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Curr. Issues Mol. Biol., Volume 45, Issue 6 (June 2023) – 46 articles

Cover Story (view full-size image): Damage to the spinal cord is a devastating process that leads to the failure of motor, sensory and autonomic functions and for which, unfortunately, there is currently no effective treatment. One of the most promising approaches in the treatment of spinal cord injury is cell therapy. Mesenchymal stromal cells (MSCs) stand out amongst a large number of investigated cells. MSCs participate in the regeneration of damaged tissue in two main ways, directly with their ability to differentiate, so they can replace damaged cells in the tissue, or indirectly using the paracrine effect. In this case, MSCs serve as a source of bioactive molecules and growth factors, as well as extracellular vesicles, so they exhibit their immunomodulating, angiogenic, and neuroprotective effects at the site of injury. View this paper
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17 pages, 1372 KiB  
Review
Genomic, Epigenomic, Transcriptomic, Proteomic and Metabolomic Approaches in Atopic Dermatitis
by Dalia Bratu, Daniel Boda and Constantin Caruntu
Curr. Issues Mol. Biol. 2023, 45(6), 5215-5231; https://doi.org/10.3390/cimb45060331 - 20 Jun 2023
Cited by 2 | Viewed by 2119
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence in the developed countries. It is associated with atopic and non-atopic diseases, and its close correlation with atopic comorbidities has been genetically demonstrated. One of the main roles of genetic [...] Read more.
Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence in the developed countries. It is associated with atopic and non-atopic diseases, and its close correlation with atopic comorbidities has been genetically demonstrated. One of the main roles of genetic studies is to comprehend the defects of the cutaneous barrier due to filaggrin deficit and epidermal spongiosis. Recently, epigenetic studies started to analyze the influence of the environmental factors on gene expression. The epigenome is considered to be a superior second code that controls the genome, which includes alterations of the chromatin. The epigenetic changes do not alter the genetic code, however, changes in the chromatin structure could activate or inhibit the transcription process of certain genes and consequently, the translation process of the new mRNA into a polypeptide chain. In-depth analysis of the transcriptomic, metabolomic and proteomic studies allow to unravel detailed mechanisms that cause AD. The extracellular space and lipid metabolism are associated with AD that is independent of the filaggrin expression. On the other hand, around 45 proteins are considered as the principal components in the atopic skin. Moreover, genetic studies based on the disrupted cutaneous barrier can lead to the development of new treatments targeting the cutaneous barrier or cutaneous inflammation. Unfortunately, at present, there are no target therapies that focus on the epigenetic process of AD. However, in the future, miR-143 could be an important objective for new therapies, as it targets the miR-335:SOX axis, thereby restoring the miR-335 expression, and repairing the cutaneous barrier defects. Full article
(This article belongs to the Special Issue Molecular Research in Chronic Dermatoses)
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17 pages, 2794 KiB  
Review
Heme Interactions as Regulators of the Alternative Pathway Complement Responses and Implications for Heme-Associated Pathologies
by Stefanos A. Tsiftsoglou
Curr. Issues Mol. Biol. 2023, 45(6), 5198-5214; https://doi.org/10.3390/cimb45060330 - 16 Jun 2023
Viewed by 1767
Abstract
Heme (Fe2+-protoporphyrin IX) is a pigment of life, and as a prosthetic group in several hemoproteins, it contributes to diverse critical cellular processes. While its intracellular levels are tightly regulated by networks of heme-binding proteins (HeBPs), labile heme can be hazardous [...] Read more.
Heme (Fe2+-protoporphyrin IX) is a pigment of life, and as a prosthetic group in several hemoproteins, it contributes to diverse critical cellular processes. While its intracellular levels are tightly regulated by networks of heme-binding proteins (HeBPs), labile heme can be hazardous through oxidative processes. In blood plasma, heme is scavenged by hemopexin (HPX), albumin and several other proteins, while it also interacts directly with complement components C1q, C3 and factor I. These direct interactions block the classical pathway (CP) and distort the alternative pathway (AP). Errors or flaws in heme metabolism, causing uncontrolled intracellular oxidative stress, can lead to several severe hematological disorders. Direct interactions of extracellular heme with alternative pathway complement components (APCCs) may be implicated molecularly in diverse conditions at sites of abnormal cell damage and vascular injury. In such disorders, a deregulated AP could be associated with the heme-mediated disruption of the physiological heparan sulphate–CFH coat of stressed cells and the induction of local hemostatic responses. Within this conceptual frame, a computational evaluation of HBMs (heme-binding motifs) aimed to determine how heme interacts with APCCs and whether these interactions are affected by genetic variation within putative HBMs. Combined computational analysis and database mining identified putative HBMs in all of the 16 APCCs examined, with 10 exhibiting disease-associated genetic (SNPs) and/or epigenetic variation (PTMs). Overall, this article indicates that among the pleiotropic roles of heme reviewed, the interactions of heme with APCCs could induce differential AP-mediated hemostasis-driven pathologies in certain individuals. Full article
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18 pages, 826 KiB  
Review
The Role of Mesenchymal Stromal Cells and Their Products in the Treatment of Injured Spinal Cords
by Lucia Slovinska and Denisa Harvanova
Curr. Issues Mol. Biol. 2023, 45(6), 5180-5197; https://doi.org/10.3390/cimb45060329 - 16 Jun 2023
Cited by 1 | Viewed by 2057
Abstract
Spinal cord injury (SCI) is a destructive condition that results in lasting neurological damage resulting in disruption of the connection between the central nervous system and the rest of the body. Currently, there are several approaches in the treatment of a damaged spinal [...] Read more.
Spinal cord injury (SCI) is a destructive condition that results in lasting neurological damage resulting in disruption of the connection between the central nervous system and the rest of the body. Currently, there are several approaches in the treatment of a damaged spinal cord; however, none of the methods allow the patient to return to the original full-featured state of life before the injury. Cell transplantation therapies show great potential in the treatment of damaged spinal cords. The most examined type of cells used in SCI research are mesenchymal stromal cells (MSCs). These cells are at the center of interest of scientists because of their unique properties. MSCs regenerate the injured tissue in two ways: (i) they are able to differentiate into some types of cells and so can replace the cells of injured tissue and (ii) they regenerate tissue through their powerful known paracrine effect. This review presents information about SCI and the treatments usually used, aiming at cell therapy using MSCs and their products, among which active biomolecules and extracellular vesicles predominate. Full article
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16 pages, 3360 KiB  
Article
Cymbopogon citratus Essential Oil: Extraction, GC–MS, Phytochemical Analysis, Antioxidant Activity, and In Silico Molecular Docking for Protein Targets Related to CNS
by Ana G. Cortes-Torres, Guiee N. López-Castillo, Josefina L. Marín-Torres, Roberto Portillo-Reyes, Felix Luna, Beatriz E. Baca, Jesús Sandoval-Ramírez and Alan Carrasco-Carballo
Curr. Issues Mol. Biol. 2023, 45(6), 5164-5179; https://doi.org/10.3390/cimb45060328 - 16 Jun 2023
Cited by 2 | Viewed by 2494
Abstract
This study analyzed the chemical composition of Cymbopogon citratus essential oil from Puebla, México, assessed its antioxidant activity, and evaluated in silico protein–compound interactions related to central nervous system (CNS) physiology. GC–MS analysis identified myrcene (8.76%), Z-geranial (27.58%), and E-geranial (38.62%) as the [...] Read more.
