Current Issues in Molecular Biology

28 pages, 11661 KiB

Open AccessReview

Using AlphaFold Predictions in Viral Research

by Daria Gutnik, Peter Evseev, Konstantin Miroshnikov and Mikhail Shneider

Curr. Issues Mol. Biol. 2023, 45(4), 3705-3732; https://doi.org/10.3390/cimb45040240 - 21 Apr 2023

Cited by 9 | Viewed by 5944

Elucidation of the tertiary structure of proteins is an important task for biological and medical studies. AlphaFold, a modern deep-learning algorithm, enables the prediction of protein structure to a high level of accuracy. It has been applied in numerous studies in various areas [...] Read more.

Elucidation of the tertiary structure of proteins is an important task for biological and medical studies. AlphaFold, a modern deep-learning algorithm, enables the prediction of protein structure to a high level of accuracy. It has been applied in numerous studies in various areas of biology and medicine. Viruses are biological entities infecting eukaryotic and procaryotic organisms. They can pose a danger for humans and economically significant animals and plants, but they can also be useful for biological control, suppressing populations of pests and pathogens. AlphaFold can be used for studies of molecular mechanisms of viral infection to facilitate several activities, including drug design. Computational prediction and analysis of the structure of bacteriophage receptor-binding proteins can contribute to more efficient phage therapy. In addition, AlphaFold predictions can be used for the discovery of enzymes of bacteriophage origin that are able to degrade the cell wall of bacterial pathogens. The use of AlphaFold can assist fundamental viral research, including evolutionary studies. The ongoing development and improvement of AlphaFold can ensure that its contribution to the study of viral proteins will be significant in the future. Full article

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

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31 pages, 4129 KiB

Open AccessReview

Plant Antimicrobial Peptides: Insights into Structure-Function Relationships for Practical Applications

by Marina P. Slezina and Tatyana I. Odintsova

Curr. Issues Mol. Biol. 2023, 45(4), 3674-3704; https://doi.org/10.3390/cimb45040239 - 21 Apr 2023

Cited by 18 | Viewed by 2462

Abstract

Antimicrobial peptides (AMPs) are short polypeptide molecules produced by multicellular organisms that are involved in host defense and microbiome preservation. In recent years, AMPs have attracted attention as novel drug candidates. However, their successful use requires detailed knowledge of the mode of action [...] Read more.

Antimicrobial peptides (AMPs) are short polypeptide molecules produced by multicellular organisms that are involved in host defense and microbiome preservation. In recent years, AMPs have attracted attention as novel drug candidates. However, their successful use requires detailed knowledge of the mode of action and identification of the determinants of biological activity. In this review, we focused on structure-function relationships in the thionins, α-hairpinins, hevein-like peptides, and the unique Ib-AMP peptides isolated from Impatiens balsamina. We summarized the available data on the amino acid sequences and 3D structure of peptides, their biosynthesis, and their biological activity. Special attention was paid to the determination of residues that play a key role in the activity and the identification of the minimal active cores. We have shown that even subtle changes in amino acid sequences can affect the biological activity of AMPs, which opens up the possibility of creating molecules with improved properties, better therapeutic efficacy, and cheaper large-scale production. Full article

(This article belongs to the Special Issue Advanced Research in Antimicrobial and Antiviral Drugs)

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16 pages, 2456 KiB

Open AccessArticle

A Novel Anti-CD44 Variant 9 Monoclonal Antibody C₄₄Mab-1 Was Developed for Immunohistochemical Analyses against Colorectal Cancers

by Mayuki Tawara, Hiroyuki Suzuki, Nohara Goto, Tomohiro Tanaka, Mika K. Kaneko and Yukinari Kato

Curr. Issues Mol. Biol. 2023, 45(4), 3658-3673; https://doi.org/10.3390/cimb45040238 - 20 Apr 2023

Cited by 11 | Viewed by 2476

Abstract

Cluster of differentiation 44 (CD44) is a type I transmembrane glycoprotein and has been shown to be a cell surface marker of cancer stem-like cells in various cancers. In particular, the splicing variants of CD44 (CD44v) are overexpressed in cancers and play critical [...] Read more.

Cluster of differentiation 44 (CD44) is a type I transmembrane glycoprotein and has been shown to be a cell surface marker of cancer stem-like cells in various cancers. In particular, the splicing variants of CD44 (CD44v) are overexpressed in cancers and play critical roles in cancer stemness, invasiveness, and resistance to chemotherapy and radiotherapy. Therefore, the understanding of the function of each CD44v is indispensable for CD44-targeting therapy. CD44v9 contains the variant 9-encoded region, and its expression predicts poor prognosis in patients with various cancers. CD44v9 plays critical roles in the malignant progression of tumors. Therefore, CD44v9 is a promising target for cancer diagnosis and therapy. Here, we developed sensitive and specific monoclonal antibodies (mAbs) against CD44 by immunizing mice with CD44v3–10-overexpressed Chinese hamster ovary-K1 (CHO/CD44v3–10) cells. We first determined their critical epitopes using enzyme-linked immunosorbent assay and characterized their applications as flow cytometry, western blotting, and immunohistochemistry. One of the established clones, C₄₄Mab-1 (IgG₁, kappa), reacted with a peptide of the variant 9-encoded region, indicating that C₄₄Mab-1 recognizes CD44v9. C₄₄Mab-1 could recognize CHO/CD44v3–10 cells or colorectal cancer cell lines (COLO201 and COLO205) in flow cytometric analysis. The apparent dissociation constant (K_D) of C₄₄Mab-1 for CHO/CD44v3–10, COLO201, and COLO205 was 2.5 × 10⁻⁸ M, 3.3 × 10⁻⁸ M, and 6.5 × 10⁻⁸ M, respectively. Furthermore, C₄₄Mab-1 was able to detect the CD44v3–10 in western blotting and the endogenous CD44v9 in immunohistochemistry using colorectal cancer tissues. These results indicated that C₄₄Mab-1 is useful for detecting CD44v9 not only in flow cytometry or western blotting but also in immunohistochemistry against colorectal cancers. Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers)

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18 pages, 15056 KiB

Open AccessArticle

Histone Demethylation Profiles in Nonalcoholic Fatty Liver Disease and Prognostic Values in Hepatocellular Carcinoma: A Bioinformatic Analysis

by Yuanbin Liu and Mingkai Chen

Curr. Issues Mol. Biol. 2023, 45(4), 3640-3657; https://doi.org/10.3390/cimb45040237 - 20 Apr 2023

Cited by 2 | Viewed by 1916

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with multifactorial pathogenesis; histone demethylases (HDMs) are emerging as attractive targets. We identified HDM genes (including KDM5C, KDM6B, KDM8, KDM4A, and JMJD7) that were differentially expressed in NAFLD and normal samples [...] Read more.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with multifactorial pathogenesis; histone demethylases (HDMs) are emerging as attractive targets. We identified HDM genes (including KDM5C, KDM6B, KDM8, KDM4A, and JMJD7) that were differentially expressed in NAFLD and normal samples by exploring gene expression profiling datasets. There was no significant difference in the expression of genes related to histone demethylation between mild and advanced NAFLD. In vitro and in vivo studies indicated that KDM6B and JMJD7 were upregulated at the mRNA level in NAFLD. We explored the expression levels and prognostic values of the identified HDM genes in hepatocellular carcinoma (HCC). KDM5C and KDM4A were upregulated in HCC compared to normal tissue, while KDM8 showed downregulation. The abnormal expression levels of these HDMs could provide prognostic values. Furthermore, KDM5C and KDM4A were associated with immune cell infiltration in HCC. HDMs were associated with cellular and metabolic processes and may be involved in the regulation of gene expression. Differentially expressed HDM genes identified in NAFLD may provide value to understanding pathogenesis and in the development of epigenetic therapeutic targets. However, on the basis of the inconsistent results of in vitro studies, future in vivo experiments combined with transcriptomic analysis are needed for further validation. Full article

(This article belongs to the Topic Computer-Based Solutions to Investigate Biological- and Health-Related Problems)

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12 pages, 3167 KiB

Open AccessArticle

Identification and Genome Characterization of Novel Feline Parvovirus Strains Isolated in Shanghai, China

by Chengqian Liu, Fusheng Si, Hong Li, Jun Gao, Fengping Sun, Huili Liu and Jianzhong Yi

Curr. Issues Mol. Biol. 2023, 45(4), 3628-3639; https://doi.org/10.3390/cimb45040236 - 20 Apr 2023

Cited by 5 | Viewed by 2700

Abstract

Feline panleukopenia virus (FPV) is the causative agent of hemorrhagic gastroenteritis in feline animals. FPV has been evolving over time, and there have been several different strains of the virus identified. Some of these strains may be more virulent or more resistant to [...] Read more.

