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20 pages, 4055 KiB  
Article
Biphasic Salt Effects on Lycium ruthenicum Germination and Growth Linked to Carbon Fixation and Photosynthesis Gene Expression
by Xinmeng Qiao, Ruyuan Wang, Lanying Liu, Boya Cui, Xinrui Zhao, Min Yin, Pirui Li, Xu Feng and Yu Shan
Int. J. Mol. Sci. 2025, 26(15), 7537; https://doi.org/10.3390/ijms26157537 (registering DOI) - 4 Aug 2025
Abstract
Since the onset of industrialization, the safety of arable land has become a pressing global concern, with soil salinization emerging as a critical threat to agricultural productivity and food security. To address this challenge, the cultivation of economically valuable salt-tolerant plants has been [...] Read more.
Since the onset of industrialization, the safety of arable land has become a pressing global concern, with soil salinization emerging as a critical threat to agricultural productivity and food security. To address this challenge, the cultivation of economically valuable salt-tolerant plants has been proposed as a viable strategy. In the study, we investigated the physiological and molecular responses of Lycium ruthenicum Murr. to varying NaCl concentrations. Results revealed a concentration-dependent dual effect: low NaCl levels significantly promoted seed germination, while high concentrations exerted strong inhibitory effects. To elucidate the mechanisms underlying these divergent responses, a combined analysis of metabolomics and transcriptomics was applied to identify key metabolic pathways and genes. Notably, salt stress enhanced photosynthetic efficiency through coordinated modulation of ribulose 5-phosphate and erythrose-4-phosphate levels, coupled with the upregulation of critical genes encoding RPIA (Ribose 5-phosphate isomerase A) and RuBisCO (Ribulose-1,5-bisphosphate carboxylase/oxygenase). Under low salt stress, L. ruthenicum maintained intact cellular membrane structures and minimized oxidative damage, thereby supporting germination and early growth. In contrast, high salinity severely disrupted PS I (Photosynthesis system I) functionality, blocking energy flow into this pathway while simultaneously inducing membrane lipid peroxidation and triggering pronounced cellular degradation. This ultimately suppressed seed germination rates and impaired root elongation. These findings suggested a mechanistic framework for understanding L. ruthenicum adaptation under salt stress and pointed out a new way for breeding salt-tolerant crops and understanding the mechanism. Full article
(This article belongs to the Section Molecular Biology)
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10 pages, 236 KiB  
Review
The Concept of “Platinum Sensitivity” in Endometrial Cancer
by Shoji Nagao, Atsushi Fujikawa, Ryoko Imatani, Yoshinori Tani, Hirofumi Matsuoka, Naoyuki Ida, Junko Haraga, Chikako Ogawa, Keiichiro Nakamura and Hisashi Masuyama
Cancers 2025, 17(15), 2557; https://doi.org/10.3390/cancers17152557 - 2 Aug 2025
Viewed by 160
Abstract
The concept of “platinum sensitivity” has long guided prognostic assessment and treatment selection in recurrent ovarian cancer. However, the emergence of targeted agents, such as bevacizumab and poly (ADP-ribose) polymerase inhibitors, has complicated its clinical utility. In contrast, emerging evidence suggests that platinum [...] Read more.