This study analyzed the chemical composition of Cymbopogon citratus essential oil from Puebla, México, assessed its antioxidant activity, and evaluated in silico protein–compound interactions related to central nervous system (CNS) physiology. GC–MS analysis identified myrcene (8.76%), Z-geranial (27.58%), and E-geranial (38.62%) as the main components, with 45 other compounds present, which depends on the region and growing conditions. DPPH and Folin–Ciocalteu assays using the leaves extract show a promising antioxidant effect (EC50 = 48.5 µL EO/mL), reducing reactive oxygen species. The bioinformatic tool SwissTargetPrediction (STP) shows 10 proteins as potential targets associated with CNS physiology. Moreover, protein–protein interaction diagrams suggest that muscarinic and dopamine receptors are related to each other through a third party. Molecular docking reveals that Z-geranial has higher binding energy than M1 commercial blocker and blocks M2, but not M4 muscarinic acetylcholine receptors, whereas β-pinene and myrcene block M1, M2, and M4 receptors. These actions may positively affect cardiovascular activity, memory, Alzheimer’s disease, and schizophrenia. This study highlights the significance of understanding natural product interactions with physiological systems to uncover potential therapeutic agents and advanced knowledge on their benefits for human health. Full article
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19 pages, 3483 KiB  
Article
Study of The Molecular Nature of Congenital Cataracts in Patients from The Volga–Ural Region
by Irina Khidiyatova, Indira Khidiyatova, Rena Zinchenko, Andrey Marakhonov, Alexandra Karunas, Svetlana Avkhadeeva, Marat Aznzbaev and Elza Khusnutdinova
Curr. Issues Mol. Biol. 2023, 45(6), 5145-5163; https://doi.org/10.3390/cimb45060327 - 15 Jun 2023
Viewed by 1242
Abstract
Hereditary cataracts are characterized by significant clinical and genetic heterogeneity, which can pose challenges for early DNA diagnosis. To comprehensively address this problem, it is essential to investigate the epidemiology of the disease, perform population studies to determine the spectrum and frequencies of [...] Read more.
Hereditary cataracts are characterized by significant clinical and genetic heterogeneity, which can pose challenges for early DNA diagnosis. To comprehensively address this problem, it is essential to investigate the epidemiology of the disease, perform population studies to determine the spectrum and frequencies of mutations in the responsible genes, and examine clinical and genetic correlations. Based on modern concepts, non-syndromic hereditary cataracts are predominantly caused by genetic disease forms associated with mutations in crystallin and connexin genes. Therefore, a comprehensive approach to studying hereditary cataracts is necessary for early diagnosis and improved treatment outcomes. The crystallin (CRYAA, CRYAB, CRYGC, CRYGD, and CRYBA1) and connexin (GJA8, GJA3) genes were analyzed in 45 unrelated families from the Volga–Ural Region (VUR) with hereditary congenital cataracts. Pathogenic and probably pathogenic nucleotide variants were identified in ten unrelated families, nine of which had cataracts in an autosomal dominant pattern of inheritance. Two previously undescribed likely pathogenic missense variants were identified in the CRYAA gene: c.253C > T (p.L85F) in one family and c.291C > G (p.H97Q) in two families. The known mutation c.272_274delGAG (p.G91del) was found in the CRYBA1 gene in one family, while no pathogenic variants were found in the CRYAB, CRYGC, or CRYGD genes in the examined patients. In the GJA8 gene, the known mutation c.68G > C (p.R23T) was found in two families, and previously undescribed variants were identified in two other families: a c.133_142del deletion (p.W45Sfs*72) and a missense variant, c.179G > A (p.G60D). In one patient with a recessive form of cataract, two compound-heterozygous variants were identified—a previously undescribed likely pathogenic missense variant, c.143A > G (p.E48G), and a known variant with uncertain pathogenetic significance, c.741T > G (p.I24M). Additionally, a previously undescribed deletion, c.del1126_1139 (p.D376Qfs*69), was identified in the GJA3 gene in one family. In all families where mutations were identified, cataracts were diagnosed either immediately after birth or during the first year of life. The clinical presentation of the cataracts varied depending on the type of lens opacity, resulting in various clinical forms. This information emphasizes the importance of early diagnosis and genetic testing for hereditary congenital cataracts to guide appropriate management and improve outcomes. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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13 pages, 3266 KiB  
Article
Bactericidal Mechanisms of Chlorine Dioxide against Beta-Hemolytic Streptococcus CMCC 32210
by Huan Liu, Jingju Zhang, Jing Liu, Guangjie Cao, Fei Xu and Xiubo Li
Curr. Issues Mol. Biol. 2023, 45(6), 5132-5144; https://doi.org/10.3390/cimb45060326 - 13 Jun 2023
Viewed by 1909
Abstract
Chlorine dioxide is a globally recognized green and efficient disinfectant. This study aims to investigate the bactericidal mechanism of chlorine dioxide using beta-hemolytic Streptococcus (BHS) CMCC 32210 as a representative strain. BHS was exposed to chlorine dioxide, the minimum bactericidal concentration (MBC) values [...] Read more.
Chlorine dioxide is a globally recognized green and efficient disinfectant. This study aims to investigate the bactericidal mechanism of chlorine dioxide using beta-hemolytic Streptococcus (BHS) CMCC 32210 as a representative strain. BHS was exposed to chlorine dioxide, the minimum bactericidal concentration (MBC) values of chlorine dioxide against BHS were determined by the checkerboard method in preparation for subsequent tests. Cell morphology was observed using electron microscopy. Protein content leakage, adenosine triphosphatase (ATPase) activity, and lipid peroxidation were determined by kits, and DNA damage was determined using agar gel electrophoresis. The concentration of chlorine dioxide during disinfection showed a linear relationship with the concentration of BHS. Scanning electron microscopy (SEM) results showed that chlorine dioxide caused significant damage to the cell walls of BHS at a concentration of 50 mg/L, but had no significant effect on Streptococcus exposed to different exposure times. Furthermore, the extracellular protein concentration increased with increasing chlorine dioxide concentration, while the total protein content remained unchanged. The activities of Na+/K+-ATPase and Ca2+/Mg2+-ATPase decreased with increasing chlorine dioxide concentration. Chlorine dioxide treatment led to significant lipid peroxidation and DNA degradation in BHS. Leakage of intracellular components indicated that chlorine dioxide damaged the cell membrane of BHS. Chlorine dioxide exposure resulted in oxidative damage to lipids and proteins, which negatively impacted the cell wall and membrane of Streptococcus. This caused increased permeability and inactivation of key enzymes (Na+/K+-ATPase and Ca2+/Mg2+-ATPase) involved in respiratory metabolism, ultimately leading to DNA degradation and bacterial death due to either content leakage or metabolic failure. Full article
(This article belongs to the Section Molecular Microbiology)
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14 pages, 1570 KiB  
Review
Repurposing of the Drug Tezosentan for Cancer Therapy
by Eduarda Ribeiro and Nuno Vale
Curr. Issues Mol. Biol. 2023, 45(6), 5118-5131; https://doi.org/10.3390/cimb45060325 - 11 Jun 2023
Cited by 1 | Viewed by 1869
Abstract
Tezosentan is a vasodilator drug that was originally developed to treat pulmonary arterial hypertension. It acts by inhibiting endothelin (ET) receptors, which are overexpressed in many types of cancer cells. Endothelin-1 (ET1) is a substance produced by the body that causes blood vessels [...] Read more.
Tezosentan is a vasodilator drug that was originally developed to treat pulmonary arterial hypertension. It acts by inhibiting endothelin (ET) receptors, which are overexpressed in many types of cancer cells. Endothelin-1 (ET1) is a substance produced by the body that causes blood vessels to narrow. Tezosentan has affinity for both ETA and ETB receptors. By blocking the effects of ET1, tezosentan can help to dilate blood vessels, improve the blood flow, and reduce the workload on the heart. Tezosentan has been found to have anticancer properties due to its ability to target the ET receptors, which are involved in promoting cellular processes such as proliferation, survival, neovascularization, immune cell response, and drug resistance. This review intends to demonstrate the potential of this drug in the field of oncology. Drug repurposing can be an excellent way to improve the known profiles of first-line drugs and to solve several resistance problems of these same antineoplastic drugs. Full article
(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)
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19 pages, 378 KiB  
Review
Antioxidant Intake and Biomarkers of Asthma in Relation to Smoking Status—A Review
by Naser A. Alsharairi
Curr. Issues Mol. Biol. 2023, 45(6), 5099-5117; https://doi.org/10.3390/cimb45060324 - 10 Jun 2023
Cited by 2 | Viewed by 1777
Abstract
Asthma is considered a chronic inflammatory disorder associated with airway hyperresponsiveness (AHR). Increased oxidative stress (OS) is a clinical feature of asthma, which promotes the inflammatory responses in bronchial/airway epithelial cells. Smokers and nonsmokers with asthma have been shown to have increases in [...] Read more.
