International Journal of Molecular Sciences

2025

33 pages, 2755 KB

Open AccessReview

Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies

by Nabanita Mukherjee, James Sheetz and Yiqun G. Shellman

Int. J. Mol. Sci. 2025, 26(20), 9859; https://doi.org/10.3390/ijms26209859 - 10 Oct 2025

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The BCL2 family of proteins plays a pivotal role in regulating apoptosis and cellular homeostasis, making them critical therapeutic targets in cancer and other diseases characterized by pathological cell survival. BH3 mimetics, small molecules that selectively inhibit anti-apoptotic BCL2 family members, have achieved [...] Read more.

The BCL2 family of proteins plays a pivotal role in regulating apoptosis and cellular homeostasis, making them critical therapeutic targets in cancer and other diseases characterized by pathological cell survival. BH3 mimetics, small molecules that selectively inhibit anti-apoptotic BCL2 family members, have achieved significant clinical success, particularly in hematologic malignancies. However, several challenges remain, including resistance mechanisms, toxicity (such as MCL1 inhibitor-associated cardiotoxicity), and the intricate balance between apoptotic and non-apoptotic functions. This review provides a comprehensive overview of BCL2 family biology, the development and clinical application and outcomes of BH3 mimetics, and the emerging resistance mechanism known as double-bolt locking. We also examine strategies to overcome resistance, including combination therapies and immunomodulatory approaches. Beyond oncology, we highlight the expanding therapeutic potential of BH3 mimetics in autoimmune, fibrotic, and infectious diseases, as well as regenerative and anti-aging medicine. Finally, we discuss predictive biomarkers and tissue-specific responses that inform precision therapy. Together, these insights underscore the promise of BH3 mimetics and the need for continued multidisciplinary research to optimize their clinical impact. Full article

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14 pages, 3474 KB

Open AccessArticle

Silk Fibroin Protective Coating for Washable and Reusable Textile Electronics

by Anna Baranowska-Korczyc, Dorota Kowalczyk and Małgorzata Cieślak

Int. J. Mol. Sci. 2025, 26(20), 9848; https://doi.org/10.3390/ijms26209848 - 10 Oct 2025

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Abstract

In this study, a new way of protecting textile wearable electronics is proposed. A natural product, silk fibroin, known for its high biocompatibility, biodegradability, and low cytotoxicity, was selected to cover the functionalized fabric to improve its stability and enable washability. Silk fabric [...] Read more.

In this study, a new way of protecting textile wearable electronics is proposed. A natural product, silk fibroin, known for its high biocompatibility, biodegradability, and low cytotoxicity, was selected to cover the functionalized fabric to improve its stability and enable washability. Silk fabric was selected as a non-toxic material, suitable for further application on skin and for wearable devices. Silk fabric was functionalized with various amounts of high-pressure carbon monoxide single-walled carbon nanotubes (HiPCO SWNTs). HiPCO SWNTs made the fabric electroconductive, but they are easily washed out of the fabric. The fabric functionalized with HiPCO SWNTs was covered with silk fibroin (SF) protein, which was subsequently crystallized by ethanol vapor to make it insoluble in water. The functionalization and silk fibroin coverage processes were studied using electrical resistance measurements, infrared and Raman spectroscopies, thermogravimetric technique, and surface wettability analysis. The coverage of the fabric with crystallized silk fibroin enables the washing process. The resistance of the functionalized fabric with silk fibroin did not increase significantly. The presented silk fibroin coating can facilitate the construction of future wearable electronics, protect the electroconductive nanomaterials on the fabric surface, and make textile structures reusable. Full article

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14 pages, 1285 KB

Open AccessArticle

Edible Herb Aster glehni Alleviates Inflammation and Oxidative Stress in Chondrocytes by Regulating p38 and NF-κB Signaling Pathways with Partial Involvement of Its Major Component, 3,5-Dicaffeoylqunic Acid

by Jihyeon Baek, Hanhee Choi, Sung Ran Yoon, Yong Jin Jeong, Shin Young Oh, Min-Sook Kang, Haeng-Ran Kim, Han-Seung Shin and Seok-Seong Kang

