International Journal Of Molecular Sciences[JOURNAL]
Sun
200 papers
Prediction of Novel Disease-Related Regions in SIGLEC-7 by and Biochemical Analyses.
Morishita S, Hane M, Wu D … +4 more , Kitajima K, Ohno S, Yamaguchi Y, Sato C
Int J Mol Sci · 2026 Jun · PMID 42353205 · Full text
SIGLECs are well-known receptors that distinguish self from non-self by binding to sialic acid-containing glycoconjugates, thereby regulating normal immune functions. They have also been associated with several diseases,...
SIGLECs are well-known receptors that distinguish self from non-self by binding to sialic acid-containing glycoconjugates, thereby regulating normal immune functions. They have also been associated with several diseases, including systemic sclerosis, leukemia, and Alzheimer's disease. To identify pathogenic regions related to ligand binding in SIGLECs using a novel approach, we employed the Individual Meta Random Forest (InMeRF) program, which predicts disease-related amino acid substitutions. InMeRF predicted a novel three-amino-acid motif (LSI) consisting of highly pathogenic amino acid residues in SIGLEC-7 and other CD33-related SIGLECs. Alanine substitution experiments and point-mutation energy calculations using SIGLEC-7 as a representative model member of the SIGLEC family showed that mutations in the LSI motif altered binding to ganglioside ligands compared with the wild type (WT) and affected structural stability, as reflected by changes in mutation energy. Structural analysis based on the crystal structure of SIGLEC-7 revealed that the LSI motif forms a buried β-strand located beneath the previously identified sialic acid-binding region (Site 2) in CD33-related SIGLEC-7. Taken together, these findings demonstrate the utility of InMeRF for identifying previously unrecognized pathogenic regions and provide new structural and functional insights into the SIGLEC family.
From Tradition to Translation: A Critical Appraisal of for Neuroprotection from Preclinical and Clinical Perspectives and Challenges in Utilization.
Olajide AT, Aunsorn S, Kehinde SA … +2 more , Kaewmanee T, Chusri S
Int J Mol Sci · 2026 Jun · PMID 42353204 · Full text
Dementia, and more specifically Alzheimer's disease (AD), is a progressive neurodegenerative disorder that has become a growing health menace in the world with an escalation in incidence as well as enormous social and ec...
Dementia, and more specifically Alzheimer's disease (AD), is a progressive neurodegenerative disorder that has become a growing health menace in the world with an escalation in incidence as well as enormous social and economic consequences. Existing pharmacological treatment including cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists are not very effective in reducing the symptoms and fail to prevent the disease process. The non-pharmacological treatment interventions such as diet, exercise and cognitive training have supportive effects and cannot be used as standalone treatments. Therapeutic gap has resulted in increased interest in complementary and alternative therapies, especially that of pleiotropic action of herbal medicines. (BM) is an Ayurvedic herb that has historically been used to treat memory enhancement and now has both preclinical and clinical evidence supporting its ability to modulate neurotransmission, reduce oxidative stress and suppress neuroinflammation. However, such difficulties as low bioavailability, instability of the environmental factors, and variations in formulations restrict its clinical applicability. New technologies with a lot of potential such as microencapsulation technology can provide the solution to this problem by increasing stability, solubility, and targeted delivery of compounds that will increase treatment efficacy. This narrative review is a synthesis of the existing information on the pathogenesis of dementia, therapeutic approaches, and the effectiveness of BM as a complementary intervention. It points out links between traditional medicine and modern neuroscience, strengths and limitations of on-going evidence, gaps that need further research, such as long-term clinical trials, standardized formulations, and discovery of the role of BM in the gut-brain axis. BM is a prime example of how herbal medicines can be used as a complement to conventional treatment and play a role in multi-modal approaches aimed at reducing the cognitive impairment associated with dementia.
Associations Between Previously Identified Genetic Variants and Clinical Phenotypes of Diabetic Neuropathy in Type 2 Diabetes: An Exploratory Analysis of the Discovery Cohort.
