Journal Description
Current Issues in Molecular Biology
Current Issues in Molecular Biology
is an international, scientific, peer-reviewed, open access journal on molecular biology, published monthly online by MDPI (from Volume 43 Issue 1-2021).
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PMC, PubMed, Embase, CAPlus / SciFinder, FSTA, AGRIS, and other databases.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 15.8 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the second half of 2024).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names are published annually in the journal.
Impact Factor:
2.8 (2023);
5-Year Impact Factor:
2.9 (2023)
Latest Articles
Screening of the Antimelanoma Activity of Monoterpenes—In Vitro Experiments on Four Human Melanoma Lines
Curr. Issues Mol. Biol. 2025, 47(2), 97; https://doi.org/10.3390/cimb47020097 (registering DOI) - 3 Feb 2025
Abstract
(1) Malignant melanoma is the most aggressive type of malignant tumor caused by a dysfunction of melanocytes. Despite progress in the treatment of melanoma, further research and search for new potential drugs are necessary to optimize the therapy. (2) The aim of this
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(1) Malignant melanoma is the most aggressive type of malignant tumor caused by a dysfunction of melanocytes. Despite progress in the treatment of melanoma, further research and search for new potential drugs are necessary to optimize the therapy. (2) The aim of this study was to evaluate the antiproliferative activity of eight selected monoterpenes by MTT and LDH assays on four malignant melanoma cell lines. (3) Myrcene, rhodinol and nerol did not show any significant anticancer effect on melanoma cell lines, but citral, carvacrol, citronellol, thymol and geraniol showed a significant anti-viability effect. Our studies have shown that the most effective terpene among those tested in inhibiting melanoma cell viability was carvacrol, with the lowest IC50 in the range of 0.05 ± 0.00 to 0.06 ± 0.01 mM. Moreover, it did not negatively affect normal human keratinocyte cells. (4) Metastatic melanoma is very difficult to treat, and some terpenes have the ability to sensitize cells to other chemicals; so, it is worth investigating their antimelanoma potential, as terpenes could become an adjuvant to traditional treatment.
Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer Therapy)
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Meroterpenoids from Terrestrial and Marine Fungi: Promising Agents for Neurodegenerative Disorders—An Updated Review
by
Daniela Dimitrova, Simeonka Dimitrova, Gabriela Kehayova and Stela Dragomanova
Curr. Issues Mol. Biol. 2025, 47(2), 96; https://doi.org/10.3390/cimb47020096 (registering DOI) - 3 Feb 2025
Abstract
Background: Meroterpenoids represent a remarkably diverse class of natural secondary metabolites, some of which are synthesized via terpenoid biosynthetic pathways. Over the past ten years, these compounds have gained interest because of their wide range of biological activities, such as anti-cholinesterase, COX-2 inhibitory,
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Background: Meroterpenoids represent a remarkably diverse class of natural secondary metabolites, some of which are synthesized via terpenoid biosynthetic pathways. Over the past ten years, these compounds have gained interest because of their wide range of biological activities, such as anti-cholinesterase, COX-2 inhibitory, antibacterial, antiviral, antidiabetic, antioxidant, anti-inflammatory, antineoplastic, and cardioprotective properties. This review aims to consolidate the recognized neuroprotective effects of meroterpenoids from marine and terrestrial fungi. Methods: Data compiled from several databases, including PubMed, Science Direct, Scopus, and Google Scholar, include articles published since 2000 using keywords such as “neuroprotective”, “fungi”, “mushroom”, “marine sponge”, “neurodegeneration”, and “dementia” in connection with “meroterpenoids”. Results: Meroterpenoids modulate different cell signaling pathways and exhibit different and often combined mechanisms of action to ameliorate neuronal damage and dysfunction. Reported activities include anti-cholinesterase, antioxidant, BACE1 inhibition, and anti-inflammatory activities, all of which have potential in the treatment of dementia associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Conclusions: Meroterpenoids have the potential to be developed as effective tools for neuropathological diseases. Ongoing research to elucidate the various neuroprotective pathways remains essential and requires further investigation.
Full article
(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products, 2nd Edition)
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Open AccessArticle
The Immune-Enhancing Effects of a Lactobacillus paracasei L-30 Extract Through the NF-κB and MAPK Pathways in RAW264.7
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Soyeon Kim, Inwook Kim, Sangkyu Park and Jeongmin Seo
Curr. Issues Mol. Biol. 2025, 47(2), 95; https://doi.org/10.3390/cimb47020095 (registering DOI) - 3 Feb 2025
Abstract
Immune enhancement is an important factor that not only helps prevent infections but also affects overall health. This study aims to evaluate the immunostimulatory effects of a novel Lactobacillus strain, Lactobacillus paracasei L-30, and to elucidate its underlying mechanisms. The extract obtained from
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Immune enhancement is an important factor that not only helps prevent infections but also affects overall health. This study aims to evaluate the immunostimulatory effects of a novel Lactobacillus strain, Lactobacillus paracasei L-30, and to elucidate its underlying mechanisms. The extract obtained from Lactobacillus paracasei L-30 significantly increased phagocytosis and the production of NO and ROS in RAW264.7 macrophages. The protein and mRNA expression levels of COX-2 and iNOS which are immune regulators were upregulated by the L-30 extract. The levels of cytokines and chemokines, such as G-CSF, IL-6, MIP-1α, MIP-1γ, RANTES, sTNF RI, and sTNF RII, were increased by the treatment with the L-30 extract. In addition, the L-30 extract degraded IκB-α and induced the phosphorylation of NF-κB. Furthermore, the MAPK signaling pathways ERK, JNK, and p38 were activated by the L-30 extract. The production of iNOS, COX-2, and NO was inhibited by MAPK pathway inhibitors. Therefore, our data suggest that the Lactobacillus paracasei L-30 extract has the potential to be developed as a healthy functional food that can enhance immune responses by activating macrophages.
Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
Open AccessArticle
Metabolomics and Transcriptomics Jointly Explore the Mechanism of Pod Color Variation in Purple Pod Pea
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Xiaojuan Zhong, Mei Yang, Xiaoyan Zhang, Yuanfang Fan, Xianshu Wang and Chao Xiang
Curr. Issues Mol. Biol. 2025, 47(2), 94; https://doi.org/10.3390/cimb47020094 (registering DOI) - 1 Feb 2025
Abstract
Although the pod color was one of the seven characteristics Mendel studied in peas, the mechanism of color variation in peas with purple pods has not been reported. This study systemically analyzed the difference between two pea accessions with green pods (GPs) and
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Although the pod color was one of the seven characteristics Mendel studied in peas, the mechanism of color variation in peas with purple pods has not been reported. This study systemically analyzed the difference between two pea accessions with green pods (GPs) and purple pods (PPs) at two pod developmental stages from the metabolome and transcriptome levels, aiming to preliminarily explore the mechanism and of color variation in PPs and screen out the candidate genes. A total of 180 differentially accumulated metabolites (DAMs) belonged to seven flavonoid subgroups and 23 flavonoid-related differentially expressed genes (DEGs) were identified from the analysis of the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment, respectively. Among the 180 flavonoid metabolites, ten anthocyanin compounds, which were the principal pigments in PPs and might be the major reason for the purple color formation, were significantly up-accumulated in both of the different pod development stages of PPs. A transcriptome analysis revealed that eight genes encoding enzymes (C4H, CHI, F3H, F3’H, F3’5’H, DFR, ANS, and FLS) involved in the flavonoid synthesis pathway were significantly upregulated in PPs and finally resulted in the significant accumulation of flavonoid and anthocyanin metabolites. The joint analysis of two omics and a weighted gene co-expression network analysis (WGCNA) also screened out that the WD-40 protein-encoding gene, one WRKY and three MYB transcription factor genes exhibited significant upregulation in PPs, and highly correlated with several structural genes in flavonoid synthesis pathways, indicating that these genes are involved in the regulation of pod color formation in PPs. Overall, the results of this study first explored the mechanism underlying the purple color variation between PPs and GPs, and then preliminarily screened out some candidate genes responsible for the pod color formation in PPs.
Full article
(This article belongs to the Special Issue Advances in Multi-Omics for Functional Genomics Studies and Molecular Breeding)
Open AccessReview
NGF in Neuropathic Pain: Understanding Its Role and Therapeutic Opportunities
by
Mario García-Domínguez
Curr. Issues Mol. Biol. 2025, 47(2), 93; https://doi.org/10.3390/cimb47020093 (registering DOI) - 31 Jan 2025
Abstract
Nerve growth factor (NGF) is one of the essential components that have been implicated in the pathophysiology of neuropathic pain, a condition that develops following nerve injury or dysfunction. This neurotrophin is critical for the survival and maintenance of sensory neurons, and its
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Nerve growth factor (NGF) is one of the essential components that have been implicated in the pathophysiology of neuropathic pain, a condition that develops following nerve injury or dysfunction. This neurotrophin is critical for the survival and maintenance of sensory neurons, and its dysregulation has been implicated in the sensitization of pain pathways. NGF interacts with its receptor TrkA and p75NTR to activate intracellular signaling pathways associated with nociception and the emergence of allodynia and hyperalgesia. Therapeutic approaches employing neutralizing antibodies and molecule inhibitors have been highly effective at both preclinical and clinical levels, hence giving hope again for the use of NGF as an important biomarker and therapeutic target in the management of neuropathic pain. By exploiting the unique properties of NGF and its interactions within the nervous system, new therapeutic modalities could be designed to enhance efficacy while minimizing side effects. In conclusion, taking advantage of the multifaceted dynamics of NGF could provide effective pain management therapies to finally respond to the unmet needs of patients experiencing neuropathic pain.
