Current Issues in Molecular Biology

20 pages, 8291 KB

Open AccessArticle

Analysis of Potential Q-Markers for Salt-Processed Alismatis Rhizoma in Diuresis Based on Fingerprinting Technology and Network Analysis

by Lin Yan, Zemin Ou, Yun Wang, Yan Tong, Jinyu Wang and Dewen Liu

Curr. Issues Mol. Biol. 2025, 47(9), 783; https://doi.org/10.3390/cimb47090783 (registering DOI) - 21 Sep 2025

Abstract

Introduction: The ability of salt-processed Alismatis Rhizoma (SAR) (Alisma plantago-aquqtica L.) to nourish Yin and promote urination is stronger than that of Alismatis Rhizoma (AR). However, there are few studies focused on evaluating the quality of its medicinal materials. Objectives: This study [...] Read more.

Introduction: The ability of salt-processed Alismatis Rhizoma (SAR) (Alisma plantago-aquqtica L.) to nourish Yin and promote urination is stronger than that of Alismatis Rhizoma (AR). However, there are few studies focused on evaluating the quality of its medicinal materials. Objectives: This study aimed to identify potential quality markers (Q-markers) for SAR, thereby providing a more reliable basis for its quality control and clinical application. Methods: Q-markers were identified through fingerprinting and chemical pattern recognition analysis of 15 batches of SAR. The diuretic effects of these markers were then verified by network analysis and molecular docking. Results: HPLC fingerprints of 15 SAR batches were established, with similarity analysis showing values > 0.85 (0.852–0.990). Chemical pattern recognition identified six critical compounds contributing to SAR quality: alisol F, alisol C 23-acetate, alisol A, alisol A 24-acetate, alisol B 23-acetate, and an alisol O isomer (VIP > 1.0). Network analysis revealed 76 overlapping targets between these compounds and diuretic-related diseases, with core targets including non-receptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), which were identified through protein–protein interaction (PPI) network analysis, with degrees of 27, 24, and 22, respectively. Key pathways involved were the EGFR tyrosine kinase inhibitor resistance pathway, calcium signaling pathway, tumor necrosis factor signaling pathway, etc. Molecular docking confirmed strong binding interactions between the Q-markers and the hub targets, particularly alisol B 23-acetate with MAPK1 (−60.10 kcal·mol⁻¹) and alisol A 24-acetate with EGFR (−46.14 kcal·mol⁻¹) and SRC (−48.86 kcal·mol⁻¹). The diuretic effects of SAR are likely mediated through anti-inflammatory actions and regulation of water–sodium balance via multi-target and multi-pathway mechanisms. Conclusion: This study provides a robust foundation for quality control and clinical application of SAR, though further in vivo validation is warranted. Full article

(This article belongs to the Section Molecular Pharmacology)

2 pages, 152 KB

Open AccessRetraction

RETRACTED: Haghmorad et al. Oral Administration of Myelin Oligodendrocyte Glycoprotein Attenuates Experimental Autoimmune Encephalomyelitis through Induction of Th2/Treg Cells and Suppression of Th1/Th17 Immune Responses. Curr. Issues Mol. Biol. 2022, 44, 5728–5740

by Dariush Haghmorad, Bahman Yousefi, Majid Eslami, Ali Rashidy-Pour, Mahdieh Tarahomi, Maryam Jadid Tavaf, Azita Soltanmohammadi, Simin Zargarani, Aleksandr Kamyshnyi and Valentyn Oksenych

Curr. Issues Mol. Biol. 2025, 47(9), 781; https://doi.org/10.3390/cimb47090781 (registering DOI) - 20 Sep 2025

Abstract

The journal retracts the article “Oral Administration of Myelin Oligodendrocyte Glycoprotein Attenuates Experimental Autoimmune Encephalomyelitis through Induction of Th2/Treg Cells and Suppression of Th1/Th17 Immune Responses” [...] Full article

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

22 pages, 1549 KB

Open AccessReview

Natural Products Targeting the Androgen Receptor Signaling Pathway: Therapeutic Potential and Mechanisms

by Sitong Wu, Esveidy Isabel Oceguera Nava, Dennis Ashong, Guanglin Chen and Qiao-Hong Chen

Curr. Issues Mol. Biol. 2025, 47(9), 780; https://doi.org/10.3390/cimb47090780 (registering DOI) - 19 Sep 2025

Abstract

The androgen receptor (AR) signaling pathway is the primary driver of prostate cancer initiation and progression, including the development of castration-resistant prostate cancer (CRPC). Because current AR-targeted therapies inevitably encounter drug resistance, novel strategies to suppress AR signaling are urgently needed. Natural products [...] Read more.