The concept of “platinum sensitivity” has long guided prognostic assessment and treatment selection in recurrent ovarian cancer. However, the emergence of targeted agents, such as bevacizumab and poly (ADP-ribose) polymerase inhibitors, has complicated its clinical utility. In contrast, emerging evidence suggests that platinum sensitivity may also be applicable to recurrent endometrial cancer. As in ovarian cancer, a prolonged platinum-free interval (PFI) in recurrent endometrial cancer is associated with an improved efficacy of subsequent platinum-based chemotherapy. The PFI is linearly correlated with the response rate to platinum re-administration, progression-free survival, and overall survival. Patients are typically classified as having platinum-resistant or platinum-sensitive disease based on a PFI cutoff of 6 or 12 months. However, unlike in ovarian cancer—where the duration of response to second-line platinum-based chemotherapy rarely exceeds the prior PFI (~3%)—approximately 30% of patients with recurrent endometrial cancer exhibit a sustained response to platinum rechallenge that extends beyond their preceding PFI. Despite the incorporation of immune checkpoint inhibitors into the treatment landscape of endometrial cancer, the role of platinum sensitivity in clinical decision-making—particularly regarding treatment sequencing and drug selection—remains a critical and unresolved issue. Further research is warranted to elucidate the mechanisms underlying platinum resistance and to guide optimal therapeutic strategies. Full article
(This article belongs to the Special Issue Endometrial Cancer—from Diagnosis to Management)
29 pages, 1351 KiB  
Review
Molecular Targets for Pharmacotherapy of Head and Neck Squamous Cell Carcinomas
by Robert Sarna, Robert Kubina, Marlena Paździor-Heiske, Adrianna Halama, Patryk Chudy, Paulina Wala, Kamil Krzykawski and Ilona Nowak
Curr. Issues Mol. Biol. 2025, 47(8), 609; https://doi.org/10.3390/cimb47080609 - 1 Aug 2025
Viewed by 95
Abstract
Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of tumors with a complex molecular profile. Despite therapeutic advances, patient prognosis remains poor, emphasizing the need for more effective treatment strategies. Traditional chemotherapy, with cisplatin and 5-fluorouracil (5-FU), remains the gold [...] Read more.
Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of tumors with a complex molecular profile. Despite therapeutic advances, patient prognosis remains poor, emphasizing the need for more effective treatment strategies. Traditional chemotherapy, with cisplatin and 5-fluorouracil (5-FU), remains the gold standard but is limited by toxicity and tumor resistance. Immunotherapy, particularly immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and its ligand (PD-L1), has improved overall survival, especially in patients with high PD-L1 expression. In parallel, targeted therapies such as poly (ADP-ribose) polymerase 1 (PARP1) inhibitors—which impair DNA repair and increase replication stress—have shown promising activity in HNSCC. Cyclin-dependent kinase (CDK) inhibitors are also under investigation due to their potential to correct dysregulated cell cycle control, a hallmark of HNSCC. This review aims to summarize current and emerging pharmacotherapies for HNSCC, focusing on chemotherapy, immunotherapy, and PARP and CDK inhibitors. It also discusses the evolving role of targeted therapies in improving clinical outcomes. Future research directions include combination therapies, nanotechnology-based delivery systems to enhance treatment specificity, and the development of diagnostic tools such as PARP1-targeted imaging to better guide personalized treatment approaches. Full article
(This article belongs to the Special Issue Future Challenges of Targeted Therapy of Cancers: 2nd Edition)
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12 pages, 1095 KiB  
Article
Barriers and Breakthroughs in Precision Oncology: A National Registry Study of BRCA Testing and PARP Inhibitor Uptake in Women from the National Gynae-Oncology Registry (NGOR)
by Mahendra Naidoo, Clare L Scott, Mike Lloyd, Orla McNally, Robert Rome, Sharnel Perera and John R Zalcberg
Cancers 2025, 17(15), 2541; https://doi.org/10.3390/cancers17152541 - 31 Jul 2025
Viewed by 161
Abstract
Background: The identification of pathogenic variants in the Breast Cancer Genes 1 and 2 (BRCA1/2) is a critical predictive biomarker for poly (ADP-ribose) polymerase inhibitor (PARPi) therapy in epithelial ovarian cancer (EOC). The aim of this study is to define real-world [...] Read more.
