Current Issues in Molecular Biology

11 pages, 661 KiB

Open AccessArticle

Glutathione and Its Metabolic Enzymes in Gliomal Tumor Tissue and the Peritumoral Zone at Different Degrees of Anaplasia

by Larisa Obukhova, Tatiana Kopytova, Elena Murach, Natalya Shchelchkova, Claudia Kontorshchikova, Igor Medyanik, Natalia Orlinskaya, Artem Grishin, Michael Kontorshchikov and Dariya Badanina

Curr. Issues Mol. Biol. 2022, 44(12), 6439-6449; https://doi.org/10.3390/cimb44120439 - 19 Dec 2022

Cited by 1 | Viewed by 2217

Abstract

This research was aimed at investigating the features of free radical activity and the parameters of glutathione metabolism in tumor tissues and the peritumoral zone at different degrees of glial tumor anaplasia. We analyzed postoperative material from 20 patients with gliomas of different [...] Read more.

This research was aimed at investigating the features of free radical activity and the parameters of glutathione metabolism in tumor tissues and the peritumoral zone at different degrees of glial tumor anaplasia. We analyzed postoperative material from 20 patients with gliomas of different degrees of anaplasia. The greatest differences compared to adjacent noncancerous tissues were found in the tumor tissue: an increased amount of glutathione and glutathione-related enzymes at Grades I and II, and a decrease of these parameters at Grades III and IV. For the peritumoral zone of Grades I and II, the indices changed in different directions, while for Grades III and IV, they occurred synchronously with the tumor tissue changes. For Low Grade and High Grade gliomas, opposite trends were revealed regarding changes in the level of glutathione and the enzymes involved in its metabolism and in the free radical activity in the peritumoral zone. The content of glutathione and the enzymes involved in its metabolism decreased with the increasing degree of glioma anaplasia. In contrast, free radical activity increased. The glutathione system is an active participant in the antioxidant defense of the body and can be used to characterize the cell condition of gliomas at different stages of tumor development. Full article

(This article belongs to the Special Issue Metabolic Reprogramming of Immune Cells in Tumor Microenvironment)

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11 pages, 1302 KiB

Open AccessArticle

Antileukemic Activity of hsa-miR-203a-5p by Limiting Glutathione Metabolism in Imatinib-Resistant K562 Cells

by Priyanka Singh, Radheshyam Yadav, Malkhey Verma and Ravindresh Chhabra

Curr. Issues Mol. Biol. 2022, 44(12), 6428-6438; https://doi.org/10.3390/cimb44120438 - 19 Dec 2022

Cited by 1 | Viewed by 2007

Abstract

Imatinib has been the first and most successful tyrosine kinase inhibitor (TKI) for chronic myeloid leukemia (CML), but many patients develop resistance to it after a satisfactory response. Glutathione (GSH) metabolism is thought to be one of the factors causing the emergence of [...] Read more.

Imatinib has been the first and most successful tyrosine kinase inhibitor (TKI) for chronic myeloid leukemia (CML), but many patients develop resistance to it after a satisfactory response. Glutathione (GSH) metabolism is thought to be one of the factors causing the emergence of imatinib resistance. Since hsa-miR-203a-5p was found to downregulate Bcr-Abl1 oncogene and also a link between this oncogene and GSH metabolism is reported, the present study aimed to investigate whether hsa-miR-203a-5p could overcome imatinib resistance by targeting GSH metabolism in imatinib-resistant CML cells. After the development of imatinib-resistant K562 (IR-K562) cells by gradually exposing K562 (C) cells to increasing doses of imatinib, resistant cells were transfected with hsa-miR-203a-5p (R+203). Thereafter, cell lysates from various K562 cell sets (imatinib-sensitive, imatinib-resistant, and miR-transfected imatinib-resistant K562 cells) were used for GC-MS-based metabolic profiling. L-alanine, 5-oxoproline (also known as pyroglutamic acid), L-glutamic acid, glycine, and phosphoric acid (Pi)—five metabolites from our data, matched with the enumerated 28 metabolites of the MetaboAnalyst 5.0 for the GSH metabolism. All of these metabolites were present in higher concentrations in IR-K562 cells, but intriguingly, they were all reduced in R+203 and equated to imatinib-sensitive K562 cells (C). Concludingly, the identified metabolites associated with GSH metabolism could be used as diagnostic markers. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Leukemia)

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24 pages, 5579 KiB

Open AccessArticle

Comprehensive Analysis of Glutamate Receptor-like Genes in Rice (Oryza sativa L.): Genome-Wide Identification, Characteristics, Evolution, Chromatin Accessibility, gcHap Diversity, Population Variation and Expression Analysis

by Yingyao Shi, Wei Zeng, Minhui Xu, Hua Li, Fanlin Zhang, Zulong Chen, Gatera Anicet, Shiji Huang, Yuheng Huang, Xiyu Wang, Junhao Li, Xinyu Zhang, Yuxing Zheng and Shamsur Rehman

Curr. Issues Mol. Biol. 2022, 44(12), 6404-6427; https://doi.org/10.3390/cimb44120437 - 16 Dec 2022

Cited by 3 | Viewed by 2078

Abstract

Glutamate receptors (GLR) are widely present in animals and plants, playing essential roles in regulating plant growth, development and stress response. At present, most studies of GLRs in plants are focused on Arabidopsis thaliana, while there have been few studies on rice. [...] Read more.

Glutamate receptors (GLR) are widely present in animals and plants, playing essential roles in regulating plant growth, development and stress response. At present, most studies of GLRs in plants are focused on Arabidopsis thaliana, while there have been few studies on rice. In this study, we identified 26 OsGLR genes in rice (Oryza sativa L.). Then, we analyzed the chromosomal location, physical and chemical properties, subcellular location, transmembrane (TM) helices, signal peptides, three-dimensional (3D) structure, cis-acting elements, evolution, chromatin accessibility, population variation, gene-coding sequence haplotype (gcHap) and gene expression under multiple abiotic stress and hormone treatments. The results showed that out of the 26 OsGLR genes, ten genes had the TM domain, signal peptides and similar 3D structures. Most OsGLRs exhibited high tissue specificity in expression under drought stress. In addition, several OsGLR genes were specifically responsive to certain hormones. The favorable gcHap of many OsGLR genes in modern varieties showed obvious differentiation between Xian/indica and Geng/japonica subspecies. This study, for the first time, comprehensively analyzes the OsGLR genes in rice, and provides an important reference for further research on their molecular function. Full article

(This article belongs to the Section Molecular Plant Sciences)

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7 pages, 1338 KiB

Open AccessCase Report

The First Homozygote Mutation c.499G>T (Asp167Tyr) in the RPE65 Gene Encoding Retinoid Isomerohydrolase Causing Retinal Dystrophy

by Mirjana Bjeloš, Ana Ćurić, Benedict Rak, Mladen Bušić and Biljana Kuzmanović Elabjer

Curr. Issues Mol. Biol. 2022, 44(12), 6397-6403; https://doi.org/10.3390/cimb44120436 - 16 Dec 2022

Viewed by 1508

Abstract

RPE65, an abundant membrane-associated protein present in the retinal pigment epithelium (RPE), is a vital retinoid isomerase necessary for regenerating 11-cis-retinaldehyde from all-trans retinol in the visual cycle. In patients with inherited retinal dystrophy (IRD), precise genetic diagnosis is an indispensable [...] Read more.

