Current Issues in Molecular Biology

13 pages, 1918 KiB

Open AccessArticle

Screening of the Antimelanoma Activity of Monoterpenes—In Vitro Experiments on Four Human Melanoma Lines

by Paula Wróblewska-Łuczka, Laura Kulenty, Katarzyna Załuska-Ogryzek, Agnieszka Góralczyk and Jarogniew J. Łuszczki

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 [...] Read more.

(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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22 pages, 1108 KiB

Open AccessReview

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, [...] Read more.

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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15 pages, 1255 KiB

Open AccessArticle

The Immune-Enhancing Effects of a Lactobacillus paracasei L-30 Extract Through the NF-κB and MAPK Pathways in RAW264.7

by 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 [...] Read more.

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)

16 pages, 5709 KiB

Open AccessArticle

Metabolomics and Transcriptomics Jointly Explore the Mechanism of Pod Color Variation in Purple Pod Pea

by 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

Viewed by 178

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 [...] Read more.

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)

25 pages, 697 KiB

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

Viewed by 258

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 [...] Read more.

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 p75^NTR 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)

12 pages, 3703 KiB

Open AccessArticle

Genetic Variation in a Crossing Population of Camellia oleifera Based on ddRAD Sequencing and Analysis of Association with Fruit Traits

by 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

Viewed by 249

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 [...] Read more.

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)

15 pages, 2163 KiB

Open AccessArticle

Electroporation Induces Unexpected Alterations in Gene Expression: A Tip for Selection of Optimal Transfection Method

by 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

Viewed by 282

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 [...] Read more.

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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19 pages, 1559 KiB

Open AccessReview

Chimeric Antigen Receptor Cell Therapy: Empowering Treatment Strategies for Solid Tumors

by 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

Viewed by 324

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, [...] Read more.

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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36 pages, 684 KiB

Open AccessReview

Immunomodulatory Effects of Selected Non-Nutritive Bioactive Compounds and Their Role in Optimal Nutrition

by 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

Viewed by 267

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 [...] Read more.

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)

12 pages, 2124 KiB

Open AccessArticle

Evaluation of the Antioxidant and Anti-Cancer Potential of Microwave-Assisted Opuntia humifusa (Korean Cheonnyencho) Aqueous Extract

by 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

Viewed by 285

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 [...] Read more.

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. Full article

(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)

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26 pages, 4660 KiB

Open AccessArticle

Anthocyanin-Binding Affinity and Non-Covalent Interactions with IIS-Pathway-Related Protein Through Molecular Docking

by 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

Viewed by 259

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 [...] Read more.

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)

16 pages, 3461 KiB

Open AccessArticle

Respiratory Muscle Injury Following Acute Monocled Cobra (Naja kaouthia) Envenoming: Histopathological Study in Rat Diaphragm

by 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

Viewed by 553

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 [...] Read more.

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)

21 pages, 5101 KiB

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

Viewed by 390

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 [...] Read more.

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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17 pages, 1192 KiB

Open AccessReview

Significance of Malic Enzyme 1 in Cancer: A Review

by 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

Viewed by 366

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 [...] Read more.

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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15 pages, 1472 KiB

Open AccessArticle

Effect of Partial Root Drying Stress on Improvement in Tomato Production

by 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

Viewed by 367

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 [...] Read more.

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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11 pages, 1472 KiB

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

Viewed by 421

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Genomic Analysis of Common Disease, 2nd Edition)

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15 pages, 278 KiB

Open AccessArticle

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

Viewed by 536

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 ± [...] Read more.

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. Full article

(This article belongs to the Special Issue The Protection and Toxic Reactions of Dietary Supplements: Focusing on Molecular Mechanisms and Treatment)

24 pages, 3281 KiB

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

Viewed by 438

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. [...] Read more.

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. Full article

(This article belongs to the Special Issue Novel Drugs and Natural Products Discovery)

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21 pages, 2675 KiB

Open AccessReview

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

Viewed by 279

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 [...] Read more.