The androgen receptor (AR) signaling pathway is the primary driver of prostate cancer initiation and progression, including the development of castration-resistant prostate cancer (CRPC). Because current AR-targeted therapies inevitably encounter drug resistance, novel strategies to suppress AR signaling are urgently needed. Natural products represent a rich and structurally diverse source of bioactive compounds capable of targeting AR at multiple regulatory levels. This review overviews the interactions between natural products and the AR signaling axis through distinct mechanisms, including inhibition of testosterone production and 5α-reductase activity, direct antagonism of AR, and induction of AR degradation. In addition, several compounds disrupt AR nuclear translocation, downregulate AR splice variants, or suppress AR signaling indirectly through epigenetic regulation, microRNA modulation, or interference with co-regulator networks. Preclinical studies provide compelling evidence that these agents can effectively interrupt AR signaling, thereby suppressing prostate cancer growth. However, challenges remain, particularly the limited pharmacokinetic characterization, lack of in vivo validation, and scarcity of clinical studies. Future research should focus on improving bioavailability, exploring synergistic combinations with existing therapies, and advancing well-designed in vivo and clinical investigations. Collectively, these efforts may establish natural products as lead compounds to modulate AR signaling for prostate cancer prevention and treatment. Full article

(This article belongs to the Special Issue Natural Phytochemicals as Modulators of Cellular Pathways and Therapeutic Targets in Disease Models)

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22 pages, 5983 KB

Open AccessArticle

Bioactive Component Screening and Mechanistic Study of the Anti-Diabetic Activity of Lophatherum gracile Brongn Extract

by Rong Wang, Xuefeng Liu, Kuan Yang, Shaojing Liu, Lili Yu, Yunmei Chen, Nana Wang, Yaqi Hu and Bei Qin

Curr. Issues Mol. Biol. 2025, 47(9), 779; https://doi.org/10.3390/cimb47090779 (registering DOI) - 19 Sep 2025

Abstract

Type 2 diabetes mellitus (T2DM), a metabolic disorder defined by glucose and lipid metabolism dysregulation, has become a major global health issue. Hence, effective measures to prevent T2DM are urgently required. Lophatherum gracile Brongn (LGB) has been used in managing diabetes-related systemic diseases. [...] Read more.

Type 2 diabetes mellitus (T2DM), a metabolic disorder defined by glucose and lipid metabolism dysregulation, has become a major global health issue. Hence, effective measures to prevent T2DM are urgently required. Lophatherum gracile Brongn (LGB) has been used in managing diabetes-related systemic diseases. However, the hypoglycemic bioactive components in LGB and the mechanisms underlying their hypoglycemic activity remain elusive. The current study sought to characterize the bioactive components of LGB and elucidate its mechanism of action against T2DM. Six common characteristic peaks were identified from six batches of LGB, with 39 characteristic chemical components preliminarily identified. Through component–activity correlation analysis, three functional components—namely isoorientin, orientin, and isovitexin—were selected as key candidates. In T2DM mice, LGB effectively improved glucose and lipid metabolic dysfunction. Untargeted metabolomics analysis revealed that LGB modulated pathways related to lipid and carbon metabolism. 16S rRNA gene sequencing and targeted metabolomics analysis revealed that LGB decreased the ratio of Firmicutes to Bacteroidetes and increased the abundance of bacterial groups such as Lactobacillales and Bacteroides. Additionally, LGB elevated the levels of SCFAs, specifically acetic and butyric acid. Moreover, LGB alleviated intestinal inflammation and upregulated the expression of tight junction proteins by inhibiting the LPS/TLR4/NF-κB signaling pathway. This study demonstrated that LGB treated T2DM, with isoorientin, orientin, and isovitexin identified as the main contributing components. The hypoglycemic mechanism is linked to the “gut microbiota−SCFAs−inflammatory response” signaling axis. Full article

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

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17 pages, 2851 KB

Open AccessArticle

Pharmacological Potential of Arthrospira platensis in Mitigating Sub-Chronic Colitis: Redox Homeostasis and Gut Microbiota Modulation

by Meriem Aziez, Betitera Yanat, Cristina Rodriguez-Diaz, Ramona Suharoschi, Romana Vulturar, Simona-Codruta Heghes, Nawel Guenaoui, Awadh M. Ali, Eduardo Garcia-Fuentes and Noureddine Bribi

Curr. Issues Mol. Biol. 2025, 47(9), 778; https://doi.org/10.3390/cimb47090778 (registering DOI) - 19 Sep 2025

Abstract

Inflammatory bowel diseases (IBDs) are complex disorders involving interconnected immune, oxidative, and microbial dysregulations. Arthrospira platensis (Spirulina) is a rich source of bioactive compounds with antioxidant, anti-inflammatory, and immunomodulatory properties. This study investigates the pharmacological efficacy of its aqueous extract (APA) in mitigating [...] Read more.

