Kim J, Lee H, Lim J
… +3 more, Oh J, Shin SS, Yoon M
Int J Mol Sci
· 2026 Jun · PMID 42378369
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The journal retracts the article titled "The Angiogenesis Inhibitor ALS-L1023 from Lemon-Balm Leaves Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease through Regulating the Visceral Adipose-Tissue Functi...The journal retracts the article titled "The Angiogenesis Inhibitor ALS-L1023 from Lemon-Balm Leaves Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease through Regulating the Visceral Adipose-Tissue Function" [...].
Int J Mol Sci
· 2026 Jun · PMID 42353364
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The following reference [59] has been retracted and has to be removed from the original publication [...].The following reference [59] has been retracted and has to be removed from the original publication [...].
Guo Z, Yuan X, Li T
… +4 more, Wang S, Yu Y, Liu C, Duan C
Int J Mol Sci
· 2026 Jun · PMID 42353361
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The authors realized that the Supplementary Materials are missing in the original published version of [...].The authors realized that the Supplementary Materials are missing in the original published version of [...].
Trigueiro-Louro J, Correia V, Ali IDS
… +2 more, Ahmed B, Rebelo-de-Andrade H
Int J Mol Sci
· 2026 Jun · PMID 42353353
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Dengue is the most common vector-borne viral disease worldwide, posing an increasing global health threat. Despite its high burden, no approved antiviral treatments or widely applicable vaccines exist, and patient manage...Dengue is the most common vector-borne viral disease worldwide, posing an increasing global health threat. Despite its high burden, no approved antiviral treatments or widely applicable vaccines exist, and patient management remains limited to supportive care, underscoring the urgent need for antiviral development. The NS5 protein is a prime antiviral target, owing to its crucial role in viral replication, high conservation across dengue virus (DENV) serotypes and lack of a human orthologue. We conducted a comprehensive sequence-to-structure analysis to identify conserved druggable regions within NS5, integrating large-scale sequence analysis with structural characterization across all four DENV serotypes. We identified four highly promising Consensus Druggable Pockets within the NS5 dimer-CDP1d, CDP3d, CDP5d and CDP12d-that overlap functionally critical regions, alongside 149 new potential hot spot residues. Domain-specific analysis revealed that MTase offers more densely conserved targets, whereas RdRp provides broader druggable surfaces, revealing complementary features for pharmacological modulation. Several identified pockets spatially overlap known inhibitor binding sites, and preliminary docking analyses support their capacity to accommodate small molecules, reinforcing their therapeutic relevance as candidate targets. Collectively, these findings provide a robust framework for the rational design of pan-serotype anti-DENV NS5 antivirals with an enhanced barrier to resistance.
Alhashel AF, Almasrahi AA, Alsaleh MA
… +3 more, Widyawan A, El-Komy MH, Ibrahim YE
Int J Mol Sci
· 2026 Jun · PMID 42353352
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Huanglongbing, a destructive citrus disease of global importance that is also present in Saudi Arabia, is associated with Liberibacter asiaticus (CLas) and remains a major threat to citrus production. Although previous...Huanglongbing, a destructive citrus disease of global importance that is also present in Saudi Arabia, is associated with Liberibacter asiaticus (CLas) and remains a major threat to citrus production. Although previous studies have documented sequence variation and prophage polymorphism in CLas, broader comparisons of prophage-associated gene content remain limited. In particular, comparative orthogroup analysis of prophage gene-content conservation across geographically structured CLas populations has rarely been explored. In this study, we analyzed 42 CLas prophage genomes from Saudi Arabia and other geographic regions using a comparative orthogroup framework. OrthoFinder assigned 99.1% of predicted proteins (1825 of 1841) to 64 orthogroups, with only 16 genes remaining unassigned. A small number of rare orthogroups restricted to only a few genomes were identified, and no orthogroup was detected in all genomes. Presence-absence analyses supported a predominantly conserved prophage gene repertoire together with a small accessory component, while also indicating that apparent absences should be interpreted in light of mixed assembly status and prophage-region completeness. Saudi Arabian genomes were distributed within the broader global framework and exhibited generally similar gene-content profiles rather than a deeply separated lineage. Functional interpretation of representative orthogroups identified conserved prophage-associated genes related to replication, helicase activity, and phage packaging, whereas variable orthogroups were primarily associated with hypothetical or accessory prophage-related functions. Overall, these results are consistent with a model in which CLas prophage diversification is associated more with sequence-level variation and localized structural differences than with extensive gain or loss of prophage genes. These findings further refine current understanding of CLas genome evolution and highlight conserved prophage-associated targets that may support molecular diagnostics and epidemiological surveillance.