Feline panleukopenia virus (FPV) is the causative agent of hemorrhagic gastroenteritis in feline animals. FPV has been evolving over time, and there have been several different strains of the virus identified. Some of these strains may be more virulent or more resistant to current vaccines than others, which highlights the importance of ongoing research and monitoring of FPV evolution. For FPV genetic evolution analysis, many studies focus on the main capsid protein (VP2), but limited information is available on the nonstructural gene NS1 and structural gene VP1. In the present study, we firstly isolated two novel FPV strains circulating in Shanghai, China, and performed full-length genome sequencing for the desired strains. Subsequently, we focused on analyzing the NS1, VP1 gene, and the encoding protein, and conducted a comparative analysis among the worldwide circulating FPV and Canine parvovirus Type 2 (CPV-2) strains, which included the strains isolated in this study. We found that the 2 structural viral proteins, VP1 and VP2, are splice variants, and VP1 has a 143 amino-acid-long N-terminal compared to VP2. Furthermore, phylogenetic analysis showed that divergent evolution between FPV and CPV-2 virus strains were clustered mostly by country and year of detection. In addition, much more continuous antigenic type changes happened in the process of CPV-2 circulating and evolution compared to FPV. These results stress the importance of the continuous study of viral evolution and provide a comprehensive perspective of the association between viral epidemiology and genetic evolution. Full article

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

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25 pages, 3833 KiB

Open AccessArticle

Protein Profiling in Human Papillomavirus-Associated Cervical Carcinogenesis: Cornulin as a Biomarker for Disease Progression

by Gaayathri Kumarasamy, Mohd Nazri Ismail, Sharifah Emilia Tuan Sharif, Christopher Desire, Parul Mittal, Peter Hoffmann and Gurjeet Kaur

Curr. Issues Mol. Biol. 2023, 45(4), 3603-3627; https://doi.org/10.3390/cimb45040235 - 20 Apr 2023

Cited by 3 | Viewed by 2237

Abstract

Nearly 90% of cervical cancers are linked to human papillomavirus (HPV). Uncovering the protein signatures in each histological phase of cervical oncogenesis provides a path to biomarker discovery. The proteomes extracted from formalin-fixed paraffin-embedded tissues of the normal cervix, HPV16/18-associated squamous intraepithelial lesion [...] Read more.

Nearly 90% of cervical cancers are linked to human papillomavirus (HPV). Uncovering the protein signatures in each histological phase of cervical oncogenesis provides a path to biomarker discovery. The proteomes extracted from formalin-fixed paraffin-embedded tissues of the normal cervix, HPV16/18-associated squamous intraepithelial lesion (SIL), and squamous cell carcinoma (SCC) were compared using liquid chromatography-mass spectrometry (LC-MS). A total of 3597 proteins were identified, with 589, 550, and 1570 proteins unique to the normal cervix, SIL, and SCC groups, respectively, while 332 proteins overlapped between the three groups. In the transition from normal cervix to SIL, all 39 differentially expressed proteins were downregulated, while all 51 proteins discovered were upregulated in SIL to SCC. The binding process was the top molecular function, while chromatin silencing in the SIL vs. normal group, and nucleosome assembly in SCC vs. SIL groups was the top biological process. The PI3 kinase pathway appears crucial in initiating neoplastic transformation, while viral carcinogenesis and necroptosis are important for cell proliferation, migration, and metastasis in cervical cancer development. Annexin A2 and cornulin were selected for validation based on LC-MS results. The former was downregulated in the SIL vs. normal cervix and upregulated in the progression from SIL to SCC. In contrast, cornulin exhibited the highest expression in the normal cervix and lowest in SCC. Although other proteins, such as histones, collagen, and vimentin, were differentially expressed, their ubiquitous expression in most cells precluded further analysis. Immunohistochemical analysis of tissue microarrays found no significant difference in Annexin A2 expression between the groups. Conversely, cornulin exhibited the strongest expression in the normal cervix and lowest in SCC, supporting its role as a tumor suppressor and potential biomarker for disease progression. Full article

(This article belongs to the Special Issue Adhesion, Metastasis and Inhibition of Cancer Cells)

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12 pages, 1955 KiB

Open AccessArticle

Galectin-3 Mediates Tumor Progression in Astrocytoma by Regulating Glycogen Synthase Kinase-3β Activity

by Hung-Pei Tsai, Chien-Ju Lin, Ann-Shung Lieu, Yi-Ting Chen, Tzu-Ting Tseng, Aij-Lie Kwan and Joon-Khim Loh

Curr. Issues Mol. Biol. 2023, 45(4), 3591-3602; https://doi.org/10.3390/cimb45040234 - 19 Apr 2023

Cited by 1 | Viewed by 1701

Abstract

Numerous studies have considered galectin-3 or Glycogen synthase kinase 3 beta (GSK3B) as a potential prognosis marker for various cancers. However, the correlation between the protein expression of galectin-3/GSK3B and the clinical parameters of astrocytoma has not been reported. This study aims to [...] Read more.

Numerous studies have considered galectin-3 or Glycogen synthase kinase 3 beta (GSK3B) as a potential prognosis marker for various cancers. However, the correlation between the protein expression of galectin-3/GSK3B and the clinical parameters of astrocytoma has not been reported. This study aims to validate the correlation between the clinical outcomes and protein expression of galectin-3/GSK3B in astrocytoma. Immunohistochemistry staining was performed to detect galectin-3/GSK3B protein expression in patients with astrocytoma. The Chi-square test, Kaplan−Meier evaluation, and Cox regression analysis were used to determine the correlation between clinical parameters and galectin-3/GSK3B expression. Cell proliferation, invasion, and migration were compared between a non-siRNA group and a galectin-3/GSK3B siRNA group. Protein expression in galectin-3 or GSK3B siRNA-treated cells was evaluated using western blotting. Galectin-3 and GSK3B protein expression were significantly positively correlated with the World Health Organization (WHO) astrocytoma grade and overall survival time. Multivariate analysis revealed that WHO grade, galectin-3 expression, and GSK3B expression were independent prognostic factors for astrocytoma. Galectin-3 or GSK3B downregulation induced apoptosis and decreased cell numbers, migration, and invasion. siRNA-mediated gene silencing of galectin-3 resulted in the downregulation of Ki-67, cyclin D1, VEGF, GSK3B, p-GSK3B Ser9 (p-GSK3B S9), and β-catenin. In contrast, GSK3B knockdown only decreased Ki-67, VEGF, p-GSK3B S9, and β-catenin protein expression but did not affect cyclin D1 and galectin-3 protein expression. The siRNA results indicated that GSK3B is downstream of the galectin-3 gene. These data support that galectin-3 mediated tumor progression by upregulating GSK3B and β-catenin protein expression in glioblastoma. Therefore, galectin-3 and GSK3B are potential prognostic markers, and their genes may be considered to be anticancer targets for astrocytoma therapy. Full article

(This article belongs to the Section Molecular Medicine)

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18 pages, 1463 KiB

Open AccessArticle

Study on DNA Storage Encoding Based IAOA under Innovation Constraints

by Haigui Du, Shihua Zhou, WeiQi Yan and Sijie Wang

Curr. Issues Mol. Biol. 2023, 45(4), 3573-3590; https://doi.org/10.3390/cimb45040233 - 18 Apr 2023

Cited by 1 | Viewed by 1633

Abstract

With the informationization of social processes, the amount of related data has greatly increased, making traditional storage media unable to meet the current requirements for data storage. Due to its advantages of a high storage capacity and persistence, deoxyribonucleic acid (DNA) has been [...] Read more.