Inflammatory bowel diseases (IBDs) are complex disorders involving interconnected immune, oxidative, and microbial dysregulations. Arthrospira platensis (Spirulina) is a rich source of bioactive compounds with antioxidant, anti-inflammatory, and immunomodulatory properties. This study investigates the pharmacological efficacy of its aqueous extract (APA) in mitigating 2,4-Dinitrobenzene Sulfonic Acid (DNBS)-induced sub-chronic colitis with a focus on restoring redox balance and modulating gut microbiota composition. APA’s antioxidant capacity was assessed in vitro by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulphonic) acid (ABTS) radical scavenging, and metal chelation assays. In vivo, BALB/c mice received two DNBS inductions to establish sub-chronic colitis and were treated with APA (50, 100, and 200 mg/kg). Therapeutic efficacy was assessed through clinical scoring, histopathological assessment, biochemical analysis, and gut microbiota profiling based on 16S rRNA gene sequencing. APA exhibited strong antioxidant activity and significantly attenuated colitis severity, as evidenced by reduced Disease Activity Index (DAI) scores, decreased colon inflammation, suppression of Myeloperoxidase (MPO)-mediated neutrophil infiltration, and modulation of redox biomarkers. Moreover, metagenomic profiling revealed APA-induced modulation of the gut microbiota, mainly through a decreased abundance of pathogenic genera such as Staphylococcus and Enterobacteriaceae. APA demonstrates potent antioxidant, anti-inflammatory, and microbiota-modulating activities, supporting its potential as a complementary therapy for IBDs and encouraging further clinical studies. Full article

(This article belongs to the Special Issue Microalga Biotechnology and Applications: Molecular and Cellular Mechanisms)

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15 pages, 5753 KB

Open AccessArticle

In Silico Study of Natural Polyphenols as Potential Metabolic Modulators in Mitigating Lipotoxicity in Non-Alcoholic Fatty Liver Disease via Thyroid Hormone Receptor Alpha Activation

by Evangelia K. Konstantinou, Athanasios A. Panagiotopoulos and Maria Dimitriou

Curr. Issues Mol. Biol. 2025, 47(9), 777; https://doi.org/10.3390/cimb47090777 - 19 Sep 2025

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder described by the deposition of triglycerides in the liver, which primarily occurs due to insulin resistance and obesity. Thyroid hormone receptor alpha (THRA) is involved in metabolic pathways that promote lipolysis, which can prevent [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder described by the deposition of triglycerides in the liver, which primarily occurs due to insulin resistance and obesity. Thyroid hormone receptor alpha (THRA) is involved in metabolic pathways that promote lipolysis, which can prevent the accumulation of liver fat. As a possible treatment for NAFLD, this in silico study examines the binding interactions between THRA and polyphenols and flavonoids present in fruits and vegetables. Including caffeic acid, curcumin, and chlorogenic acid, the binding affinities of the natural substances to THRA were found comparable to the hormone T3, boosting the THRA–TRAP220 complex, promoting fatty acid oxidation, while decreasing lipid accumulation in the liver. Full article

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

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18 pages, 780 KB

Open AccessReview

Anti-TB Drugs for Drug-Sensitive and Drug-Resistant Mycobacterium tuberculosis: A Review

by Kara Lukas, Madeleine T. Dang, Clare Necas and Vishwanath Venketaraman

Curr. Issues Mol. Biol. 2025, 47(9), 776; https://doi.org/10.3390/cimb47090776 - 19 Sep 2025

Abstract

Tuberculosis (TB) is a global health challenge caused by Mycobacterium tuberculosis, with drug resistance, treatment toxicity, and treatment adherence challenges continuing to impede control efforts. The objective of this review is to explore current advancements in TB treatment, for both drug-sensitive and drug-resistant [...] Read more.

Tuberculosis (TB) is a global health challenge caused by Mycobacterium tuberculosis, with drug resistance, treatment toxicity, and treatment adherence challenges continuing to impede control efforts. The objective of this review is to explore current advancements in TB treatment, for both drug-sensitive and drug-resistant TB, focusing on pharmacologic regimens, diagnostics, and adjunctive therapies. For drug-sensitive TB, a 4-month rifapentine–moxifloxacin regimen has been proven to be non-inferior to the traditional 6-month standard, while optimized pyrazinamide dosing or faropenem substitution may improve culture conversion and reduce adverse events. In drug-resistant TB, regimens such as the bedaquiline, pretomanid, linezolid, and moxifloxacin have demonstrated efficacy with substantially shorter treatment duration; however, incidents of hepatotoxicity and linezolid-related neuropathy require careful monitoring. Adjunctive therapies, such as metformin, N-Acetylcysteine, aspirin, and statins, show promising effects in modulating host immunity and reducing long-term lung damage. Advances in diagnostics, including whole genome sequencing and CRISPR-based methods, are enabling rapid detection of resistance mutations and directed therapy. Vaccine development has advanced beyond the BCG vaccine to explore vaccines with enhanced immunogenicity or ones that are safe for immunocompromised patients. Implementation strategies such as video directly observed therapy are improving adherence; additionally, community-based, technology-supported interventions significantly improve TB knowledge and compliance. An integrated approach that combines optimized pharmacologic regimens, host-directed therapies, advanced diagnostics, and patient-centered public health strategies is essential to reduce TB incidence, long-term morbidity, and mortality. Full article

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

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24 pages, 1399 KB

Open AccessReview

Combination of the First-in-Class Imipridone ONC201 and Standard Anticancer Therapies as a Rational Approach for Therapeutic Benefit

by Brahmi Shenoy, Miloni Mandani, Meena Chintamaneni and Sonal M. Manohar

Curr. Issues Mol. Biol. 2025, 47(9), 775; https://doi.org/10.3390/cimb47090775 - 18 Sep 2025

Abstract

The development of drugs for cancer treatment faces critical challenges due to the heterogeneity in cancers, metastatic nature of the disease, lack of efficacy, toxicity, and drug resistance. This makes it quite important to understand the complexities of cancer as well as the [...] Read more.