Hajdú N, Ludvig Z, Rácz R … +15 more , Istenes I, Békeffy M, Vági OE, Körei AE, Horváth E, Tóbiás B, Illés A, Pikó H, Kósa JP, Árvai K, Posta M, Lakatos PA, Kempler P, Putz Z, Tordai DZ
Int J Mol Sci · 2026 Jun · PMID 42353203 · Full text
Diabetic neuropathy is a common and multifactorial complication of type 2 diabetes, in which genetic susceptibility is increasingly recognized as a contributing factor. This study (cross-sectional case-control) aimed to...
Diabetic neuropathy is a common and multifactorial complication of type 2 diabetes, in which genetic susceptibility is increasingly recognized as a contributing factor. This study (cross-sectional case-control) aimed to investigate the associations between previously identified genetic variants and clinically relevant neurophysiological and symptomatic parameters. A total of 48 individuals with type 2 diabetes (24 with neuropathy and 24 without) were included. Neuropathy was assessed using standardized neurological, sensory, and cardiovascular autonomic function tests. Genetic variants were selected in a prior discovery analysis of this same cohort and re-tested here, precluding independent validation. Associations between genetic variants and clinical parameters were assessed through group-based comparisons using Mann-Whitney U tests and Fisher's exact test, correlation analysis using Spearman's rank correlation, permutation-based testing to improve robustness, and multivariable linear regression adjusted for age and sex to account for potential demographic confounding (q < 0.1). Mann-Whitney U test analysis identified several associations between genetic variants and neuropathy-related clinical parameters. In the Mann-Whitney U test analysis, only the rs6682221 variant remained significantly associated with heat detection threshold in the left hand after false discovery rate correction ( = 0.000150; q = 0.02736), although this association did not remain significant in the complementary permutation analysis based on median differences. Spearman's rank correlation analysis identified a significant positive association between rs6682221 allele burden and heat detection threshold in the left hand, which remained significant after permutation correction (r = 0.552, = 0.000086, q = 0.016). Multivariable regression adjusted for age and sex revealed several independent associations between selected variants and sensory neuropathy-related parameters. These findings should be considered exploratory, as all analyses were performed within the original discovery cohort and no independent validation cohort was available. Independent replication and functional studies are required before any clinical relevance can be inferred.
Is Essential for Maintaining Spermatogenesis and the Proper Functioning of Biological Barriers in .
Ryabova EV, Ivanova EA, Komissarov AE … +6 more , Bolobolova EU, Dorogova NV, Slepneva EE, Latypova EM, Ogneva IV, Sarantseva SV
Int J Mol Sci · 2026 Jun · PMID 42353202 · Full text
Functional changes in (Patatin-like phospholipase domain-containing protein 6), caused by gene mutations or inhibition by organophosphates, affect the levels of various phospholipids. In humans, this leads to organophos...
Functional changes in (Patatin-like phospholipase domain-containing protein 6), caused by gene mutations or inhibition by organophosphates, affect the levels of various phospholipids. In humans, this leads to organophosphorus compound-induced delayed neurotoxicity syndrome (OPIDN) and a number of rare diseases. In this study, we analyze the role of the gene (), an ortholog of , in spermatogenesis in . We report that the mutation affects membrane remodeling during spermatid individualization, as well as spermatid coiling during the late stages of spermatogenesis. In addition, the mutation leads to changes in the transcriptome in the testes of flies. We also demonstrate that is required for the proper functioning of important biological barriers in .
Machine Learning for CRISPR-Based Diagnostics.
Walflor HSM, Medeiros LCS
Int J Mol Sci · 2026 Jun · PMID 42353201 · Full text
CRISPR-based diagnostics now detect viral, bacterial, and cancer-associated nucleic acids with sensitivities approaching quantitative PCR; however, their translation to decentralized care rests on computational design an...