RPE65, an abundant membrane-associated protein present in the retinal pigment epithelium (RPE), is a vital retinoid isomerase necessary for regenerating 11-cis-retinaldehyde from all-trans retinol in the visual cycle. In patients with inherited retinal dystrophy (IRD), precise genetic diagnosis is an indispensable approach as it is required to establish eligibility for the genetic treatment of RPE65-associated IRDs. This case report aims to report the specific phenotype–genotype correlation of the first patient with a homozygous missense variant RPE65 c.499G>T, p. (Asp167Tyr). We report a case of a 66-year-old male who demonstrated a unique phenotype manifesting less severe functional vision deterioration in childhood and adolescence, and extensive nummular pigment clusters. The underlying causes of the differences in the typical bone spicule and atypical nummular pigment clumping are unknown, but suggest that the variant itself influenced the rate of photoreceptor death. Functional studies are needed to define whether the substitution of aspartate impairs the folding of the tertiary RPE65 structure only and does not lead to the complete abolishment of chromophore production, thus explaining the less severe phenotype in adolescence. Full article

(This article belongs to the Special Issue Complex Molecular Mechanism of Monogenic Diseases)

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12 pages, 2308 KiB

Open AccessArticle

Genome-Wide Identification of Brassica napus PEN1-LIKE Genes and Their Expression Profiling in Insect-Susceptible and Resistant Cultivars

by Lei Sheng, Zengbei Feng, Zhongping Hao and Shumin Hou

Curr. Issues Mol. Biol. 2022, 44(12), 6385-6396; https://doi.org/10.3390/cimb44120435 - 15 Dec 2022

Viewed by 1812

Abstract

Recently, it has been reported that a gene (PEN1) in Arabidopsis thaliana is highly resistant to Plutella xylostella. We screened all the homologous genes of PEN1 in Arabidopsis thaliana and found that the motif of these genes was very conserved. At present, [...] Read more.

Recently, it has been reported that a gene (PEN1) in Arabidopsis thaliana is highly resistant to Plutella xylostella. We screened all the homologous genes of PEN1 in Arabidopsis thaliana and found that the motif of these genes was very conserved. At present, few insect resistance genes have been identified and characterized in Brassica napus. Therefore, we screened all the homologous genes containing this motif in the Brassica napus genome and systematically analyzed the basic information, conserved domain, evolutionary relationship, chromosomal localization and expression analysis of these genes. In this study, 12 PEN1 homologous genes were identified in the Brassica napus genome, which is more than the number in Arabidopsis thaliana. These genes are unevenly distributed on the 12 chromosomes in Brassica napus. Furthermore, all the PEN1 homologous genes contained light responsiveness elements, and most of the genes contained gibberellin-responsive elements, meJA-responsive elements and abscisic-acid-responsive elements. The results will provide a theoretical basis for screening insect resistance genes from the genome of Brassica napus and analyzing the molecular mechanism of insect resistance in Brassica napus. Full article

(This article belongs to the Special Issue Functional Genomics and Comparative Genomics Analysis in Plants)

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17 pages, 3349 KiB

Open AccessArticle

Identification of Candidate Genes Associated with Pulp Color by Transcriptomic Analysis of ‘Huaxiu’ Plum (Prunus salicina Lindl.) during Fruit-Ripening

by Gang Wang, Wenxin Weng, Zhanhui Jia, Jiyu Zhang, Tao Wang and Jiping Xuan

Curr. Issues Mol. Biol. 2022, 44(12), 6368-6384; https://doi.org/10.3390/cimb44120434 - 15 Dec 2022

Cited by 2 | Viewed by 2084

Abstract

The plum (Prunus salicina Lindl.) is one of the traditional and economically important stone fruit trees in China. Anthocyanins are important pigments in plums. However, little is known about the molecular mechanisms underlying anthocyanin accumulation in plum fruits, which has hindered research [...] Read more.

The plum (Prunus salicina Lindl.) is one of the traditional and economically important stone fruit trees in China. Anthocyanins are important pigments in plums. However, little is known about the molecular mechanisms underlying anthocyanin accumulation in plum fruits, which has hindered research on the molecular mechanism of its utilization. Our research shows that the chlorophyll content was gradually decreased and the contents of anthocyanin and flavonoid increased during the coloring process of the pulp in ‘Huaxiu’ plums (P. salicina). Then, the RNA-Seq technique was used to analyze the transcriptome of pulp color changes with three different stages (yellow, orange, and red) in the ‘Huaxiu’ plum (P. salicina). A total of 57,119 unigenes with a mean length of 953 bp were generated, and 61.6% of them were annotated to public databases. The Gene Ontology (GO) database assigned 21,438 unigenes with biological process, cellular components, and molecular function. In addition, 32,146 unigenes were clustered into 25 categories for functional classification by the COG database, and 7595 unigenes were mapped to 128 KEGG pathways by the KEGG pathway database. Of these, 1095 (YS-versus-OS), 4947 (YS-versus-RS), and 3414 (OS-versus-RS) genes were significantly expressed differentially between two coloration stages. The GO and KEGG pathway enrichment analysis revealed that 20 and 1 differentially expressed genes (DEG) are involved in flavonoid biosynthesis and anthocyanin biosynthesis, respectively. Finally, we mainly identified three structural genes as candidate genes. The transcriptome information in this study provide a basis for further studies of pulp colors in plum and contribute to our understanding of the molecular mechanisms underlying anthocyanin biosynthesis in pulp. Full article

(This article belongs to the Special Issue Genetic Sight: Plant Traits during Postharvest)

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22 pages, 2131 KiB

Open AccessReview

Application and Molecular Mechanisms of Extracellular Vesicles Derived from Mesenchymal Stem Cells in Osteoporosis

by Yajing Yang, Lei Yuan, Hong Cao, Jianmin Guo, Xuchang Zhou and Zhipeng Zeng

Curr. Issues Mol. Biol. 2022, 44(12), 6346-6367; https://doi.org/10.3390/cimb44120433 - 15 Dec 2022

Cited by 6 | Viewed by 2599

Abstract

Osteoporosis (OP) is a chronic bone disease characterized by decreased bone mass, destroyed bone microstructure, and increased bone fragility. Accumulative evidence shows that extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) (MSC-EVs), especially exosomes (Exos), exhibit great potential in the treatment of [...] Read more.

Osteoporosis (OP) is a chronic bone disease characterized by decreased bone mass, destroyed bone microstructure, and increased bone fragility. Accumulative evidence shows that extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) (MSC-EVs), especially exosomes (Exos), exhibit great potential in the treatment of OP. However, the research on MSC-EVs in the treatment of OP is still in the initial stage. The potential mechanism has not been fully clarified. Therefore, by reviewing the relevant literature of MSC-EVs and OP in recent years, we summarized the latest application of bone targeted MSC-EVs in the treatment of OP and further elaborated the potential mechanism of MSC-EVs in regulating bone formation, bone resorption, bone angiogenesis, and immune regulation through internal bioactive molecules to alleviate OP, providing a theoretical basis for the related research of MSC-EVs in the treatment of OP. Full article

(This article belongs to the Special Issue Recent Advances in Musculoskeletal Regenerative Medicine)

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13 pages, 990 KiB

Open AccessArticle

TRPA1 Polymorphisms Modify the Hypotensive Responses to Propofol with No Change in Nitrite or Nitrate Levels

by Isabela Borges de Melo, Gustavo H. Oliveira-Paula, Letícia Perticarrara Ferezin, Graziele C. Ferreira, Lucas C. Pinheiro, Jose E. Tanus-Santos, Luis V. Garcia, Riccardo Lacchini and Waynice N. Paula-Garcia

Curr. Issues Mol. Biol. 2022, 44(12), 6333-6345; https://doi.org/10.3390/cimb44120432 - 14 Dec 2022

Viewed by 1823

Abstract

Anesthesia with propofol is frequently associated with hypotension. The TRPA1 gene contributes to the vasodilator effect of propofol. Hypotension is crucial for anesthesiologists because it is deleterious in the perioperative period. We tested whether the TRPA1 gene polymorphisms or haplotypes interfere with the [...] Read more.