The development of drugs for cancer treatment faces critical challenges due to the heterogeneity in cancers, metastatic nature of the disease, lack of efficacy, toxicity, and drug resistance. This makes it quite important to understand the complexities of cancer as well as the limitations of druggable targets. ONC201 (also known as dordaviprone/TIC10/Modeyso^TM), a first-in-class member of the imipridone family, has been shown to kill cancer cells selectively. Recently, it has received FDA approval as the first and only treatment for recurrent H3K27M-mutant diffuse midline glioma. The unique pharmacophore, favorable therapeutic index, ability to induce TRAIL and the integrated stress response (ISR), activation of natural killer cells, and ability to diffuse across the blood–brain barrier are the unique characteristics of ONC201. ONC201 has shown effectiveness against various cancers, and this has been evident in many preclinical studies. ONC201 as a single agent, although useful, has some limitations, which could be addressed by using combination strategies. ONC201 has shown synergism with other drugs, leading to greater tumor cell death or reduced tumor growth. Next-generation imipridones, viz. ONC206 and ONC212, are more potent analogs of ONC201 and exhibit similar characteristics. In this review, we discuss the therapeutic potential of ONC201 and its analogs using combination strategies across different cancers. Full article

(This article belongs to the Special Issue Advances in Pharmacotherapeutic Strategies to Prevent Tumor Development, Progression and Treatment Resistance, 2nd Edition)

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18 pages, 3893 KB

Open AccessArticle

Metabolome and Transcriptome Analyses of the Molecular Mechanism Underlying Light-Induced Anthocyanin Accumulation in Pepper (Capsicum annuum L.) Peel

by Qinqin He, Liming He, Zongqin Feng, Yunyi Xiao, Qiucheng Qiu, Jiefeng Liu, Hanbing Han and Xinmin Huang

Curr. Issues Mol. Biol. 2025, 47(9), 774; https://doi.org/10.3390/cimb47090774 - 18 Sep 2025

Abstract

Under light exposure, certain pepper cultivars synthesize large amounts of anthocyanins in their pericarps, with the illuminated areas exhibiting black coloration. However, research on light-induced anthocyanin formation in pepper fruit, particularly the related metabolites and genetic changes, remains limited. To identify the key [...] Read more.

Under light exposure, certain pepper cultivars synthesize large amounts of anthocyanins in their pericarps, with the illuminated areas exhibiting black coloration. However, research on light-induced anthocyanin formation in pepper fruit, particularly the related metabolites and genetic changes, remains limited. To identify the key genes involved in localized anthocyanin synthesis under light conditions, we investigated the black pericarps (light-exposed) and green pericarps of pepper variety MSCJ1 under illumination. Metabolomics analysis identified 579 metabolites in the black and green pepper pericarps, with 50 differentially accumulated metabolites. Petunidin-3-(6″-p-coumaroyl-glucoside) and delphinidin-3-p-coumaroyl-rutinoid accumulation represented the main factor underlying light-induced blackening of the pericarp. RNA-seq identified 121 differentially expressed genes that were significantly enriched in the flavonoid biosynthesis pathway. The genes for phenylalanine ammonia lyase (Capana09g002200, Capna09g002190), cinnamic acid hydroxylase (Capana06g000273), chalcone synthase (Capana05g002274), flavonoid 3-hydroxylase (Capana02g002586), flavonoid 3′-hydroxylase (MSTRG.15987), dihydroflavonol 4-reductase (Capana02g002763), anthocyanin synthase (Capana01g000365), UDP glucosyltransferase (Capana03g000135), and glutathione S-transferase (Capana02g002285) were key genes for anthocyanin synthesis and transport. Transcription factors bHLH (Capana09g001426, Capana09g001427), HSFB3 (Capana05g000086), and TCP4 (Capana07g002142) participated in the regulation of anthocyanin synthesis. These results broaden our understanding of the mechanism of light-induced anthocyanin synthesis in pepper peel. Full article

(This article belongs to the Special Issue Advances in Multi-Omics for Functional Genomics Studies and Molecular Breeding, 2nd Edition)

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14 pages, 863 KB

Open AccessReview

Insulin-like Growth Factor 1 (IGF-1) in Hair Regeneration: Mechanistic Pathways and Therapeutic Potential

by Wang-Ju Hsieh, Wei-Yin Qiu, Ivona Percec and Tsong-Min Chang

Curr. Issues Mol. Biol. 2025, 47(9), 773; https://doi.org/10.3390/cimb47090773 - 18 Sep 2025

Abstract

IGF-1 (insulin-like growth factor 1) is a growth factor primarily secreted by dermal papilla cells on hair-bearing skin that stimulates hair follicle proliferation and vascularization, and promotes the transition to the anagen growth phase of the hair follicle by activating key pathways such [...] Read more.