Full article
(This article belongs to the Section Molecular Medicine)
Open AccessArticle
Genetic Variation in a Crossing Population of Camellia oleifera Based on ddRAD Sequencing and Analysis of Association with Fruit Traits
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Lexin Zhou, Yu Li, Ling Ye, Jiani Li, Tian Liang, Yanxuan Liu, Weiwei Xie, Yiqing Xie, Shipin Chen and Hui Chen
Curr. Issues Mol. Biol. 2025, 47(2), 92; https://doi.org/10.3390/cimb47020092 (registering DOI) - 31 Jan 2025
Abstract
Tea oil is an important high-quality edible oil derived from woody plants. Camellia oleifera is the largest and most widely planted oil-producing plant in the Camellia genus in China, and its seeds are the most important source for obtaining tea oil. In current
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Tea oil is an important high-quality edible oil derived from woody plants. Camellia oleifera is the largest and most widely planted oil-producing plant in the Camellia genus in China, and its seeds are the most important source for obtaining tea oil. In current research, improving the yield and quality of tea oil is the main goal of oil tea genetic breeding. The aim of this study was to investigate the degree of genetic variation in an early crossing population of C. oleifera and identify single nucleotide polymorphisms (SNPs) and genes significantly associated with fruit traits, which can provide a basis for marker-assisted selection and gene editing for achieving trait improvement in the future. In this study, we selected a crossing population of approximately 40-year-old C. oleifera with a total of 330 samples. Then, ddRAD sequencing was used for SNP calling and population genetic analysis, and association analysis was performed on fruit traits measured repeatedly for two consecutive years. The research results indicate that over 8 million high-quality SNPs have been identified, but the vast majority of SNPs occur in intergenic regions. The nucleotide polymorphism of this population is at a low level, and Tajima’s D values are mostly greater than 0, indicating that the change in this population was not suitable for the model of central evolution. The population structure analysis shows that the population has seven theoretical sources of genetic material and can be divided into seven groups, and the clustering analysis results support the population structure analysis results. Association analysis identified significant SNPs associated with genes related to the seed number of a single fruit and seed kernel oil content. Our findings provide a basis for molecular breeding and future genetic improvement of cultivated oil tea.
Full article
(This article belongs to the Section Molecular Plant Sciences)
Open AccessArticle
Electroporation Induces Unexpected Alterations in Gene Expression: A Tip for Selection of Optimal Transfection Method
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Taiji Hamada, Seiya Yokoyama, Toshiaki Akahane, Kei Matsuo, Ikumi Kitazono, Tatsuhiko Furukawa and Akihide Tanimoto
Curr. Issues Mol. Biol. 2025, 47(2), 91; https://doi.org/10.3390/cimb47020091 - 31 Jan 2025
Abstract
Electroporation is an efficient method for nucleotide and protein transfer, and is used for clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9)-mediated genome editing. In this study, we investigated the effects of electroporation on platelet-derived growth factor receptor alpha (PDGFRA
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Electroporation is an efficient method for nucleotide and protein transfer, and is used for clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9)-mediated genome editing. In this study, we investigated the effects of electroporation on platelet-derived growth factor receptor alpha (PDGFRA) and receptor tyrosine kinase (RTK) expression in U-251 and U-87 MG cells. PDGFRA mRNA and protein expression decreased 2 days after electroporation in both cell lines, with recovery observed after 13 days in U-87 MG cells. However, in U-251 MG cells, PDGFRα expression remained suppressed, despite mRNA recovery after 13 days. Similar expression profiles were observed for lipofection in the U-251 MG cells. Comprehensive RNA sequencing confirmed electroporation-induced up- and down-regulation of RTK mRNA in U-251 MG cells 2 days post-electroporation. In contrast, recombinant adeno-associated virus (rAAV) transfected with mNeonGreen fluorescent protein or Cas9 did not affect PDGFRA, RTKs, or inflammatory cytokine expression, suggesting fewer adverse effects of rAAV on U-251 MG cells. These findings emphasize the need for adequate recovery periods following electroporation or the adoption of alternative methods, such as rAAV transfection, to ensure the accurate assessment of CRISPR-mediated gene editing outcomes.
Full article
(This article belongs to the Special Issue The Contribution and Application of Molecular Biology in the Applied Biosciences — Focusing on Medicine, Biomaterials and Tissue Engineering Fields)
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Open AccessReview
Chimeric Antigen Receptor Cell Therapy: Empowering Treatment Strategies for Solid Tumors
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Tang-Her Jaing, Yi-Wen Hsiao and Yi-Lun Wang
Curr. Issues Mol. Biol. 2025, 47(2), 90; https://doi.org/10.3390/cimb47020090 - 31 Jan 2025
Abstract
Chimeric antigen receptor-T (CAR-T) cell therapy has demonstrated impressive efficacy in the treatment of blood cancers; however, its effectiveness against solid tumors has been significantly limited. The differences arise from a range of difficulties linked to solid tumors, including an unfriendly tumor microenvironment,
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Chimeric antigen receptor-T (CAR-T) cell therapy has demonstrated impressive efficacy in the treatment of blood cancers; however, its effectiveness against solid tumors has been significantly limited. The differences arise from a range of difficulties linked to solid tumors, including an unfriendly tumor microenvironment, variability within the tumors, and barriers to CAR-T cell infiltration and longevity at the tumor location. Research shows that the reasons for the decreased effectiveness of CAR-T cells in treating solid tumors are not well understood, highlighting the ongoing need for strategies to address these challenges. Current strategies frequently incorporate combinatorial therapies designed to boost CAR-T cell functionality and enhance their capacity to effectively target solid tumors. However, these strategies remain in the testing phase and necessitate additional validation to assess their potential benefits. CAR-NK (natural killer), CAR-iNKT (invariant natural killer T), and CAR-M (macrophage) cell therapies are emerging as promising strategies for the treatment of solid tumors. Recent studies highlight the construction and optimization of CAR-NK cells, emphasizing their potential to overcome the unique challenges posed by the solid tumor microenvironment, such as hypoxia and metabolic barriers. This review focuses on CAR cell therapy in the treatment of solid tumors.