Background: The identification of pathogenic variants in the Breast Cancer Genes 1 and 2 (BRCA1/2) is a critical predictive biomarker for poly (ADP-ribose) polymerase inhibitor (PARPi) therapy in epithelial ovarian cancer (EOC). The aim of this study is to define real-world rates and determinants of germline and somatic BRCA1/2 testing and subsequent PARPi utilisation in Australia using a national clinical quality registry. Methods: This multi-centre cohort study analysed data from 1503 women with non-mucinous EOC diagnosed between May 2017 and July 2022, captured by the Australian National Gynae-Oncology Registry (NGOR). We evaluated rates of germline and somatic testing and PARPi use, using multivariate logistic regression to identify associated clinical and demographic factors. Results: Overall germline and somatic testing rates were 68% and 32%, respectively. For the high-grade serous ovarian cancer (HGSOC) cohort, rates were higher, at 78% and 39%, respectively. Germline testing was significantly less likely for women aged >80 years (OR 0.49), those in regional areas (OR 0.61), and those receiving single-modality treatment. Somatic testing uptake increased significantly following public reimbursement for PARPi (p = 0.004). Among eligible women with a newly diagnosed BRCA pathogenic variant and advanced disease (n = 110), 52% commenced first-line maintenance PARPi. Conclusions: This national study offers valuable insights into Australian ovarian cancer care, highlighting opportunities to enhance testing equity for older women (aged >80) and regional patients. Furthermore, it identifies the translation of a positive test into PARPi therapy as a complex area that warrants further collaborative investigation to optimise patient outcomes. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Clinical and Translational Research)
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17 pages, 1710 KiB  
Article
Physiological, Genetic, and Fermentative Traits of Oenococcus oeni Isolates from Spontaneous Malolactic Fermentation in Koshu Wine
by Misa Otoguro, Sayaka Inui, Taichi Aoyanagi, Ayana Misawa, Hiromi Nakano, Yoshimi Shimazu and Shigekazu Misawa
Fermentation 2025, 11(8), 440; https://doi.org/10.3390/fermentation11080440 - 31 Jul 2025
Viewed by 189
Abstract
Koshu wine, produced from the indigenous Japanese grape Vitis vinifera L. cv. Koshu exhibits a lower pH than other white wines, hindering malolactic fermentation (MLF) by lactic acid bacteria (LAB). Here, we aimed to isolate LAB strains capable of performing MLF under these [...] Read more.
Koshu wine, produced from the indigenous Japanese grape Vitis vinifera L. cv. Koshu exhibits a lower pH than other white wines, hindering malolactic fermentation (MLF) by lactic acid bacteria (LAB). Here, we aimed to isolate LAB strains capable of performing MLF under these challenging conditions to improve wine quality. Sixty-four Oenococcus oeni and one Lactobacillus hilgardii strain were isolated from Koshu grapes and wines that had undergone spontaneous MLF. MLF activity was assessed under varying pH, SO2, and ethanol conditions in modified basal medium (BM) and Koshu model wine media. Expression of stress-related genes was analyzed using real-time PCR. Carbon source utilization was evaluated via API 50CH assays. All isolates degraded malic acid and produced lactic acid at 15 °C and pH 3.2 in BM without reducing sugars. Seven strains, all identified as O. oeni, demonstrated MLF activity at pH 3.0 in modified BM lacking added reducing sugars or tomato juice. Six wine-derived strains tolerated up to 12% ethanol, whereas the grape-derived strain was inhibited at 10%. In a synthetic Koshu wine model (13% ethanol, pH 3.0), wine-derived isolates exhibited higher MLF activity than commercial starter strains. In high-performing strains, mleA was upregulated, and most isolates preferred fructose, arabinose, and ribose over glucose. These findings suggest that indigenous O. oeni strains from Koshu wine possess unique stress tolerance and metabolic traits, making them promising candidates for region-specific MLF starter cultures that could enhance Koshu wine quality and terroir expression. Full article
(This article belongs to the Special Issue Fermentation and Biotechnology in Wine Making)
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21 pages, 879 KiB  
Article
Multiblock Metabolomics Responses of the Diatom Phaeodactylum tricornutum Under Benthic and Planktonic Culture Conditions
by Andrea Castaldi, Mohamed Nawfal Triba, Laurence Le Moyec, Cédric Hubas, Gaël Le Pennec and Marie-Lise Bourguet-Kondracki
Mar. Drugs 2025, 23(8), 314; https://doi.org/10.3390/md23080314 - 31 Jul 2025
Viewed by 291
Abstract
This study investigates the metabolic responses of the model diatom Phaeodactylum tricornutum under different growth conditions, comparing benthic (adherent) and planktonic states. Using a multiblock metabolomics approach combining LC-HRMS2, NMR, and GC-MS techniques, we compared the metabolome of P. tricornutum cultivated [...] Read more.