Anesthesia with propofol is frequently associated with hypotension. The TRPA1 gene contributes to the vasodilator effect of propofol. Hypotension is crucial for anesthesiologists because it is deleterious in the perioperative period. We tested whether the TRPA1 gene polymorphisms or haplotypes interfere with the hypotensive responses to propofol. PCR-determined genotypes and haplotype frequencies were estimated. Nitrite, nitrates, and NOx levels were measured. Propofol induced a more expressive lowering of the blood pressure (BP) without changing nitrite or nitrate levels in patients carrying CG+GG genotypes for the rs16937976 TRPA1 polymorphism and AG+AA genotypes for the rs13218757 TRPA1 polymorphism. The CGA haplotype presented the most remarkable drop in BP. Heart rate values were not impacted. The present exploratory analysis suggests that TRPA1 genotypes and haplotypes influence the hypotensive responses to propofol. The mechanisms involved are probably other than those related to NO bioavailability. With better genetic knowledge, planning anesthesia with fewer side effects may be possible. Full article

(This article belongs to the Topic Nitrite and Nitric Oxide in Life)

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10 pages, 629 KiB

Open AccessReview

Non-Peptide Agonists and Antagonists of the Prokineticin Receptors

by Roberta Lattanzi and Rossella Miele

Curr. Issues Mol. Biol. 2022, 44(12), 6323-6332; https://doi.org/10.3390/cimb44120431 - 12 Dec 2022

Cited by 11 | Viewed by 2167

Abstract

The prokineticin family comprises a group of secreted peptides that can be classified as chemokines based on their structural features and chemotactic and immunomodulatory functions. Prokineticins (PKs) bind with high affinity to two G protein-coupled receptors (GPCRs). Prokineticin receptor 1 (PKR1) and prokineticin [...] Read more.

The prokineticin family comprises a group of secreted peptides that can be classified as chemokines based on their structural features and chemotactic and immunomodulatory functions. Prokineticins (PKs) bind with high affinity to two G protein-coupled receptors (GPCRs). Prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2) are involved in a variety of physiological functions such as angiogenesis and neurogenesis, hematopoiesis, the control of hypothalamic hormone secretion, the regulation of circadian rhythm and the modulation of complex behaviors such as feeding and drinking. Dysregulation of the system leads to an inflammatory process that is the substrate for many pathological conditions such as cancer, pain, neuroinflammation and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. The use of PKR’s antagonists reduces PK2/PKRs upregulation triggered by various inflammatory processes, suggesting that a pharmacological blockade of PKRs may be a successful strategy to treat inflammatory/neuroinflammatory diseases, at least in rodents. Under certain circumstances, the PK system exhibits protective/neuroprotective effects, so PKR agonists have also been developed to modulate the prokineticin system. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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17 pages, 760 KiB

Open AccessReview

The Use of Salivary Levels of Matrix Metalloproteinases as an Adjuvant Method in the Early Diagnosis of Oral Squamous Cell Carcinoma: A Narrative Literature Review

by Monica Monea and Anca Maria Pop

Curr. Issues Mol. Biol. 2022, 44(12), 6306-6322; https://doi.org/10.3390/cimb44120430 - 12 Dec 2022

Cited by 10 | Viewed by 2830

Abstract

Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with increased mortality, in which the early diagnosis is the most important step in increasing patients’ survival rate. Extensive research has evaluated the role of saliva as a source of diagnostic biomarkers, among which [...] Read more.

Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with increased mortality, in which the early diagnosis is the most important step in increasing patients’ survival rate. Extensive research has evaluated the role of saliva as a source of diagnostic biomarkers, among which matrix metalloproteinases (MMPs) have shown a valuable potential for detecting even early stages of OSCC. The aim of this review was to present recent clinical data regarding the significance of salivary MMPs in the detection of early malignant transformation of the oral mucosa. A narrative review was conducted on articles published in PubMed, Cochrane Library, Web of Science, EBSCO and SciELO databases, using specific terms. Our search revealed that MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-12 and MMP-13 had significantly higher levels in saliva from patients with OSCC compared to controls. However, the strength of evidence is limited, as most information regarding their use as adjuvant diagnostic tools for OSCC comes from studies with a low number of participants, variable methodologies for saliva sampling and diagnostic assays, and insufficient adjustment for all covariates. MMP-1, MMP-3 and MMP-9 were considered the most promising candidates for salivary diagnosis of OSCC, but larger studies are needed in order to validate their clinical application. Full article

(This article belongs to the Special Issue Advances of Molecular Sciences in Dental Diseases Detection and Treatment)

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16 pages, 2597 KiB

Open AccessArticle

Development of Post-Stroke Cognitive and Depressive Disturbances: Associations with Neurohumoral Indices

by Marina Y. Zhanina, Tatyana A. Druzhkova, Alexander A. Yakovlev, Elena E. Vladimirova, Sofia V. Freiman, Natalia N. Eremina, Alla B. Guekht and Natalia V. Gulyaeva

Curr. Issues Mol. Biol. 2022, 44(12), 6290-6305; https://doi.org/10.3390/cimb44120429 - 11 Dec 2022

Cited by 12 | Viewed by 2286

Abstract

Neuropsychiatric complications, in particular cognitive and depressive disorders, are common consequences of ischemic stroke (IS) and complicate the rehabilitation, quality of life, and social adaptation of patients. The hypothalamic–pituitary–adrenal (HPA) system, sympathoadrenal medullary system (SAMS), and inflammatory processes are believed to be involved [...] Read more.

Neuropsychiatric complications, in particular cognitive and depressive disorders, are common consequences of ischemic stroke (IS) and complicate the rehabilitation, quality of life, and social adaptation of patients. The hypothalamic–pituitary–adrenal (HPA) system, sympathoadrenal medullary system (SAMS), and inflammatory processes are believed to be involved in the pathogenesis of these disorders. This study aimed to explore these systems in IS patients, including those with post-stroke cognitive and depressive disorders, within a year after IS. Indices of the HPA axis, inflammatory system, and SAMS were measured in blood serum (cortisol, interleukin-6 (IL-6)), plasma (adrenocorticotropic hormone), and saliva (cortisol, α-amylase). During one year after mild/moderate IS (NIHSS score 5.9 ± 4.3), serum cortisol and salivary α-amylase levels remained elevated in the total cohort. In the group with further cognitive decline, serum and salivary cortisol levels were elevated during the acute period of IS. In the group with poststroke depressive disorder, salivary α-amylase was constantly elevated, while serum IL-6 was minimal during the acute period. The results suggest prolonged hyperactivation of the HPA axis and SAMS after IS. Specifically, post-stroke cognitive impairment was associated with hyperactivation of the HPA axis during the acute IS period, while post-stroke depressive disorder was associated with the chronic inflammatory process and hyperactivation of SAMS during the follow-up period. Full article

(This article belongs to the Special Issue Pathophysiology and Molecular Mechanisms of Acute Stroke)

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10 pages, 1491 KiB

Open AccessArticle

An Exploratory In Vivo Study on the Effect of Annurca Apple Extract on Hair Growth in Mice

by Young In Lee, Seoyoon Ham, Sang Gyu Lee, Inhee Jung, Jangmi Suk, Jinhee Yoo, Su-Young Choi and Ju Hee Lee

Curr. Issues Mol. Biol. 2022, 44(12), 6280-6289; https://doi.org/10.3390/cimb44120428 - 9 Dec 2022

Cited by 4 | Viewed by 4993

Abstract

Hair loss is an important problem affecting the quality of life in modern society. Recent studies show that Annurca apple extract (AAE), enriched in procyanidin B2 and nutraceuticals, promotes hair growth and induces keratin production. In this study, we investigated the effects of [...] Read more.