Kandy SK, Nimonkar MM, Dash SS
… +3 more, Vashista PN, Mehta B, Markandeya YS
Int J Mol Sci
· 2026 Jun · PMID 42353351
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Glutamate excitotoxicity is a critical pathological mechanism underlying neuronal death in ischemic stroke, epilepsy, and neurodegenerative diseases. Caveolin-1 (Cav-1), a structural protein of caveolae membrane microdom...Glutamate excitotoxicity is a critical pathological mechanism underlying neuronal death in ischemic stroke, epilepsy, and neurodegenerative diseases. Caveolin-1 (Cav-1), a structural protein of caveolae membrane microdomains, has emerged as a potential modulator of neuronal survival, yet its precise mechanisms in excitotoxicity remain incompletely understood. In this study, we investigated the role of Cav-1 in regulating glutamate-induced calcium dysregulation, reactive oxygen species (ROS) generation, and mitochondrial dysfunction in primary hippocampal neurons. Using Cav-1 overexpression (Cav-1OE) and Cav-1 knockdown (Cav-1KD) approaches, we demonstrate that Cav-1OE significantly attenuates glutamate-stimulated intracellular Ca elevation, reduces ROS generation, and prevents mitochondrial membrane potential (Ψ) depolarization. Further investigation revealed that Cav-1OE reduces, while Cav-1KD enhances, calcium responses mediated by NMDA, AMPA, and KA receptors. These findings establish that Cav-1 functionally attenuates excitotoxic signaling by negatively regulating ionotropic glutamate receptor-mediated Ca influx.
Trifonova EA, Ivanov RA, Kochetov AV
… +1 more, Lashin SA
Int J Mol Sci
· 2026 Jun · PMID 42353350
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Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impaired social interaction, communication deficits, and repetitive behaviors. Recent research highlights the role of the gut micr...Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impaired social interaction, communication deficits, and repetitive behaviors. Recent research highlights the role of the gut microbiota in ASD pathophysiology, particularly through the microbiota-gut-brain axis. The microbiota may influence neurodevelopment via multiple signaling pathways, including the GABAergic and serotonergic systems, as well as the mTOR signaling pathway. This analytical review examines current evidence on microbiota alterations in ASD and evaluates microbiota-targeted strategies for diagnosis and treatment, focusing on fecal microbiota transplantation (FMT), probiotics, and diet-based therapeutic approaches. The review also provides a critical appraisal of the microbiota-gut-brain axis in the context of autism spectrum disorder.