Asthma is considered a chronic inflammatory disorder associated with airway hyperresponsiveness (AHR). Increased oxidative stress (OS) is a clinical feature of asthma, which promotes the inflammatory responses in bronchial/airway epithelial cells. Smokers and nonsmokers with asthma have been shown to have increases in several OS and inflammatory biomarkers. However, studies suggest significant differences in OS and inflammation biomarkers between smokers and nonsmokers. A few studies suggest associations between antioxidant intake from diet/supplements and asthma in patients with different smoking status. Evidence is lacking on the protective role of antioxidant vitamin and/or mineral consumption against asthma by smoking status with respect to inflammation and OS biomarkers. Therefore, the aim of this review is to highlight current knowledge regarding the relations between antioxidant intake, asthma, and its associated biomarkers, according to smoking status. This paper can be used to guide future research directions towards the health consequences of antioxidant intake in smoking and nonsmoking asthmatics. Full article
15 pages, 1806 KiB  
Article
Potential Diagnostic Value of Salivary Tumor Markers in Breast, Lung and Ovarian Cancer: A Preliminary Study
by Lyudmila V. Bel’skaya, Elena A. Sarf, Alexandra I. Loginova, Dmitry M. Vyushkov and En Djun Choi
Curr. Issues Mol. Biol. 2023, 45(6), 5084-5098; https://doi.org/10.3390/cimb45060323 - 10 Jun 2023
Cited by 2 | Viewed by 2123
Abstract
The aim of the study was to determine the content of tumor markers for breast, lung and ovarian cancer in saliva, as well as for benign diseases of the corresponding organs and in the control group, and to evaluate their diagnostic significance. Strictly [...] Read more.
The aim of the study was to determine the content of tumor markers for breast, lung and ovarian cancer in saliva, as well as for benign diseases of the corresponding organs and in the control group, and to evaluate their diagnostic significance. Strictly before the start of treatment, saliva samples were obtained and the concentrations of tumor markers (AFP, NSE, HE4, CA15-3, CA72-4, CA125 and CEA) were determined using an enzyme immunoassay (ELISA). CA125 and HE4 were simultaneously determined to be in the blood serum of patients with ovarian cancer. The concentrations of salivary CEA, NSE, CA15-3, CA72-4 and CA125 of the control group were significantly lower than in oncological diseases; however, these tumor markers also increased in saliva with benign diseases. The content of tumor markers depends on the stage of cancer, and the presence of lymph node metastasis; however, the identified patterns are statistically unreliable. The determination of HE4 and AFP in saliva was not informative. In general, the area of potential use of tumor markers in saliva is extremely narrow. Thus, CEA may be diagnostic for breast and lung cancer, but not for ovarian cancer. CA72-4 is most informative for ovarian mucinous carcinoma. None of the markers showed significant differences between malignant and non-malignant pathologies. Full article
(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)
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13 pages, 2969 KiB  
Article
Hair Growth Effect of DN106212 in C57BL/6 Mouse and Its Network Pharmacological Mechanism of Action
by Ji Yun Baek, Byoung Ha Kim, Dong-Wook Kim, Won-Yung Lee, Chang Eop Kim, Hyun-Young Kim, Jaesung Pyo, Eun-Seok Park and Ki Sung Kang
Curr. Issues Mol. Biol. 2023, 45(6), 5071-5083; https://doi.org/10.3390/cimb45060322 - 9 Jun 2023
Cited by 2 | Viewed by 3112
Abstract
Centipeda minima (CMX) has been widely investigated using network pharmacology and clinical studies for its effects on hair growth via the JAK/STAT signaling pathway. Human hair follicle papilla cells exhibit hair regrowth through the expression of Wnt signaling-related proteins. However, the mechanism of [...] Read more.
Centipeda minima (CMX) has been widely investigated using network pharmacology and clinical studies for its effects on hair growth via the JAK/STAT signaling pathway. Human hair follicle papilla cells exhibit hair regrowth through the expression of Wnt signaling-related proteins. However, the mechanism of action of CMX in animals has not been elucidated fully. This study examined the effect of induced hair loss and its side-effects on the skin, and observed the mechanism of action of an alcoholic extract of CMX (DN106212) on C57BL/6 mice. Our results showed that DN106212 was more effective in promoting hair growth than dimethyl sulfoxide in the negative control and tofacitinib (TF) in the positive control when mice were treated with DN106212 for 16 days. We confirmed that DN106212 promotes the formation of mature hair follicles through hematoxylin and eosin staining. We also found that the expression of vascular endothelial growth factor (Vegfa), insulin-like growth factor 1 (Igf1), and transforming growth factor beta 1 (Tgfb1) is related to hair growth using PCR. DN106212-treated mice had significantly higher expression of Vegfa and Igf1 than TF-treated ones, and inhibiting the expression of Tgfb1 had similar effects as TF treatment. In conclusion, we propose that DN106212 increases the expression of hair growth factors, promotes the development of hair follicles, and promotes hair growth. Although additional experiments are needed, DN106212 may serve as an experimental basis for research on natural hair growth-promoting agents. Full article
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19 pages, 4390 KiB  
Article
SIRT1 Activator E1231 Alleviates Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism
by Jiangxue Han, Shunwang Li, Weizhi Wang, Xinhai Jiang, Chao Liu, Lijuan Lei, Yining Li, Ren Sheng, Yuyan Zhang, Yexiang Wu, Jing Zhang, Yuhao Zhang, Yanni Xu and Shuyi Si
Curr. Issues Mol. Biol. 2023, 45(6), 5052-5070; https://doi.org/10.3390/cimb45060321 - 8 Jun 2023
Cited by 3 | Viewed by 1786
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. Silencing information regulator 1 (SIRT1) was demonstrated to modulate cholesterol and lipid metabolism in NAFLD. Here, a novel SIRT1 activator, E1231, was studied for its potential improvement effects on NAFLD. [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. Silencing information regulator 1 (SIRT1) was demonstrated to modulate cholesterol and lipid metabolism in NAFLD. Here, a novel SIRT1 activator, E1231, was studied for its potential improvement effects on NAFLD. C57BL/6J mice were fed a high-fat and high-cholesterol diet (HFHC) for 40 weeks to create a NAFLD mouse model, and E1231 was administered by oral gavage (50 mg/kg body weight, once/day) for 4 weeks. Liver-related plasma biochemistry parameter tests, Oil Red O staining, and hematoxylin-eosin staining results showed that E1231 treatment ameliorated plasma dyslipidemia, plasma marker levels of liver damage (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), liver total cholesterol (TC) and triglycerides (TG) contents, and obviously decreased hepatic steatosis score and NAFLD Activity Score (NAS) in the NAFLD mouse model. Western blot results showed that E1231 treatment significantly regulated lipid-metabolism-related protein expression. In particular, E1231 treatment increased SIRT1, PGC-1α, and p-AMPKα protein expression but decreased ACC and SCD-1 protein expression. Additionally, in vitro studies demonstrated that E1231 inhibited lipid accumulation and improved mitochondrial function in free-fatty-acid-challenged hepatocytes, and required SIRT1 activation. In conclusion, this study illustrated that the SIRT1 activator E1231 alleviated HFHC-induced NAFLD development and improved liver injury by regulating the SIRT1-AMPKα pathway, and might be a promising candidate compound for NAFLD treatment. Full article
(This article belongs to the Special Issue Lipid Metabolism in Obesity)
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16 pages, 1770 KiB  
Article
Potential Diagnostic Biomarker Detection for Prostate Cancer Using Untargeted and Targeted Metabolomic Profiling
by Diana Nitusca, Carmen Socaciu, Andreea Iulia Socaciu, Ioan Ovidiu Sirbu, Razvan Bardan, Alin Adrian Cumpanas, Edward Seclaman and Catalin Marian
Curr. Issues Mol. Biol. 2023, 45(6), 5036-5051; https://doi.org/10.3390/cimb45060320 - 8 Jun 2023
Viewed by 1333
Abstract
Prostate cancer (PCa) remains one of the leading causes of cancer mortality in men worldwide, currently lacking specific, early detection and staging biomarkers. In this regard, modern research focuses efforts on the discovery of novel molecules that could represent potential future non-invasive biomarkers [...] Read more.