With the informationization of social processes, the amount of related data has greatly increased, making traditional storage media unable to meet the current requirements for data storage. Due to its advantages of a high storage capacity and persistence, deoxyribonucleic acid (DNA) has been considered the most prospective storage media to solve the data storage problem. Synthesis is an important process for DNA storage, and low-quality DNA coding can increase errors during sequencing, which can affect the storage efficiency. To reduce errors caused by the poor stability of DNA sequences during storage, this paper proposes a method that uses the double-matching and error-pairing constraints to improve the quality of the DNA coding set. First, the double-matching and error-pairing constraints are defined to solve problems of sequences with self-complementary reactions in the solution that are prone to mismatch at the 3′ end. In addition, two strategies are introduced in the arithmetic optimization algorithm, including a random perturbation of the elementary function and a double adaptive weighting strategy. An improved arithmetic optimization algorithm (IAOA) is proposed to construct DNA coding sets. The experimental results of the IAOA on 13 benchmark functions show a significant improvement in its exploration and development capabilities over the existing algorithms. Moreover, the IAOA is used in the DNA encoding design under both traditional and new constraints. The DNA coding sets are tested to estimate their quality regarding the number of hairpins and melting temperature. The DNA storage coding sets constructed in this study are improved by 77.7% at the lower boundary compared to existing algorithms. The DNA sequences in the storage sets show a reduction of 9.7–84.1% in the melting temperature variance, and the hairpin structure ratio is reduced by 2.1–80%. The results indicate that the stability of the DNA coding sets is improved under the two proposed constraints compared to traditional constraints. Full article

(This article belongs to the Section Bioinformatics and Systems Biology)

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21 pages, 2647 KiB

Open AccessReview

Interstitial Cells of Cajal and Enteric Nervous System in Gastrointestinal and Neurological Pathology, Relation to Oxidative Stress

by Laura López-Pingarrón, Henrique Almeida, Marisol Soria-Aznar, Marcos C. Reyes-Gonzales, Ana B. Rodríguez-Moratinos, Antonio Muñoz-Hoyos and Joaquín J. García

Curr. Issues Mol. Biol. 2023, 45(4), 3552-3572; https://doi.org/10.3390/cimb45040232 - 18 Apr 2023

Cited by 12 | Viewed by 9080

Abstract

The enteric nervous system (ENS) is organized into two plexuses—submucosal and myenteric—which regulate smooth muscle contraction, secretion, and blood flow along the gastrointestinal tract under the influence of the rest of the autonomic nervous system (ANS). Interstitial cells of Cajal (ICCs) are mainly [...] Read more.

The enteric nervous system (ENS) is organized into two plexuses—submucosal and myenteric—which regulate smooth muscle contraction, secretion, and blood flow along the gastrointestinal tract under the influence of the rest of the autonomic nervous system (ANS). Interstitial cells of Cajal (ICCs) are mainly located in the submucosa between the two muscle layers and at the intramuscular level. They communicate with neurons of the enteric nerve plexuses and smooth muscle fibers and generate slow waves that contribute to the control of gastrointestinal motility. They are also involved in enteric neurotransmission and exhibit mechanoreceptor activity. A close relationship appears to exist between oxidative stress and gastrointestinal diseases, in which ICCs can play a prominent role. Thus, gastrointestinal motility disorders in patients with neurological diseases may have a common ENS and central nervous system (CNS) nexus. In fact, the deleterious effects of free radicals could affect the fine interactions between ICCs and the ENS, as well as between the ENS and the CNS. In this review, we discuss possible disturbances in enteric neurotransmission and ICC function that may cause anomalous motility in the gut. Full article

(This article belongs to the Special Issue Interstitial Cells of Cajal and Nervous System in Aging and Oxidative Stress)

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27 pages, 2186 KiB

Open AccessReview

Regulated Arginine Metabolism in Immunopathogenesis of a Wide Range of Diseases: Is There a Way to Pass between Scylla and Charybdis?

by Eleonora A. Starikova, Artem A. Rubinstein, Jennet T. Mammedova, Dmitry V. Isakov and Igor V. Kudryavtsev

Curr. Issues Mol. Biol. 2023, 45(4), 3525-3551; https://doi.org/10.3390/cimb45040231 - 18 Apr 2023

Cited by 10 | Viewed by 2872

Abstract

More than a century has passed since arginine was discovered, but the metabolism of the amino acid never ceases to amaze researchers. Being a conditionally essential amino acid, arginine performs many important homeostatic functions in the body; it is involved in the regulation [...] Read more.

More than a century has passed since arginine was discovered, but the metabolism of the amino acid never ceases to amaze researchers. Being a conditionally essential amino acid, arginine performs many important homeostatic functions in the body; it is involved in the regulation of the cardiovascular system and regeneration processes. In recent years, more and more facts have been accumulating that demonstrate a close relationship between arginine metabolic pathways and immune responses. This opens new opportunities for the development of original ways to treat diseases associated with suppressed or increased activity of the immune system. In this review, we analyze the literature describing the role of arginine metabolism in the immunopathogenesis of a wide range of diseases, and discuss arginine-dependent processes as a possible target for therapeutic approaches. Full article

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

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8 pages, 1125 KiB

Open AccessCommunication

How Does the Sample Preparation of Phytophthora infestans Mycelium Affect the Quality of Isolated RNA?

by Artemii A. Ivanov, Alexandr V. Tyapkin and Tatiana S. Golubeva

Curr. Issues Mol. Biol. 2023, 45(4), 3517-3524; https://doi.org/10.3390/cimb45040230 - 18 Apr 2023

Viewed by 1456

Abstract

RNA isolation from fungi and fungus-like organisms is not an easy task. Active endogenous RNases quickly hydrolyze RNA after the sample collection, and the thick cell wall prevents inhibitors from penetrating the cells. Therefore, the initial collection and grinding steps may be crucial [...] Read more.

RNA isolation from fungi and fungus-like organisms is not an easy task. Active endogenous RNases quickly hydrolyze RNA after the sample collection, and the thick cell wall prevents inhibitors from penetrating the cells. Therefore, the initial collection and grinding steps may be crucial for the total RNA isolation from the mycelium. When isolating RNA from Phytophthora infestans, we varied the grinding time of the Tissue Lyser and used TRIzol and beta-mercaptoethanol to inhibit the RNase. In addition, we tested the mortar and pestle grinding of mycelium in liquid nitrogen, with this method showing the most consistent results. During the sample grinding with the Tissue Lyser device, adding an RNase inhibitor proved to be a prerequisite, and the best results were achieved using TRIzol. We considered ten different combinations of grinding conditions and isolation methods. The classical combination of a mortar and pestle, followed by TRIzol, has proved to be the most efficient. Full article

(This article belongs to the Special Issue Microbial Engineering: Gene Expression Regulation and Its Application)

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2 pages, 177 KiB

Open AccessEditorial

Editorial for the Special Issue “Genetic Sight: Plant Traits during Postharvest”

by Shimeles Tilahun

Curr. Issues Mol. Biol. 2023, 45(4), 3515-3516; https://doi.org/10.3390/cimb45040229 - 18 Apr 2023

Viewed by 1209

Abstract

Modern breeding alternatives are less costly and sustainable solutions to increase quality, resistance to biotic and abiotic stresses, and to reduce postharvest losses of crops [...] Full article

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

36 pages, 666 KiB

Open AccessReview

Cannabis Pharmacogenomics: A Path to Personalized Medicine

by Mariana Babayeva and Zvi G. Loewy

Curr. Issues Mol. Biol. 2023, 45(4), 3479-3514; https://doi.org/10.3390/cimb45040228 - 17 Apr 2023

Cited by 9 | Viewed by 5543

Abstract

Cannabis and related compounds have created significant research interest as a promising therapy in many disorders. However, the individual therapeutic effects of cannabinoids and the incidence of side effects are still difficult to determine. Pharmacogenomics may provide the answers to many questions and [...] Read more.