Hair loss is an important problem affecting the quality of life in modern society. Recent studies show that Annurca apple extract (AAE), enriched in procyanidin B2 and nutraceuticals, promotes hair growth and induces keratin production. In this study, we investigated the effects of AAE by orally administering AAE in six-week-old C57BL/6 mice once a day for 21 d. We observed improvement in hair length, thickness, weight, and density. The gene expression of two growth factors related to hair growth, vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 7 (FGF-7), were measured using the quantitative reverse transcription polymerase chain reaction (qRT-PCR). The gene expression of both VEGFA and FGF-7 increased significantly in the AAE-treated group. Additionally, treatment with AAE suppressed the gene expression of type 1 5α-reductase. Histological analysis showed that protein levels of cytokeratin 5 and 10 were increased in the skin tissues of the AAE-treated group. These results suggest that AAE might be a potential therapeutic natural product that prevents hair loss by promoting the expression of hair growth-related factors. Full article

(This article belongs to the Special Issue Anthocyanins: Bioactivity and Chemistry)

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23 pages, 3117 KiB

Open AccessReview

Microalgal Carotenoids: Therapeutic Application and Latest Approaches to Enhance the Production

by Priyanka Sirohi, Hariom Verma, Sandeep Kumar Singh, Vipin Kumar Singh, Jyoti Pandey, Saksham Khusharia, Dharmendra Kumar, Kaushalendra, Pratibha Teotia and Ajay Kumar

Curr. Issues Mol. Biol. 2022, 44(12), 6257-6279; https://doi.org/10.3390/cimb44120427 - 9 Dec 2022

Cited by 18 | Viewed by 4198

Abstract

Microalgae are microscopic photosynthetic organisms frequently found in fresh and marine water ecosystems. Various microalgal species have been considered a reservoir of diverse health-value products, including vitamins, proteins, lipids, and polysaccharides, and are broadly utilized as food and for the treatment of human [...] Read more.

Microalgae are microscopic photosynthetic organisms frequently found in fresh and marine water ecosystems. Various microalgal species have been considered a reservoir of diverse health-value products, including vitamins, proteins, lipids, and polysaccharides, and are broadly utilized as food and for the treatment of human ailments such as cancer, cardiovascular diseases, allergies, and immunodeficiency. Microalgae-derived carotenoids are the type of accessory pigment that possess light-absorbing potential and play a significant role in metabolic functions. To date, nearly a thousand carotenoids have been reported, but a very less number of microalgae have been used for the commercial production of carotenoids. This review article briefly discussed the carotenoids of microalgal origin and their therapeutic application. In addition, we have briefly compiled the optimization of culture parameters used to enhance microalgal carotenoid production. In addition, the latest biotechnological approaches used to improve the yields of carotenoid has also been discussed. Full article

(This article belongs to the Special Issue Advanced Research on Algae Biology)

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10 pages, 2040 KiB

Open AccessArticle

Phosphodiesterase 5 Inhibitor Potentiates Epigallocatechin 3-O-Gallate-Induced Apoptotic Cell Death via Activation of the cGMP Signaling Pathway in Caco-2 Cells

by Jaehoon Bae, Kwanwoo Lee, Ji-Sun Park, Jinseok Jung, Hirofumi Tachibana, Yoshinori Fujimura, Motofumi Kumazoe, Jae Sung Lim, Young-Chang Cho, Seung-Jae Lee and Su-Jin Park

Curr. Issues Mol. Biol. 2022, 44(12), 6247-6256; https://doi.org/10.3390/cimb44120426 - 9 Dec 2022

Cited by 1 | Viewed by 2478

Abstract

Epigallocatechin 3-O-gallate (EGCG) is a predominant component in green tea with various health benefits. The 67 kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that is overexpressed in various types of cancer; 67LR was identified a cell surface EGCG [...] Read more.

Epigallocatechin 3-O-gallate (EGCG) is a predominant component in green tea with various health benefits. The 67 kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that is overexpressed in various types of cancer; 67LR was identified a cell surface EGCG target that plays a pivotal role in tumor growth, metastasis, and resistance to chemotherapy. However, the plasma concentration of EGCG is limited, and its molecular mechanisms remain unelucidated in colon cancer. In this study, we found that the phosphodiesterase 5 (PDE5) inhibitor, vardenafil (VDN), potentiates EGCG-induced apoptotic cell death in colon cancer cells. The combination of EGCG and VDN induced apoptosis via activation of the endothelial nitric oxide synthase/cyclic guanosine monophosphate/protein kinase Cδ signaling pathway. In conclusion, the PDE5 inhibitor, VDN, may reduce the intracellular PDE5 enzyme activity that potentiates EGCG-induced apoptotic cell death in Caco-2 cells. These results suggest that PDE5 inhibitors can be used to elevate cGMP levels to induce 67LR-mediated, cancer-specific cell death. Therefore, EGCG may be employed as a therapeutic candidate for colon cancer. Full article

(This article belongs to the Special Issue New Sight: Enzymes as Targets for Drug Development)

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18 pages, 4643 KiB

Open AccessArticle

The Study of Nanosized Silicate-Substituted Hydroxyapatites Co-Doped with Sr²⁺ and Zn²⁺ Ions Related to Their Influence on Biological Activities

by Justyna Rewak-Soroczynska, Nicole Nowak, Sara Targonska, Agata Piecuch and Rafal J. Wiglusz

Curr. Issues Mol. Biol. 2022, 44(12), 6229-6246; https://doi.org/10.3390/cimb44120425 - 9 Dec 2022

Cited by 6 | Viewed by 2257

Abstract

Nanosized silicate-substituted hydroxyapatites, characterized by the general formula Ca_9.8−x−nSr_nZn_x(PO₄)_6−y(SiO₄)_y(OH)₂ (where: n = 0.2 [mol%]; x = 0.5–3.5 [mol%]; y = 4–5 [mol%]), co-doped with Zn²⁺ and Sr [...] Read more.

Nanosized silicate-substituted hydroxyapatites, characterized by the general formula Ca_9.8−x−nSr_nZn_x(PO₄)_6−y(SiO₄)_y(OH)₂ (where: n = 0.2 [mol%]; x = 0.5–3.5 [mol%]; y = 4–5 [mol%]), co-doped with Zn²⁺ and Sr²⁺ ions, were synthesized with the help of a microwave-assisted hydrothermal technique. The structural properties were determined using XRD (X-ray powder diffraction) and Fourier-transformed infrared spectroscopy (FT-IR). The morphology, size and shape of biomaterials were detected using scanning electron microscopy techniques (SEM). The reference strains of Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa were used to assess bacterial survivability and the impact on biofilm formation in the presence of nanosilicate-substituted strontium-hydroxyapatites. Safety evaluation was also performed using the standard cytotoxicity test (MTT) and hemolysis assay. Moreover, the mutagenic potential of the materials was assessed (Ames test). The obtained results suggest the dose-dependent antibacterial activity of nanomaterials, especially observed for samples doped with 3.5 mol% Zn²⁺ ions. Moreover, the modification with five SiO₄ groups enhanced the antibacterial effect; however, a rise in the toxicity was observed as well. No harmful activity was detected in the hemolysis assay as well as in the mutagenic assay (Ames test). Full article

(This article belongs to the Special Issue Effects of Nanoparticles on Living Organisms)

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11 pages, 2673 KiB

Open AccessArticle

Therapeutic Potential of 6-Gingerol in Prevention of Colon Cancer Induced by Azoxymethane through the Modulation of Antioxidant Potential and Inflammation

by Abdulaziz A. Aloliqi

Curr. Issues Mol. Biol. 2022, 44(12), 6218-6228; https://doi.org/10.3390/cimb44120424 - 8 Dec 2022

Cited by 6 | Viewed by 1827

Abstract

A polyphenolic component of ginger, 6-gingerol, is widely reported to possess antioxidant, anti-inflammatory and anticancer activities. In the current study, it was aimed to investigate the anticancer effects of 6-gingerol (6-Gin) on azoxymethane (AOM)-induced colon cancer in rats. The results reveal that 6-Gin [...] Read more.