This study investigates the metabolic responses of the model diatom Phaeodactylum tricornutum under different growth conditions, comparing benthic (adherent) and planktonic states. Using a multiblock metabolomics approach combining LC-HRMS2, NMR, and GC-MS techniques, we compared the metabolome of P. tricornutum cultivated on three laboratory substrates (glass, polystyrene, and polydimethylsiloxane) and under planktonic conditions. Our results revealed metabolic differences between adherent and planktonic cultures, particularly concerning the lipid and carbohydrate contents. Adherent cultures showed a metabolic profile with an increase in betaine lipids (DGTA/S), fatty acids (tetradecanoic and octadecenoic acids), and sugars (myo-inositol and ribose), suggesting modifications in membrane composition and lipid remodeling, which play a potential role in adhesion. In contrast, planktonic cultures displayed a higher content of cellobiose, specialized metabolites such as dihydroactinidiolide, quinic acid, catechol, and terpenes like phytol, confirming different membrane composition, energy storage capacity, osmoregulation, and stress adaptation. The adaptative strategies do not only concern adherent and planktonic states, but also different adherent culture conditions, with variations in lipid, amino acid, terpene, and carbohydrate contents depending on the physical properties of the support. Our results highlight the importance of metabolic adaptation in adhesion, which could explain the fouling process. Full article
(This article belongs to the Special Issue Marine Omics for Drug Discovery and Development, 2nd Edition)
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19 pages, 1716 KiB  
Review
Combination Therapy Using Phytochemicals and PARP Inhibitors in Hybrid Nanocarriers: An Optimistic Approach for the Management of Colon Cancer
by Mohammad Javed Qureshi, Gurpreet Kaur Narde, Alka Ahuja, Dhanalekshmi Unnikrishnan Meenakshi and Khalid Al Balushi
Int. J. Mol. Sci. 2025, 26(15), 7350; https://doi.org/10.3390/ijms26157350 - 30 Jul 2025
Viewed by 309
Abstract
DNA damage repair is a hallmark of any cancer growth, eventually leading to drug resistance and death. The poly ADP-ribose polymerase (PARP) enzyme is vital in repairing damaged DNA in normal and cancer cells with mutated DNA damage response (DDR) genes. [...] Read more.
DNA damage repair is a hallmark of any cancer growth, eventually leading to drug resistance and death. The poly ADP-ribose polymerase (PARP) enzyme is vital in repairing damaged DNA in normal and cancer cells with mutated DNA damage response (DDR) genes. Inhibitors of the PARP enzyme aid in chemotherapy, as shown by drug combinations such as Olaparib and Irinotecan in breast cancer treatment. However, the effect of Olaparib in colon cancer has not been studied extensively. Synthetic drugs have a significant limitation in cancer treatment due to drug resistance, leading to colon cancer relapse. Bioavailability of Olaparib and other PARP inhibitors is limited due to their hydrophobicity, which poses a significant challenge. These limitations and challenges can be addressed by encapsulating Olaparib in nanoparticles that could possibly increase the bioavailability of the drug at the site of action. New age nanoparticles, such as hybrid nanoparticles, provide superior quality in terms of design and circulatory time of the drug in the plasma. The side effects of Olaparib as a chemotherapeutic pave the way for exploring phytochemicals that may have similar effects. The combined impact of Olaparib and phytochemicals such as genistein, resveratrol and others in nano-encapsulated form can be explored in the treatment of colon cancer. Full article
(This article belongs to the Special Issue Anticancer Drug Discovery Based on Natural Products)
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24 pages, 1990 KiB  
Article
Metabolomic Analysis of Breast Cancer in Colombian Patients: Exploring Molecular Signatures in Different Subtypes and Stages
by Lizeth León-Carreño, Daniel Pardo-Rodriguez, Andrea Del Pilar Hernandez-Rodriguez, Juliana Ramírez-Prieto, Gabriela López-Molina, Ana G. Claros, Daniela Cortes-Guerra, Julian Alberto-Camargo, Wilson Rubiano-Forero, Adrian Sandoval-Hernandez, Mónica P. Cala and Alejandro Ondo-Mendez
Int. J. Mol. Sci. 2025, 26(15), 7230; https://doi.org/10.3390/ijms26157230 - 26 Jul 2025
Viewed by 354
Abstract
Breast cancer (BC) is a neoplasm characterized by high heterogeneity and is influenced by intrinsic molecular subtypes and clinical stage, aspects that remain underexplored in the Colombian population. This study aimed to characterize metabolic alterations associated with subtypes and disease progression in a [...] Read more.