Int. J. Mol. Sci. 2025, 26(19), 9691; https://doi.org/10.3390/ijms26199691 - 4 Oct 2025

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Abstract

Osteoarthritis (OA) is primarily a degenerative disease triggered by joint inflammation and oxidative stress. While Aster glehni is an edible and traditionally medicinal herb, the beneficial effect of A. glehni on OA progression remains unknown. This study aimed to investigate the effect of [...] Read more.

Osteoarthritis (OA) is primarily a degenerative disease triggered by joint inflammation and oxidative stress. While Aster glehni is an edible and traditionally medicinal herb, the beneficial effect of A. glehni on OA progression remains unknown. This study aimed to investigate the effect of A. glehni extract (AGE) and its primary biological compound—3,5-dicaffeoylquinic acid (3,5-DCQA)—on inflammation and oxidative stress in chondrocytes. AGE effectively inhibited the expression of interleukin (IL)-6, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-1, and MMP-13 in chondrocytes stimulated by IL-1β for 24 h. In contrast, 3,5-DCQA did not inhibit IL-6, COX-2, and MMP expressions under the same conditions. However, when chondrocytes were stimulated by IL-1β for a short duration (6 h), 3,5-DCQA suppressed IL-6, COX-2, and MMP expressions. The inhibition of IL-6, COX-2, and MMP expressions by AGE was associated with the p38 kinase and nuclear factor-κB signaling pathways, but not ERK and JNK signaling pathways. Furthermore, AGE prevented cell apoptosis and reduced intracellular reactive oxygen species levels in chondrocytes induced by hydrogen peroxide (H₂O₂). AGE restored the decreased superoxide dismutase 1 and catalase mRNA expressions caused by H₂O₂. Collectively, AGE may protect against cartilage deterioration by inhibiting inflammation and oxidative stress, making it a promising therapeutic agent for alleviating OA. Full article

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16 pages, 3427 KB

Open AccessArticle

From Bioinformatics Analysis to Recombinant Expression: Advancing Public Health with Taenia solium Proteins

by Juana Muñoz, María Camila Jurado Guacaneme, Clemencia Ovalle-Bracho, Julián Trujillo Trujillo, Sofía Duque-Beltrán, Adriana Arévalo and Carlos Franco-Muñoz

Int. J. Mol. Sci. 2025, 26(19), 9585; https://doi.org/10.3390/ijms26199585 - 1 Oct 2025

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Abstract

Taeniasis and neurocysticercosis (NCC), caused by Taenia solium, are significant public health concerns recognised by the World Health Organization (WHO) in developing countries across the Americas, Asia, and Africa. Taeniasis occurs in humans after consuming undercooked pork containing the larval stage ( [...] Read more.

Taeniasis and neurocysticercosis (NCC), caused by Taenia solium, are significant public health concerns recognised by the World Health Organization (WHO) in developing countries across the Americas, Asia, and Africa. Taeniasis occurs in humans after consuming undercooked pork containing the larval stage (Cysticerci), which matures into the adult reproductive form in the intestine, releasing eggs through faeces. Accidental ingestion of these eggs by humans is the primary cause of NCC, a principal contributor to acquired epilepsy in endemic regions. Interrupting this transmission cycle is crucial to reducing the incidence of human NCC and porcine cysticercosis, thereby underscoring the need for accurate diagnosis and timely treatment of taeniasis. Current diagnostic tests for taeniasis, including microscopy, serology, copro-DNA, and coproantigen assays, exhibit variability in sensitivity, reproducibility, cross-reactivity, and accessibility. To overcome these limitations, bioinformatics tools were integrated with recombinant DNA technology to identify protein sequences with immunological potential. These sequences were evaluated in silico and used to construct an expression system. Subsequently, the antigens were expressed in a eukaryotic system, yielding two purified recombinant protein variants of 21 and 30 kDa. Their purification validated via Western blotting of the molecular tag, paves the way for the development of a direct immunological assay for the specific detection of Taenia solium carriers. Full article