Cannabis and related compounds have created significant research interest as a promising therapy in many disorders. However, the individual therapeutic effects of cannabinoids and the incidence of side effects are still difficult to determine. Pharmacogenomics may provide the answers to many questions and concerns regarding the cannabis/cannabinoid treatment and help us to understand the variability in individual responses and associated risks. Pharmacogenomics research has made meaningful progress in identifying genetic variations that play a critical role in interpatient variability in response to cannabis. This review classifies the current knowledge of pharmacogenomics associated with medical marijuana and related compounds and can assist in improving the outcomes of cannabinoid therapy and to minimize the adverse effects of cannabis use. Specific examples of pharmacogenomics informing pharmacotherapy as a path to personalized medicine are discussed. Full article

(This article belongs to the Special Issue Drugs: Mechanisms of Action, Molecular Targets and Biological Activities)

17 pages, 2247 KiB

Open AccessArticle

Molecular Heterogeneity of the Brain Endothelium

by Nada Alnaqbi, Mohammad G. Mohammad, Rifat Hamoudi, Aloïse Mabondzo and Rania Harati

Curr. Issues Mol. Biol. 2023, 45(4), 3462-3478; https://doi.org/10.3390/cimb45040227 - 16 Apr 2023

Cited by 3 | Viewed by 2348

Abstract

The blood–brain barrier (BBB) is part of a neurovascular structure located in the brain’s micro vessels, that is essential to maintain brain homeostasis, but prevents the brain uptake of most drugs. Because of its importance in neuro-pharmacotherapy, the BBB has been the subject [...] Read more.

The blood–brain barrier (BBB) is part of a neurovascular structure located in the brain’s micro vessels, that is essential to maintain brain homeostasis, but prevents the brain uptake of most drugs. Because of its importance in neuro-pharmacotherapy, the BBB has been the subject of extensive research since its discovery over 100 years ago. Major advances in understanding the structure and function of the barrier have been made. Drugs are re-designed to cross the BBB. However, despite these efforts, overcoming the BBB efficiently to treat brain diseases safely remains challenging. The majority of BBB research studies focus on the BBB as a homogenous structure throughout the different brain regions. However, this simplification may lead to an inadequate understanding of the BBB function with significant therapeutic consequences. From this perspective, we analyzed the gene and protein expression profiles of the BBB in the micro vessels from the brains of mice that were isolated from two different brain regions, namely the cortex and the hippocampus. The expression profile of the inter-endothelial junctional protein (claudin-5), three ABC transporters (P-glycoprotein, Bcrp and Mrp-1), and three BBB receptors (lrp-1, TRF and GLUT-1) were analyzed. Our gene and protein analysis showed that the brain endothelium in the hippocampus exhibits different expression profiles compared to the brain cortex. Specifically, brain endothelial cells (BECs) of the hippocampus express higher gene levels of abcb1, abcg2, lrp1, and slc2a1 compared to the BECs of the cortex regions with a trend of increase for claudin-5, while BECs of the cortex express higher gene levels of abcc1 and trf compared to the hippocampus. At the protein levels, the P-gp expression was found to be significantly higher in the hippocampus compared to the cortex, while TRF was found to be up-regulated in the cortex. These data suggest that the structure and function of the BBB are not homogeneous, and imply that drugs are not delivered similarly among the different brain regions. Appreciation of the BBB heterogeneity by future research programs is thus critical for efficient drug delivery and the treatment of brain diseases. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning, 2nd Volume)

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16 pages, 3028 KiB

Open AccessCommunication

Mouse CCL9 Chemokine Acts as Tumor Suppressor in a Murine Model of Colon Cancer

by Marzena Łazarczyk, Ewa Kurzejamska, Michel-Edwar Mickael, Piotr Poznański, Dominik Skiba, Mariusz Sacharczuk, Zbigniew Gaciong and Piotr Religa

Curr. Issues Mol. Biol. 2023, 45(4), 3446-3461; https://doi.org/10.3390/cimb45040226 - 15 Apr 2023

Viewed by 2245

Abstract

Colorectal cancer is the third most frequently diagnosed cancer in the world. Despite extensive studies and apparent progress in modern strategies for disease control, the treatment options are still not sufficient and effective, mostly due to frequently encountered resistance to immunotherapy of colon [...] Read more.

Colorectal cancer is the third most frequently diagnosed cancer in the world. Despite extensive studies and apparent progress in modern strategies for disease control, the treatment options are still not sufficient and effective, mostly due to frequently encountered resistance to immunotherapy of colon cancer patients in common clinical practice. In our study, we aimed to uncover the CCL9 chemokine action employing the murine model of colon cancer to seek new, potential molecular targets that could be promising in the development of colon cancer therapy. Mouse CT26.CL25 colon cancer cell line was used for introducing lentivirus-mediated CCL9 overexpression. The blank control cell line contained an empty vector, while the cell line marked as CCL9+ carried the CCL9-overexpressing vector. Next, cancer cells with empty vector (control) or CCL9-overexpressing cells were injected subcutaneously, and the growing tumors were measured within 2 weeks. Surprisingly, CCL9 contributed to a decline in tumor growth in vivo but had no effect on CT26.CL25 cell proliferation or migration in vitro. Microarray analysis of the collected tumor tissues revealed upregulation of the immune system-related genes in the CCL9 group. Obtained results suggest that CCL9 reveals its anti-proliferative functions by interplay with host immune cells and mediators that were absent in the isolated, in vitro system. Under specific study conditions, we determined unknown features of the murine CCL9 that have so far bee reported to be predominantly pro-oncogenic. Full article

(This article belongs to the Special Issue Adhesion, Metastasis and Inhibition of Cancer Cells)

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12 pages, 2060 KiB

Open AccessArticle

Elicitation of Inhibitory Effects for AGE-Induced Oxidative Stress in Rotator Cuff-Derived Cells by Apocynin

by Takahiro Furukawa, Takashi Kurosawa, Yutaka Mifune, Atsuyuki Inui, Hanako Nishimoto, Yasuhiro Ueda, Takeshi Kataoka, Kohei Yamaura, Shintaro Mukohara, Tomoya Yoshikawa, Issei Shinohara, Tatsuo Kato, Shuya Tanaka, Masaya Kusunose, Yuichi Hoshino, Takehiko Matsushita and Ryosuke Kuroda

Curr. Issues Mol. Biol. 2023, 45(4), 3434-3445; https://doi.org/10.3390/cimb45040225 - 14 Apr 2023

Cited by 2 | Viewed by 1887

Abstract

Advanced glycation end-products (AGEs) play a critical supportive role during musculoskeletal disorders via glycosylation and oxidative stress. Though apocynin, identified as a potent and selective inhibitor of NADPH oxidase, has been reported to be involved in pathogen-induced reactive oxygen species (ROS), its role [...] Read more.