IGF-1 (insulin-like growth factor 1) is a growth factor primarily secreted by dermal papilla cells on hair-bearing skin that stimulates hair follicle proliferation and vascularization, and promotes the transition to the anagen growth phase of the hair follicle by activating key pathways such as PI3K/Akt and MAPK/ERK. IGF-1 also inhibits apoptosis, prolongs the follicular growth phase, and boosts VEGF expression, which supports microcirculation and nutrient delivery to hair follicles. The combined effects of IGF-1 and other growth factors, including VEGF, KGF (FGF-7), and PDGF, further amplify its effects on follicular cell proliferation and tissue repair. IGF-1’s ability to regulate the hair growth cycle and its interactions with other signaling pathways make it a compelling therapeutic target for hair loss disorders. Both preclinical models and clinical evidence highlight IGF-1 as a promising therapeutic option for conditions like androgenetic alopecia (AGA), where IGF-1 levels are typically diminished. While topical IGF-1 treatments have shown efficacy and safety with minimal systemic absorption, additional research is needed to improve delivery methods, such as liposomal gels and exosome-based carriers, and to evaluate long-term effects. Full article

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

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19 pages, 10294 KB

Open AccessArticle

Protective Effect of Hepcidin on Sepsis-Associated Acute Kidney Injury via Activating the Nrf2/GPX4 Signaling Pathway

by Liang-Bo Guo, Shao-Sheng Wu, Feng Xu, Xin-Xing Chen and Heng Fan

Curr. Issues Mol. Biol. 2025, 47(9), 772; https://doi.org/10.3390/cimb47090772 - 18 Sep 2025

Abstract

Background: Hepcidin not only sustains systemic iron homeostasis but also functions as an antimicrobial peptide. During this study, we sought to analyze the ability of hepcidin to protect against sepsis-associated acute kidney injury (SAKI) and elucidated its underlying mechanisms in mediating ferroptotic pathways. [...] Read more.

Background: Hepcidin not only sustains systemic iron homeostasis but also functions as an antimicrobial peptide. During this study, we sought to analyze the ability of hepcidin to protect against sepsis-associated acute kidney injury (SAKI) and elucidated its underlying mechanisms in mediating ferroptotic pathways. Methods: A SAKI mouse model was created via cecal ligation and puncture (CLP), along with an LPS-induced Human Kidney-2 (HK-2) cell model, to study the protective mechanism of hepcidin against SAKI. Through the analysis of renal injury biomarkers and ferroptosis-related molecules, combined with quantitative detection of nuclear factor-erythroid 2-related factor-2 (Nrf2) nuclear translocation and glutathione peroxidase 4 (GPX4), a regulatory protein of ferroptosis, we uncovered the hepcidin-mediated mechanisms underlying ferroptosis in SAKI. Results: Hepcidin significantly attenuated renal function impairment in mice with SAKI and reduced the sepsis-driven increase in inflammatory mediators. As sepsis was associated with enhanced renal ferroptosis, hepcidin exerted a therapeutic effect by mitigating ferroptosis to a degree comparable with that of the ferroptosis inhibitor Ferrostatin-1 (Fer-1). Furthermore, hepcidin conferred renoprotective effects in SAKI by promoting the nuclear translocation of Nrf2, which in turn mediated the upregulation of the downstream anti-ferroptotic protein GPX4. Importantly, the Nrf2 inhibitor ML385 abrogated both the hepcidin-induced nuclear translocation of Nrf2 and the subsequent increase in GPX4 expression. Conclusions: Protective effects of hepcidin against SAKI are mediated by the Nrf2/GPX4 ferroptosis pathway, underscoring its therapeutic potential for SAKI. Full article

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

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11 pages, 1779 KB

Open AccessArticle

The First Complete Chloroplast Genome Sequence of the Cyrtomium hemionitis Fern

by Junxi Zhao, Panpan Shi, Xiaoxuan Wang, Shuosheng Zhang and Haixian Zhan

Curr. Issues Mol. Biol. 2025, 47(9), 771; https://doi.org/10.3390/cimb47090771 - 18 Sep 2025

Abstract

Cyrtomium hemionitis is a Cyrtomium fern with potential medicinal value; however, the lack of chloroplast genome data for this species limits its utilization and exploitation. In this study, the Illumina NovoSeq 6000 platform and SPAdes v3.14.1 were used to sequence and assemble the [...] Read more.