A polyphenolic component of ginger, 6-gingerol, is widely reported to possess antioxidant, anti-inflammatory and anticancer activities. In the current study, it was aimed to investigate the anticancer effects of 6-gingerol (6-Gin) on azoxymethane (AOM)-induced colon cancer in rats. The results reveal that 6-Gin treatment significantly improves the antioxidant status disturbed by AOM intoxication. The 6-Gin treatment animal group showed enhanced activity of catalase (CAT) (46.6 ± 6.4 vs. 23.3 ± 4.3 U/mg protein), superoxide dismutase (SOD) (81.3 ± 7.6 vs. 60.4 ± 3.5 U/mg protein) and glutathione-S-transferase (GST) (90.3 ± 9.4 vs. 53.8 ± 10 mU/mg protein) (p < 0.05) as compared to the disease control group. Furthermore, the results reveal that AOM significantly enhances the inflammatory response and 6-gingerol potentially attenuates this response, estimated by markers, such as tumor necrosis factor-α (TNF-α) (1346 ± 67 vs. 1023 ± 58 pg/g), C-reactive protein (CRP) (1.12 ± 0.08 vs. 0.92 ± 0.7 ng/mL) and interleukin-6 (IL-6) (945 ± 67 vs. 653 ± 33 pg/g). In addition, the lipid peroxidation estimated in terms of malondialdehyde (MDA) provoked by AOM exposure is significantly reduced by 6-gingerol treatment (167 ± 7.5 vs. 128.3 nmol/g). Furthermore, 6-gingerol significantly maintains the colon tissue architecture disturbed by the AOM treatment. Loss of tumor suppressor protein, phosphatase and tensin homolog (PTEN) expression was noticed in the AOM treated group, whereas in the animals treated with 6-gingerol, the positivity of PTEN expression was high. In conclusion, the current findings advocate the health-promoting effects of 6-gingerol on colon cancer, which might be due to its antioxidant and anti-inflammatory potential. Full article

(This article belongs to the Special Issue Food-Derived Bioactive Compounds in Health and Disease)

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13 pages, 2864 KiB

Open AccessArticle

DELAY OF GERMINATION 1, the Master Regulator of Seed Dormancy, Integrates the Regulatory Network of Phytohormones at the Transcriptional Level to Control Seed Dormancy

by Qiujia Li, Xi Chen, Shengnan Zhang, Siyao Shan and Yong Xiang

Curr. Issues Mol. Biol. 2022, 44(12), 6205-6217; https://doi.org/10.3390/cimb44120423 - 8 Dec 2022

Cited by 3 | Viewed by 2244

Abstract

Seed dormancy, an important adaptive trait that governs germination timing, is endogenously controlled by phytohormones and genetic factors. DELAY OF GERMINATION 1 (DOG1) is the vital genetic regulator of dormancy, significantly affecting the expression of numerous ABA and GA metabolic genes. However, whether [...] Read more.

Seed dormancy, an important adaptive trait that governs germination timing, is endogenously controlled by phytohormones and genetic factors. DELAY OF GERMINATION 1 (DOG1) is the vital genetic regulator of dormancy, significantly affecting the expression of numerous ABA and GA metabolic genes. However, whether DOG1 could influence the expression of other phytohormone-related genes is still unknown. Here, we comprehensively investigated all well-documented hormone-related genes which might be affected in dog1–2 dry or imbibed seeds by using whole-transcriptome sequencing (RNA-seq). We found that DOG1 could systematically control the expression of phytohormone-related genes. An evident decrease was observed in the endogenous signal intensity of abscisic acid (ABA) and indole-3-acetic acid (IAA), while a dramatic increase appeared in that of gibberellins (GA), brassinosteroids (BR), and cytokinin (CK) in the dog1–2 background, which may contribute considerably to its dormancy-deficient phenotype. Collectively, our data highlight the role of DOG1 in balancing the expression of phytohormone-related genes and provide inspirational evidence that DOG1 may integrate the phytohormones network to control seed dormancy. Full article

(This article belongs to the Special Issue Stress and Signal Transduction in Plants)

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16 pages, 4637 KiB

Open AccessArticle

Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis

by Zhi-Hui Yi, Shu-Qing Li, Jun-Ya Ke, Yun Wang, Ming-Zhi Zhao, Jing Li, Ming-Qing Li and Zhi-Ling Zhu

Curr. Issues Mol. Biol. 2022, 44(12), 6189-6204; https://doi.org/10.3390/cimb44120422 - 7 Dec 2022

Cited by 11 | Viewed by 3054

Abstract

Iron overload and oxidative stress have been reported to contribute to ferroptosis in endometriotic lesions. However, the possible roles of iron overload on macrophages in endometriosis (EMs) remain unknown. Based on recent reports by single-cell sequencing data of endometriosis, here we found significant [...] Read more.

Iron overload and oxidative stress have been reported to contribute to ferroptosis in endometriotic lesions. However, the possible roles of iron overload on macrophages in endometriosis (EMs) remain unknown. Based on recent reports by single-cell sequencing data of endometriosis, here we found significant upregulations of ferroptosis-associated genes in the macrophage of the endometriotic lesion. Additionally, there was an elevated expression of HMOX1, FTH1, and FTL in macrophages of peritoneal fluid in EMs, as well as iron accumulation in the endometriotic lesions. Notably, cyst fluid significantly up-regulated levels of intracellular iron and ferroptosis in Phorbol-12-myristate-13-acetate (PMA)-stimulated THP-1 cells. Additionally, high iron-induced ferroptosis obviously reduced PMA-stimulated THP-1 cells’ phagocytosis and increased the expression of angiogenic cytokines, such as vascular endothelial growth factor A (VEGFA) and interleukin 8 (IL8). Baicalein, a potential anti-ferroptosis compound, increased GPX4 expression, significantly inhibited ferroptosis, and restored phagocytosis of THP-1 cells in vitro. Collectively, our study reveals that ferroptosis triggered by high iron in cyst fluid promotes the development of EMs by impairing macrophage phagocytosis and producing more angiogenic cytokines (e.g., IL8 and VEGFA). Baicalein displays the potential for the treatment of EMs, especially in patients with high ferroptosis and low phagocytosis of macrophages. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology)

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17 pages, 1049 KiB

Open AccessReview

The Strategies for Treating “Alzheimer’s Disease”: Insulin Signaling May Be a Feasible Target

by Guanying You, Jinyi Yao, Qiong Liu and Nan Li

Curr. Issues Mol. Biol. 2022, 44(12), 6172-6188; https://doi.org/10.3390/cimb44120421 - 7 Dec 2022

Cited by 6 | Viewed by 2578

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by senile plaques formed by amyloid-beta (Aβ) extracellularly and neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau protein intracellularly. Apart from these two features, insulin deficiency and insulin resistance have also been observed in AD brains. [...] Read more.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by senile plaques formed by amyloid-beta (Aβ) extracellularly and neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau protein intracellularly. Apart from these two features, insulin deficiency and insulin resistance have also been observed in AD brains. Thus, AD has also been referred to as type 3 diabetes by some of the scientists in this field. Insulin plays a pivotal role in learning and memory and is involved in regulating tau phosphorylation though the PI3KAkt-GSK3b signaling pathway. Interestingly, recent studies revealed that in AD brains the microglia transformed into a disease-associated microglia (DAM) status in a TREM2-dependent manner to restrain the toxicity of Aβ and propagation of tau. This also correlated with PI3K-Akt signaling through the adaptor of TREM2. Whether insulin has any effect on microglia activation in AD pathology is unclear so far. However, many studies demonstrated that diabetes increased the risk of AD. In this review, we summarize the main strategies for curing AD, including lowering the level of Aβ, suppressing the phosphorylation of tau, the ablation and/or repopulation of microglia, and especially the supply of insulin. We also propose that attention should be given to the influences of insulin on microglia in AD. Full article

(This article belongs to the Special Issue Aging, Age-Related Changes in the Brain and the Progression of Alzheimer’s Disease)

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14 pages, 2421 KiB

Open AccessArticle

Artemisiae argyi Water Extract Alleviates Obesity-Induced Metabolic Disorder

by Youngji Han, Hae-Jin Park, Min-Kyeong Hong, Mi-Rae Shin, Seong-Soo Roh and Eun-Young Kwon

Curr. Issues Mol. Biol. 2022, 44(12), 6158-6171; https://doi.org/10.3390/cimb44120420 - 7 Dec 2022

Cited by 3 | Viewed by 2196

Abstract

Artemisiae argyi is a well-known traditional herbal medicine used in East Asia. Although the antibacterial and anti-inflammatory effects of A. argyi have been reported, its efficacy in improving obesity has not been yet evaluated. In this study, mice were fed a normal diet [...] Read more.