Breast cancer (BC) is a neoplasm characterized by high heterogeneity and is influenced by intrinsic molecular subtypes and clinical stage, aspects that remain underexplored in the Colombian population. This study aimed to characterize metabolic alterations associated with subtypes and disease progression in a group of newly diagnosed, treatment-naive Colombian women using an untargeted metabolomics approach. To improve metabolite coverage, samples were analyzed using LC-QTOF-MS and GC-QTOF-MS, along with amino acid profiling. The Luminal B subtype exhibited elevated levels of long-chain acylcarnitines and higher free fatty acid concentrations than the other subtypes. It also presented elevated levels of carbohydrates and essential glycolytic intermediates, suggesting that this subtype may adopt a hybrid metabolic phenotype characterized by increased glycolytic flux as well as enhanced fatty acid catabolism. Tumor, Node, and Metastasis (TNM) staging analysis revealed progressive metabolic reprogramming of BC. In advanced stages, a sustained increase in phosphatidylcholines and a decrease in lysophosphatidylcholines were observed, reflecting lipid alterations associated with key roles in tumor progression. In early stages (I-II), plasma metabolites with high discriminatory power were identified, such as glutamic acid, ribose, and glycerol, which are associated with dysfunctions in energy and carbohydrate metabolism. These results highlight metabolomics as a promising tool for the early diagnosis, clinical follow-up, and molecular characterization of BC. Full article
(This article belongs to the Special Issue Molecular Crosstalk in Breast Cancer Progression and Therapies)
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29 pages, 4988 KiB  
Article
Amphiphilic Oligonucleotide Derivatives as a Tool to Study DNA Repair Proteins
by Svetlana N. Khodyreva, Alexandra A. Yamskikh, Ekaterina S. Ilina, Mikhail M. Kutuzov, Ekaterina A. Belousova, Maxim S. Kupryushkin, Timofey D. Zharkov, Olga A. Koval, Sofia P. Zvereva and Olga I. Lavrik
Int. J. Mol. Sci. 2025, 26(15), 7078; https://doi.org/10.3390/ijms26157078 - 23 Jul 2025
Viewed by 150
Abstract
Modified oligonucleotides (oligos) are widely used as convenient tools in many scientific fields, including biomedical applications and therapies. In particular, oligos with lipophilic groups attached to the backbone ensure penetration of the cell membrane without the need for transfection. This study examines the [...] Read more.
Modified oligonucleotides (oligos) are widely used as convenient tools in many scientific fields, including biomedical applications and therapies. In particular, oligos with lipophilic groups attached to the backbone ensure penetration of the cell membrane without the need for transfection. This study examines the interaction between amphiphilic DNA duplexes, in which one of the chains contains a lipophilic substituent, and several DNA repair proteins, particularly DNA-damage-dependent PARPs, using various biochemical approaches. DNA with a lipophilic substituent (LS-DNA) demonstrates more efficient binding with DNA damage activated poly(AD-ribose) polymerases 1-3 (PARP1, PARP2, PARP3) and DNA polymerase β. Chemically reactive LS-DNA derivatives containing a photoactivatable nucleotide (photo-LS-DNAs) or a 5′ deoxyribose phosphate (dRP) group in the vicinity of double-strand breaks (DSBs) are used for the affinity labelling of PARPs and other proteins in several whole-cell extracts of human cells. In particular, photo-LS-DNAs are used to track the level of Ku antigen in the extracts of neuron-like differentiated SH-SY5Y, undifferentiated SH-SY5Y, and olfactory epithelial cells. In vitro, PARP1–PARP3 are shown to be able to slowly excise the 5′ dRP group at DSBs. LS-DNAs can activate PARP1 and PARP2 for autoPARylation, albeit less effectively than regular DNA duplexes. Full article
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13 pages, 1147 KiB  
Hypothesis
Possible Enantioseparation of Racemic Ribose on Chiral Surface Formed by Adsorption of Nucleobases
by Roman Bielski and Michal Tencer
Life 2025, 15(8), 1160; https://doi.org/10.3390/life15081160 - 23 Jul 2025
Viewed by 248
Abstract
The paper proposes a putative prebiotic scenario leading to homochirality in the RNA world. In this scenario, racemic ribose, the only chiral moiety in RNA, was enantioseparated (in its pyranose form) on a chiral surface formed by the adsorption of (prochiral) nucleobases (NBs) [...] Read more.