Prostate cancer (PCa) remains one of the leading causes of cancer mortality in men worldwide, currently lacking specific, early detection and staging biomarkers. In this regard, modern research focuses efforts on the discovery of novel molecules that could represent potential future non-invasive biomarkers for the diagnosis of PCa, as well as therapeutic targets. Mounting evidence shows that cancer cells express an altered metabolism in their early stages, making metabolomics a promising tool for the discovery of altered pathways and potential biomarker molecules. In this study, we first performed untargeted metabolomic profiling on 48 PCa plasma samples and 23 healthy controls using ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-[ESI+]-MS) for the discovery of metabolites with altered profiles. Secondly, we selected five molecules (L-proline, L-tryptophan, acetylcarnitine, lysophosphatidylcholine C18:2 and spermine) for the downstream targeted metabolomics and found out that all the molecules, regardless of the PCa stage, were decreased in the PCa plasma samples when compared to the controls, making them potential biomarkers for PCa detection. Moreover, spermine, acetylcarnitine and L-tryptophan had very high diagnostic accuracy, with AUC values of 0.992, 0.923 and 0.981, respectively. Consistent with other literature findings, these altered metabolites could represent future specific and non-invasive candidate biomarkers for PCa detection, which opens novel horizons in the field of metabolomics. Full article
(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)
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18 pages, 6365 KiB  
Article
Synergistic Effects of New Curcumin Analog (PAC) and Cisplatin on Oral Cancer Therapy
by Abdelhabib Semlali, Sarra Beji, Ikram Ajala, Mohammed Al-Zharani and Mahmoud Rouabhia
Curr. Issues Mol. Biol. 2023, 45(6), 5018-5035; https://doi.org/10.3390/cimb45060319 - 8 Jun 2023
Cited by 3 | Viewed by 1710
Abstract
Oral cancer has traditionally been treated with surgery, radiotherapy, chemotherapy, or a combination of these therapies. Although cisplatin, a chemotherapy drug, can effectively kill oral cancer cells by forming DNA adducts, its clinical use is limited due to adverse effects and chemo-resistance. Therefore, [...] Read more.
Oral cancer has traditionally been treated with surgery, radiotherapy, chemotherapy, or a combination of these therapies. Although cisplatin, a chemotherapy drug, can effectively kill oral cancer cells by forming DNA adducts, its clinical use is limited due to adverse effects and chemo-resistance. Therefore, there is a need to develop new, targeted anticancer drugs to complement chemotherapy, allowing for reduced cisplatin doses and minimizing adverse effects. Recent studies have shown that 3,5-Bis (4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidine (PAC), a new curcumin analog, possesses anticancer properties and could be considered a complementary or alternative therapy. In this study, we aimed to assess the potential complementary effects of PAC in combination with cisplatin for treating oral cancer. We conducted experiments using oral cancer cell lines (Ca9-22) treated with different concentrations of cisplatin (ranging from 0.1 μM to 1 μM), either alone or in conjunction with PAC (2.5 and 5 μM). Cell growth was measured using the MTT assay, while cell cytotoxicity was evaluated using an LDH assay. Propidium iodide and annexin V staining were employed to examine the impact on cell apoptosis. Flow cytometry was used to investigate the effects of the PAC/cisplatin combination on cancer cell autophagy, oxidative stress, and DNA damage. Additionally, a Western Blot analysis was performed to assess the influence of this combination on pro-carcinogenic proteins involved in various signaling pathways. The results demonstrated that PAC enhanced the efficacy of cisplatin in a dose-dependent manner, leading to a significant inhibition of oral cancer cell proliferation. Importantly, treatment with PAC (5 μM) alongside different concentrations of cisplatin reduced the IC50 of cisplatin tenfold. Combining these two agents increased apoptosis by further inducing caspase activity. In addition, the concomitant use of PAC and cisplatin enhances oral cancer cell autophagy, ROS, and MitoSOX production. However, combined PAC with cisplatin inhibits the mitochondrial membrane potential (ΔΨm), which is a marker for cell viability. Finally, this combination further enhances the inhibition of oral cancer cell migration via the inhibition of epithelial-to-mesenchymal transition genes, such as E-cadherin. We demonstrated that the combination of PAC and cisplatin markedly enhanced oral cancer cell death by inducing apoptosis, autophagy, and oxidative stress. The data presented indicate that PAC has the potential to serve as a powerful complementary agent to cisplatin in the treatment of gingival squamous cell carcinomas. Full article
(This article belongs to the Section Molecular Medicine)
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13 pages, 1734 KiB  
Article
Impact of HepG2 Cells Glutathione Depletion on Neutral Sphingomyelinases mRNA Levels and Activity
by Marie Gamal, Hatem Tallima, Hassan M. E. Azzazy and Anwar Abdelnaser
Curr. Issues Mol. Biol. 2023, 45(6), 5005-5017; https://doi.org/10.3390/cimb45060318 - 8 Jun 2023
Viewed by 1539
Abstract
Liver cancer is a prevalent form of cancer worldwide. While research has shown that increasing sphingomyelin (SM) hydrolysis by activating the cell surface membrane-associated neutral sphingomyelinase 2 (nSMase2) can control cell proliferation and apoptosis, the role of total glutathione depletion in inducing tumor [...] Read more.
Liver cancer is a prevalent form of cancer worldwide. While research has shown that increasing sphingomyelin (SM) hydrolysis by activating the cell surface membrane-associated neutral sphingomyelinase 2 (nSMase2) can control cell proliferation and apoptosis, the role of total glutathione depletion in inducing tumor cell apoptosis via nSMase2 activation is still under investigation. Conversely, glutathione-mediated inhibition of reactive oxygen species (ROS) accumulation is necessary for the enzymatic activity of nSMase1 and nSMase3, increased ceramide levels, and cell apoptosis. This study evaluated the effects of depleting total glutathione in HepG2 cells using buthionine sulfoximine (BSO). The study assessed nSMases RNA levels and activities, intracellular ceramide levels, and cell proliferation using RT-qPCR, Amplex red neutral sphingomyelinase fluorescence assay, and colorimetric assays, respectively. The results indicated a lack of nSMase2 mRNA expression in treated and untreated HepG2 cells. Depletion of total glutathione resulted in a significant increase in mRNA levels but a dramatic reduction in the enzymatic activity of nSMase1 and nSMase3, a rise in ROS levels, a decrease in intracellular levels of ceramide, and an increase in cell proliferation. These findings suggest that total glutathione depletion may exacerbate liver cancer (HCC) and not support using total glutathione-depleting agents in HCC management. It is important to note that these results are limited to HepG2 cells, and further studies are necessary to determine if these effects will also occur in other cell lines. Additional research is necessary to explore the role of total glutathione depletion in inducing tumor cell apoptosis. Full article
(This article belongs to the Special Issue Advances in Molecular Pathogenesis Regulation in Cancer)
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20 pages, 2935 KiB  
Article
How Do Cancer-Related Mutations Affect the Oligomerisation State of the p53 Tetramerisation Domain?
by Federica Nicolini, Toni Todorovski, Eduard Puig, Mireia Díaz-Lobo, Marta Vilaseca, Jesús García, David Andreu and Ernest Giralt
Curr. Issues Mol. Biol. 2023, 45(6), 4985-5004; https://doi.org/10.3390/cimb45060317 - 7 Jun 2023
Viewed by 1266
Abstract
Tumour suppressor p53 plays a key role in the development of cancer and has therefore been widely studied in recent decades. While it is well known that p53 is biologically active as a tetramer, the tetramerisation mechanism is still not completely understood. p53 [...] Read more.