Artemisiae argyi is a well-known traditional herbal medicine used in East Asia. Although the antibacterial and anti-inflammatory effects of A. argyi have been reported, its efficacy in improving obesity has not been yet evaluated. In this study, mice were fed a normal diet (AIN-93), a high-fat diet (HFD, 60% of kcal from fat), and an HFD with 0.1% of A. argyi water extract for 16 weeks. The body weight and body fat in A. argyi-fed mice significantly decreased via upregulation of the mRNA expression of fatty acid oxidation-related genes, with a simultaneous decrease in plasma lipid content and leptin levels. A. argyi water extract also ameliorated hepatic steatosis by restricting lipogenesis via lowering the activities of fatty acid synthase and phosphatidic acid phosphatase. Consistently, hepatic histological analysis indicated that A. argyi water extract decreased hepatic lipid accumulation in accordance with the hepatic H, E and Oil Red O-stained area. Additionally, A. argyi ameliorated the impaired glucose homeostasis by increasing the mRNA expression of AMP-activated kinase and glycolysis-related genes. In conclusion, our results indicate that A. argyi can be used to treat obesity-related metabolic conditions. Full article

(This article belongs to the Topic The Effect of Phytochemicals and Food Bioactive Compounds on the Metabolic Syndrome and Diabetes including Ethnopharmacological Aspects)

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13 pages, 2059 KiB

Open AccessArticle

Gastric Cancer Cell-Derived Exosomal GRP78 Enhances Angiogenesis upon Stimulation of Vascular Endothelial Cells

by Kanako Iha, Akane Sato, Hsin-Yi Tsai, Hikaru Sonoda, Satoshi Watabe, Teruki Yoshimura, Ming-Wei Lin and Etsuro Ito

Curr. Issues Mol. Biol. 2022, 44(12), 6145-6157; https://doi.org/10.3390/cimb44120419 - 6 Dec 2022

Cited by 10 | Viewed by 2374

Abstract

Exosomes containing glucose-regulated protein 78 (GRP78) are involved in cancer malignancy. GRP78 is thought to promote the tumor microenvironment, leading to angiogenesis. No direct evidence for this role has been reported, however, mainly because of difficulties in accurately measuring the GRP78 concentration in [...] Read more.

Exosomes containing glucose-regulated protein 78 (GRP78) are involved in cancer malignancy. GRP78 is thought to promote the tumor microenvironment, leading to angiogenesis. No direct evidence for this role has been reported, however, mainly because of difficulties in accurately measuring the GRP78 concentration in the exosomes. Recently, exosomal GRP78 concentrations were successfully measured using an ultrasensitive ELISA. In the present study, GRP78 concentrations in exosomes collected from gastric cancer AGS cells with overexpression of GRP78 (OE), knockdown of GRP78 (KD), or mock GRP78 (mock) were quantified. These three types of exosomes were then incubated with vascular endothelial cells to examine their effects on endothelial cell angiogenesis. Based on the results of a tube formation assay, GRP78-OE exosomes accelerated angiogenesis compared with GRP78-KD or GRP78-mock exosomes. To investigate the mechanisms underlying this effect, we examined the Ser473 phosphorylation state ratio of AKT, which is involved in the angiogenesis process, and found that AKT phosphorylation was increased by GRP78-OE exosome application to the endothelial cells. An MTT assay showed that GRP78-OE exosome treatment increased the proliferation rate of endothelial cells, and a wound healing assay showed that this treatment increased the migration capacity of the endothelial cells. These findings demonstrated that GRP78-containing exosomes promote the tumor microenvironment and induce angiogenesis. Full article

(This article belongs to the Special Issue Advances in Molecular Pathogenesis Regulation in Cancer)

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13 pages, 1268 KiB

Open AccessArticle

The Role of MRE11 in the IL-6/STAT3 Pathway of Lung Cancer Cells

by Ching-Yuan Wu, Li-Hsin Shu, Hung-Te Liu, Yu-Ching Cheng, Yu-Huei Wu and Yu-Heng Wu

Curr. Issues Mol. Biol. 2022, 44(12), 6132-6144; https://doi.org/10.3390/cimb44120418 - 5 Dec 2022

Cited by 1 | Viewed by 2133

Abstract

MRE11 is a pivotal protein for ATM activation during double-strand DNA break. ATM kinase activations may act as lung cancer biomarkers. The IL-6/STAT3 pathway plays an important role in tumor metastasis, including lung cancer. However, the mechanism between MRE11 and the IL-6/STAT3 pathway [...] Read more.

MRE11 is a pivotal protein for ATM activation during double-strand DNA break. ATM kinase activations may act as lung cancer biomarkers. The IL-6/STAT3 pathway plays an important role in tumor metastasis, including lung cancer. However, the mechanism between MRE11 and the IL-6/STAT3 pathway is still unclear. In this study, we discovered that MRE11 can interact with STAT3 under IL-6 treatment and regulate STAT3 Tyr705 phosphorylation. After the knockdown of MRE11 in lung cancer cells, we discovered that IL-6 or the conditional medium of THP-1 cells can induce the mRNA expression of STAT3 downstream genes, including CCL2, in the control cells, but not in MRE11-knockdown lung cancer cells. Moreover, CCL2 secretion was lower in MRE11-knockdown lung cancer cells than in control cells after treatment with the conditional medium of RAW264.7 cells. In addition, MRE11 deficiency in lung cancer cells decreases their ability to recruit RAW 264.7 cells. Furthermore, MRE11 is a potential target for lung cancer therapy. Full article

(This article belongs to the Special Issue Molecular Research in Lung Cancer)

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15 pages, 2882 KiB

Open AccessArticle

Development and Validation of ScriptTaq COVID PCR: An In-House Multiplex rRT-PCR for Low-Cost Detection

by Dana Abdalghani AbuObead, Tasnim Khalid Alhomsi, Mahmoud Zhra, Bandar Alosaimi, Muaawia Hamza, Maaweya Awadalla, Osama Ezzeldin Abdelhadi, Joud Abdullah Alsharif, Liliane Okdah, Khaled AlKattan, Saeed Al Turki, Hana M. A. Fakhoury and Ahmad Aljada

Curr. Issues Mol. Biol. 2022, 44(12), 6117-6131; https://doi.org/10.3390/cimb44120417 - 5 Dec 2022

Cited by 1 | Viewed by 2653

Abstract

The COVID-19 pandemic necessitated an extensive testing for active SARS-CoV-2 infection. However, securing affordable diagnostic tests is a struggle for low-resource settings. We report herein the development and validation of an in-house multiplex real-time RT-PCR diagnostic test for the detection of active COVID-19 [...] Read more.

The COVID-19 pandemic necessitated an extensive testing for active SARS-CoV-2 infection. However, securing affordable diagnostic tests is a struggle for low-resource settings. We report herein the development and validation of an in-house multiplex real-time RT-PCR diagnostic test for the detection of active COVID-19 infection (ScriptTaq COVID PCR). Furthermore, we describe two methods for RNA extraction using either an in-house silica column or silica-coated magnetic beads to replace commercial RNA extraction kits. Different buffer formulations for silica column and silica-coated magnetic beads were tested and used for RNA isolation. Taq polymerase enzyme and thermostable reverse transcriptase enzyme were purified from bacterial clones. Primers/probes sequences published by the WHO and CDC were used for the qualitative detection of the RNA-dependent RNA polymerase (RdRp) and nucleocapsid (N) genes, respectively. ScriptTaq COVID PCR assay was able to detect up to 100 copies per reaction of the viral RdRP and N genes. The test demonstrated an overall agreement of 95.4%, a positive percent agreement (PPA) of 90.2%, and a negative percent agreement (NPA) of 100.0% when compared with two commercially available kits. ScriptTaq COVID PCR diagnostic test is a specific, sensitive, and low-cost alternative for low-resource settings. Full article

(This article belongs to the Special Issue Tailored Molecular and Pathophysiological Approach to COVID-19: Ambition and Need)

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13 pages, 4817 KiB

Open AccessArticle

The Effects of Co-Culture of Embryonic Stem Cells with Neural Stem Cells on Differentiation

by Ye Rim Kim, Si Won Jang, Jae Ho Han, Ga Rim Na, Hoon Jang and Hyun Woo Choi

Curr. Issues Mol. Biol. 2022, 44(12), 6104-6116; https://doi.org/10.3390/cimb44120416 - 5 Dec 2022

Cited by 1 | Viewed by 2989

Abstract

Researching the technology for in vitro differentiation of embryonic stem cells (ESCs) into neural lineages is very important in developmental biology, regenerative medicine, and cell therapy. Thus, studies on in vitro differentiation of ESCs into neural lineages by co-culture are expected to improve [...] Read more.