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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11 pages, 3910 KiB

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

Viewed by 299

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 [...] Read more.

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. Full article

(This article belongs to the Section Molecular Medicine)

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11 pages, 529 KiB

Open AccessArticle

The Role of Cytokines and Chemokines as Biomarkers of Disease Activity in Idiopathic Nephrotic Syndrome in Children

by Matjaž Kopač, Aleš Jerin, Agnese Petrera and Joško Osredkar

Curr. Issues Mol. Biol. 2025, 47(2), 77; https://doi.org/10.3390/cimb47020077 - 25 Jan 2025

Viewed by 415

Abstract

(1) This study investigates the association of plasma concentrations of various cytokines and chemokines with the disease activity of idiopathic nephrotic syndrome (INS) in children in Slovenia. (2) In a prospective single-center study lasting 18 months, we took sequential plasma samples from children [...] Read more.

(1) This study investigates the association of plasma concentrations of various cytokines and chemokines with the disease activity of idiopathic nephrotic syndrome (INS) in children in Slovenia. (2) In a prospective single-center study lasting 18 months, we took sequential plasma samples from children with INS at disease onset or relapse (prior to corticosteroid (CS) therapy), at remission, and after discontinuation of CS therapy. The Olink^®Target 48 Cytokine Panel was applied to analyze 45 analytes in the plasma samples, adhering to the manufacturer’s protocol. We performed a statistical analysis with a paired samples analysis with a t-test as well as with a non-parametric Wilcoxon correction test. (3) We included 18 pediatric patients with INS in the study. We demonstrated statistically significant differences in the concentrations of CSF1, IL4, FLT3LG, CCL19, and MMP12 in the patients at disease onset or relapse compared to those in remission, differences in the concentrations of CSF1 and IL17F in the patients at disease onset or relapse compared to those in remission after CS treatment, and differences in the concentrations of CCL19, MMP12, and CCL13 in the patients in remission compared to those in remission after CS treatment. (4) The findings support potential roles of certain cytokines and chemokines, especially CSF1, CCL19, and MMP12, in influencing the disease activity of INS. Full article

(This article belongs to the Section Molecular Medicine)

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14 pages, 1469 KiB

Open AccessArticle

Lychee Peel Extract Ameliorates Hyperuricemia by Regulating Uric Acid Production and Excretion in Mice

by Zhenwang Guo, Li Zhang, Jinlei Liu and Ziming Yang

Curr. Issues Mol. Biol. 2025, 47(2), 76; https://doi.org/10.3390/cimb47020076 - 25 Jan 2025

Viewed by 317

Abstract

Lychee peel generated during the industrial processing of lychee fruit are currently disposed of as agricultural waste. This study investigates the primary components of lychee peel extract (LPE) and the regulatory mechanisms of LPE on reducing uric acid (UA). Mice were injected with [...] Read more.

Lychee peel generated during the industrial processing of lychee fruit are currently disposed of as agricultural waste. This study investigates the primary components of lychee peel extract (LPE) and the regulatory mechanisms of LPE on reducing uric acid (UA). Mice were injected with hypoxanthine and potassium oxonate to induce hyperuricemia and concurrently orally administered LPE. The analysis of the LPE composition reveals a predominance of polyphenolic compounds, including (-)-epicatechin, (-)-epigallocatechin, and procyanidin A2. In vitro tests have demonstrated that the LPE significantly inhibits the activity of xanthine oxidase (XOD). In vivo studies showed that LPE can reduce UA levels in hyperuricemia mice. Further mechanistic insights indicate that LPE inhibits hepatic XOD activity, thereby reducing UA synthesis within the organism. It also decreases the protein expression of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), which leads to diminished UA reabsorption and increased excretion of UA. Additionally, LPE enhances the activity of superoxide dismutase (SOD) while simultaneously reducing malondialdehyde (MDA) contents, thereby improving antioxidant capacity in mice. Our findings indicate that LPE not only inhibits the production of UA but also promotes its elimination, positioning it as a promising candidate for UA-lowering agents. Full article