Li X, Zhou L, Lei Z
… +8 more, Li S, Wang Q, Zhao H, Xu L, Chen J, Wan X, Huang Y, Lei T
Int J Mol Sci
· 2026 Jun · PMID 42353349
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Pituitary apoplexy is an uncommon but clinically urgent complication that often involves intrasellar hemorrhage and tissue necrosis. The mechanisms linking acute tissue injury to the inflammatory tumor microenvironment r...Pituitary apoplexy is an uncommon but clinically urgent complication that often involves intrasellar hemorrhage and tissue necrosis. The mechanisms linking acute tissue injury to the inflammatory tumor microenvironment remain incompletely defined. Here, we characterized the apoplexy-associated microenvironment and examined whether macrophage mechanosensitive signaling contributes to inflammatory amplification and tissue damage in pituitary neuroendocrine tumors (PitNETs). We combined single-cell RNA sequencing (scRNA-seq), histological validation, clinical stratification, and in vitro functional assays using apoplectic and non-apoplectic human PitNET specimens. Macrophage state transitions, intercellular communication, and transcriptional regulatory programs were analyzed, followed by an experimental assessment of the PIEZO1-Ca axis and macrophage-conditioned medium-induced tumor cell death. Histological validation confirmed macrophage accumulation in apoplectic PitNETs, including a 1.67-fold increase in IBA-1-positive cells ( < 0.001). CellChat-inferred interaction metrics increased descriptively in apoplectic samples. Apoplectic tissues showed higher TNF-α expression (3.00-fold; < 0.0001) and higher PIEZO1 fluorescence in IBA-1-positive regions (1.39-fold; = 0.001). Yoda1 increased Calcium 520 fluorescence in macrophages (1.72-fold; = 0.002), whereas knockdown reduced the Yoda1-associated response ( = 0.003). Conditioned medium from activated macrophages increased total Annexin V/PI-positive death in AtT-20 cells (0.53 ± 0.53% to 32.48 ± 1.14%; < 0.001) and GH3 cells (0.82 ± 0.50% to 30.92 ± 1.11%; < 0.001); knockdown or TNF-α neutralization attenuated this effect. Clinically, pathological necrosis was associated with higher symptom frequencies and a greater adjusted likelihood of two or more clinical symptoms. Together, these findings indicate that PIEZO1-related macrophage signaling may participate in TNF-α-associated tumor cell necroptosis in pituitary apoplexy. Pathological necrosis was linked to greater acute symptom burden and perioperative hormonal abnormalities, suggesting that it may identify a clinically severe apoplexy subtype.
Int J Mol Sci
· 2026 Jun · PMID 42353348
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Relict yew plants ( L.) are not only ornamental plants with valuable wood but also have the ability to synthesize the unique compound taxol, which is successfully used in the treatment of cancer due to its powerful cytot...Relict yew plants ( L.) are not only ornamental plants with valuable wood but also have the ability to synthesize the unique compound taxol, which is successfully used in the treatment of cancer due to its powerful cytotoxic effect. Due to the presence of taxol, all parts of yew plants are extremely poisonous, but there have been cases where animals have eaten yew cones without fatal consequences. The biosynthesis of taxol is carried out due to the interaction of the isoprenoid and phenolic pathways of the secondary metabolism of plants. Despite the close attention of researchers to the peculiarities of taxol metabolism, there is very little data on the tissue and intracellular localization of both taxols and phenolic compounds in yew plants. Polyphenols are known to be physiologically active mediators involved in respiration, photosynthesis, plant growth and development, as well as in the process of in vitro dedifferentiation. Since is a relict species and has a limited and hard-to-reach range in nature, technologies that allow yew plants to be restored without removing plant material from the natural environment are of great practical importance: overcoming deep physiological dormancy of seeds, microclonal reproduction and initiation of plant growth. In vitro cultures are possible sources of biologically active and medicinal products. The aims and objectives of this study are to determine the characteristics of the formation and localization of phenolic compounds with high biological activity in various organs of plants of the genus and to determine the biological activity of ethanolic extracts from this plant. The objects of this study were the generative organs of , collected during the entire growing season (April-October) from plants growing in the Moscow region. The localization of various classes of polyphenols was determined by histochemical methods using light microscopy. Histochemical studies have shown the abundant presence of polyphenols in yew megastrobiles, microstrobiles, cones, seeds and aril. Ethanolic plant extracts were used to determine the biological activity. Flavans were dominant in the aril at various stages of vegetation, which was confirmed by our biochemical and histochemical studies. Extractive substances of show high antibacterial activity, especially in its shoot extracts. Ethanolic extracts from plant shoots showed greater biological activity than seed extracts. Aril extracts had the lowest cytotoxicity.