CRISPR-based diagnostics now detect viral, bacterial, and cancer-associated nucleic acids with sensitivities approaching quantitative PCR; however, their translation to decentralized care rests on computational design and interpretation that current datasets cannot sustain. Pandemic-era Cas12a assays reached 95% positive predictive agreement against reverse transcription quantitative PCR (RT-qPCR) at 10 copies/μL, and deep neural networks now design Cas13 detection assays spanning 1933 vertebrate-infecting viruses, ranking candidate guides at Spearman correlations of 0.69 to 0.84 across internal and external validation. Generative deep-learning systems improve single-nucleotide discrimination two- to three-fold, computer vision classifies lateral flow outputs at 96.5% accuracy, and multi-biomarker fusion reaches an area under the receiver operating characteristic curve (AUC) of 0.998 in lung cancer detection. These results mask a narrow data foundation. Cas13a guide prediction still draws from a single screening library of 19,209 guide-target pairs, Cas12a has one published diagnostic model, and signal classifiers almost uniformly validate on single-site cohorts. This review synthesizes mechanistic constraints, predictive and generative models, and point-of-care classifiers, and maps the path beyond this data ceiling. Evolutionary pretraining on RNA corpora and lab-in-the-loop agents that convert model failure into targeted data acquisition define the route forward.
Corneal Endothelial Progenitors for Ocular Regeneration: Translating Discovery into Clinical Therapies.
Nay Yaung K, Neo D, Mehta JS
Int J Mol Sci · 2026 Jun · PMID 42353200 · Full text
The corneal endothelium is essential for maintaining corneal transparency through active fluid transport and barrier function. Corneal cell loss from disease, ageing or surgical trauma underlies a significant proportion...
The corneal endothelium is essential for maintaining corneal transparency through active fluid transport and barrier function. Corneal cell loss from disease, ageing or surgical trauma underlies a significant proportion of corneal blindness worldwide, with Fuchs' endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK) representing the dominant clinical indications for corneal transplantation. While Descemet's membrane endothelial keratoplasty (DMEK) has substantially improved surgical outcomes, the procedure remains constrained by global donor tissue shortage. Regenerative medicine offers a compelling alternative by exploiting the latent proliferative and reparative potential of corneal endothelial progenitor populations. This review synthesises current knowledge on the foundational biology of corneal endothelial progenitor populations and the optimisation of expansion platforms to emerging preclinical and clinical evidence for both cell-based and pharmacological regenerative strategies. We also consider the outstanding translational challenges of potency standardisation, GMP-compliant manufacturing and regulatory navigation, as well as the longer-term potential of biomaterial-cell platforms and personalised iPSC-based medicine. The cumulative evidence positions progenitor-based approaches as viable and increasingly well-characterised alternatives to conventional donor transplantation, although their routine clinical use awaits the optimisation of manufacturing and regulatory platforms.
Modulation of Triplet-State Reactivity and Enhanced Singlet Oxygen Generation in Tricyclic Thiopurine Analogues.
Taras-Goslinska K, Krancewicz K, Marciniak B
Int J Mol Sci · 2026 Jun · PMID 42353199 · Full text
Thiopurines are efficient triplet-state photosensitisers; however, the practical application of canonical derivatives such as 6-thioguanine (6TG) and 6-thioguanosine (6TGuo) is limited by competing deactivation pathways...
Thiopurines are efficient triplet-state photosensitisers; however, the practical application of canonical derivatives such as 6-thioguanine (6TG) and 6-thioguanosine (6TGuo) is limited by competing deactivation pathways that reduce the fraction of triplet states available for productive interaction with molecular oxygen. In this work, we investigated how structural modification of the thiopurine scaffold through introducing of an additional five-membered etheno ring affects triplet-state energetics, deactivation pathways, and singlet oxygen sensitisation. The photophysical properties of four tricyclic thiopurine analogues-9-thio-1,N-ethenoguanine (TEGua), 9-thio-1,N-ethenoguanosine (TEGuo), 6-methyl-9-thio-1,N-ethenoguanine (6MeTEGua), and 6-methyl-9-thio-1,N-ethenoguanosine (6MeTEGuo)-were investigated using steady-state spectroscopy, low-temperature phosphorescence, nanosecond transient absorption spectroscopy, and direct detection of singlet oxygen phosphorescence. All investigated compounds exhibited efficient intersystem crossing and microsecond-lived triplet states. Compared with canonical thiopurines, the tricyclic analogues displayed lower triplet-state energies and significantly enhanced singlet oxygen generation. Quantum yields of singlet oxygen sensitisation reached ~0.56 in acetonitrile, approximately twofold higher than those observed for 6TG and 6TGuo under identical conditions. Analysis of triplet-state deactivation pathways showed that the enhanced photosensitising efficiency does not result from increased triplet formation, but from more effective use of the triplet-state population for energy transfer to molecular oxygen leading to singlet oxygen formation. These findings demonstrate that structural modification of the thiopurine scaffold enables control over triplet-state reactivity and provides a strategy for designing improved thiopurine-based photosensitisers for photodynamic therapy applications (PDT).