Full article
(This article belongs to the Special Issue Adhesion, Metastasis and Inhibition of Cancer Cells, 2nd Edition)
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Immunomodulatory Effects of Selected Non-Nutritive Bioactive Compounds and Their Role in Optimal Nutrition
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Katarzyna Napiórkowska-Baran, Paweł Treichel, Anita Dardzińska, Agata Majcherczak, Anastazja Pilichowicz, Maciej Szota, Bartłomiej Szymczak, Ewa Alska, Justyna Przybyszewska and Zbigniew Bartuzi
Curr. Issues Mol. Biol. 2025, 47(2), 89; https://doi.org/10.3390/cimb47020089 - 31 Jan 2025
Abstract
The contemporary approach to nutrition increasingly considers the role of non-nutritive bioactive compounds in modulating the immune system and maintaining health. This article provides up-to-date insight into the immunomodulatory effects of selected bioactive compounds, including micro- and macronutrients, vitamins, as well as other
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The contemporary approach to nutrition increasingly considers the role of non-nutritive bioactive compounds in modulating the immune system and maintaining health. This article provides up-to-date insight into the immunomodulatory effects of selected bioactive compounds, including micro- and macronutrients, vitamins, as well as other health-promoting substances, such as omega-3 fatty acids, probiotics, prebiotics, postbiotics (including butyric acid and sodium butyrate), coenzyme Q10, lipoic acid, and plant-derived components such as phenolic acids, flavonoids, coumarins, alkaloids, polyacetylenes, saponins, carotenoids, and terpenoids. Micro- and macronutrients, such as zinc, selenium, magnesium, and iron, play a pivotal role in regulating the immune response and protecting against oxidative stress. Vitamins, especially vitamins C, D, E, and B, are vital for the optimal functioning of the immune system as they facilitate the production of cytokines, the differentiation of immunological cells, and the neutralization of free radicals, among other functions. Omega-3 fatty acids exhibit strong anti-inflammatory effects and enhance immune cell function. Probiotics, prebiotics, and postbiotics modulate the intestinal microbiota, thereby promoting the integrity of the intestinal barrier and communication between the microbiota and the immune system. Coenzyme Q10, renowned for its antioxidant attributes, participates in the protection of cells from oxidative stress and promotes energy processes essential for immune function. Sodium butyrate and lipoic acid exhibit anti-inflammatory effects and facilitate the regeneration of the intestinal epithelium, which is crucial for the maintenance of immune homeostasis. This article emphasizes the necessity of an integrative approach to optimal nutrition that considers not only nutritional but also non-nutritional bioactive compounds to provide adequate support for immune function. Without them, the immune system will never function properly, because it has been adapted to this in the course of evolution. The data presented in this article may serve as a foundation for further research into the potential applications of bioactive components in the prevention and treatment of diseases associated with immune dysfunction.
Full article
(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products, 2nd Edition)
Open AccessArticle
Evaluation of the Antioxidant and Anti-Cancer Potential of Microwave-Assisted Opuntia humifusa (Korean Cheonnyencho) Aqueous Extract
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Poojitha Yanamala, Jeong-Yun Youn, Prakash Thangavel, Ju-Young Moon and Young-Chul Lee
Curr. Issues Mol. Biol. 2025, 47(2), 88; https://doi.org/10.3390/cimb47020088 - 31 Jan 2025
Abstract
O. humifusa (Korean Cheonnyencho), a prickly pear cactus species, has garnered increased attention owing to its rich phytochemical composition and potential health benefits. In this study, the antioxidant and anti-cancer activities of a microwave-assisted aqueous extract derived from O. humifusa were investigated, and
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O. humifusa (Korean Cheonnyencho), a prickly pear cactus species, has garnered increased attention owing to its rich phytochemical composition and potential health benefits. In this study, the antioxidant and anti-cancer activities of a microwave-assisted aqueous extract derived from O. humifusa were investigated, and its phytochemical content was characterized. High-performance liquid chromatography (HPLC) was used to identify various bioactive compounds, including polyphenols, flavonoids, and other antioxidants known for their potential health-promoting properties. Furthermore, the individual compounds in the flavonoids were separated using the HPLC fractionation technique. The antioxidant potential of the aqueous extract was evaluated using 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity. The results demonstrated the significant antioxidant activity of the extract, as evidenced by its ability to scavenge free radicals and effectively reduce oxidized molecules. The experiments involved treating colon cancer cells with varying concentrations of the extract (25 to 125 mg/mL) over a 24-h period, resulting in a remarkable dose-dependent inhibition of cell growth. Notably, this inhibitory effect was absent in HDFa cells, highlighting the potential selectivity of O. humifusa in targeting colon cancer cells.