(This article belongs to the Special Issue Pharmacological Activities and Mechanisms of Action of Natural Products)

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14 pages, 1562 KiB

Open AccessArticle

GC-MS Profiling of Ethanol-Extracted Polyherbal Compounds from Medicinal Plant (Citrullus colocynthis, Curcuma longa, and Myristica fragrans): In Silico and Analytical Insights into Diabetic Neuropathy Therapy via Targeting the Aldose Reductase

by Mohd Adnan Kausar, Sadaf Anwar, Halima Mustafa Elagib, Kehkashan Parveen, Malik Asif Hussain, Mohammad Zeeshan Najm, Abhinav Nair and Subhabrata Kar

Curr. Issues Mol. Biol. 2025, 47(2), 75; https://doi.org/10.3390/cimb47020075 - 23 Jan 2025

Viewed by 618

Abstract

Diabetic neuropathy is one of the severe complications of diabetes, which affects the quality of life in a patient and increases the risk of amputations and chronic wounds. Current therapeutic approaches are symptomatically oriented, focusing on comfort and non-inflammatory aspects without addressing the [...] Read more.

Diabetic neuropathy is one of the severe complications of diabetes, which affects the quality of life in a patient and increases the risk of amputations and chronic wounds. Current therapeutic approaches are symptomatically oriented, focusing on comfort and non-inflammatory aspects without addressing the mechanism or molecular target of the disease. The present study investigates the therapeutic effects of an ethanolic polyherbal extract from Citrullus colocynthis (Bitter Apple), Curcuma longa (Turmeric), and Myristica fragrans (Nutmeg) using advanced in silico and analytical methods. According to the findings, PHE showed the presence of a total of 39 bioactive compounds in GC–MS analysis, which include alcohols, fatty acids, terpenoids, esters, neolignans, phenylpropanoids, and steroids. Three of the compounds—-4-isopropyl-1,6-dimethyl-1,2,3,4-tetrahydronaphthalene (−11.4 kcal/mol), (1S,2R)-2-(4-allyl-2,6-dimethoxyphenoxy)-1-(3,4,5-trimethoxyphenyl)-1-propanol (−9.8 kcal/mol) and (S)-5-Allyl-2-((1-(3,4-dimethoxyphenyl)propan-2-yl)oxy)-1,3-dimethoxybenzene (−10.3 kcal/mol)—followed the Lipinski rule and showed the binding affinity with aldol reductase. Docking experiments showed that compound 4-isopropyl-1,6-dimethyl-1,2,3,4-tetrahydronaphthalene (−11.4 kcal/mol) has high-affinity binding to aldose reductase, an enzyme involved in diabetic neuropathy pathophysiology, whereas molecular dynamics simulations show long-range persistence of the interaction of (S)-5-Allyl-2-((1-(3,4-dimethoxyphenyl)propan-2-yl)oxy)-1,3-dimethoxybenzene with aldol reductase in physiological conditions. Therefore, this combination of herbal therapy and advanced computational/analytical techniques could be leading towards innovative, multi-targeted therapies against diabetic neuropathy. Nevertheless, further studies in vivo are required to confirm the efficacy, safety, and pharmacokinetics of the PHE in biological systems. Full article

(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds, 2nd Edition)

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22 pages, 5559 KiB

Open AccessArticle

Comparative Chloroplast Genomes and Phylogenetic Relationships of True Mangrove Species Brownlowia tersa and Brownlowia argentata (Malvaceae)

by Panthita Ruang-areerate, Duangjai Sangsrakru, Thippawan Yoocha, Wasitthee Kongkachana, Sonicha U-Thoomporn, Onnitcha Prathip Na Thalang, Pranom Chumriang, Poonsri Wanthongchai, Sithichoke Tangphatsornruang and Wirulda Pootakham

Curr. Issues Mol. Biol. 2025, 47(2), 74; https://doi.org/10.3390/cimb47020074 - 23 Jan 2025

Viewed by 495

Abstract

Brownlowia tersa and Brownlowia argentata are two true mangroves in the genus Brownlowia in Malvaceae, and they are a near-threatened and a data-deficient species, respectively. However, the genomic resources of Brownlowia have not been reported for studying their phylogeny and evolution. Here, we [...] Read more.