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41 pages, 3684 KB

Open AccessReview

Chrysin as a Bioactive Scaffold: Advances in Synthesis and Pharmacological Evaluation

by Chae Yun Jeong, Chae-Eun Kim, Eui-Baek Byun and Jongho Jeon

Int. J. Mol. Sci. 2025, 26(19), 9467; https://doi.org/10.3390/ijms26199467 - 27 Sep 2025

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Abstract

Chrysin (5,7-dihydroxyflavone) is a flavonoid widely distributed in propolis, honey, and various plant sources. It exhibits a wide range of pharmacological activities, including anti-inflammatory, antioxidant, anticancer, antimicrobial, and anti-diabetic effects. However, its clinical translation is hampered by poor aqueous solubility, low bioavailability, and [...] Read more.

Chrysin (5,7-dihydroxyflavone) is a flavonoid widely distributed in propolis, honey, and various plant sources. It exhibits a wide range of pharmacological activities, including anti-inflammatory, antioxidant, anticancer, antimicrobial, and anti-diabetic effects. However, its clinical translation is hampered by poor aqueous solubility, low bioavailability, and rapid metabolic clearance. To address these limitations and expand the chemical space of this natural scaffold, extensive synthetic efforts have focused on generating structurally diverse chrysin derivatives that possess improved drug-like properties. This review systematically categorizes synthetic methodologies—such as etherification, esterification, transition-metal-mediated couplings, sigmatropic rearrangements, and electrophilic substitutions—and integrates them with corresponding biological outcomes. Particular emphasis is placed on recent (2020–present) advances that directly link structural modifications with pharmacological enhancements, thereby offering comparative structure–activity relationship (SAR) insights. In addition, transition-metal-catalyzed C–C bond-forming reactions are highlighted in a dedicated section, underscoring their growing role in accessing bioactive chrysin analogs previously unattainable by conventional chemistry. Unlike prior reviews that mainly summarized biological activities or broadly covered flavonoid scaffolds, this article bridges synthetic diversification with pharmacological evaluation. It provides both critical synthesis and mechanistic interpretation. Overall, this work consolidates current knowledge and suggests future directions that integrate synthetic innovation with pharmacological validation and address pharmacokinetic challenges in chrysin derivatives. Full article

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19 pages, 4596 KB

Open AccessArticle

Decreased Expression of a Phosphoribosylanthranilate Transferase-Encoding Gene, OsPAT1, Causes Lesion Mimics in Rice

by Jun Ren, Qingwen Zhang, Yafei Xu, Biaoming Zhang, Haitao Li, Yan Li, Haitao Zhang and Wenya Yuan

Int. J. Mol. Sci. 2025, 26(19), 9428; https://doi.org/10.3390/ijms26199428 - 26 Sep 2025

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Abstract

Lesion mimic mutants (LMMs) represent valuable biological tools for investigating plant defense mechanisms and cell death. Although multiple genes triggering lesion mimic formation have been identified, the connection between the lesion mimic phenotype and primary nutrient biosynthesis remains poorly understood. In our study, [...] Read more.