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(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)
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Open AccessArticle
Anthocyanin-Binding Affinity and Non-Covalent Interactions with IIS-Pathway-Related Protein Through Molecular Docking
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Haroon, Zahid Khan, Wasim Javaid and Lian-Xi Xing
Curr. Issues Mol. Biol. 2025, 47(2), 87; https://doi.org/10.3390/cimb47020087 - 29 Jan 2025
Abstract
Anthocyanins compounds, including cyanidin, malvidin, pelargonidin, peonidin, and petunidin, have demonstrated remarkable anti-aging and insulin-sensitizing properties through their interactions with proteins associated with the insulin/insulin-like growth factor signaling (IIS) pathway in Reticulitermes chinensis, employing advanced molecular docking techniques to elucidate strong binding
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Anthocyanins compounds, including cyanidin, malvidin, pelargonidin, peonidin, and petunidin, have demonstrated remarkable anti-aging and insulin-sensitizing properties through their interactions with proteins associated with the insulin/insulin-like growth factor signaling (IIS) pathway in Reticulitermes chinensis, employing advanced molecular docking techniques to elucidate strong binding affinities between specific anthocyanins and key proteins such as Pdk1, EIF4E, and Tsc2 in R. chinensis, suggesting a potential mechanism for their anti-aging effects. These findings not only provide critical insights into the therapeutic potential of anthocyanins for mitigating insulin resistance and promoting longevity, but also highlight the efficacy of in silico molecular docking as a predictive tool for small-molecule–protein interactions. Our research opens new avenues for the development of innovative therapeutic strategies targeting age-related diseases. However, further investigations, including a comprehensive chromosomal analysis and in vivo studies, are essential in order to fully elucidate the molecular mechanism underlying these interactions and their physiological implications. The detailed characterization of anthocyanin-binding affinities and their interactions with key regulatory genes presents exciting opportunities for advancement in molecular medicine, pharmacology, and the development of novel nutraceuticals.
Full article
(This article belongs to the Section Bioinformatics and Systems Biology)
Open AccessArticle
Respiratory Muscle Injury Following Acute Monocled Cobra (Naja kaouthia) Envenoming: Histopathological Study in Rat Diaphragm
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Wanida Chuaikhongthong, Wipapan Khimmaktong, Natyamee Thipthong, Nissara Lorthong and Janeyuth Chaisakul
Curr. Issues Mol. Biol. 2025, 47(2), 86; https://doi.org/10.3390/cimb47020086 - 29 Jan 2025
Abstract
Clinical symptoms of monocled cobra (Naja kaouthia) envenoming include the paralysis of extraocular muscles, local tissue necrosis and death through respiratory failure. These neurotoxic outcomes are mainly due to the inhibitory action of postsynaptic neurotoxins to nicotinic acetylcholine receptors. However, injuries
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Clinical symptoms of monocled cobra (Naja kaouthia) envenoming include the paralysis of extraocular muscles, local tissue necrosis and death through respiratory failure. These neurotoxic outcomes are mainly due to the inhibitory action of postsynaptic neurotoxins to nicotinic acetylcholine receptors. However, injuries involving respiratory muscles have rarely been investigated. In this study, we determined the effect of N. kaouthia envenoming on morphological changes in the rat diaphragm. The efficacy of cobra monovalent antivenom in neutralising the histopathological effects of N. kaouthia venom was also evaluated. The intramuscular (i.m.) administration of N. kaouthia venom (2 mg/kg) caused skeletal muscle fibre atrophy and ruptures of myofibrils shown via a light microscope study. Transmission electron microscopy (TEM) revealed the zig-zagging of the Z-band, mitochondrial damages and degeneration of the synaptic fold of the neuromuscular junction following experimental cobra envenoming for 4 h. Intravenous administration of cobra antivenom at manufacturer-recommended doses diminished histopathological changes in the diaphragm following the administration of cobra venom. The expression of NF-kB and MuRF1 in the experimentally N. kaouthia-envenomed diaphragm indicated inflammation and tissue atrophy in the immunofluorescence analysis, respectively. In this study, we found that there were respiratory muscle injuries following N. kaouthia envenoming. The early administration of monovalent N. kaouthia antivenom is capable of neutralising neurotoxic outcomes following cobra envenoming.