Brownlowia tersa and Brownlowia argentata are two true mangroves in the genus Brownlowia in Malvaceae, and they are a near-threatened and a data-deficient species, respectively. However, the genomic resources of Brownlowia have not been reported for studying their phylogeny and evolution. Here, we report the chloroplast genomes of B. tersa and B. argentata based on stLFR data that were 159,478 and 159,510 base pairs in length, respectively. Both chloroplast genomes contain 110 unique genes and one infA pseudogene. Sixty-eight RNA-editing sites were detected in 26 genes in B. argentata. A comparative analysis with related species showed similar genome sizes, genome structures, and gene contents as well as high sequence divergence in non-coding regions. Abundant SSRs and dispersed repeats were identified. Five hotspots, psbI-trnS, trnR-atpA, petD-rpoA, rpl16-rps3, and trnN-ndhF, were detected among four species in Brownlowioideae. One hotspot, rps14-psaB, was observed in the two Brownlowia species. Additionally, phylogenetic analysis supported that the Brownlowia species has a close relationship with Pentace triptera. Moreover, rpoC2 was a candidate gene for adaptive evolution in the Brownlowia species compared to P. triptera. Thus, these chloroplast genomes present valuable genomic resources for further evolutionary and phylogenetic studies of mangroves and plant species in Malvaceae. Full article

(This article belongs to the Special Issue Functional Genomics and Comparative Genomics Analysis in Plants, 2nd Edition)

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12 pages, 4544 KiB

Open AccessArticle

Donor Variability Alters the Characteristics of Human Brain Microvascular Endothelial Cells

by Jingyuan Ya and Ulvi Bayraktutan

Curr. Issues Mol. Biol. 2025, 47(2), 73; https://doi.org/10.3390/cimb47020073 - 23 Jan 2025

Viewed by 438

Abstract

Primary brain microvascular endothelial cells (BMECs) are widely used in a large number of in vitro studies each year to better mimic their physiological characteristics in vivo. However, potential changes in primary endothelial cells stemming from donor variability or culture conditions may affect [...] Read more.

Primary brain microvascular endothelial cells (BMECs) are widely used in a large number of in vitro studies each year to better mimic their physiological characteristics in vivo. However, potential changes in primary endothelial cells stemming from donor variability or culture conditions may affect the reliability and reproducibility of the experiments. While working on a project regarding BMEC senescence, we noticed behavioral differences between two different batches of cells. Comparative analyses of cellular characteristics revealed that while one batch of BMECs developed a typical cobblestone morphology, the other batch displayed a spindle-shape morphology. Despite showing similar tubulogenic and barrier-forming capacities, the spindle-shaped BMECs displayed greater proliferation rates, stronger staining for CD34, a marker of stemness and higher resistance to oxidative stress-induced senescence and replicative senescence. Conversely, the spindle-shaped cells demonstrated a much weaker staining for the endothelial marker CD31. Taken together, these findings indicate that it is important to scrutinize endothelial characteristics to ensure experimental accuracy when cellular responses markedly vary between the so-called endothelial cells. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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16 pages, 1422 KiB

Open AccessReview

The Impact of Ozone on Periodontal Cell Line Viability and Function

by Nada Tawfig Hashim, Rasha Babiker, Shahistha Parveen Dasnadi, Md Sofiqul Islam, Nallan CSK Chaitanya, Riham Mohammed, Nancy Soliman Farghal, Bakri Gobara and Muhammed Mustahsen Rahman

Curr. Issues Mol. Biol. 2025, 47(2), 72; https://doi.org/10.3390/cimb47020072 - 23 Jan 2025

Viewed by 423

Abstract

Periodontal diseases, including gingivitis and periodontitis, are chronic inflammatory conditions of the teeth’ supporting structures that can lead to progressive tissue destruction and loss if left untreated. Basic treatments like scaling and root planing, alone or combined with antimicrobial agents, are the standard [...] Read more.

