KiB

Open AccessArticle

SPR-Based Detection of ASF Virus in Cells

by Alessandro Capo, Alessia Calabrese, Maciej Frant, Marek Walczak, Anna Szczotka-Bochniarz, Georgios Manessis, Ioannis Bossis, Maria Staiano, Sabato D’Auria and Antonio Varriale

Int. J. Mol. Sci. 2022, 23(13), 7463; https://doi.org/10.3390/ijms23137463 - 5 Jul 2022

Cited by 6 | Viewed by 2701

Abstract

African swine fever (ASF) is one of the most dangerous hemorrhagic infectious diseases that affect domestic and wild pigs. Currently, neither a vaccine nor effective treatments are available for this disease. As regards the degree of virulence, ASFV strains can be divided into [...] Read more.

African swine fever (ASF) is one of the most dangerous hemorrhagic infectious diseases that affect domestic and wild pigs. Currently, neither a vaccine nor effective treatments are available for this disease. As regards the degree of virulence, ASFV strains can be divided into high, moderate, or low virulence. The main detection methods are based on the use of the polymerase chain reaction (PCR). In order to prevent an uncontrolled spread of ASF, new on-site techniques that can enable the identification of an early-stage disease are needed. We have developed a specific immunological SPR-based assay for ASFV antigen detection directly in liquid samples. The developed assay allows us to detect the presence of ASFV at the dose of 10³ HAD₅₀/_mL. Full article

(This article belongs to the Special Issue 25th Anniversary of IJMS: Advances in Biochemistry)

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19 pages, 3691 KiB

Open AccessArticle

Bamboo Lignin Fractions with In Vitro Tyrosinase Inhibition Activity Downregulate Melanogenesis in B16F10 Cells via PKA/CREB Signaling Pathway

by Moon-Hee Choi, Seung-Hwa Yang, Won-Keun Park and Hyun-Jae Shin

Int. J. Mol. Sci. 2022, 23(13), 7462; https://doi.org/10.3390/ijms23137462 - 5 Jul 2022

Cited by 2 | Viewed by 2879

Abstract

Cosmetic ingredients originating from natural resources have garnered considerable attention, and the demand for whitening ingredients is increasing, particularly in Asian countries. Lignin is a natural phenolic biopolymer significantly effective as a natural sunscreen, as its ultraviolet protection efficacy ranges from 250 to [...] Read more.

Cosmetic ingredients originating from natural resources have garnered considerable attention, and the demand for whitening ingredients is increasing, particularly in Asian countries. Lignin is a natural phenolic biopolymer significantly effective as a natural sunscreen, as its ultraviolet protection efficacy ranges from 250 to 400 nm. However, using different types of lignin as cosmetic ingredients is difficult owing to the heterogeneity of lignin and the lack of in vitro and in vivo safety and efficacy data. Thus, steam-exploded lignin (SEL) was prepared from bamboo, fractionated via successive organic solvent extraction, and sequentially fractionated using ethyl acetate, methanol, and acetone to investigate its potential as a natural whitening material. Gel permeation chromatography showed that the molecular weight of acetone-soluble and acetone-insoluble SEL fractions were the lowest and the highest, respectively. Monomer structures of the four lignin fractions were elucidated using ¹H, ¹³C, and 2D heteronuclear single quantum coherence nuclear magnetic resonance and pyrolysis gas chromatography/mass spectrometry. The antioxidant and tyrosinase inhibition activities of the four fractions were compared. The methanol-soluble SEL fraction (SEL-F2) showed the highest antioxidant activity (except 2,2-diphenyl-1-picrylhydrazyl scavenging activity), and the enzyme inhibition kinetics were confirmed. In this study, the expression pattern of the anti-melanogenic-related proteins by SEL-F2 was confirmed for the first time via the protein kinase A (PKA)/cAMP-response element-binding (CREB) protein signaling pathway in B16F10 melanoma cells. Thus, SEL may serve as a valuable cosmetic whitening ingredient. Full article

(This article belongs to the Special Issue Melanins and Melanogenesis 3.0: From Nature to Applications)

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16 pages, 16090 KiB

Open AccessArticle

Investigation of the Molecular Mechanisms Underlying the Antiatherogenic Actions of Kaempferol in Human THP-1 Macrophages

by Etimad Huwait, Maha Ayoub and Sajjad Karim

Int. J. Mol. Sci. 2022, 23(13), 7461; https://doi.org/10.3390/ijms23137461 - 5 Jul 2022

Cited by 7 | Viewed by 3048

Abstract

Cardiovascular disease (CVD) is causing high mortality worldwide (World Health Organization-WHO, 2015). Atherosclerosis, the hardening and narrowing of arteries caused by the accumulation of fatty acids and lipids (cholesterol plaques), is a main reason of stroke, myocardial infarction, and angina. Present therapies for [...] Read more.