Tumour suppressor p53 plays a key role in the development of cancer and has therefore been widely studied in recent decades. While it is well known that p53 is biologically active as a tetramer, the tetramerisation mechanism is still not completely understood. p53 is mutated in nearly 50% of cancers, and mutations can alter the oligomeric state of the protein, having an impact on the biological function of the protein and on cell fate decisions. Here, we describe the effects of a number of representative cancer-related mutations on tetramerisation domain (TD) oligomerisation defining a peptide length that permits having a folded and structured domain, thus avoiding the effect of the flanking regions and the net charges at the N- and C-terminus. These peptides have been studied under different experimental conditions. We have applied a variety of techniques, including circular dichroism (CD), native mass spectrometry (MS) and high-field solution NMR. Native MS allows us to detect the native state of complexes maintaining the peptide complexes intact in the gas phase; the secondary and quaternary structures were analysed in solution by NMR, and the oligomeric forms were assigned by diffusion NMR experiments. A significant destabilising effect and a variable monomer population were observed for all the mutants studied. Full article
(This article belongs to the Special Issue Advances in Molecular Pathogenesis Regulation in Cancer)
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15 pages, 7123 KiB  
Article
Biochemical and Antioxidant Properties as well as Antimicrobial and Antibiofilm Activities of Allium scorodoprasum subsp. jajlae (Vved.) Stearn
by Kerem Canli, Dilay Turu, Atakan Benek, Mustafa Eray Bozyel, Özcan Simsek and Ergin Murat Altuner
Curr. Issues Mol. Biol. 2023, 45(6), 4970-4984; https://doi.org/10.3390/cimb45060316 - 7 Jun 2023
Cited by 1 | Viewed by 1157
Abstract
In this study, the chemical composition and biological activity of Allium scorodoprasum subsp. jajlae (Vved.) Stearn were investigated for the first time, focusing on its antimicrobial, antioxidant, and antibiofilm properties. A GC-MS analysis was employed to evaluate the composition of its secondary metabolites, [...] Read more.
In this study, the chemical composition and biological activity of Allium scorodoprasum subsp. jajlae (Vved.) Stearn were investigated for the first time, focusing on its antimicrobial, antioxidant, and antibiofilm properties. A GC-MS analysis was employed to evaluate the composition of its secondary metabolites, identifying linoleic acid, palmitic acid, and octadecanoic acid 2,3-dihydroxypropyl ester as the major compounds in ethanol extract. The antimicrobial activity of A. scorodoprasum subsp. jajlae was assessed against 26 strains, including standard, food isolate, clinical isolate, and multidrug-resistant ones, as well as three Candida species using the disc diffusion method and the determination of the minimum inhibitory concentration (MIC). The extract showed strong antimicrobial activity against Staphylococcus aureus strains, including methicillin-resistant and multidrug-resistant strains, as well as Candida tropicalis and Candida glabrata. Its antioxidant capacity was evaluated using the DPPH method, revealing a high level of antioxidant activity in the plant. Additionally, the antibiofilm activity of A. scorodoprasum subsp. jajlae was determined, demonstrating a reduction in biofilm formation for the Escherichia coli ATCC 25922 strain and an increase in biofilm formation for the other tested strains. The findings suggest potential applications of A. scorodoprasum subsp. jajlae in the development of novel antimicrobial, antioxidant, and antibiofilm agents. Full article
22 pages, 5108 KiB  
Article
Adenosine A2A Receptor Activation Regulates Niemann–Pick C1 Expression and Localization in Macrophages
by Adrienn Skopál, Gyula Ujlaki, Attila Tibor Gerencsér, Csaba Bankó, Zsolt Bacsó, Francisco Ciruela, László Virág, György Haskó and Endre Kókai
Curr. Issues Mol. Biol. 2023, 45(6), 4948-4969; https://doi.org/10.3390/cimb45060315 - 7 Jun 2023
Viewed by 1994
Abstract
Adenosine plays an important role in modulating immune cell function, particularly T cells and myeloid cells, such as macrophages and dendritic cells. Cell surface adenosine A2A receptors (A2AR) regulate the production of pro-inflammatory cytokines and chemokines, as well as the [...] Read more.
Adenosine plays an important role in modulating immune cell function, particularly T cells and myeloid cells, such as macrophages and dendritic cells. Cell surface adenosine A2A receptors (A2AR) regulate the production of pro-inflammatory cytokines and chemokines, as well as the proliferation, differentiation, and migration of immune cells. In the present study, we expanded the A2AR interactome and provided evidence for the interaction between the receptor and the Niemann–Pick type C intracellular cholesterol transporter 1 (NPC1) protein. The NPC1 protein was identified to interact with the C-terminal tail of A2AR in RAW 264.7 and IPMФ cells by two independent and parallel proteomic approaches. The interaction between the NPC1 protein and the full-length A2AR was further validated in HEK-293 cells that permanently express the receptor and RAW264.7 cells that endogenously express A2AR. A2AR activation reduces the expression of NPC1 mRNA and protein density in LPS-activated mouse IPMФ cells. Additionally, stimulation of A2AR negatively regulates the cell surface expression of NPC1 in LPS-stimulated macrophages. Furthermore, stimulation of A2AR also altered the density of lysosome-associated membrane protein 2 (LAMP2) and early endosome antigen 1 (EEA1), two endosomal markers associated with the NPC1 protein. Collectively, these results suggested a putative A2AR-mediated regulation of NPC1 protein function in macrophages, potentially relevant for the Niemann–Pick type C disease when mutations in NPC1 protein result in the accumulation of cholesterol and other lipids in lysosomes. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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12 pages, 6837 KiB  
Article
M2 Macrophages-Derived Exosomal miRNA-23a-3p Promotes the Progression of Oral Squamous Cell Carcinoma by Targeting PTEN
by Jun Li, Yongjie Bao, Sisi Peng, Chao Jiang, Luying Zhu, Sihai Zou, Jie Xu and Yong Li
Curr. Issues Mol. Biol. 2023, 45(6), 4936-4947; https://doi.org/10.3390/cimb45060314 - 7 Jun 2023
Cited by 1 | Viewed by 1476
Abstract
Exosomes from tumor cells and immune cells regulate the tumor microenvironment through the biomolecules or microRNAs (miRNAs) they carry. This research aims to investigate the role of miRNA in exosomes derived from tumor-associated macrophages (TAMs) in the progression of oral squamous cell carcinoma [...] Read more.