Periodontal diseases, including gingivitis and periodontitis, are chronic inflammatory conditions of the teeth’ supporting structures that can lead to progressive tissue destruction and loss if left untreated. Basic treatments like scaling and root planing, alone or combined with antimicrobial agents, are the standard of care. However, with the increasing prevalence of antibiotic resistance and the need for new ideas in therapy, adjunctive treatments like ozone therapy have gained attention. Ozone (O₃), a triatomic oxygen molecule, is used because of its strong antimicrobial, anti-inflammatory, and regenerative activity and, hence, as a potential tool in periodontal therapy. This review of the use of ozone therapy in periodontal disease breaks down the multifaceted mechanism of ozone therapy, which includes the selective antimicrobial action against biofilm-associated pathogens, immunomodulatory effects on host cells, and stimulation of tissue repair. O₃ therapy disrupts microbial biofilms, enhances immune cell function, and promotes healing by activating Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways that regulate oxidative stress, inflammation, and apoptosis. Additional findings include its ability to upregulate growth factors and extracellular matrix proteins, which is significant for periodontal tissue regeneration. This review also discusses the application of O₃ therapy in periodontal cell lines, emphasizing its impact on cell viability, proliferation, and differentiation. Advances in periodontal regenerative techniques, combined with the antimicrobial and healing properties of O₃, have demonstrated significant clinical benefits. Challenges, including the need for standardized dosages, effective delivery systems, and long-term studies, are also addressed to ensure safe and effective clinical integration. O₃ therapy, with its dual antimicrobial and regenerative capabilities, offers an innovative adjunctive approach to periodontal treatment. Future research focusing on optimized protocols and evidence-based guidelines is essential to fully realize its potential in enhancing periodontal health and improving patient outcomes. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2024)

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15 pages, 1157 KiB

Open AccessReview

Prostaglandins: Biological Action, Therapeutic Aspects, and Pathophysiology of Autism Spectrum Disorders

by Kunio Yui, George Imataka and Mariko Ichihashi

Curr. Issues Mol. Biol. 2025, 47(2), 71; https://doi.org/10.3390/cimb47020071 - 21 Jan 2025

Viewed by 587

Abstract

Esterified ARA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2), which is further metabolized by COXs and lipoxygenases (LOXs) and cytochrome P450 (CYP) enzymes. PGs produce detrimental effects due to their proinflammatory properties. [...] Read more.

Esterified ARA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2), which is further metabolized by COXs and lipoxygenases (LOXs) and cytochrome P450 (CYP) enzymes. PGs produce detrimental effects due to their proinflammatory properties. The generation of prostaglandin (PG)G₂ and PGH₂ is triggered by cyclooxygenase (COX) isozymes such as COX-1 and COX-2. Prostaglandin E2 (PGE2) is significantly elevated in ASD. Considerable data indicate that COX enzymes and their metabolites of ARA play important roles in the initiation and development of human neurodevelopmental diseases. The involvement of disrupted COX2/PGE2 signaling in ASD pathology in changing neuronal cell behavior and the expression of ASD-related genes and proteins is due to disrupted COX2/PGE2 signaling. Prostacyclin (PGI2) is synthesized from arachidonic acid by metabolic-pathway-dependent cyclooxygenase (COX) and synthesized in a primary step of ARA transformation (PGG2, PGH2), by degradation of the abovementioned prostaglandins. Full article

(This article belongs to the Topic Autism: Molecular Bases, Diagnosis and Therapies, 2nd Volume)