The paper proposes a putative prebiotic scenario leading to homochirality in the RNA world. In this scenario, racemic ribose, the only chiral moiety in RNA, was enantioseparated (in its pyranose form) on a chiral surface formed by the adsorption of (prochiral) nucleobases (NBs) on a mineral or metal. Purine bases (adenine and guanine) are more likely candidates for this process than pyrimidine bases because they have more H-bond donors and acceptors. Another possible candidate surface for the enantioseparation of ribose would be formed by the adsorption of nucleobase pairs, e.g., guanine–cytosine (GC). Interactions of ribose molecules with hydrogen bond donors and acceptors of NBs or NB pairs (located on the surface) enforced the orientation of ribose molecules in two directions perpendicular to each other and parallel to the surface. Consequently, the energy of interactions of enantiomers of the sugar with the surface was not the same. Thus, a solvent moving along the surface caused the enantiomers of ribose to move with different rates, resulting in the enantioseparation of ribose in a chromatography-like process. The same process would also separate ribose from other monosaccharides in the mix. Hydrogen bonding between nucleobases was also pivotal in the formation of large homochiral domains on the surfaces. Full article
(This article belongs to the Special Issue Origin of Life in Chemically Complex Messy Environments: 2nd Edition)
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25 pages, 2198 KiB  
Review
Oxidative Stress in HIV-Associated Neurodegeneration: Mechanisms of Pathogenesis and Therapeutic Targets
by Sophia Gagliardi, Tristan Hotchkin, Grace Hillmer, Maeve Engelbride, Alexander Diggs, Hasset Tibebe, Coco Izumi, Cailyn Sullivan, Cecelia Cropp, Olive Lantz, Dacia Marquez, Jason Chang, Jiro Ezaki, Alexander George Zestos, Anthony L. Riley and Taisuke Izumi
Int. J. Mol. Sci. 2025, 26(14), 6724; https://doi.org/10.3390/ijms26146724 - 13 Jul 2025
Viewed by 1654
Abstract
Treatment for HIV infection has become more manageable due to advances in combination antiretroviral therapy (cART). However, HIV still significantly affects the central nervous system (CNS) in infected individuals, even with effective plasma viral suppression, due to persistent viral reservoirs and chronic neuroinflammation. [...] Read more.
Treatment for HIV infection has become more manageable due to advances in combination antiretroviral therapy (cART). However, HIV still significantly affects the central nervous system (CNS) in infected individuals, even with effective plasma viral suppression, due to persistent viral reservoirs and chronic neuroinflammation. This ongoing inflammation contributes to the development of HIV-associated neurocognitive disorders (HANDs), including dementia and Alzheimer’s disease-like pathology. These complications are particularly prevalent among the aging population with HIV. This review aims to provide a comprehensive overview of HAND, with a focus on the contribution of oxidative stress induced by HIV-mediated reactive oxygen species (ROS) production through viral proteins such as gp120, Tat, Nef, Vpr, and reverse transcriptase. In addition, we discuss current and emerging therapeutic interventions targeting HAND, including antioxidant strategies and poly (ADP-ribose) polymerase (PARP) inhibitors. These are potential adjunctive approaches to mitigate neuroinflammation and oxidative damage in the CNS. Full article
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18 pages, 3608 KiB  
Article
Biochemical Insights into the Effects of a Small Molecule Drug Candidate on Imatinib-Induced Cardiac Inflammation
by Renáta Szabó, Denise Börzsei, András Nagy, Viktória Kiss, Zoltán Virág, Gyöngyi Kis, Nikoletta Almási, Szilvia Török, Médea Veszelka, Mária Bagyánszki, Nikolett Bódi, Bence Pál Barta, Patrícia Neuperger, Gabor J. Szebeni and Csaba Varga
Int. J. Mol. Sci. 2025, 26(14), 6661; https://doi.org/10.3390/ijms26146661 - 11 Jul 2025
Viewed by 431
Abstract
BGP-15, a poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor exerts cardioprotective effects; however, the underlying mechanisms remain unclear. Therefore, our study aimed to investigate the effects of BGP-15 on the imatinib (Imtb)-induced cardiac inflammation at the biochemical level. Male rats were divided to control, Imtb-treated (60 [...] Read more.