Advanced glycation end-products (AGEs) play a critical supportive role during musculoskeletal disorders via glycosylation and oxidative stress. Though apocynin, identified as a potent and selective inhibitor of NADPH oxidase, has been reported to be involved in pathogen-induced reactive oxygen species (ROS), its role in age-related rotator cuff degeneration has not been well clarified. Therefore, this study aims to evaluate the in vitro effects of apocynin on human rotator cuff-derived cells. Twelve patients with rotator cuff tears (RCTs) participated in the study. Supraspinatus tendons from patients with RCTs were collected and cultured. After the preparation of RC-derived cells, they were divided into four groups (control group, control + apocynin group, AGEs group, AGEs + apocynin group), and gene marker expression, cell viability, and intracellular ROS production were evaluated. The gene expression of NOX, IL-6, and the receptor for AGEs (RAGE) was significantly decreased by apocynin. We also examined the effect of apocynin in vitro. The results showed that ROS induction and increasing apoptotic cells after treatment of AGEs were significantly decreased, and cell viability increased considerably. These results suggest that apocynin can effectively reduce AGE-induced oxidative stress by inhibiting NOX activation. Thus, apocynin is a potential prodrug in preventing degenerative changes of the rotor cuff. Full article

(This article belongs to the Topic Oxidative Stress and Mitochondrial Dysfunction in Metabolic and Inflammatory Diseases)

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15 pages, 2650 KiB

Open AccessArticle

Genetic Mapping and QTL Analysis of Fruit Traits in Melon (Cucumis melo L.)

by Haiyong Zhao, Taifeng Zhang, Xiaobing Meng, Jiayan Song, Chen Zhang and Peng Gao

Curr. Issues Mol. Biol. 2023, 45(4), 3419-3433; https://doi.org/10.3390/cimb45040224 - 14 Apr 2023

Cited by 8 | Viewed by 2872

Abstract

Melon (Cucumis melo L.) is an important horticultural cash crop and its quality traits directly affect consumer choice and market price. These traits are controlled by genetic as well as environmental factors. In this study, a quantitative trait locus (QTL) mapping strategy [...] Read more.

Melon (Cucumis melo L.) is an important horticultural cash crop and its quality traits directly affect consumer choice and market price. These traits are controlled by genetic as well as environmental factors. In this study, a quantitative trait locus (QTL) mapping strategy was used to identify the potential genetic loci controlling quality traits of melons (i.e., exocarp and pericarp firmness and soluble solid content) based on newly derived whole-genome single nucleotide polymorphism-based cleaved amplified polymorphic sequence (SNP-CAPS) markers. Specifically, SNPs of two melon varieties, M4-5 and M1-15, as revealed by whole-genome sequencing, were converted to the CAPS markers, which were used to construct a genetic linkage map comprising 12 chromosomes with a total length of 1414.88 cM, in the F₂ population of M4-5 and M1-15. The six identified QTLs included: SSC6.1 and SSC11.1 related to soluble solid content; EF12.1 associated with exocarp firmness; and EPF3.1, EPF3.2 and EPF7.1 related to edible pericarp firmness. These genes were located on five chromosomes (3, 6, 7, 11, and 12) in the flanking regions of the CAPS markers. Moreover, the newly developed CAPS markers will be useful in guiding genetic engineering and molecular breeding in melon. Full article

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

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13 pages, 3231 KiB

Open AccessReview

Identification of Potential Therapeutic Targets on the Level of DNA/mRNAs, Proteins and Metabolites: A Systematic Mapping Review of Scientific Texts’ Fragments from Open Targets

by Pavel V. Pogodin, Olga I. Kiseleva and Ekaterina V. Ilgisonis

Curr. Issues Mol. Biol. 2023, 45(4), 3406-3418; https://doi.org/10.3390/cimb45040223 - 13 Apr 2023

Viewed by 1427

Abstract

Database records contain useful information, which is readily available, but, unfortunately, limited compared to the source (publications). Our study reviewed the text fragments supporting the association between the biological macromolecules and diseases from Open Targets to map them on the biological level of [...] Read more.

Database records contain useful information, which is readily available, but, unfortunately, limited compared to the source (publications). Our study reviewed the text fragments supporting the association between the biological macromolecules and diseases from Open Targets to map them on the biological level of study (DNA/RNA, proteins, metabolites). We screened records using a dictionary containing terms related to the selected levels of study, reviewed 600 hits manually and used machine learning to classify 31,260 text fragments. Our results indicate that association studies between diseases and macromolecules conducted on the level of DNA and RNA prevail, followed by the studies on the level of proteins and metabolites. We conclude that there is a clear need to translate the knowledge from the DNA/RNA level to the evidence on the level of proteins and metabolites. Since genes and their transcripts rarely act in the cell by themselves, more direct evidence may be of greater value for basic and applied research. Full article

(This article belongs to the Special Issue Drugs: Mechanisms of Action, Molecular Targets and Biological Activities)

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15 pages, 2275 KiB

Open AccessArticle

AKR1B1 Represses Glioma Cell Proliferation through p38 MAPK-Mediated Bcl-2/BAX/Caspase-3 Apoptotic Signaling Pathways

by Yu-Kai Huang, Kun-Che Chang, Chia-Yang Li, Ann-Shung Lieu and Chih-Lung Lin

Curr. Issues Mol. Biol. 2023, 45(4), 3391-3405; https://doi.org/10.3390/cimb45040222 - 13 Apr 2023

Cited by 13 | Viewed by 2501

Abstract

This study aimed to investigate the regulatory role of Aldo-keto reductase family 1 member B1 (AKR1B1) in glioma cell proliferation through p38 MAPK activation to control Bcl-2/BAX/caspase-3 apoptosis signaling. AKR1B1 expression was quantified in normal human astrocytes, glioblastoma multiforme (GBM) cell lines, and [...] Read more.

This study aimed to investigate the regulatory role of Aldo-keto reductase family 1 member B1 (AKR1B1) in glioma cell proliferation through p38 MAPK activation to control Bcl-2/BAX/caspase-3 apoptosis signaling. AKR1B1 expression was quantified in normal human astrocytes, glioblastoma multiforme (GBM) cell lines, and normal tissues by using quantitative real-time polymerase chain reaction. The effects of AKR1B1 overexpression or knockdown and those of AKR1B1-induced p38 MAPK phosphorylation and a p38 MAPK inhibitor (SB203580) on glioma cell proliferation were determined using an MTT assay and Western blot, respectively. Furthermore, the AKR1B1 effect on BAX and Bcl-2 expression was examined in real-time by Western blot. A luminescence detection reagent was also utilized to identify the effect of AKR1B1 on caspase-3/7 activity. The early and late stages of AKR1B1-induced apoptosis were assessed by performing Annexin V-FITC/PI double-staining assays. AKR1B1 expression was significantly downregulated in glioma tissues and GBM cell lines (T98G and 8401). Glioma cell proliferation was inhibited by AKR1B1 overexpression but was slightly increased by AKR1B1 knockdown. Additionally, AKR1B1-induced p38 MAPK phosphorylation and SB203580 reversed AKR1B1′s inhibitory effect on glioma cell proliferation. AKR1B1 overexpression also inhibited Bcl-2 expression but increased BAX expression, whereas treatment with SB203580 reversed this phenomenon. Furthermore, AKR1B1 induced caspase-3/7 activity. The induction of early and late apoptosis by AKR1B1 was confirmed using an Annexin V-FITC/PI double-staining assay. In conclusion, AKR1B1 regulated glioma cell proliferation through the involvement of p38 MAPK-induced BAX/Bcl-2/caspase-3 apoptosis signaling. Therefore, AKR1B1 may serve as a new therapeutic target for glioma therapy development. Full article

(This article belongs to the Section Molecular Medicine)

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16 pages, 5221 KiB

Open AccessArticle

FtbZIP85 Is Involved in the Accumulation of Proanthocyanidin by Regulating the Transcription of FtDFR in Tartary Buckwheat

by Shuangshuang Liu, Jianmei Wang, Zhibin Liu, Yi Yang and Xiaoyi Li

Curr. Issues Mol. Biol. 2023, 45(4), 3375-3390; https://doi.org/10.3390/cimb45040221 - 13 Apr 2023

Cited by 1 | Viewed by 1577

Abstract

As a drought-tolerant crop, Tartary buckwheat survives under adverse environmental conditions, including drought stress. Proanthocyanidins (PAs) and anthocyanins are flavonoid compounds, and they participate in the regulation of resistance to both biotic and abiotic stresses by triggering genes’ biosynthesis of flavonoids. In this [...] Read more.