Exosomes from tumor cells and immune cells regulate the tumor microenvironment through the biomolecules or microRNAs (miRNAs) they carry. This research aims to investigate the role of miRNA in exosomes derived from tumor-associated macrophages (TAMs) in the progression of oral squamous cell carcinoma (OSCC). RT-qPCR and Western blotting assays were used to determine the expression of genes and proteins in OSCC cells. CCK-8, Scratch assay and invasion-related proteins were utilized to detect the malignant progression of tumor cells. High-throughput sequencing predicted differentially expressed miRNAs in exosomes secreted by M0 and M2 macrophages. Compared with exosomes from M0 macrophages, exosomes from M2 macrophages led to enhanced proliferation and invasion of OSCC cells and inhibited their apoptosis. High-throughput sequencing results show that miR-23a-3p is differentially expressed in exosomes from M0 and M2 macrophages. MiRNA target gene database predicts that phosphatase and tensin homolog (PTEN) are target genes of miR-23a-3p. Further studies revealed that transfection of miR-23a-3p mimics inhibited PTEN expression in vivo and in vitro and promoted the malignant progression of OSCC cells, which was reversed by miR-23a-3p inhibitors. MiR-23a-3p in exosomes derived from M2 macrophages promotes malignant progression of OSCC. PTEN is a potential intracellular target of miR-23a-3p. MiR-23a-3p, an M2 macrophage-associated exosome, is a promising target for the future treatment of OSCC. Full article
(This article belongs to the Special Issue Oral Cancer: Prophylaxis, Etiopathogenesis and Treatment)
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13 pages, 626 KiB  
Review
Oxytocin’s Regulation of Thermogenesis May Be the Link to Prader–Willi Syndrome
by Claudia Camerino
Curr. Issues Mol. Biol. 2023, 45(6), 4923-4935; https://doi.org/10.3390/cimb45060313 - 6 Jun 2023
Cited by 1 | Viewed by 2232
Abstract
Prader–Willi Syndrome (PWS) is a genetic neurodevelopmental disorder that is caused by either the deletion of the paternal allele of 15q11-q13, maternal uniparental disomy of chromosome 15 or defects in the chromosome 15 imprinting centre and is characterized by cognitive impairment, hyperphagia and [...] Read more.
Prader–Willi Syndrome (PWS) is a genetic neurodevelopmental disorder that is caused by either the deletion of the paternal allele of 15q11-q13, maternal uniparental disomy of chromosome 15 or defects in the chromosome 15 imprinting centre and is characterized by cognitive impairment, hyperphagia and low metabolic rate with significant risk of obesity, as well as a variety of other maladaptive behaviours and autistic spectrum disorder (ASD). Many of the features seen in PWS are thought to be due to hypothalamic dysfunction resulting in hormonal abnormalities and impaired social functioning. The preponderance of evidence indicates that the Oxytocin system is dysregulated in PWS individuals and that this neuropeptide pathways may provide promising targets for therapeutic intervention although the process by which this dysregulation occurs in PWS awaits mechanistic investigation. PWS individuals present abnormalities in thermoregulation an impaired detection for temperature change and altered perception of pain indicating an altered autonomic nervous system. Recent studies indicate that Oxytocin is involved in thermoregulation and pain perception. This review will describe the update on PWS and the recent discoveries on Oxytocin regulation of thermogenesis together with the potential link between Oxytocin regulation of thermogenesis and PWS to create a new groundwork for the treatment of this condition. Full article
(This article belongs to the Collection Feature Papers in Current Issues in Molecular Biology)
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15 pages, 2215 KiB  
Article
Synergistic Chemopreventive Effects of a Novel Combined Plant Extract Comprising Gallic Acid and Hesperidin on Colorectal Cancer
by Szu-Jung Chen, Jui-Hua Lu, Chih-Cheng Lin, Shao-Wei Zeng, Jia-Feng Chang, Yuan-Chiang Chung, Hsiang Chang and Chih-Ping Hsu
Curr. Issues Mol. Biol. 2023, 45(6), 4908-4922; https://doi.org/10.3390/cimb45060312 - 5 Jun 2023
Viewed by 1614
Abstract
Background/Aim: Colorectal cancer (CRC) is the third most common cancer with a high mortality rate worldwide. Although gallic acid and hesperidin exert anticancer activity, synergistic effects of gallic acid and hesperidin against CRC remain elusive. This study aims to investigate the therapeutic mechanism [...] Read more.
Background/Aim: Colorectal cancer (CRC) is the third most common cancer with a high mortality rate worldwide. Although gallic acid and hesperidin exert anticancer activity, synergistic effects of gallic acid and hesperidin against CRC remain elusive. This study aims to investigate the therapeutic mechanism of a novel combination of gallic acid and hesperidin against CRC cell growth, including cell viability, cell-cycle-associated proteins, spheroid formation, and stemness. Methods: Gallic acid and hesperidin derived from Hakka pomelo tea (HPT) were detected by colorimetric methods and high-performance liquid chromatography using ethyl acetate as an extraction medium. CRC cell lines (HT-29 and HCT-116) treated with the combined extract were investigated in our study for cell viability (trypan blue or soft agar colony formation assay), cell cycle (propidium iodide staining), cell-cycle-associated proteins (immunoblotting), and stem cell markers (immunohistochemistry staining). Results: Compared with other extraction methods, HPT extraction using an ethyl acetate medium exerts the most potent effect on inhibiting HT-29 cell growth in a dose-dependent manner. Furthermore, the treatment with combined extract had a higher inhibitory effect on CRC cell viability than gallic acid or hesperidin alone. The underlying mechanism was involved in G1-phase arrest and Cip1/p21 upregulation that could attenuate HCT-116 cell proliferation (Ki-67), stemness (CD-133), and spheroid growth in a 3D formation assay mimicking in vivo tumorigenesis. Conclusion: Gallic acid and hesperidin exert synergistic effects on cell growth, spheroids, and stemness of CRC and may serve as a potential chemopreventive agent. Further testing for the safety and effectiveness of the combined extract in large-scale randomized trials is required. Full article
(This article belongs to the Special Issue Molecular Research in Food Science)
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17 pages, 3777 KiB  
Article
An Evaluation of the Anti-Inflammatory Effects of a Thai Traditional Polyherbal Recipe TPDM6315 in LPS-Induced RAW264.7 Macrophages and TNF-α-Induced 3T3-L1 Adipocytes
by Phetpawi Subin, Pattraporn Sabuhom, Alisa Naladta, Prathan Luecha, Somsak Nualkaew and Natsajee Nualkaew
Curr. Issues Mol. Biol. 2023, 45(6), 4891-4907; https://doi.org/10.3390/cimb45060311 - 5 Jun 2023
Cited by 3 | Viewed by 1749
Abstract
TPDM6315 is an antipyretic Thai herbal recipe that contains several herbs with anti-inflammatory and anti-obesity activities. This study aimed to investigate the anti-inflammatory effects of TPDM6315 extracts in lipopolysaccharide (LPS)-induced RAW264.7 macrophages and TNF-α-induced 3T3-L1 adipocytes, and the effects of TPDM6315 extracts on [...] Read more.
TPDM6315 is an antipyretic Thai herbal recipe that contains several herbs with anti-inflammatory and anti-obesity activities. This study aimed to investigate the anti-inflammatory effects of TPDM6315 extracts in lipopolysaccharide (LPS)-induced RAW264.7 macrophages and TNF-α-induced 3T3-L1 adipocytes, and the effects of TPDM6315 extracts on lipid accumulation in 3T3-L1 adipocytes. The results showed that the TPDM6315 extracts reduced the nitric oxide production and downregulated the iNOS, IL-6, PGE2, and TNF-α genes regulating fever in LPS-stimulated RAW264.7 macrophages. The treatment of 3T3-L1 pre-adipocytes with TPDM6315 extracts during a differentiation to the adipocytes resulted in the decreasing of the cellular lipid accumulation in adipocytes. The ethanolic extract (10 µg/mL) increased the mRNA level of adiponectin (the anti-inflammatory adipokine) and upregulated the PPAR-γ in the TNF-α induced adipocytes. These findings provide evidence-based support for the traditional use of TPDM6315 as an anti-pyretic for fever originating from inflammation. The anti-obesity and anti-inflammatory actions of TPDM6315 in TNF-α induced adipocytes suggest that this herbal recipe could be useful for the treatment of metabolic syndrome disorders caused by obesity. Further investigations into the modes of action of TPDM6315 are needed for developing health products to prevent or regulate disorders resulting from inflammation. Full article
(This article belongs to the Topic Nitrite and Nitric Oxide in Life)
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16 pages, 3676 KiB  
Article
Magnolia kobus Extract Suppresses Porphyromonas gingivalis LPS-Induced Proinflammatory Cytokine and MMP Expression in HGF-1 Cells and Regulates Osteoclastogenesis in RANKL-Stimulated RAW264.7 Cells
by Hae Jin Lee, So Jung Lee, Sung Kwon Lee, Bong Keun Choi, Dong Ryung Lee, Ju-Hyoung Park and Joa Sub Oh
Curr. Issues Mol. Biol. 2023, 45(6), 4875-4890; https://doi.org/10.3390/cimb45060310 - 3 Jun 2023
Viewed by 1549
Abstract
Clinical prevention is of utmost importance for the management of periodontal diseases. Periodontal disease starts with an inflammatory response in the gingival tissue, and results in alveolar bone destruction and subsequent tooth loss. This study aimed to confirm the anti-periodontitis effects of MKE. [...] Read more.