Cyrtomium hemionitis is a Cyrtomium fern with potential medicinal value; however, the lack of chloroplast genome data for this species limits its utilization and exploitation. In this study, the Illumina NovoSeq 6000 platform and SPAdes v3.14.1 were used to sequence and assemble the chloroplast genome of C. hemionitis. The chloroplast genome was 151,295 bp in length and exhibited a typical circular, double-stranded, quadripartite plastome architecture, with a GC content of 42.43%. Additionally, it included 30 high-frequency codons, 26 of which ended with A or U. In total, we annotated 130 coding genes, which included 88 protein-coding genes, 8 rRNA genes, and 34 tRNA genes. The IR (inverted repeat) boundaries of the genus Cyrtomium differed from those of common plants, with differences discovered in the JLB (large single-copy, inverted repeat b) and JLA (large single-copy, inverted repeat a) boundaries in this genus. Additionally, the phylogeny of this genus showed that C. hemionitis was more closely related to C. falcatum, whereas Dryopteris crassirhizoma was closely related to the genus Cyrtomium. These findings have significant implications for future research and can serve as a reference for the molecular evolution, systematic development, and utilization of C. hemionitis. Full article

(This article belongs to the Section Molecular Plant Sciences)

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17 pages, 7817 KB

Open AccessArticle

French Maritime Pine Bark Extract Alleviates Lung Injury by Regulating Inflammatory–Oxidative–Apoptotic Pathway and P2X7 Receptor Expression in LPS-Induced Sepsis

by Nergis Ulas, Seckin Ozkanlar, Serkan Yildirim, Omer Aydin and Yunusemre Ozkanlar

Curr. Issues Mol. Biol. 2025, 47(9), 770; https://doi.org/10.3390/cimb47090770 - 18 Sep 2025

Abstract

Introduction: Sepsis is a dysregulated systemic immune response to infection which may result in mortality. It may also lead to organ injury, including injury to the lung. French maritime pine bark extract (MPBE) has been proposed to prevent/treat various inflammatory diseases due to [...] Read more.

Introduction: Sepsis is a dysregulated systemic immune response to infection which may result in mortality. It may also lead to organ injury, including injury to the lung. French maritime pine bark extract (MPBE) has been proposed to prevent/treat various inflammatory diseases due to its strong anti-inflammatory and antioxidant effects. This study evaluates the protective and therapeutic effects of MPBE on lung injury induced by intraperitoneal E. coli lipopolysaccharide (LPS) in rats. Materials and Methods: The study design was as follows: Control, MPBE20, MPBE50, LPS, LPS+MPBE20 and LPS+MPBE50. Blood and lung tissue samples were collected 6 h after the LPS induction following a 10-day administration of MPBE. Results: LPS-induced sepsis was confirmed by the overproduction of IL-1β and TNF-α in bloodstream compared to the Control (p < 0.001). Lung injury was determined by severe histopathological changes and neutrophil infiltration in the lung tissue following intraperitoneal LPS injection. In lung tissue, MPBE improved the levels of P2X7R, TLR4, NLRP3, IL-1β, TNF-α, JNK, H2AX, 8-OHdG, MDA, GSH, Caspase-1 and Caspase-3, and pathological changes in MPBE+LPS groups compared to the LPS group. Conclusions: MPBE appears to regulate P2X7R signaling and the inflammatory–apoptotic pathway by protecting the lung from oxidative cell damage in LPS-induced sepsis in vivo. Full article

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

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16 pages, 2937 KB

Open AccessArticle

The Analysis of Solanum lycopersicum Sap Dark Proteome Reveals Ordered and Disordered Protein Abundance

by Francisco Antonio Reyes-Soria, Francisco Guillén-Chable, Enrique Castaño de la Serna, Lorenzo Felipe Sánchez-Teyer, Miguel Angel Herrera-Alamillo, Alejandro Pereira-Santana and Luis Carlos Rodriguez-Zapata

Curr. Issues Mol. Biol. 2025, 47(9), 769; https://doi.org/10.3390/cimb47090769 - 18 Sep 2025

Abstract

Protein identity and functional roles within the cell provide the landscape of proteomics and other high-throughput technologies. However, not all protein sequences are cataloged with an identity or a functional protein family. The lack of identity and functional role of a set of [...] Read more.

Protein identity and functional roles within the cell provide the landscape of proteomics and other high-throughput technologies. However, not all protein sequences are cataloged with an identity or a functional protein family. The lack of identity and functional role of a set of proteins are collectively named as the dark proteome. Key structural features are, for example, ordered sequences (with a defined structural arrangement) and disordered sequences (presenting one or more intrinsically disordered stretches). Here, we reanalyzed eight proteomic datasets and the subset of the “unknown” proteome of S. lycopersicum to describe if there is a relationship between disorder, length, and tissue-specific abundance of proteins with key structural features in the relation of ordered/disordered abundance in the protein sequences. Intriguingly, we unveil that from the S. lycopersicum proteome, the “unknown” subset represents around 10% only. We further cataloged dark proteome in terms of ordered and disordered sequences and found that proteins with disorder represent around 23% of the total “unknown” proteins. Also, we describe an amino acid composition and sequence length enrichment both, in the ordered and disordered fraction of the dark proteome. Finally, we describe that proteins within the dark proteome can be related to a specific location and abundance in an organ or tissue. An unknown protein sequence presenting a combination of specific length and degree of disorder can be explored with other biotechnological alternatives to improve responses or tolerate abiotic stress, also serving as sensors during development or ripening stages. These findings suggest an opportunity to study “protein darkness” in terms of disorder and functional associations. Full article