Lesion mimic mutants (LMMs) represent valuable biological tools for investigating plant defense mechanisms and cell death. Although multiple genes triggering lesion mimic formation have been identified, the connection between the lesion mimic phenotype and primary nutrient biosynthesis remains poorly understood. In our study, we characterized a novel rice LMM, lmm9, which exhibited persistent reddish-brown necrotic lesions from seedling stage to maturity, coupled with compromised agronomic traits and increased mortality rates. Map-based cloning and whole-genome sequencing identified a causal insertion in the promoter of Os03g03450/OsPAT1, the sole homolog of Arabidopsis PAT1 in rice, resulting in reduced gene expression. Genetic complementation and RNAi assays confirmed that downregulation of OsPAT1 led to lesion mimic formation in lmm9. OsPAT1 could translate into two variants—the predominant OsPAT1.1 and the C-terminal variant OsPAT1.2. Structural modeling demonstrated high conservation between OsPAT1 and yeast TRP4, and OsPAT1.1 combining the plastid signal sequence of Arabidopsis PAT1 successfully complemented the trp4 mutant in yeast. Notably, OsPAT1.1 and OsPAT1.2 showed different localization patterns, with OsPAT1.1 targeted to mitochondria and OsPAT1.2 localized to chloroplasts. Transcription analysis showed significant upregulation of tryptophan biosynthesis pathway genes in lmm9, consequently increasing the relative abundance of tryptophan and associated metabolites. Our findings provided further evidence that mutations in tryptophan biosynthetic genes can induce lesion mimic phenotypes in rice and would enhance the understanding of metabolic homeostasis in plant stress responses and cell death regulation. Full article

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15 pages, 2687 KB

Open AccessArticle

Recombinant Production and Characterization of a Novel α-L-Fucosidase from Bifidobacterium castoris

by Burcu Pekdemir and Sercan Karav

Int. J. Mol. Sci. 2025, 26(19), 9344; https://doi.org/10.3390/ijms26199344 - 24 Sep 2025

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Abstract

α-L-fucosidases (EC 3.2.1.51) are of particular interest due to their ability to cleave terminal α-L-fucose residues from glycoconjugates, a property associated with numerous biological and therapeutic effects. They have also been investigated for their potential use in glycan remodeling, disease biomarker analysis, and [...] Read more.

α-L-fucosidases (EC 3.2.1.51) are of particular interest due to their ability to cleave terminal α-L-fucose residues from glycoconjugates, a property associated with numerous biological and therapeutic effects. They have also been investigated for their potential use in glycan remodeling, disease biomarker analysis, and particularly as therapeutic agents in the context of fucosidosis, a rare lysosomal storage disorder, caused by a deficiency in α-L-fucosidase activity. However, limitations in enzyme availability, stability, and substrate specificity highlight the need for novel and more efficient enzyme sources. Bifidobacterium castoris (B. castor is) is a newly identified species first discovered in the beaver gut microbiota in 2019. Phylogenetic studies have revealed its advanced metabolic capacity, and genomic analyses have demonstrated its extensive carbohydrate metabolism potential. This research article focuses on the recombinant production and biochemical characterization of a novel α-L-fucosidase from B. castoris LMG (Laboratorium voor Microbiologie Gent) 30937, predicted to belong to glycoside hydrolase family 29 (GH29) according to Universal Protein Resource (UniProt) annotation. Under optimized reaction conditions the recombinant α-L-fucosidase exhibited a specific activity of 0.264 U/mg to pNP-Fuc (4-Nitrophenyl-α-L-fucopyranoside). The results indicate that the enzyme is active in the pH range of 3.0–8.0 and temperatures of 24–42 °C, but its optimum conditions are the slightly acidic pH of 5.5 and the elevated temperature of 42 °C. This profile suggests that the enzyme is adapted to acidic intestinal-like environments. This novel enzyme expands the GH29 α-L-fucosidase repertoire and offers a promising new candidate for future biotechnological applications. Full article

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10 pages, 693 KB

Open AccessArticle

Exploring the Bioactive Potential and Biocompatibility of Extracts from Agro-Industrial Residues for Cosmetic Applications

by Sandra M. Gomes, Filipa Campos, M. Cristina L. Martins, Cláudia Monteiro and Lúcia Santos

Int. J. Mol. Sci. 2025, 26(18), 9169; https://doi.org/10.3390/ijms26189169 - 19 Sep 2025

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Abstract

Every year, significant amounts of agro-industrial residues are generated. These residues contain several antioxidant compounds that can be extracted and applied to cosmetic products. In this study, phenolic-rich extracts from different agro-industrial residues (chestnut shell—CS, grape seed—GS, kiwi peel—KP, onion peel—OP, and pomegranate [...] Read more.