Researching the technology for in vitro differentiation of embryonic stem cells (ESCs) into neural lineages is very important in developmental biology, regenerative medicine, and cell therapy. Thus, studies on in vitro differentiation of ESCs into neural lineages by co-culture are expected to improve our understanding of this process. A co-culture system has long been used to study interactions between cell populations, improve culture efficiency, and establish synthetic interactions between populations. In this study, we investigated the effect of a co-culture of ESCs with neural stem cells (NSCs) in two-dimensional (2D) or three-dimensional (3D) culture conditions. Furthermore, we examined the effect of an NSC-derived conditioned medium (CM) on ESC differentiation. OG2-ESCs lost the specific morphology of colonies and Oct4-GFP when co-cultured with NSC. Additionally, real-time PCR analysis showed that ESCs co-cultured with NSCs expressed higher levels of ectoderm markers Pax6 and Sox1 under both co-culture conditions. However, the differentiation efficiency of CM was lower than that of the non-conditioned medium. Collectively, our results show that co-culture with NSCs promotes the differentiation of ESCs into the ectoderm. Full article

(This article belongs to the Special Issue Reproductive Biology and Germ Cell Development)

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11 pages, 637 KiB

Open AccessReview

Autonomic Nervous System Regulation of Epicardial Adipose Tissue: Potential Roles for Regulator of G Protein Signaling-4

by Alexandra M. Carbone, Giselle Del Calvo, Deepika Nagliya, Karina Sharma and Anastasios Lymperopoulos

Curr. Issues Mol. Biol. 2022, 44(12), 6093-6103; https://doi.org/10.3390/cimb44120415 - 5 Dec 2022

Cited by 7 | Viewed by 3771

Abstract

The epicardial adipose tissue (EAT) or epicardial fat is a visceral fat depot in the heart that contains intrinsic adrenergic and cholinergic nerves, through which it interacts with the cardiac sympathetic (adrenergic) and parasympathetic (cholinergic) nervous systems. These EAT nerves represent a significant [...] Read more.

The epicardial adipose tissue (EAT) or epicardial fat is a visceral fat depot in the heart that contains intrinsic adrenergic and cholinergic nerves, through which it interacts with the cardiac sympathetic (adrenergic) and parasympathetic (cholinergic) nervous systems. These EAT nerves represent a significant source of several adipokines and other bioactive molecules, including norepinephrine, epinephrine, and free fatty acids. The production of these molecules is biologically relevant for the heart, since abnormalities in EAT secretion are implicated in the development of pathological conditions, including coronary atherosclerosis, atrial fibrillation, and heart failure. Sympathetic hyperactivity and parasympathetic (cholinergic) derangement are associated with EAT dysfunction, leading to a variety of adverse cardiac conditions, such as heart failure, diastolic dysfunction, atrial fibrillation, etc.; therefore, several studies have focused on exploring the autonomic regulation of EAT as it pertains to heart disease pathogenesis and progression. In addition, Regulator of G protein Signaling (RGS)-4 is a protein with significant regulatory roles in both adrenergic and muscarinic receptor signaling in the heart. In this review, we provide an overview of the autonomic regulation of EAT, with a specific focus on cardiac RGS4 and the potential roles this protein plays in this regulation. Full article

(This article belongs to the Collection Feature Papers in Current Issues in Molecular Biology)

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18 pages, 1139 KiB

Open AccessReview

Exploring and Identifying Candidate Genes and Genomic Regions Related to Economically Important Traits in Hanwoo Cattle

by Masoumeh Naserkheil, Zeinab Manzari, Chang Gwon Dang, Seung Soo Lee and Mi Na Park

Curr. Issues Mol. Biol. 2022, 44(12), 6075-6092; https://doi.org/10.3390/cimb44120414 - 4 Dec 2022

Cited by 3 | Viewed by 2556

Abstract

The purpose of the current review was to explore and summarize different studies concerning the detection and characterization of candidate genes and genomic regions associated with economically important traits in Hanwoo beef cattle. Hanwoo cattle, the indigenous premium beef cattle of Korea, were [...] Read more.

The purpose of the current review was to explore and summarize different studies concerning the detection and characterization of candidate genes and genomic regions associated with economically important traits in Hanwoo beef cattle. Hanwoo cattle, the indigenous premium beef cattle of Korea, were introduced for their marbled fat, tenderness, characteristic flavor, and juiciness. To date, there has been a strong emphasis on the genetic improvement of meat quality and yields, such as backfat thickness (BFT), marbling score (MS), carcass weight (CW), eye muscle area (EMA), and yearling weight (YW), as major selection criteria in Hanwoo breeding programs. Hence, an understanding of the genetics controlling these traits along with precise knowledge of the biological mechanisms underlying the traits would increase the ability of the industry to improve cattle to better meet consumer demands. With the development of high-throughput genotyping, genomewide association studies (GWAS) have allowed the detection of chromosomal regions and candidate genes linked to phenotypes of interest. This is an effective and useful tool for accelerating the efficiency of animal breeding and selection. The GWAS results obtained from the literature review showed that most positional genes associated with carcass and growth traits in Hanwoo are located on chromosomes 6 and 14, among which LCORL, NCAPG, PPARGC1A, ABCG2, FAM110B, FABP4, DGAT1, PLAG1, and TOX are well known. In conclusion, this review study attempted to provide comprehensive information on the identified candidate genes associated with the studied traits and genes enriched in the functional terms and pathways that could serve as a valuable resource for future research in Hanwoo breeding programs. Full article

(This article belongs to the Collection Feature Papers in Current Issues in Molecular Biology)

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16 pages, 3159 KiB

Open AccessArticle

MicroRNA-10 Family Promotes the Epithelial-to-Mesenchymal Transition in Renal Fibrosis by the PTEN/Akt Pathway

by Chaokun Wang, Yichen Shuai, Chuan Zhao, Fengrui Yang, Weilian Su, Zhifen Ning and Guoxia Li

Curr. Issues Mol. Biol. 2022, 44(12), 6059-6074; https://doi.org/10.3390/cimb44120413 - 2 Dec 2022

Cited by 3 | Viewed by 1890

Abstract

Renal fibrosis (RF) is a common reason for renal failure, and epithelial-mesenchymal transition (EMT) is a vital mechanism that promotes the development of RF. It is known that microRNA-10 (miR-10) plays an important role in cancer EMT; however, whether it takes part in [...] Read more.