(This article belongs to the Special Issue Technological Advances Around Next-Generation Sequencing Application)

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27 pages, 1769 KB

Open AccessReview

Beyond Purification: Evolving Roles of Fusion Tags in Biotechnology

by Tsutomu Arakawa and Teruo Akuta

Curr. Issues Mol. Biol. 2025, 47(9), 768; https://doi.org/10.3390/cimb47090768 - 17 Sep 2025

Abstract

Genetic fusion of a tag sequence to a target protein, or protein of interest (POI), is one of the most widely used technologies for recombinant expression. Tag-fusion proteins can enhance soluble expression, prolong half-life, increase binding avidity, and facilitate protein purification or refolding. [...] Read more.

Genetic fusion of a tag sequence to a target protein, or protein of interest (POI), is one of the most widely used technologies for recombinant expression. Tag-fusion proteins can enhance soluble expression, prolong half-life, increase binding avidity, and facilitate protein purification or refolding. In addition, tag-fusion proteins can be used to identify POI-binding partners through pull-down or immunoprecipitation assays. Beyond these classical applications, tags have evolved to serve as multifunctional tools, enabling real-time imaging, spatial localization, targeted delivery, and regulation of protein activity in living systems. Some engineered tags also allow conditional control, such as pH or ligand-dependent stabilization, thus expanding their utility in synthetic biology and therapeutic design. Here, we summarize protein-based and peptide-based tags, as well as methods for tag removal. While not fully comprehensive, this review aims to help researchers design suitable tag formats for specific goals. Full article

(This article belongs to the Special Issue Recombinant Proteins for Molecular Biology Research: Technologies and Applications)

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24 pages, 2508 KB

Open AccessReview

Mechanistic Insights into the Abiotic Stress Adaptation of Salix Species: A Comprehensive Review of Physiological, Molecular, and Sex-Dimorphic Responses

by Pengcheng Sun, Fangjing Fan, Yinggao Liu and Fuyuan Zhu

Curr. Issues Mol. Biol. 2025, 47(9), 767; https://doi.org/10.3390/cimb47090767 - 17 Sep 2025

Abstract

As key species for ecological restoration, Salix spp. thrive in harsh environments, including high-altitude regions, arid zones, and saline–alkaline soils, demonstrating remarkable resilience to abiotic stressors. Recent advances in genomics, transcriptomics, and functional gene research have shed light on the mechanisms underlying Salix [...] Read more.

As key species for ecological restoration, Salix spp. thrive in harsh environments, including high-altitude regions, arid zones, and saline–alkaline soils, demonstrating remarkable resilience to abiotic stressors. Recent advances in genomics, transcriptomics, and functional gene research have shed light on the mechanisms underlying Salix species’ responses to drought, salinity, heavy metals, and low-temperature stresses. This review systematically synthesizes the physiological, biochemical, and molecular adaptations of Salix to abiotic stress, with a particular focus on underexplored areas such as sex-dimorphic regulation and integrated hormone-ROS signaling pathways. We emphasize the dynamic interplay between transcription factors, hormonal crosstalk, and ROS signaling that underpins the stress response, highlighting sex-specific variations that modulate adaptive capacity. Moreover, we discuss the synergistic roles of exogenous additives and rhizosphere microorganisms in enhancing stress resistance. This comprehensive analysis provides critical insights for breeding stress-resilient Salix cultivars and for future research into stress adaptation mechanisms in woody plants. Full article

(This article belongs to the Special Issue New Advances in Plant Responses to Environmental Stresses)

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21 pages, 3927 KB

Open AccessReview

Mechanisms Linking Obesity with Non-Alcoholic Fatty Liver Disease (NAFLD) and Cardiovascular Diseases (CVDs)—The Role of Oxidative Stress

by Fani-Niki Varra, Michail Varras, Viktoria-Konstantina Varra and Panagiotis Theodosis-Nobelos

Curr. Issues Mol. Biol. 2025, 47(9), 766; https://doi.org/10.3390/cimb47090766 - 16 Sep 2025

Abstract

Obesity concerns a wide range of the population, tending to become a major factor for diseases’ progression and fatality rate increases, with implications concerning the cardiovascular system’s deterioration. Obesity is closely linked with metabolic derangements concerning lipid storage and circulation, and the cellular [...] Read more.