Cardiovascular disease (CVD) is causing high mortality worldwide (World Health Organization-WHO, 2015). Atherosclerosis, the hardening and narrowing of arteries caused by the accumulation of fatty acids and lipids (cholesterol plaques), is a main reason of stroke, myocardial infarction, and angina. Present therapies for cardiovascular disease basically use statins such as β-Hydroxy β-methylglutaryl-CoA, with <70% efficacy and multiple side effects. An in vitro investigation was conducted to evaluate the impact of kaempferol, a natural medication, in an atherosclerotic cell model. We used cytotoxicity assays, Boyden chamber invasion assays, and quantitative PCR. Affymetrix microarrays were used to profile the entire transcriptome of kaempferol-treated cell lines, and Partek Genomic Suite was used to interpret the results. Kaempferol was not cytotoxic to THP-1 macrophages. In comparison to the control, kaempferol reduced monocyte migration mediated by monocyte chemotactic protein 1 (MCP-1) by 80%. The qPCR results showed a 73.7-fold reduction in MCP-1 and a 2.5-fold reduction in intercellular adhesion molecule 1 (ICAM-1) expression in kaempferol-treated cells. In interferon gamma (IFN-γ) without kaempferol and IFN-γ with kaempferol treated cells, we found 295 and 168 differentially expressed genes (DEGs), respectively. According to DEG pathway analysis, kaempferol exhibits anti-atherosclerosis and anti-inflammatory characteristics. Kaempferol is an effective and safe therapy for atherosclerosis. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Cardiovascular Disease 2022)

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17 pages, 4796 KiB

Open AccessArticle

A Novel Artificial Hemoglobin Carrier Based on Heulandite-Calcium Mesoporous Aluminosilicate Particles

by Dino Jordanoski, Damjana Drobne, Neža Repar, Iztok Dogsa, Polona Mrak, Romana Cerc-Korošec, Andrijana Sever Škapin, Peter Nadrah and Natasa Poklar Ulrih

Int. J. Mol. Sci. 2022, 23(13), 7460; https://doi.org/10.3390/ijms23137460 - 5 Jul 2022

Cited by 1 | Viewed by 2499

Abstract

Tetraethyl-orthosilicate (TEOS)-based nanoparticles are most extensively used as a silica-based hemoglobin carrier system. However, TEOS-based nanoparticles induce adverse effects on the hemoglobin structure. Therefore, a heulandite-calcium-based carrier was investigated as a novel silica-based hemoglobin carrier system. The heulandite-calcium mesoporous aluminosilicate particles (MSPs) were [...] Read more.

Tetraethyl-orthosilicate (TEOS)-based nanoparticles are most extensively used as a silica-based hemoglobin carrier system. However, TEOS-based nanoparticles induce adverse effects on the hemoglobin structure. Therefore, a heulandite-calcium-based carrier was investigated as a novel silica-based hemoglobin carrier system. The heulandite-calcium mesoporous aluminosilicate particles (MSPs) were fabricated by a patented tribo-mechanical activation process, according to the manufacturer, and its structure was assessed by X-ray diffraction analysis. Upon hemoglobin encapsulation, alternation in the secondary and tertiary structure was observed. The hemoglobin-particle interactions do not cause heme degradation or decreased activity. Once encapsulated inside the particle pores, the hemoglobin shows increased thermal stability, and higher loading capacity per gram of particles (by a factor of >1.4) when compared to TEOS-based nanoparticles. Futhermore, we introduced a PEGlyted lipid bilayer which significantly decreases the premature hemoglobin release and increases the colloidal stability. The newly developed hemoglobin carrier shows no cytotoxicity to human umbilical vein endothelial cells (HUVEC). Full article

(This article belongs to the Collection Feature Papers in Materials Science)

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12 pages, 1975 KiB

Open AccessReview

SAGA-Dependent Histone H2Bub1 Deubiquitination Is Essential for Cellular Ubiquitin Balance during Embryonic Development

by Farrah El-Saafin, Didier Devys, Steven A. Johnsen, Stéphane D. Vincent and László Tora

Int. J. Mol. Sci. 2022, 23(13), 7459; https://doi.org/10.3390/ijms23137459 - 5 Jul 2022

Cited by 8 | Viewed by 3408

Abstract

Ubiquitin (ub) is a small, highly conserved protein widely expressed in eukaryotic cells. Ubiquitination is a post-translational modification catalyzed by enzymes that activate, conjugate, and ligate ub to proteins. Substrates can be modified either by addition of a single ubiquitin molecule (monoubiquitination), or [...] Read more.

Ubiquitin (ub) is a small, highly conserved protein widely expressed in eukaryotic cells. Ubiquitination is a post-translational modification catalyzed by enzymes that activate, conjugate, and ligate ub to proteins. Substrates can be modified either by addition of a single ubiquitin molecule (monoubiquitination), or by conjugation of several ubs (polyubiquitination). Monoubiquitination acts as a signaling mark to control diverse biological processes. The cellular and spatial distribution of ub is determined by the opposing activities of ub ligase enzymes, and deubiquitinases (DUBs), which remove ub from proteins to generate free ub. In mammalian cells, 1–2% of total histone H2B is monoubiquitinated. The SAGA (Spt Ada Gcn5 Acetyl-transferase) is a transcriptional coactivator and its DUB module removes ub from H2Bub1. The mammalian SAGA DUB module has four subunits, ATXN7, ATXN7L3, USP22, and ENY2. Atxn7l3^−/− mouse embryos, lacking DUB activity, have a five-fold increase in H2Bub1 retention, and die at mid-gestation. Interestingly, embryos lacking the ub encoding gene, Ubc, have a similar phenotype. Here we provide a current overview of data suggesting that H2Bub1 retention on the chromatin in Atxn7l3^−/− embryos may lead to an imbalance in free ub distribution. Thus, we speculate that ATXN7L3-containing DUBs impact the free cellular ub pool during development. Full article

(This article belongs to the Special Issue Ubiquitination and Deubiquitination in Cellular Homeostasis)

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