As a drought-tolerant crop, Tartary buckwheat survives under adverse environmental conditions, including drought stress. Proanthocyanidins (PAs) and anthocyanins are flavonoid compounds, and they participate in the regulation of resistance to both biotic and abiotic stresses by triggering genes’ biosynthesis of flavonoids. In this study, a basic leucine zipper, basic leucine zipper 85 (FtbZIP85), which was predominantly expressed in seeds, was isolated from Tartary buckwheat. Our study shows that the expressions of FtDFR, FtbZIP85 and FtSnRK2.6 were tissue-specific and located in both the nucleus and the cytosol. FtbZIP85 could positively regulate PA biosynthesis by binding to the ABA-responsive element (ABRE) in the promoter of dihydroflavonol 4-reductase (FtDFR), which is a key enzyme in the phenylpropanoid biosynthetic pathway. Additionally, FtbZIP85 was also involved in the regulation of PA biosynthesis via interactions with FtSnRK2.6 but not with FtSnRK2.2/2.3. This study reveals that FtbZIP85 is a positive regulator of PA biosynthesis in TB. Full article

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

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16 pages, 795 KiB

Open AccessReview

The Current Status and Future Perspectives of Chimeric Antigen Receptor-Engineered T Cell Therapy for the Management of Patients with Endometrial Cancer

by Ji-Young Choi and Tae-Jin Kim

Curr. Issues Mol. Biol. 2023, 45(4), 3359-3374; https://doi.org/10.3390/cimb45040220 - 12 Apr 2023

Cited by 2 | Viewed by 2525

Abstract

Endometrial cancer (EC) is a gynecological neoplasm that is increasing in occurrence and mortality rates. Although endometrial cancer in the early stages shows a relatively favorable prognosis, there is an increase in cancer-related mortality rates in the advanced or recurrent endometrial carcinoma population [...] Read more.

Endometrial cancer (EC) is a gynecological neoplasm that is increasing in occurrence and mortality rates. Although endometrial cancer in the early stages shows a relatively favorable prognosis, there is an increase in cancer-related mortality rates in the advanced or recurrent endometrial carcinoma population and patients in the metastatic setting. This discrepancy has presented an opportunity for research and development of target therapies in this population. After obtaining promising results with hematologic cancers, chimeric antigen receptor (CAR)-T cell immunotherapy is gaining acceptance as a treatment for solid neoplasms. This treatment platform allows T cells to express tumor-specific CARs on the cell surface, which are administered to the patient to treat neoplastic cells. Given that CAR-T cell therapy has shown potential and clinical benefit compared to other T cell treatment platforms, additional research is required to overcome physiological limitations such as CAR-T cell depletion, immunosuppressive tumor microenvironment, and the lack of specific target molecules. Different approaches and development are ongoing to overcome these complications. This review examines CAR-T cell therapy’s current use for endometrial carcinomas. We also discuss the significant adverse effects and limitations of this immunotherapeutic approach. Finally, we consolidate signal-seeking early-phase clinical trials and advancements that have shown promising results, leading to the approval of new immunotherapeutic agents for the disease. Full article

(This article belongs to the Special Issue Targeting Tumor Microenvironment for Cancer Therapy)

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12 pages, 1790 KiB

Open AccessArticle

Specific Targeting and Labeling of Colonic Polyps in CPC-APC Mice with Mucin 5AC Fluorescent Antibodies: A Model for Detection of Early Colon Cancer

by Michael A. Turner, Kristin E. Cox, Shanglei Liu, Nicholas Neel, Siamak Amirfakhri, Hiroto Nishino, Mojgan Hosseini, Joshua A. Alcantara, Amer Ali Abd El-Hafeez, Thinzar M. Lwin, Kavita Mallya, Joseph R. Pisegna, Satish K. Singh, Pradipta Ghosh, Robert M. Hoffman, Surinder K. Batra and Michael Bouvet

Curr. Issues Mol. Biol. 2023, 45(4), 3347-3358; https://doi.org/10.3390/cimb45040219 - 11 Apr 2023

Cited by 1 | Viewed by 2553

Abstract

Poor visualization of polyps can limit colorectal cancer screening. Fluorescent antibodies to mucin5AC (MUC5AC), a glycoprotein upregulated in adenomas and colorectal cancer, could improve screening colonoscopy polyp detection rate. Adenomatous polyposis coli flox mice with a Cdx2-Cre transgene (CPC-APC) develop colonic [...] Read more.

Poor visualization of polyps can limit colorectal cancer screening. Fluorescent antibodies to mucin5AC (MUC5AC), a glycoprotein upregulated in adenomas and colorectal cancer, could improve screening colonoscopy polyp detection rate. Adenomatous polyposis coli flox mice with a Cdx2-Cre transgene (CPC-APC) develop colonic polyps that contain both dysplastic and malignant tissue. Mice received MUC5AC-IR800 or IRdye800 as a control IV and were sacrificed after 48 h for near-infrared imaging of their colons. A polyp-to-background ratio (PBR) was calculated for each polyp by dividing the mean fluorescence intensity of the polyp by the mean fluorescence intensity of the background tissue. The mean 25 μg PBR was 1.70 (±0.56); the mean 50 μg PBR was 2.64 (±0.97); the mean 100 μg PBR was 3.32 (±1.33); and the mean 150 μg PBR was 3.38 (±0.87). The mean PBR of the dye-only control was 2.22 (±1.02), significantly less than the 150 μg arm (p-value 0.008). The present study demonstrates the ability of fluorescent anti-MUC5AC antibodies to specifically target and label colonic polyps containing high-grade dysplasia and intramucosal adenocarcinoma in CPC-APC mice. This technology can potentially improve the detection rate and decrease the miss rate of advanced colonic neoplasia and early cancer at colonoscopy. Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers)

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14 pages, 3698 KiB

Open AccessArticle

The Involvement of Hypoxia in the Response of Neuroblastoma Cells to the Exposure of Atorvastatin

by Ana Salomé Correia, Lara Marques and Nuno Vale

Curr. Issues Mol. Biol. 2023, 45(4), 3333-3346; https://doi.org/10.3390/cimb45040218 - 11 Apr 2023

Cited by 2 | Viewed by 1944

Abstract

Cancer is a set of complex diseases, being one of the leading causes of death worldwide. Despite a lot of research on the molecular pathways and effective treatments, there are still huge gaps. Indeed, the development of new anti-cancer drugs is a complex [...] Read more.