Full article
(This article belongs to the Special Issue Neuropharmacology and Brain Physiology: From Molecular Mechanisms to Medicines Application)
Open AccessArticle
Insights on the Anti-Inflammatory and Anti-Melanogenic Effects of 2′-Hydroxy-2,6′-dimethoxychalcone in RAW 264.7 and B16F10 Cells
by
Sung-Min Bae and Chang-Gu Hyun
Curr. Issues Mol. Biol. 2025, 47(2), 85; https://doi.org/10.3390/cimb47020085 - 29 Jan 2025
Abstract
Chalcones are recognized for their diverse pharmacological properties, including anti-inflammatory and anti-melanogenic effects. However, studies on 2′-hydroxy-2-methoxychalcone derivatives remain limited. This study investigated the anti-inflammatory and melanin synthesis-inhibitory effects of three derivatives: 2′-hydroxy-2,4-dimethoxychalcone (2,4-DMC), 2′-hydroxy-2,5′-dimethoxychalcone (2,5′-DMC), and 2′-hydroxy-2,6′-dimethoxychalcone (2,6′-DMC). In lipopolysaccharide (LPS)-stimulated RAW
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Chalcones are recognized for their diverse pharmacological properties, including anti-inflammatory and anti-melanogenic effects. However, studies on 2′-hydroxy-2-methoxychalcone derivatives remain limited. This study investigated the anti-inflammatory and melanin synthesis-inhibitory effects of three derivatives: 2′-hydroxy-2,4-dimethoxychalcone (2,4-DMC), 2′-hydroxy-2,5′-dimethoxychalcone (2,5′-DMC), and 2′-hydroxy-2,6′-dimethoxychalcone (2,6′-DMC). In lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, 2,6′-DMC demonstrated a superior inhibition of nitric oxide (NO) production, pro-inflammatory cytokines, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) compared to the other derivatives. A mechanistic analysis revealed that 2,6′-DMC modulates the NF-κB and MAPK signaling pathways to attenuate inflammation. Additionally, 2,6′-DMC exhibited a significant inhibition of α-melanocyte-stimulating hormone (α-MSH)-induced melanin synthesis in B16F10 melanoma cells by downregulating tyrosinase, TRP-1, TRP-2, and MITF expression. This regulation was achieved through the suppression of the Wnt/β-catenin, PI3K/AKT, MAPK, and PKA/CREB pathways. Compared to 2,4-DMC and 2,5′-DMC, 2,6′-DMC’s structural configuration, characterized by methoxy groups at the 2- and 6′-positions, contributed to its enhanced molecular stability and binding affinity, amplifying its inhibitory effects. A primary skin irritation test confirmed that 2,6′-DMC exhibited minimal irritation, demonstrating its safety for dermal applications. These findings suggest that 2,6′-DMC holds promise as a dual-function agent for managing inflammatory conditions and hyperpigmentation-related disorders.
Full article
(This article belongs to the Special Issue Molecular Insights into Melanogenesis and Melanoma Development)
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Open AccessReview
Significance of Malic Enzyme 1 in Cancer: A Review
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Rina Fujiwara-Tani, Chie Nakashima, Hitoshi Ohmori, Kiyomu Fujii, Yi Luo, Takamitsu Sasaki, Ruiko Ogata and Hiroki Kuniyasu
Curr. Issues Mol. Biol. 2025, 47(2), 83; https://doi.org/10.3390/cimb47020083 - 29 Jan 2025
Abstract
Malic enzyme 1 (ME1) plays a key role in promoting malignant phenotypes in various types of cancer. ME1 promotes epithelial–mesenchymal transition (EMT) and enhances stemness via glutaminolysis, energy metabolism reprogramming from oxidative phosphorylation to glycolysis. As a result, ME1 promotes the malignant phenotypes
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Malic enzyme 1 (ME1) plays a key role in promoting malignant phenotypes in various types of cancer. ME1 promotes epithelial–mesenchymal transition (EMT) and enhances stemness via glutaminolysis, energy metabolism reprogramming from oxidative phosphorylation to glycolysis. As a result, ME1 promotes the malignant phenotypes of cancer cells and poor patient prognosis. In particular, ME1 expression is promoted in hypoxic environments associated with hypoxia-inducible factor (HIF1) α. ME1 is overexpressed in budding cells at the cancer invasive front, promoting cancer invasion and metastasis. ME1 also generates nicotinamide adenine dinucleotide (NADPH), which, together with glucose-6-phosphate dehydrogenase (G6PD) and isocitrate dehydrogenase (IDH1), expands the NADPH pool, maintaining the redox balance in cancer cells, suppressing cell death by neutralizing mitochondrial reactive oxygen species (ROS), and promoting stemness. This review summarizes the latest research insights into the mechanisms by which ME1 contributes to cancer progression. Because ME1 is involved in various aspects of cancer and promotes many of its malignant phenotypes, it is expected that ME1 will become a novel drug target in the near future.
Full article
(This article belongs to the Special Issue New Insight: Enzymes as Targets for Drug Development, 2nd Edition)
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Open AccessArticle
Effect of Partial Root Drying Stress on Improvement in Tomato Production
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Huilian Xu, Hairong Jing, Runyu Shi, Minghao Chen, Chunfang Wang, Qicong Xu, Jianfang Bai, Xiaoyong Liu and Mengmeng Kong
Curr. Issues Mol. Biol. 2025, 47(2), 84; https://doi.org/10.3390/cimb47020084 - 28 Jan 2025
Abstract
Several countries around the world are facing the issue of freshwater availability, where agriculture is highly dependent on irrigation, consuming 70% of this vital resource. Water availability is the most limiting factor for the crop production sector and one of the main regulators
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Several countries around the world are facing the issue of freshwater availability, where agriculture is highly dependent on irrigation, consuming 70% of this vital resource. Water availability is the most limiting factor for the crop production sector and one of the main regulators of the spatial distribution of plants. It is noted that in recent years, the methods of irrigation water application have been improved. Currently, research is directed towards irrigation strategies that reduce water applications. A partial root drying (PRD) technique involves irrigating one-half of the root zone while leaving the other half in relatively dry soil. This method is used in the production of various crops, such as potatoes and cotton. However, the mechanism of PRD, including the physiological and molecular biological processes involved, is not fully understood. In this study, tomato plants were treated with PRD and nitrogen (N) top-dressing. The results showed that PRD could significantly increase the fruit yield, photosynthetic activities, nitrate reductase activity, and fruit quality in the tomato plants, and PRD could also promote the concentrations of oxygen species (O2−), malondialdehyde (MDA) and proline contents, and activities of antioxidant enzymes. In addition, PRD could enhance stress resistance by increasing disease resistance and NP1 and DRED3 antioxidant enzyme activity. Tomato plants treated with PRD compared to the control showed high photosynthetic activity, high yield, better quality of production, and low leaf blight incidence. Overall, the results indicate that PRD is a feasible approach that could be effectively utilized in tomato fields to improve plant growth and production compared with the control.