Renal fibrosis (RF) is a common reason for renal failure, and epithelial-mesenchymal transition (EMT) is a vital mechanism that promotes the development of RF. It is known that microRNA-10 (miR-10) plays an important role in cancer EMT; however, whether it takes part in the EMT process of RF remains unclear. Therefore, we established an in vivo model of unilateral ureteral obstruction (UUO), and an in vitro model using TGF-β1, to investigate whether and how miR-10a and miR-10b take part in the EMT of RF. In addition, the combinatorial effects of miR-10a and miR-10b were assessed. We discovered that miR-10a and miR-10b are overexpressed in UUO mice, and miR-10a, miR-10b, and miRs-10a/10b knockout attenuated RF and EMT in UUO-treated mouse kidneys. Moreover, miR-10a and miR-10b overexpression combinatorially promoted RF and EMT in TGF-β1-treated HK-2 cells. Inhibiting miR-10a and miR-10b attenuated RF and EMT induced by TGF-β1. Mechanistically, miR-10a and miR-10b suppressed PTEN expression by binding to its mRNA3′-UTR and promoting the Akt pathway. Moreover, PTEN overexpression reduced miR-10a and miR-10b effects on Akt phosphorylation (p-Akt), RF, and EMT in HK-2 cells treated with TGF-β1. Taken together, miR-10a and miR-10b act combinatorially to negatively regulate PTEN, thereby activating the Akt pathway and promoting the EMT process, which exacerbates RF progression. Full article

(This article belongs to the Special Issue Recent Development of Bioinformatics Tools of RNA)

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13 pages, 4121 KiB

Open AccessArticle

Regulatory Effects and Mechanism of Action of Green Tea Polyphenols on Osteogenesis and Adipogenesis in Human Adipose Tissue-Derived Stem Cells

by Weiguo Lao, Yi Zhao, Yi Tan, Michael Johnson, Yan Li, Linda Xiao, Jing Cheng, Yiguang Lin and Xianqin Qu

Curr. Issues Mol. Biol. 2022, 44(12), 6046-6058; https://doi.org/10.3390/cimb44120412 - 30 Nov 2022

Cited by 3 | Viewed by 2536

Abstract

We previously showed that green tea polyphenols (GTPs) exert antiadipogenic effects on preadipocyte proliferation. Here, we investigated the regulatory effects of GTPs on osteogenesis and adipogenesis during early differentiation of human adipose tissue-derived stem cells (hADSC). Adipogenesis of hADSCs was determined by oil-red-O [...] Read more.

We previously showed that green tea polyphenols (GTPs) exert antiadipogenic effects on preadipocyte proliferation. Here, we investigated the regulatory effects of GTPs on osteogenesis and adipogenesis during early differentiation of human adipose tissue-derived stem cells (hADSC). Adipogenesis of hADSCs was determined by oil-red-O staining and triglycerides synthesis measurement. Osteoporosis of hADSC was measured using alkaline phosphatase assays and intracellular calcium levels. Immunofluorescence staining and qRT-PCR were used to detect PPARγ-CEBPA regulated adipogenic pathway regulated by PPAR-CEBPA and the osteogenic pathway mediated by RUNX2-BMP2. We found that GTPs treatment significantly decreased lipid accumulation and cellular triglyceride synthesis in mature adipocytes and attenuated pioglitazone-induced adipogenesis in a dose-dependent manner. GTPs downregulated protein and mRNA expression of Pparγ and attenuated pioglitazone-stimulated-Cebpa expression. GTPs treatment significantly enhanced hADSCs differentiation into osteoblasts compared to control and pioglitazone-treated cells. GTPs upregulated RunX2 and Bmp2 proteins and mRNA expression compared to control and significantly attenuated decreased RunX2 and Bmp2 mRNA expression by pioglitazone. In conclusion, our data demonstrates GTPs possesses great ability to facilitate osteogenesis and simultaneously inhibits hADSC differentiation into adipogenic lineage by upregulating the RUNX2-BMP2 mediated osteogenic pathway and suppressing PPARγ-induced signaling of adipogenesis. These findings highlight GTPs’ potential to combat osteoporosis associated with obesity. Full article

(This article belongs to the Special Issue Polyphenols as Cellular Metabolic Regulators)

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18 pages, 2859 KiB

Open AccessArticle

Human Blood Extracellular Vesicles Activate Transcription of NF-kB-Dependent Genes in A549 Lung Adenocarcinoma Cells

by Yulya I. Savinovskaya, Anna A. Nushtaeva, Anna V. Savelyeva, Vitaliy V. Morozov, Elena I. Ryabchikova, Elena V. Kuligina, Vladimir A. Richter and Dmitriy V. Semenov

Curr. Issues Mol. Biol. 2022, 44(12), 6028-6045; https://doi.org/10.3390/cimb44120411 - 30 Nov 2022

Viewed by 2069

Abstract

Extracellular vesicles (EVs) produced by various cell types are heterogeneous in size and composition. Changes in the RNA sets of EVs in biological fluids are considered the basis for the development of new approaches to minimally invasive diagnostics and the therapy of human [...] Read more.

Extracellular vesicles (EVs) produced by various cell types are heterogeneous in size and composition. Changes in the RNA sets of EVs in biological fluids are considered the basis for the development of new approaches to minimally invasive diagnostics and the therapy of human diseases. In this study, EVs were obtained from the blood of healthy donors by centrifugation, followed by ultracentrifugation. It was shown that EVs consist of several populations including small exosome-like vesicles and larger microvesicle-like particles. The composition of EVs’ RNAs was determined. A549 lung adenocarcinoma cells were incubated with EV and the NGS analysis of differentially expressed genes was performed. During the incubation of A549 cells with EVs, the levels of mRNA encoding components for the NF-kB signaling pathway increased, as well as the expression of genes controlled by the NF-kB transcription factor. Overall, our results suggest that components of EVs trigger the NF-kB signaling cascade in A549 cells, leading to the transcription of genes including cytokines, adhesion molecules, cell cycle regulators, and cell survival factors. Our data provide insight into the interaction between blood EVs and human cells and can be used for designing new tools for the diagnosis and treatment of human diseases. Full article

(This article belongs to the Special Issue Next-Generation Sequencing (NGS) Technique and Personalized Medicine)

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13 pages, 2398 KiB

Open AccessArticle

Reduced Tyrosine and Serine-632 Phosphorylation of Insulin Receptor Substrate-1 in the Gastrocnemius Muscle of Obese Zucker Rat

by Mohammad Shamsul Ola

Curr. Issues Mol. Biol. 2022, 44(12), 6015-6027; https://doi.org/10.3390/cimb44120410 - 29 Nov 2022

Cited by 1 | Viewed by 1630

Abstract

Obesity has become a serious health problem in the world, with increased morbidity, mortality, and financial burden on patients and health-care providers. The skeletal muscle is the most extensive tissue, severely affected by a sedentary lifestyle, which leads to obesity and type 2 [...] Read more.

Obesity has become a serious health problem in the world, with increased morbidity, mortality, and financial burden on patients and health-care providers. The skeletal muscle is the most extensive tissue, severely affected by a sedentary lifestyle, which leads to obesity and type 2 diabetes. Obesity disrupts insulin signaling in the skeletal muscle, resulting in decreased glucose disposal, a condition known as insulin resistance. Although there is a large body of evidence on obesity-induced insulin resistance in various skeletal muscles, the molecular mechanism of insulin resistance due to a disruption in insulin receptor signaling, specifically in the gastrocnemius skeletal muscle of obese Zucker rats (OZRs), is not fully understood. This study subjected OZRs to a glucose tolerance test (GTT) to analyze insulin sensitivity. In addition, immunoprecipitation and immunoblotting techniques were used to determine the expression and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and insulin receptor-β (IRβ), and the activation of serine-632-IRS-1 phosphorylation in the gastrocnemius muscle of Zucker rats. The results show that the GTT in the OZRs was impaired. There was a significant decrease in IRS-1 levels, but no change was observed in IRβ in the gastrocnemius muscle of OZRs, compared to Zucker leans. Obese rats had a higher ratio of tyrosine phosphorylation of IRS-1 and IRβ than lean rats. In obese rats, however, insulin was unable to induce tyrosine phosphorylation. Moreover, insulin increased the phosphorylation of serine 632-IRS-1 in the gastrocnemius muscle of lean rats. However, obese rats had a low basal level of serine-632-IRS-1 and insulin only mildly increased serine phosphorylation in obese rats, compared to those without insulin. Thus, we addressed the altered steps of the insulin receptor signal transduction in the gastrocnemius muscle of OZRs. These findings may contribute to a better understanding of human obesity and type 2 diabetes. Full article

(This article belongs to the Collection Feature Papers in Current Issues in Molecular Biology)

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Curr. Issues Mol. Biol., Volume 44, Issue 12 (December 2022) – 44 articles

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