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23 pages, 903 KiB

Open AccessReview

The Therapeutic Potential of MicroRNA-21 in the Treatment of Spinal Cord Injury

by Ahmed Hasan, Alessio Ardizzone, Domenico Giosa, Sarah Adriana Scuderi, Elsa Calcaterra, Emanuela Esposito and Anna Paola Capra

Curr. Issues Mol. Biol. 2025, 47(2), 70; https://doi.org/10.3390/cimb47020070 - 21 Jan 2025

Viewed by 528

Abstract

Spinal cord injury (SCI) involves complex pathological processes that often result in significant and long-term neurological deficits. Increasingly, research has identified microRNA-21 (miR-21) as a pivotal regulator in SCI, with studies focusing on its roles in inflammation, apoptosis, and tissue repair. This review [...] Read more.

Spinal cord injury (SCI) involves complex pathological processes that often result in significant and long-term neurological deficits. Increasingly, research has identified microRNA-21 (miR-21) as a pivotal regulator in SCI, with studies focusing on its roles in inflammation, apoptosis, and tissue repair. This review synthesizes current findings on miR-21’s involvement in post-injury molecular events, emphasizing its interactions with regulatory targets such as Phosphatase and Tensin Homolog (PTEN) and Programmed Cell Death Protein 4 (PDCD4), as well as its broader effects on inflammatory and apoptotic signaling pathways. Evidence from both in vitro and in vivo studies suggests that modulating miR-21 influences lesion size, cellular dynamics, and functional recovery, highlighting its potential as a therapeutic target for SCI. Nonetheless, the clinical translation of miR-21-based therapies poses significant challenges, including the need to optimize dosages, delivery mechanisms, and long-term safety profiles. Further research is crucial to fully delineate miR-21’s therapeutic potential and determine its feasibility for integration into SCI treatment protocols. This review aims to provide a comprehensive overview of miR-21’s roles in SCI pathology, offering insights into the molecular mechanisms underlying recovery and the emerging potential of miR-21 in SCI management to enhance outcomes and quality of life for affected patients. Full article

(This article belongs to the Special Issue Molecular Mechanism and Regulation in Neuroinflammation, 2nd Edition)

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35 pages, 1097 KiB

Open AccessReview

Photodynamic Therapy in Cancer: Insights into Cellular and Molecular Pathways

by Vincenzo Papa, Fabiana Furci, Paola Lucia Minciullo, Marco Casciaro, Alessandro Allegra and Sebastiano Gangemi

Curr. Issues Mol. Biol. 2025, 47(2), 69; https://doi.org/10.3390/cimb47020069 - 21 Jan 2025

Viewed by 903

Abstract

Photodynamic therapy is a non-ionizing radiation treatment that utilizes a photosensitizer in combination with light to produce singlet oxygen. This singlet oxygen induces anti-cancer effects by causing apoptotic, necrotic, or autophagic cell death in tumor cells. Currently, photodynamic therapy is employed in oncology [...] Read more.

Photodynamic therapy is a non-ionizing radiation treatment that utilizes a photosensitizer in combination with light to produce singlet oxygen. This singlet oxygen induces anti-cancer effects by causing apoptotic, necrotic, or autophagic cell death in tumor cells. Currently, photodynamic therapy is employed in oncology to treat various cancers. In the presence of oxygen, this non-invasive approach leads to direct tumor cell death, damage to microvasculature, and the induction of a local inflammatory response. These effects allow photodynamic therapy to be effective in treating early-stage tumors, extending survival in cases where surgery is not feasible, and significantly improving quality of life. In this paper, we provide a state of the art on cytomolecular mechanisms and associated pathways involved in photodynamic therapy. By integrating these mechanistic insights with the most recent advancements in nanotechnology, this phototherapeutic approach has the potential to become a prevalent treatment option within conventional cancer therapies, enhancing its application in precision medicine. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2024)

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