Cancer is a set of complex diseases, being one of the leading causes of death worldwide. Despite a lot of research on the molecular pathways and effective treatments, there are still huge gaps. Indeed, the development of new anti-cancer drugs is a complex process. To face this problem, drug repurposing is being increasingly applied. This approach aims to identify new indications for already approved drugs. In this regard, statins (clinically used for reducing cholesterol levels) are reported to induce anti-cancer effects, particularly by inducing apoptosis and altering the tumor microenvironment. Atorvastatin is a type of statin with several potentialities as an anti-cancer agent, supported by several studies. Our study aimed to explore the effect of this drug in SH-SY5Y human neuroblastoma cells. Additionally, we also aimed to understand how this drug acts under hypoxia and the inhibition of hypoxia-inducible factor-1 (HIF-1). For that purpose, we assessed cellular viability/morphology after exposure to different concentrations of atorvastatin, with or without chemically induced hypoxia with chloride cobalt (CoCl₂) and with or without echinomycin (HIF-1α inhibitor). Our results supported the cytotoxic effects of atorvastatin. Additionally, we also revealed that besides these effects, under hypoxia, this drug induced proliferation of the neuroblastoma cells, supporting the importance of different stimuli and environment on the effect of drugs on cancer cells. Full article

(This article belongs to the Special Issue Targeting Tumor Microenvironment for Cancer Therapy)

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18 pages, 1345 KiB

Open AccessReview

Role of Oxidative Stress on the Etiology and Pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and Its Relation with the Enteric Nervous System

by Laura López-Pingarrón, Henrique Almeida, Marisol Soria-Aznar, Marcos C. Reyes-Gonzales, María Pilar Terrón and Joaquín J. García

Curr. Issues Mol. Biol. 2023, 45(4), 3315-3332; https://doi.org/10.3390/cimb45040217 - 7 Apr 2023

Cited by 14 | Viewed by 3328

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons in the spinal cord, cerebral cortex, and medulla oblongata. Most patients present a clinical phenotype of classic ALS—with predominant atrophy, muscle weakness, and fasciculations—and survival of 3 to 5 years following [...] Read more.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons in the spinal cord, cerebral cortex, and medulla oblongata. Most patients present a clinical phenotype of classic ALS—with predominant atrophy, muscle weakness, and fasciculations—and survival of 3 to 5 years following diagnosis. In the present review, we performed a literature search to provide an update on the etiology and pathophysiological mechanisms involved in ALS. There are two types of ALS: the familial form with genetic involvement, and the sporadic form with a multifactorial origin. ALS pathophysiology is characterized by involvement of multiple processes, including oxidative stress, glutamate excitotoxicity, and neuroinflammation. Moreover, it is proposed that conditioning risk factors affect ALS development, such as susceptibility to neurodegeneration in motor neurons, the intensity of performed physical activity, and intestinal dysbiosis with involvement of the enteric nervous system, which supports the existing theories of disease generation. To improve patients’ prognosis and survival, it is necessary to further deepen our understanding of the etiopathogenesis of ALS. Full article

(This article belongs to the Special Issue Interstitial Cells of Cajal and Nervous System in Aging and Oxidative Stress)

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13 pages, 459 KiB

Open AccessReview

The Role of Intravesicular Proteins and the Protein Corona of Extracellular Vesicles in the Development of Drug-Induced Polyneuropathy

by Natalia V. Yunusova, Natalia O. Popova, Irina N. Udintseva, Tatyana S. Klyushina, Daria V. Kazantseva and Liudmila P. Smirnova

Curr. Issues Mol. Biol. 2023, 45(4), 3302-3314; https://doi.org/10.3390/cimb45040216 - 7 Apr 2023

Cited by 2 | Viewed by 2063

Abstract

Extracellular vesicles (EVs) as membrane structures of cellular origin participating in intercellular communication are involved in the molecular mechanisms of the development of various variants of polyneuropathy. Taking into account the increasing role of the protein corona of EVs and protein-protein interactions on [...] Read more.

Extracellular vesicles (EVs) as membrane structures of cellular origin participating in intercellular communication are involved in the molecular mechanisms of the development of various variants of polyneuropathy. Taking into account the increasing role of the protein corona of EVs and protein-protein interactions on the surface of EVs in the pathogenesis of various diseases, we focused our attention in this review on the role of intravesicular proteins and the protein corona of EVs in the development of chemotherapy-induced polyneuropathy (CIPN). It has been shown that EVs are effectively internalized by the mechanisms of endocytosis and macropinocytosis by neurocytes and glial cells, carry markers of insulin resistance, functionally active proteins (receptors, cytokines, enzymes), and may be involved in the pathogenesis of CIPN. The mechanisms of CIPN associated with the EVs protein corona can be related with the accumulation of heavy chains of circulating IgG in it. G-class immunoglobulins in EVs are likely to have myelin hydrolyzing, superoxide dismutase, and oxidoreductase enzymatic activities. Moreover, circulating IgG-loaded EVs are a place for complement activation that can lead to membrane attack complex deposition in neuroglia and neurons. The mechanisms of CIPN development that are not associated with IgG in the EVs protein corona are somehow related to the fact that many anticancer drugs induce apoptosis of tumor cells, neurons, and neuroglial cells by various mechanisms. This process may be accompanied by the secretion of EVs with modified cargo (HSPs, 20S proteasomes, miRNAs). Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers)

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11 pages, 289 KiB

Open AccessArticle

Serum Growth Factors in Schizophrenia Patients

by Anastasiia S. Boiko, Irina A. Mednova, Elena G. Kornetova, Nikolay A. Bokhan and Svetlana A. Ivanova

Curr. Issues Mol. Biol. 2023, 45(4), 3291-3301; https://doi.org/10.3390/cimb45040215 - 7 Apr 2023

Cited by 2 | Viewed by 1613

Abstract

Some hypotheses include schizophrenia as a neurodevelopmental disorder, which indicates a special role in growth factors and neuroglia in the development of schizophrenia symptoms. Growth factors are cytokine molecules that play an important role in the regulation of tissue nucleation, cell development, survival, [...] Read more.

Some hypotheses include schizophrenia as a neurodevelopmental disorder, which indicates a special role in growth factors and neuroglia in the development of schizophrenia symptoms. Growth factors are cytokine molecules that play an important role in the regulation of tissue nucleation, cell development, survival, and migration of all tissues in organisms, including the brain and nervous system. The aim of the study was to determine the serum concentration of six growth factors (EGF, VEGF, FGF-2, TGF-α, PDGF-AA, PDGF-AB/BB) in schizophrenia patients and to identify the correlations with clinical characteristics. After signing an informed consent form, 236 schizophrenia patients (F20 according to the ICD-10) and 102 healthy people were recruited in the study. In patients with schizophrenia, we observed a significant elevation in the TGF-α and PDGF-AA serum levels. The duration of schizophrenia was significantly positively correlated with the FGF-2 level. The PANSS total score had a positive correlation with the FGF-2 level and a negative correlation with the TGF-α level. Our results and literature indicate the involvement of growth factors in the mechanisms of development of schizophrenia. Combined biomarker screening seems to be necessary to improve diagnosis and clinical follow-up of patients with severe mental illnesses. Full article

(This article belongs to the Special Issue Neuropathology: From Molecular Mechanisms to Therapeutic Solutions)

12 pages, 619 KiB

Open AccessArticle

A Comparative Study on the Carcass and Meat Chemical Composition, and Lipid-Metabolism-Related Gene Expression in Korean Hanwoo and Brindle Chikso Cattle

by Van-Ba Hoa, Dong-Heon Song, Kuk-Hwan Seol, Sun-Moon Kang, Hyun-Wook Kim, In-Seon Bae, Eun-Sung Kim, Yeon-Soo Park and Soo-Hyun Cho

Curr. Issues Mol. Biol. 2023, 45(4), 3279-3290; https://doi.org/10.3390/cimb45040214 - 7 Apr 2023

Cited by 3 | Viewed by 1991

Abstract

The objective of this study was to elucidate the effect of cattle breed on carcass and meat chemical composition, fatty acid profiles, and lipid-metabolism-related genes. For this study, same-age Hanwoo and Chikso steers (n = 6 per breed) reared under identical conditions [...] Read more.