BGP-15, a poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor exerts cardioprotective effects; however, the underlying mechanisms remain unclear. Therefore, our study aimed to investigate the effects of BGP-15 on the imatinib (Imtb)-induced cardiac inflammation at the biochemical level. Male rats were divided to control, Imtb-treated (60 mg/kg/day for 14 days), and Imtb + BGP-15-treated animals. In this group Imtb was co-administered with BGP-15 at the dose of 10 mg/kg/day. At the end of the experiment, nuclear factor-kappa B/p65 (NF-κB/p65), nuclear transcription factor erythroid-2 related factor (Nrf2), heme oxygenase-1 (HO-1), high mobility group box 1 (HMGB1), and myeloperoxidase (MPO) were measured by Western blot. Chemokine and interleukins (ILs) were determined by Legendplex. Additionally, cardiac specific changes were visualized by immunohistochemistry. We demonstrated that Imtb increased NF-κB/p65, IL-6, IL-1β, IL-18, MCP-1, HMGB1, as well as the expression and activity of MPO. Conversely, the expressions of antioxidant Nrf2 and HO-1 were decreased. Administration of BGP-15 effectively mitigated these inflammatory alterations by significantly reducing pro-inflammatory cytokines and MPO activity, while simultaneously restoring and enhancing the levels of Nrf2 and HO-1, thereby promoting antioxidant defenses. The immunohistochemical staining further supported these biochemical changes. Our study provides new and comprehensive biochemical insight for managing Imtb-induced inflammatory responses via BGP-15-induced PARP1 inhibition. Full article
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12 pages, 4263 KiB  
Article
Characterization of a Novel Lentzea Species Isolated from the Kumtagh Desert and Genomic Insights into the Secondary Metabolite Potential of the Genus
by Ying Wen, Jiahui Li, Fujun Qiao, Wanyin Luo, Tuo Chen, Guangxiu Liu and Wei Zhang
Microorganisms 2025, 13(7), 1628; https://doi.org/10.3390/microorganisms13071628 - 10 Jul 2025
Viewed by 293
Abstract
A novel actinobacterial strain, designated E54T, was isolated from a hyper-arid desert soil sample collected from the Kumtagh Desert in Dunhuang, Gansu Province, China. Phylogenetic analysis based on 16S rRNA gene sequences placed strain E54T within the genus Lentzea, [...] Read more.
A novel actinobacterial strain, designated E54T, was isolated from a hyper-arid desert soil sample collected from the Kumtagh Desert in Dunhuang, Gansu Province, China. Phylogenetic analysis based on 16S rRNA gene sequences placed strain E54T within the genus Lentzea, showing highest similarity to Lentzea waywayandensis DSM 44232T (98.9%) and Lentzea flava NBRC 15743T (98.5%). However, whole-genome comparisons revealed that the average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between E54T and these related strains were below the thresholds for species delineation. Strain E54T exhibited typical morphological characteristics of the genus Lentzea, forming a branched substrate. It grew optimally at 28–30 °C, pH 7.0–9.0, and tolerated up to 10% NaCl. The cell wall contained meso-diaminopimelic acid, the predominant menaquinone was MK-9(H4), and major fatty acids included iso-C16:0. The polar lipid profile comprised diphosphatidyl glycerol, phosphatidyl ethanolamine, phosphatidyl inositol, hydroxyphosphatidyl ethanolamine, and an unidentified lipid. The characteristic amino acid type of the cell wall was meso-DAP. Whole-cell hydrolysis experiments revealed the characteristic cell wall sugar fractions: ribose and galactose. The genome of strain E54T is approximately 8.0 Mb with a DNA G+C content of 69.38 mol%. Genome mining revealed 39 biosynthetic gene clusters (BGCs), including non-ribosomal peptide synthetases (NRPS), polyketide synthases (PKS), terpenes, and siderophores. Comparative antiSMASH-based genome analysis across 38 Lentzea strains further demonstrated the genus’ remarkable biosynthetic diversity. NRPS and type I PKS (T1PKS) were the most prevalent BGC types, indicating a capacity to synthesize structurally complex and pharmacologically relevant metabolites. Together, these findings underscore the untapped biosynthetic potential of the genus Lentzea and support the proposal of strain E54T as a novel species. The strain E54T (=JCM 34936T = GDMCC 4.216T) should represent a novel species, for which the name Lentzea xerophila sp. nov. is proposed. Full article
(This article belongs to the Section Environmental Microbiology)
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19 pages, 7102 KiB  
Article
PARG Mutation Uncovers Critical Structural Determinant for Poly(ADP-Ribose) Hydrolysis and Chromatin Regulation in Embryonic Stem Cells
by Yaroslava Karpova, Sara Piatz, Guillaume Bordet and Alexei V. Tulin
Cells 2025, 14(14), 1049; https://doi.org/10.3390/cells14141049 - 9 Jul 2025
Viewed by 408
Abstract
Poly(ADP-ribosyl)ation is a crucial posttranslational modification that governs gene expression, chromatin remodeling, and cellular homeostasis. This dynamic process is mediated by the opposing activities of poly(ADP-ribose) polymerases (PARPs), which synthesize poly(ADP-ribose) (pADPr), and poly(ADP-ribose) glycohydrolase (PARG), which degrades it. While PARP function has [...] Read more.