Clinical prevention is of utmost importance for the management of periodontal diseases. Periodontal disease starts with an inflammatory response in the gingival tissue, and results in alveolar bone destruction and subsequent tooth loss. This study aimed to confirm the anti-periodontitis effects of MKE. To confirm this, we studied its mechanism of action using qPCR and WB in LPS-treated HGF-1 cells and RANKL-induced osteoclasts. We found that MKE suppressed proinflammatory cytokine protein expression by inhibiting the TLR4/NF-κB pathway in LPS-PG-induced HGF-1 cells and blocking ECM degradation by regulating the expression of TIMPs and MMPs. We also confirmed that TRAP activity and multinucleated cell formation were reduced in RANKL-stimulated osteoclasts after exposure to MKE. These results were confirmed by inhibiting TRAF6/MAPK expression, which led to the suppression of NFATc1, CTSK, TRAP, and MMP expression at the gene and protein levels. Our results confirmed that MKE is a promising candidate for the management of periodontal disease based on its anti-inflammatory effects and inhibition of ECM degradation and osteoclastogenesis. Full article
(This article belongs to the Special Issue Bioactives and Inflammation)
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25 pages, 7983 KiB  
Article
Metabolic Deregulation in Pulmonary Hypertension
by Rajamma Mathew, Sanda Iacobas, Jing Huang and Dumitru Andrei Iacobas
Curr. Issues Mol. Biol. 2023, 45(6), 4850-4874; https://doi.org/10.3390/cimb45060309 - 3 Jun 2023
Cited by 1 | Viewed by 1449
Abstract
The high morbidity and mortality rate of pulmonary arterial hypertension (PAH) is partially explained by metabolic deregulation. The present study complements our previous publication in “Genes” by identifying significant increases of the glucose transporter solute carrier family 2 (Slc2a1), beta nerve growth factor [...] Read more.
The high morbidity and mortality rate of pulmonary arterial hypertension (PAH) is partially explained by metabolic deregulation. The present study complements our previous publication in “Genes” by identifying significant increases of the glucose transporter solute carrier family 2 (Slc2a1), beta nerve growth factor (Ngf), and nuclear factor erythroid-derived 2-like 2 (Nfe2l2) in three standard PAH rat models. PAH was induced by subjecting the animals to hypoxia (HO), or by injecting with monocrotaline in either normal (CM) or hypoxic (HM) atmospheric conditions. The Western blot and double immunofluorescent experiments were complemented with novel analyses of previously published transcriptomic datasets of the animal lungs from the perspective of the Genomic Fabric Paradigm. We found substantial remodeling of the citrate cycle, pyruvate metabolism, glycolysis/gluconeogenesis, and fructose and mannose pathways. According to the transcriptomic distance, glycolysis/gluconeogenesis was the most affected functional pathway in all three PAH models. PAH decoupled the coordinated expression of many metabolic genes, and replaced phosphomannomutase 2 (Pmm2) with phosphomannomutase 1 (Pmm1) in the center of the fructose and mannose metabolism. We also found significant regulation of key genes involved in PAH channelopathies. In conclusion, our data show that metabolic dysregulation is a major PAH pathogenic factor. Full article
(This article belongs to the Collection Feature Papers in Current Issues in Molecular Biology)
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9 pages, 884 KiB  
Brief Report
Mitogenomic Research of Silverleaf Sunflower (Helianthus argophyllus) and Its Interspecific Hybrids
by Maksim S. Makarenko, Kirill V. Azarin and Vera A. Gavrilova
Curr. Issues Mol. Biol. 2023, 45(6), 4841-4849; https://doi.org/10.3390/cimb45060308 - 2 Jun 2023
Cited by 2 | Viewed by 1342
Abstract
Interspecific hybridization is widespread for sunflowers, both in wild populations and commercial breeding. One of the most common species that can efficiently cross with Helianthus annuus is the Silverleaf sunflower—Helianthus argophyllus. The current study carried out structural and functional organization analyses of [...] Read more.
Interspecific hybridization is widespread for sunflowers, both in wild populations and commercial breeding. One of the most common species that can efficiently cross with Helianthus annuus is the Silverleaf sunflower—Helianthus argophyllus. The current study carried out structural and functional organization analyses of mitochondrial DNA in H. argophyllus and the interspecific hybrid, H. annuus (VIR114A line) × H. argophyllus. The complete mitogenome of H. argophyllus counts 300,843 bp, has a similar organization to the mitogenome of cultivated sunflower, and holds SNPs typical for wild sunflowers. RNA editing analysis predicted 484 sites in H. argophyllus mitochondrial CDS. The mitochondrial genome of the H. annuus × H. argophyllus hybrid is identical to the maternal line (VIR114A). We expected that significant rearrangements in the mitochondrial DNA of the hybrid would occur, due to the frequent recombination. However, the hybrid mitogenome lacks rearrangements, presumably due to the preservation of nuclear–cytoplasmic interaction paths. Full article
(This article belongs to the Special Issue Functional Genomics and Comparative Genomics Analysis in Plants)
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15 pages, 1990 KiB  
Review
Adenovirus as a Vector and Oncolytic Virus
by Wataru Matsunaga and Akinobu Gotoh
Curr. Issues Mol. Biol. 2023, 45(6), 4826-4840; https://doi.org/10.3390/cimb45060307 - 2 Jun 2023
Cited by 7 | Viewed by 3030
Abstract
Adenoviral vectors, both oncolytic viruses and gene delivery vectors, are among the earliest approved and commercialised vectors for gene therapy. Adenoviruses have high cytotoxicity and immunogenicity. Therefore, lentiviruses or adeno-associated viruses as viral vectors and herpes simplex virus as an oncolytic virus have [...] Read more.
Adenoviral vectors, both oncolytic viruses and gene delivery vectors, are among the earliest approved and commercialised vectors for gene therapy. Adenoviruses have high cytotoxicity and immunogenicity. Therefore, lentiviruses or adeno-associated viruses as viral vectors and herpes simplex virus as an oncolytic virus have recently drawn attention. Thus, adenoviral vectors are often considered relatively obsolete. However, their high cargo limit and transduction efficiency are significant advantages over newer viral vectors. This review provides an overview of the new-generation adenoviral vectors. In addition, we describe the modification of the fiber knob region that enhances affinity of adenoviral vectors for cancer cells and the utilisation of cancer-cell-specific promoters to suppress expression of unwanted transgenes in non-malignant tissues. Full article
(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)
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12 pages, 1269 KiB  
Communication
Molecular Detection of Nosema spp. in Three Eco Regions of Slovakia
by Beáta Hurná, Monika Sučik, Martin Staroň, Štefan Tutka, Zuzana Maková, Richard Galajda and Alexandra Valenčáková
Curr. Issues Mol. Biol. 2023, 45(6), 4814-4825; https://doi.org/10.3390/cimb45060306 - 1 Jun 2023
Viewed by 1464
Abstract
Microsporidia are unicellular obligate intracellular parasitic fungi that infect a wide range of vertebrates and invertebrates. There are two known species of microsporidia infecting honey bees in Slovakia- first Nosema apis and also Nosema ceranae. Our aim was to examine samples of honey [...] Read more.