Full article
(This article belongs to the Section Molecular Plant Sciences)
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Open AccessCase Report
The Novel Association of a Single Nucleotide Variant in the COL3A1 Gene with Diffuse Coronary Aneurysms
by
Charlene Norgan Radler, Kevin Ku, Alison Hodge, Tianci Wang, Peyton Moore and Mohanakrishnan Sathyamoorthy
Curr. Issues Mol. Biol. 2025, 47(2), 82; https://doi.org/10.3390/cimb47020082 - 27 Jan 2025
Abstract
The COL3A1 gene, encoding the pro-alpha chain of type III collagen, has been implicated in a range of collagen-mediated diseases such as Ehlers–Danlos syndrome and aortic aneurysms. In this report, we present evidence for the first time associating a single nucleotide variant p.P517R
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The COL3A1 gene, encoding the pro-alpha chain of type III collagen, has been implicated in a range of collagen-mediated diseases such as Ehlers–Danlos syndrome and aortic aneurysms. In this report, we present evidence for the first time associating a single nucleotide variant p.P517R in exon 22 of COL3A1 with the development of diffuse coronary aneurysms in a human subject without prior atherosclerotic cardiovascular disease, connective tissue disorder, or phenotypic characteristics diagnostic for vascular Ehlers–Danlos syndrome. Computational modeling of this specific variant in AlphaFold and in silico analyses predict deleterious alterations in the structure and function of the COL3A1 gene product, alpha 1 chain of type III collagen. This novel phenotype-to-genotype correlation should prompt further investigation into the mechanistic basis of this association.
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(This article belongs to the Special Issue Genomic Analysis of Common Disease, 2nd Edition)
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Dietary Oleic Acid and SCD16 and ELOVL6 Estimated Activities Can Modify Erythrocyte Membrane n-3 and n-6 HUFA Partition: A Pilot Study
by
Paulo Bispo, Pedro O. Rodrigues and Narcisa M. Bandarra
Curr. Issues Mol. Biol. 2025, 47(2), 81; https://doi.org/10.3390/cimb47020081 - 27 Jan 2025
Abstract
In this work, we studied the relationships between the most representative fatty acids (FAs) and their ratios in red blood cell (RBC) membranes and dietary fatty acids alongside several cardiometabolic risk factors. Twenty-six individuals were enrolled with a mean age of 50.4 ±
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In this work, we studied the relationships between the most representative fatty acids (FAs) and their ratios in red blood cell (RBC) membranes and dietary fatty acids alongside several cardiometabolic risk factors. Twenty-six individuals were enrolled with a mean age of 50.4 ± 12.7 years (16 males and 10 females). By bivariate analysis, dietary oleic acid (OA) correlated negatively with C20:4n-6 (AA) (p = 0.031) in RBCs. With multivariate regression analysis, dietary OA (p < 0.001) is an independent predictor and negatively associated with AA levels in RBCs, while the elongation of very-long-chain fatty acids 6 (ELOVL6) and stearoyl-CoA desaturase 16 (SCD16) activities (p < 0.05) was positively associated with AA levels in RBCs. The multivariate regression models also showed that dietary OA was an independent predictor and positively associated with C22:5n-3 (DPA) in RBCs. Furthermore, BMI positively correlated with SCD16, and both SCD16 and SCD18 were positively associated with triacylglycerols levels. In addition, SCD16 positively and significantly correlated with LDL-c and the LDL-c/HDL-c ratio and negatively correlated with the ApoA1/ApoB ratio, and SCD16 and ELOVL6 were significantly associated with HDL molecular subfractions. Therefore, our data underline that OA, SCD16 and ELOVL6 can interfere with n-3 and n-6 partition in biomembranes such as RBCs, suggesting an important molecular (patho)physiological regulatory mechanism role in controlling bioactive molecules’ availability such as those involved in the immune-inflammatory response.
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(This article belongs to the Special Issue The Protection and Toxic Reactions of Dietary Supplements: Focusing on Molecular Mechanisms and Treatment)
Open AccessReview
Cranberry: A Promising Natural Product for Animal Health and Performance
by
Sahdeo Prasad, Bhaumik Patel, Prafulla Kumar, Pranabendu Mitra and Rajiv Lall
Curr. Issues Mol. Biol. 2025, 47(2), 80; https://doi.org/10.3390/cimb47020080 - 27 Jan 2025
Abstract
Cranberries are a distinctive source of bioactive compounds, containing polyphenols such as flavonoids, anthocyanins, phenolic acids, and triterpenoids. Cranberries are often associated with potential health benefits for the urinary tract and digestive system due to their high antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties.