Poly(ADP-ribosyl)ation is a crucial posttranslational modification that governs gene expression, chromatin remodeling, and cellular homeostasis. This dynamic process is mediated by the opposing activities of poly(ADP-ribose) polymerases (PARPs), which synthesize poly(ADP-ribose) (pADPr), and poly(ADP-ribose) glycohydrolase (PARG), which degrades it. While PARP function has been extensively studied, the structural and mechanistic basis of PARG-mediated pADPr degradation remain incompletely understood. To investigate the role of PARG in pADPr metabolism, we employed CRISPR/Cas9-based genome editing to generate a novel Parg29b mutant mouse embryonic stem cell (ESC) line carrying a precise deletion within the PARG catalytic domain. This deletion completely abolished pADPr hydrolytic activity, resulting in massive nuclear pADPr accumulation, yet ESC viability, proliferation, and cell cycle progression remained unaffected. Using Drosophila melanogaster as a model system, we demonstrated that this mutation completely disrupted the pADPr pathway and halted developmental progression, highlighting the essential role of PARG and pADPr turnover in organismal development. Our results define a critical structural determinant of PARG catalytic function, underscore the distinct requirements for pADPr metabolism in cellular versus developmental contexts, and provide a genetically tractable model for studying the regulation of poly(ADP-ribose) dynamics and therapeutic responses to PARP inhibition in vivo. Full article
(This article belongs to the Section Cell Methods)
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16 pages, 4288 KiB  
Article
Functional Role of Resveratrol in Inducing Apoptosis in Breast Cancer Subtypes via Inhibition of Intracellular Fatty Acid Synthase
by Ping Li, Yan Liang and Xiaofeng Ma
Molecules 2025, 30(14), 2891; https://doi.org/10.3390/molecules30142891 - 8 Jul 2025
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Abstract
Fatty acid synthase (FASN) is frequently overexpressed in human breast cancer and has emerged as a potential therapeutic target. Resveratrol has been shown to inhibit FASN activity in vitro through both fast-reversible and slow-irreversible mechanisms. In this study, resveratrol reduced intracellular fatty acid [...] Read more.
Fatty acid synthase (FASN) is frequently overexpressed in human breast cancer and has emerged as a potential therapeutic target. Resveratrol has been shown to inhibit FASN activity in vitro through both fast-reversible and slow-irreversible mechanisms. In this study, resveratrol reduced intracellular fatty acid levels by inhibiting FASN activity and downregulating its expression across various breast cancer subtypes, including SK-BR-3, MCF-7, and MDA-MB-231 cells. Knockdown of FASN via small interfering RNA (siRNA) further enhanced resveratrol-induced cytotoxicity. Resveratrol significantly suppressed cell viability and triggered apoptosis, as evidenced by increased cleavage of poly(ADP-ribose) polymerase (PARP) and disruption of Bcl-2 family protein balance. Furthermore, resveratrol inhibited key signaling pathways involved in cell proliferation and survival, notably FAK, AKT, and ERK1/2. FASN silencing by siRNA also modulated the activation states of these signaling proteins. Collectively, these findings support resveratrol as a promising anti-cancer candidate that induces apoptosis in diverse breast cancer subtypes via FASN inhibition. Full article
(This article belongs to the Special Issue Chemical and Biological Research on Bioactive Natural Products)
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