The objective of this study was to elucidate the effect of cattle breed on carcass and meat chemical composition, fatty acid profiles, and lipid-metabolism-related genes. For this study, same-age Hanwoo and Chikso steers (n = 6 per breed) reared under identical conditions were used. Immediately after slaughter, muscle tissues were collected for analysis of mRNA expression. At 24 h post-mortem, the carcasses were assessed for carcass traits (marbling score, meat yield, etc.), and meat quality and fatty acid profiles in the longissimus lumborum (LL) and semimembranosus (SM) muscles. The results showed that no differences in the slaughter weight, dressing rate, back-fat thickness, trimmed fat, and total meat yield occurred between the two breeds (p > 0.05). However, Hanwoo cattle had a higher marbling score, intramuscular fat (IMF) content, and expression level of lipid-metabolism-related genes such as lipoprotein lipase, peroxisome proliferator-activated receptor gamma, and fatty acid binding protein 4, compared with Chikso (p < 0.05). Contrastingly, Chikso had a higher total unsaturated fatty acid content and expression level of stearoyl CoA desaturase 1 (p < 0.05). It may be said that the difference in the expression levels of lipid-metabolism-related genes could be the molecular factors underlying IMF deposition and fatty acid profile differences in the beef from the two breeds. Full article

(This article belongs to the Special Issue Understanding Adipose Tissue: A Molecular Perspective)

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11 pages, 762 KiB

Open AccessCommunication

The Potential Association between E2F2, MDM2 and p16 Protein Concentration and Selected Sociodemographic and Clinicopathological Characteristics of Patients with Oral Squamous Cell Carcinoma

by Agata Świętek, Karolina Gołąbek, Dorota Hudy, Jadwiga Gaździcka, Krzysztof Biernacki, Katarzyna Miśkiewicz-Orczyk, Natalia Zięba, Maciej Misiołek and Joanna Katarzyna Strzelczyk

Curr. Issues Mol. Biol. 2023, 45(4), 3268-3278; https://doi.org/10.3390/cimb45040213 - 7 Apr 2023

Cited by 3 | Viewed by 1647

Abstract

Background: E2F transcription factor 2 (E2F2), murine double minute 2 (MDM2) and p16 are some of the key proteins associated with the control of the cell cycle. The aim of this study was to evaluate E2F2, MDM2 and p16 concentrations in the tumour [...] Read more.

Background: E2F transcription factor 2 (E2F2), murine double minute 2 (MDM2) and p16 are some of the key proteins associated with the control of the cell cycle. The aim of this study was to evaluate E2F2, MDM2 and p16 concentrations in the tumour and margin samples of oral squamous cell carcinoma and to assess their association with some selected sociodemographic and clinicopathological characteristics of the patients. Methods: The study group consisted of 73 patients. Protein concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Results: There were no statistically significant differences in the levels of E2F2, MDM2 or p16 in the tumour samples as compared to the margin specimens. We found that patients with N0 showed significantly lower E2F2 concentrations than patients with N1 in the tumour samples and the median protein concentration of E2F2 was higher in HPV-negative patients in the tumour samples. Moreover, the level of p16 in the margin samples was lower in alcohol drinkers as compared to non-drinkers. Similar observations were found in concurrent drinkers and smokers compared to non-drinkers and non-smokers. Conclusions: E2F2 could potentially promote tumour progression and metastasis. Moreover, our results showed a differential level of the analysed proteins in response to alcohol consumption and the HPV status. Full article

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

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13 pages, 47245 KiB

Open AccessArticle

Protective Effect of Curculigo orchioides Gaertn. Extract on Heat Stress-Induced Spermatogenesis Complications in Murine Model

by Thanh-Nhan Bui-Le, Quang Hoang-Tan, Huong Hoang-Viet, Bich-Phuong Truong-Thi and Tung Nguyen-Thanh

Curr. Issues Mol. Biol. 2023, 45(4), 3255-3267; https://doi.org/10.3390/cimb45040212 - 7 Apr 2023

Cited by 5 | Viewed by 2539

Abstract

Curculigo orchioides Gaertn. is a precious herb used in traditional medicine systems in Asian countries for various health benefits. This study investigated the potential protective effects of C. orchioides extract on reproductive health under heat stress conditions in male mice. Forty-eight mice were [...] Read more.

Curculigo orchioides Gaertn. is a precious herb used in traditional medicine systems in Asian countries for various health benefits. This study investigated the potential protective effects of C. orchioides extract on reproductive health under heat stress conditions in male mice. Forty-eight mice were divided into eight groups, control condition (C group), C. orchioides extract at the dosages of 100, 200, and 400 mg/kg/day (C100, C200, C400 group), 40 °C heat exposure (H group), and combined 40 °C heat exposure and C. orchioides extract at the dosages of 100, 200, and 400 mg/kg/day (HC100, HC200, HC400 group). The result shows that the mice that received only C. orchioides extract without heat stress do not have a significant change in histological structure and testosterone level. The histological analysis of testicular tissue showed that heat stress conditions reduced reproductive function and inhibited the spermatogenesis of male mice. The C. orchioides rhizome extract treatment attenuated the heat stress-induced spermatogenesis complications in the murine model. Mice in the heat-stress group treated with C. orchioides extract had increased spermatogenic cells and spermatozoa compared with mice exposed to heat without C. orchioides treatment. Moreover, the aqueous extract of C. orchioides rhizome enhanced the serum total testosterone levels in heat-exposed mice. In conclusion, the study findings validate that C. orchioides is effective against heat stress-induced spermatogenesis complications in the murine model. Full article

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

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17 pages, 10420 KiB

Open AccessArticle

Effects of Whole-Body Vibration and Manually Assisted Locomotor Therapy on Neurotrophin-3 Expression and Microglia/Macrophage Mobilization Following Thoracic Spinal Cord Injury in Rats

by Diana Schaufler, Maria Eleni Manthou, Paschalis Theotokis, Svenja Rink-Notzon and Doychin N. Angelov

Curr. Issues Mol. Biol. 2023, 45(4), 3238-3254; https://doi.org/10.3390/cimb45040211 - 7 Apr 2023

Cited by 3 | Viewed by 2227

Abstract

Microglial cells play an important role in neuroinflammation and secondary damages after spinal cord injury (SCI). Progressive microglia/macrophage inflammation along the entire spinal axis follows SCI, and various factors may determine the microglial activation profile. Neurotrophin-3 (NT-3) is known to control the survival [...] Read more.

Microglial cells play an important role in neuroinflammation and secondary damages after spinal cord injury (SCI). Progressive microglia/macrophage inflammation along the entire spinal axis follows SCI, and various factors may determine the microglial activation profile. Neurotrophin-3 (NT-3) is known to control the survival of neurons, the function of synapses, and the release of neurotransmitters, while also stimulating axon plasticity and growth. We examined the effects of whole-body vibration (WBV) and forms of assisted locomotor therapy, such as passive flexion–extension (PFE) therapy, at the neuronal level after SCI, with a focus on changes in NT-3 expression and on microglia/macrophage reaction, as they play a major role in the reconstitution of CNS integrity after injury and they may critically account for the observed structural and functional benefits of physical therapy. More specifically, the WBV therapy resulted in the best overall functional recovery when initiated at day 14, while inducing a decrease in Iba1 and the highest increase in NT-3. Therefore, the WBV therapy at the 14th day appeared to be superior to the PFE therapy in terms of recovery. Functional deficits and subsequent rehabilitation depend heavily upon the inflammatory processes occurring caudally to the injury site; thus, we propose that increased expression of NT-3, especially in the dorsal horn, could potentially be the mediator of this favorable outcome. Full article

(This article belongs to the Topic Neuroprotection by Drugs, Nutraceuticals and Physical Activity, 2nd Volume)

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