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Cranberries are a distinctive source of bioactive compounds, containing polyphenols such as flavonoids, anthocyanins, phenolic acids, and triterpenoids. Cranberries are often associated with potential health benefits for the urinary tract and digestive system due to their high antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. Cranberry induces the production of antioxidant enzymes, suppresses lipid peroxidation, reduces inflammatory cytokines, modulates immune cells, maintains gut microbiota, and inhibits bacterial adhesion and growth. Cranberry polyphenols also have metal-binding motifs that bind with metals, particularly zinc and iron. The combination of cranberry polyphenols and metals displays increased biological activity. In this review, an attempt is made to describe the physiological properties and health benefits of cranberries for livestock, including poultry, swine, canine, feline, and ruminant animals, as either feed/food or as supplements. Cranberry, and/or its components, has the capability to potentially control infectious diseases like diarrhea, urinary tract infection, gut integrity, and intestinal probiotic health. Moreover, cranberries show efficacy in suppressing the growth of pathogenic microorganisms such as Salmonella species, Campylobacter species, Streptococcus species, and Enterococcus species bacteria. Thus, cranberry could be considered as a potential natural feed additive or food supplement for animal health improvement.
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(This article belongs to the Special Issue Novel Drugs and Natural Products Discovery)
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Advances in Understanding Lipopolysaccharide-Mediated Hepatitis: Mechanisms and Pathological Features
by
Kazuhiko Nakadate, Hayate Saitoh, Miina Sakaguchi, Fumito Miruno, Naoto Muramatsu, Nozomi Ito, Kanako Tadokoro and Kiyoharu Kawakami
Curr. Issues Mol. Biol. 2025, 47(2), 79; https://doi.org/10.3390/cimb47020079 - 27 Jan 2025
Abstract
Lipopolysaccharide (LPS), a key component of Gram-negative bacterial membranes, plays a central role in the pathogenesis of inflammatory liver diseases. In this review, we aimed to explore the role of LPS in hepatic injury. Upon hepatic infiltration, LPS activates Kupffer cells via toll-like
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Lipopolysaccharide (LPS), a key component of Gram-negative bacterial membranes, plays a central role in the pathogenesis of inflammatory liver diseases. In this review, we aimed to explore the role of LPS in hepatic injury. Upon hepatic infiltration, LPS activates Kupffer cells via toll-like receptor 4 (TLR4) signaling, inducing proinflammatory cytokines such as tumor necrosis factor-α and interleukin-1β. These mediators amplify hepatocyte apoptosis, endothelial damage, and platelet aggregation, thereby contributing to sinusoidal thrombosis and tissue ischemia. Pathological features, such as hepatocyte shrinkage, sinusoidal expansion, and fibrin deposition, are hallmark indicators of LPS-induced hepatic inflammation. Therapeutically, aspirin shows promise for attenuating cytokine release, protecting endothelial integrity, and reducing thrombogenesis. Emerging strategies include targeting TLR4 pathways, modulating the gut–liver axis, and utilizing biomolecular approaches such as RNA interference for LPS suppression. The integration of public health interventions, such as dietary optimization and microbiome regulation, offers additional preventive measures. In this review, the dual roles of LPS in inflammation and thrombosis have been emphasized. Advancing our understanding of LPS-driven mechanisms and enhancing treatment strategies are pivotal for managing hepatic inflammation and its systemic implications. Future research should focus on refining biomarkers, optimizing therapeutic efficacy, and addressing safety concerns for clinical applications.
Full article
(This article belongs to the Special Issue Advances in Molecular Biology Methods in Hepatology Research)
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Open AccessArticle
Identification of AKNA Gene and Its Role for Genetic Susceptibility in Epithelial Ovarian Cancer
by
Dwi Anita Suryandari, Miftahuzzakiyah Miftahuzzakiyah, Luluk Yunaini, Ria Kodariah, Dewi Sukmawati, Primariadewi Rustamadji, Puji Sari and Sri Suciati Ningsih
Curr. Issues Mol. Biol. 2025, 47(2), 78; https://doi.org/10.3390/cimb47020078 - 26 Jan 2025
Abstract
AKNA is identified as a gene that regulates inflammation, immune response, and Epithelial–Mesenchymal Transition (EMT), which plays an important role in the progression of epithelial ovarian cancer. In this study, we analyzed the genotype and allele distribution as well as 3D modeling of
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AKNA is identified as a gene that regulates inflammation, immune response, and Epithelial–Mesenchymal Transition (EMT), which plays an important role in the progression of epithelial ovarian cancer. In this study, we analyzed the genotype and allele distribution as well as 3D modeling of one of the AKNA rs10817595 (−1372 C>A). The distribution of genotypes and alleles was analyzed using the T-ARMS PCR method on 63 ovarian cancer samples and 65 controls. AKNA mRNA expression was analyzed using qRT-PCR on 35 low-grade and 28 high-grade samples. Fifteen low-grade and 12 high-grade samples were analyzed for AKNA protein levels using immunohistochemistry. A 3D model of protein structure was constructed using AlphaFold. Significant differences in AKNA protein levels were found. However, no significant correlation was found for relative AKNA mRNA expression with protein levels. This result is thought to be related to decreased immune system response, increased inflammation, and increased EMT in epithelial ovarian cancer. AKNA gene variant (−1372 C>A) can cause a decrease in mRNA and protein levels in the low-grade and high-grade groups, so it has the potential as a genetic susceptibility factor in epithelial ovarian cancer.
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(This article belongs to the Section Molecular Medicine)
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