Every year, significant amounts of agro-industrial residues are generated. These residues contain several antioxidant compounds that can be extracted and applied to cosmetic products. In this study, phenolic-rich extracts from different agro-industrial residues (chestnut shell—CS, grape seed—GS, kiwi peel—KP, onion peel—OP, and pomegranate peel—PP) were obtained and their antioxidant potential and biocompatibility towards human fibroblasts (HFF-1) were evaluated. The total phenolic content ranged from 37.6 mg of gallic acid equivalents (GAE)/g for KP to 343.9 mg_GAE/g for CS. Moreover, CS, GS, OP, and PP extracts exhibited strong antioxidant properties, while KP showed more moderate potential. Biocompatibility tests demonstrated that CS and GS extracts were non-cytotoxic at concentrations below 500 mg/L, while OP and PP were safe up to 1000 mg/L. KP extracts were biocompatible up to 10,000 mg/L. This work demonstrated the bioactive potential of various agro-industrial residues for application in the cosmetic industry, given their antioxidant capacity. Additionally, it was the first to establish safe application limits for Soxhlet-extracted compounds, ensuring their safety to consumers. This research emphasises the importance of evaluating the biocompatibility of each extract before its incorporation into cosmetics, as their composition is highly variable. Full article

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29 pages, 4978 KB

Open AccessArticle

HPLC-DAD-ESI/MS and 2D-TLC Analyses of Secondary Metabolites from Selected Poplar Leaves and an Evaluation of Their Antioxidant Potential

by Loretta Pobłocka-Olech, Mirosława Krauze-Baranowska, Sylwia Godlewska and Katarzyna Kimel

Int. J. Mol. Sci. 2025, 26(13), 6189; https://doi.org/10.3390/ijms26136189 - 27 Jun 2025

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Abstract

Poplar leaves (Populi folium) are a herbal remedy traditionally used for the treatment of rheumatic diseases and prostate inflammation. The aim of our study was a comprehensive identification of secondary metabolites occurring in the leaves of Populus alba, Populus × [...] Read more.

Poplar leaves (Populi folium) are a herbal remedy traditionally used for the treatment of rheumatic diseases and prostate inflammation. The aim of our study was a comprehensive identification of secondary metabolites occurring in the leaves of Populus alba, Populus × candicans, and Populus nigra, in order to search for a source of raw plant material rich in active compounds. Total salicylate (TSC), flavonoid (TFC), and phenolic compound (TPC) contents were determined, and the antioxidant potential was assessed using DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azino-bis(3-ethylbenzothiazoline- 6-sulfonic acid) diammonium salt), and FRAP (ferric reducing antioxidant power) assays as well as 2D-TLC (two-dimensional thin layer chromatography) bioautography using DPPH, riboflavin-light-NBT (nitro blue tetrazolium chloride), and xanthine oxidase inhibition tests. Secondary metabolites present in the analyzed poplar leaves were identified under the developed HPLC-DAD-ESI/MS (high performance liquid chromatography with photodiode array detection and electrospray ionization mass spectrometric detection analysis conditions and using the 2D-TLC method. Among the 80 identified compounds, 13 were shown for the first time in the genus Populus. The most diverse and similar set of flavonoids characterized the leaves of P. × candicans and P. nigra, while numerous salicylic compounds were present in the leaves of P. alba and P. × candicans. All analyzed leaves are a rich source of phenolic compounds. The highest flavonoid content was found in the leaves of P. × candicans and P. nigra, while the leaves of P. alba were characterized by the highest content of salicylates. All examined poplar leaves demonstrated antioxidant potential in all the assays used, which decreased in the following order: P. nigra, P. × candicans, P. alba. Full article

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