Microsporidia are unicellular obligate intracellular parasitic fungi that infect a wide range of vertebrates and invertebrates. There are two known species of microsporidia infecting honey bees in Slovakia- first Nosema apis and also Nosema ceranae. Our aim was to examine samples of honey bees collected from bee queen breeders in three ecoregions of the Slovak Republic in 2021 and 2022. First, microscopic diagnostics were used, and then randomly selected samples were examined using molecular methods. There were 4018 samples examined using microscopic diagnostics and the positivity was demonstrated in 922 samples. From the microscopically diagnosed positive samples, 507 samples were randomly selected, and using molecular methods, the positivity was proved in 488 samples. After sequencing the positive PCR products and comparing the sequences (BLAST) with the sequences stored in the gene bank, the Nosema ceranae species was detected in all positive samples. Full article
(This article belongs to the Collection Feature Papers in Current Issues in Molecular Biology)
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18 pages, 1662 KiB  
Article
Genetic Dissection of Salt Tolerance and Yield Traits of Geng (japonica) Rice by Selective Subspecific Introgression
by Simin Li, Ting Feng, Chenyang Zhang, Fanlin Zhang, Hua Li, Yanjun Chen, Lunping Liang, Chaopu Zhang, Wei Zeng, Erbao Liu, Yingyao Shi, Min Li and Lijun Meng
Curr. Issues Mol. Biol. 2023, 45(6), 4796-4813; https://doi.org/10.3390/cimb45060305 - 31 May 2023
Cited by 1 | Viewed by 1236
Abstract
Salinity is a major factor limiting rice productivity, and developing salt-tolerant (ST) varieties is the most efficient approach. Seventy-eight ST introgression lines (ILs), including nine promising lines with improved ST and yield potential (YP), were developed from four BC2F4 populations [...] Read more.
Salinity is a major factor limiting rice productivity, and developing salt-tolerant (ST) varieties is the most efficient approach. Seventy-eight ST introgression lines (ILs), including nine promising lines with improved ST and yield potential (YP), were developed from four BC2F4 populations from inter-subspecific crosses between an elite Geng (japonica) recipient and four Xian (indica) donors at the Institute of Crop Sciences, Chinese Academy of Agricultural Sciences. Genome-wide characterization of donor introgression identified 35 ST QTLs, 25 of which harbor 38 cloned ST genes as the most likely QTL candidates. Thirty-four are Xian-Geng differentiated ones with the donor (Xian) alleles associated with ST, suggesting differentiated responses to salt stress were one of the major phenotypic differences between the two subspecies. At least eight ST QTLs and many others affecting yield traits were identified under salt/non-stress conditions. Our results indicated that the Xian gene pool contains rich ‘hidden’ genetic variation for developing superior Geng varieties with improved ST and YP, which could be efficiently exploited by selective introgression. The developed ST ILs and their genetic information on the donor alleles for ST and yield traits would provide a useful platform for developing superior ST and high-yield Geng varieties through breeding by design in the future. Full article
(This article belongs to the Special Issue Molecular Breeding and Genetics Research in Plants)
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18 pages, 2807 KiB  
Article
Large-Scale Production of Anti-RNase A VHH Expressed in pyrG Auxotrophic Aspergillus oryzae
by Elif Karaman, Alp Ertunga Eyüpoğlu, Lena Mahmoudi Azar and Serdar Uysal
Curr. Issues Mol. Biol. 2023, 45(6), 4778-4795; https://doi.org/10.3390/cimb45060304 - 31 May 2023
Cited by 1 | Viewed by 1532
Abstract
Nanobodies, also referred to as VHH antibodies, are the smallest fragments of naturally produced camelid antibodies and are ideal affinity reagents due to their remarkable properties. They are considered an alternative to monoclonal antibodies (mAbs) with potential utility in imaging, diagnostic, and other [...] Read more.
Nanobodies, also referred to as VHH antibodies, are the smallest fragments of naturally produced camelid antibodies and are ideal affinity reagents due to their remarkable properties. They are considered an alternative to monoclonal antibodies (mAbs) with potential utility in imaging, diagnostic, and other biotechnological applications given the difficulties associated with mAb expression. Aspergillus oryzae (A. oryzae) is a potential system for the large-scale expression and production of functional VHH antibodies that can be used to meet the demand for affinity reagents. In this study, anti-RNase A VHH was expressed under the control of the glucoamylase promoter in pyrG auxotrophic A. oryzae grown in a fermenter. The feature of pyrG auxotrophy, selected for the construction of a stable and efficient platform, was established using homologous recombination. Pull-down assay, size exclusion chromatography, and surface plasmon resonance were used to confirm the binding specificity of anti-RNase A VHH to RNase A. The affinity of anti-RNase A VHH was nearly 18.3-fold higher (1.9 nM) when expressed in pyrG auxotrophic A. oryzae rather than in Escherichia coli. This demonstrates that pyrG auxotrophic A. oryzae is a practical, industrially scalable, and promising biotechnological platform for the large-scale production of functional VHH antibodies with high binding activity. Full article
(This article belongs to the Special Issue Microbial Engineering: Gene Expression Regulation and Its Application)
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15 pages, 753 KiB  
Review
Clinical Characteristics of Molecularly Defined Renal Cell Carcinomas
by Xinfeng Hu, Congzhu Tan and Guodong Zhu
Curr. Issues Mol. Biol. 2023, 45(6), 4763-4777; https://doi.org/10.3390/cimb45060303 - 31 May 2023
Cited by 1 | Viewed by 1815
Abstract
Kidney tumors comprise a broad spectrum of different histopathological entities, with more than 0.4 million newly diagnosed cases each year, mostly in middle-aged and older men. Based on the description of the 2022 World Health Organization (WHO) classification of renal cell carcinoma (RCC), [...] Read more.
Kidney tumors comprise a broad spectrum of different histopathological entities, with more than 0.4 million newly diagnosed cases each year, mostly in middle-aged and older men. Based on the description of the 2022 World Health Organization (WHO) classification of renal cell carcinoma (RCC), some new categories of tumor types have been added according to their specific molecular typing. However, studies on these types of RCC are still superficial, many types of these RCC currently lack accurate diagnostic standards in the clinic, and treatment protocols are largely consistent with the treatment guidelines for clear cell RCC (ccRCC), which might result in worse treatment outcomes for patients with these types of molecularly defined RCC. In this article, we conduct a narrative review of the literature published in the last 15 years on molecularly defined RCC. The purpose of this review is to summarize the clinical features and the current status of research on the detection and treatment of molecularly defined RCC. Full article
(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)
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14 pages, 361 KiB  
Review
Polymorphism of Genes and Their Impact on Beef Quality
by Piotr Kostusiak, Jan Slósarz, Marcin Gołębiewski, Grzegorz Grodkowski and Kamila Puppel
Curr. Issues Mol. Biol. 2023, 45(6), 4749-4762; https://doi.org/10.3390/cimb45060302 - 30 May 2023
Cited by 3 | Viewed by 1547
Abstract
The single-nucleotide polymorphism (SNP) form of genes is a valuable source of information regarding their suitability for use as specific markers of desirable traits in beef cattle breeding. For several decades, breeding work focused on improving production efficiency through optimizing the feed conversion [...] Read more.
The single-nucleotide polymorphism (SNP) form of genes is a valuable source of information regarding their suitability for use as specific markers of desirable traits in beef cattle breeding. For several decades, breeding work focused on improving production efficiency through optimizing the feed conversion ratio and improving daily gains and meat quality. Many research teams previously undertook research work on single-nucleotide polymorphism in myostatin (MSTN), thyroglobulin (TG), calpain (CAPN), and calpastatin (CAST) proteins. The literature review focuses on the most frequently addressed issues concerning these genes in beef cattle production and points to a number of relevant studies on the genes’ polymorphic forms. The four genes presented are worth considering during breeding work as a set of genes that can positively influence productivity and production quality. Full article
(This article belongs to the Collection Feature Papers in Current Issues in Molecular Biology)
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