Obesity concerns a wide range of the population, tending to become a major factor for diseases’ progression and fatality rate increases, with implications concerning the cardiovascular system’s deterioration. Obesity is closely linked with metabolic derangements concerning lipid storage and circulation, and the cellular metabolism affecting most of the internal organs, especially liver and cellular function. In this current study, an analysis of the linking mechanisms between obesity, lipid deterioration, liver, and lipid tissue homeostasis will be performed, with special attention to the pathophysiological characteristics of these detrimental effects on the NAFLD (non-alcoholic fatty liver disease) and the cellular function of the endothelial blood cells, with special reference to the additional burdening of obesity on the autonomous nervous system signaling, and the resulting hypertension. Despite the very complex and pluripotent pathogenic mechanisms with which obesity is intervening in these processes, it could be safely deduced that metabolic and lipid transport manipulation could serve as a crucial factor towards the cellular and tissue function improvement, as the interlinkages in the mechanisms, although highly analyzed, have not been completely deciphered until now. Full article

(This article belongs to the Special Issue Mechanisms and Pathophysiology of Obesity)

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42 pages, 1810 KB

Open AccessReview

Reactive Sulfur Species and Protein Persulfidation: An Emerging Redox Axis in Human Health and Disease

by Celia María Curieses Andrés, Fernando Lobo, José Manuel Pérez de la Lastra, Elena Bustamante Munguira, Celia Andrés Juan and Eduardo Pérez Lebeña

Curr. Issues Mol. Biol. 2025, 47(9), 765; https://doi.org/10.3390/cimb47090765 - 16 Sep 2025

Abstract

Reactive sulfur species (RSS)—hydrogen sulfide (H₂S), low-molecular-weight persulfides/polysulfides and protein persulfidation—constitute a third redox axis alongside ROS and RNS. Nanomolar H₂S, produced by trans-sulfuration (CBS/CSE) and 3-MST, is oxidized by sulfide–quinone reductase to persulfides that fuel the respiratory chain [...] Read more.

Reactive sulfur species (RSS)—hydrogen sulfide (H₂S), low-molecular-weight persulfides/polysulfides and protein persulfidation—constitute a third redox axis alongside ROS and RNS. Nanomolar H₂S, produced by trans-sulfuration (CBS/CSE) and 3-MST, is oxidized by sulfide–quinone reductase to persulfides that fuel the respiratory chain while curbing superoxide. Reversible persulfidation reprograms cysteine sensors in metabolism (GAPDH), inflammation (NLRP3, p47^phox) and transcription (Keap1/NRF2), linking RSS to energy balance, vasodilation, innate immunity and neuroplasticity. Disrupted sulfur signaling—deficit or overload—contributes to heart failure, sarcopenia, neurodegeneration, cancer and post-COVID syndromes. Therapeutically, slow-release donors (SG1002, GYY4137), mitochondria-targeted vectors (AP39), photo- or thiol-activated “smart” scaffolds, diet-derived polysulfides/isothiocyanates and microbiota engineering aim to restore the protective RSS window. Key challenges are a narrow therapeutic margin and real-time quantification of persulfide fluxes. Harnessing RSS therefore offers a route to rebalance redox homeostasis across diverse chronic diseases. Full article

(This article belongs to the Special Issue Mechanistic Insights into the Antioxidant Activity of Bioorganic Molecules: A Chemical Perspective)

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20 pages, 4318 KB

Open AccessArticle

IDO Activation Affects BDNF/TrkB Signaling Pathway, Oxidative Stress, and Mitochondrial Enzymatic Activities in Temporal Lobe Epilepsy

by Jingwen Xu, Liping Wei, Junling Fu, Ziting Kong and Lun Cai

Curr. Issues Mol. Biol. 2025, 47(9), 764; https://doi.org/10.3390/cimb47090764 - 16 Sep 2025

Abstract

Indoleamine 2,3-dioxygenase (IDO) activation by seizures elevates toxic tryptophan metabolites linked to seizure exacerbation. Brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) signaling, oxidative stress, and mitochondrial respiratory chain complex dysfunction contribute to temporal lobe epilepsy (TLE), but their regulatory links remain unclear. Male [...] Read more.

Indoleamine 2,3-dioxygenase (IDO) activation by seizures elevates toxic tryptophan metabolites linked to seizure exacerbation. Brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) signaling, oxidative stress, and mitochondrial respiratory chain complex dysfunction contribute to temporal lobe epilepsy (TLE), but their regulatory links remain unclear. Male Kunming mice were grouped into Control, Control + 1-Methyl-DL-tryptophan (1-MT), TLE, and TLE + 1-MT. TLE was induced with 300 mg/kg pilocarpine. Two weeks after modeling, 1-MT (50 mg/kg) was administered twice daily for two weeks in 1-MT groups. Assessments included video monitoring to record seizure frequency and duration; Nissl and Fluoro-Jade B (FJB) staining to evaluate neuronal damage; real-time quantitative PCR (qRT-PCR) and Western blot to detect IDO, BDNF, and TrkB expression; assays for the following oxidative stress markers: malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT); and detection of mitochondrial complex I/IV activities. Results showed TLE mice had significantly increased IDO expression, BDNF/TrkB over-activation, elevated oxidative stress, impaired mitochondrial complex I/IV activities, severe neuronal damage, and increased seizure frequency/duration. 1-MT intervention reversed all these pathological changes, restoring levels to near-control status. This indicates IDO activation promotes TLE progression, which is associated with modulation of the BDNF/TrkB signaling pathway, exacerbation of oxidative stress, and impairment of mitochondrial complex I/IV activities—supporting IDO as a potential therapeutic target for TLE. Full article

(This article belongs to the Section Molecular Medicine)

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