Różycka-Kosmalska M, Szymczak-Pajor I, Śliwińska A
… +3 more, Kozłowska M, Wranicz JK, Kosmalski M
Int J Mol Sci
· 2026 Jun · PMID 42353347
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p53, miR-34a, and SIRT-1 are involved in cellular stress responses, senescence, and inflammation-processes central to the pathophysiology of atrial fibrillation (AF). In this study, circulating and serum miR-34a expres...p53, miR-34a, and SIRT-1 are involved in cellular stress responses, senescence, and inflammation-processes central to the pathophysiology of atrial fibrillation (AF). In this study, circulating and serum miR-34a expression were determined in patients with and without AF, in order to assess their associations with AF. We also checked their potential diagnostic utility as systemic biomarkers associated with AF. The study included 189 adults, 94 AF+, 95 AF-. Clinical, anthropometric, and biochemical data were collected. Whole-blood and mRNA expression and serum miR-34a expression were quantified by RT-qPCR. ROC analysis and Youden-derived odds ratios assessed exploratory diagnostic performance. AF patients had significantly higher expression of (0.0352 vs. 0.0253; < 0.001) and miR-34a (0.0215 vs. 0.0099; < 0.001), but significantly lower expression of (0.0079 vs. 0.0145; < 0.001). The level of expression showed the highest discriminatory performance (exploratory AUC = 0.6987; < 0.0001). expression levels exceeding 0.0295 were associated with nearly threefold higher odds of AF (OR = 2.92, 95% CI: 1.61-5.28, = 0.0006), whereas the expression levels of and miR-34a were not significantly associated with AF in cut-off analysis. In the AF group, a positive correlation was found between the expression of and ( = 0.3609, < 0.001); however, it was not consistent with a canonical model of miR-34a-mediated suppression. In turn, the expression of miR-34a correlated positively with age and C-reactive protein level and negatively with estimated glomerular filtration rate (eGFR). The obtained results suggest that AF is associated with altered expression of circulating , , and miR-34a. However, due to the fact that the expression levels were measured in peripheral compartments, and not in atrial tissue, the obtained results should not be interpreted as direct evidence of AF-related atrial remodeling. For these reasons, further investigations involving simultaneous measurements of the TP53/miR-34a/SIRT-1 regulatory axis, both in the circulating compartment and atrial tissue, should be performed.
Wang Y, Han Y, Wang C
… +4 more, Wang Z, Guan Z, Li N, Pan J
Int J Mol Sci
· 2026 Jun · PMID 42353346
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To clarify the microbial contamination and wood degradation risk of the Nanhai No. 1 shipwreck hull and verify on-site antibacterial agent effectiveness, microbial samples were collected and analyzed via SEM, metagenomic...To clarify the microbial contamination and wood degradation risk of the Nanhai No. 1 shipwreck hull and verify on-site antibacterial agent effectiveness, microbial samples were collected and analyzed via SEM, metagenomic sequencing, bacterial isolation, enzyme activity detection, and antibacterial experiments. The results showed that Actinomycetota was the dominant phylum, and , , and were the dominant genera. Seven bacterial strains were isolated and purified, among which sp. (NH.SH-B6) had the strongest wood degradation ability, possessing cellulase, LiP, MnP, and Lac activities. When cultured with hull wood as the sole carbon source, LiP was the dominant degrading enzyme of NH.SH-B6, and its maximum enzyme activity was achieved under the optimal conditions of pH = 7, 10% NaCl, 1000 mg/L FeSO, and no PEG400 added. 50 mg/mL cinnamaldehyde and 0.5% isothiazolinone K100 had good inhibitory effects on the isolated bacteria, and bacterial proliferation was due to incomplete antibacterial agent spraying. This study clarifies the microbial degradation risk of the Nanhai No. 1 shipwreck hull and provides a scientific basis for optimizing the on-site protection strategy of the shipwreck.