Dietary Modulation of Postoperative Inflammation: Molecular Mechanisms and Implications for Tissue Repair and Healing.
Siefert CV, Baticic L
Int J Mol Sci · 2026 Jun · PMID 42353198 · Full text
Postoperative inflammation is a necessary response to surgical injury that supports tissue repair and regeneration. However, successful healing depends not only on the initial inflammatory response but also on its timely...
Postoperative inflammation is a necessary response to surgical injury that supports tissue repair and regeneration. However, successful healing depends not only on the initial inflammatory response but also on its timely resolution. Failure to resolve inflammation can impair wound healing, promote fibrosis, and increase the risk of postoperative complications. Increasing evidence suggests that effective recovery is driven by the transition from inflammation to repair and regenerative processes. Diet plays an important role in this transition, as nutrients not only provide metabolic support but also regulate key pathways involved in inflammation, tissue regeneration, redox balance, and immune function. Omega-3 polyunsaturated fatty acids could serve as precursors for specialized pro-resolving mediators that actively terminate inflammation and may promote macrophage-driven tissue repair. Polyphenols and antioxidant micronutrients modulate NF-κB and Nrf2-dependent signalling, attenuating oxidative amplification of inflammatory cascades. Micronutrients and amino acids further regulate enzymatic processes governing collagen synthesis, angiogenesis, and immune competence. Concurrently, diet-driven preservation of gut barrier integrity limits endotoxin-mediated amplification of systemic inflammatory responses. By targeting interconnected molecular networks, including inflammasome activation, mitochondrial redox signalling, and metabolic programming of immune cells, anti-inflammatory dietary patterns may promote immune resolution rather than immunosuppression. This distinction is particularly relevant in the postoperative setting, where balanced inflammation is required for both host defence and regenerative healing. This review synthesizes current molecular and translational evidence linking dietary modulation to postoperative inflammatory control and tissue regeneration. By integrating insights from immunology, metabolism, and nutritional science, it positions diet as an active, biologically grounded component of perioperative management and highlights future directions for precision nutrition strategies aimed at optimizing surgical recovery.
Hesperetin Rescues Amyloid Beta-Induced Defects in Neurite Outgrowth Under Mild Cognitive Impairment-like Cellular Conditions.
Honjo A, Yako H, Kasai M … +7 more , Chiba M, Satsuka A, Kato T, Yagi M, Nishi A, Miyamoto Y, Yamauchi J
Int J Mol Sci · 2026 Jun · PMID 42353197 · Full text
Accumulation of aggregated amyloid beta (Aβ) species is a defining pathological hallmark of Alzheimer's disease and is associated with extensive neuronal structural abnormalities. Mild cognitive impairment (MCI), a trans...
Accumulation of aggregated amyloid beta (Aβ) species is a defining pathological hallmark of Alzheimer's disease and is associated with extensive neuronal structural abnormalities. Mild cognitive impairment (MCI), a transitional stage between normal aging and the onset of dementia, is thought to represent an early phase of this pathological continuum. Studies at the cellular level suggest that the conditions impair the maintenance of established neuronal processes/networks and restrict their capacity for elongation or re-elongation. They may also attenuate the activation and process extension of quiescent neural progenitor or stem-like cells. These early cellular changes precede overt neurodegeneration in neural tissue and are likely to contribute to cognitive decline. They highlight the importance of in vitro models for identifying molecular targets involved in recovery from disease. In this study, we investigated the effects of aggregated Aβ (25-35) on neuronal process elongation and associated intracellular events in the N1E-115 cell line, a widely used model of neuronal differentiation. Addition of aggregated Aβ to cultured N1E-115 cells attenuated process elongation in a concentration-dependent manner. This morphological impairment was accompanied by decreased expression of neuronal differentiation markers. In contrast, at the half-maximal inhibitory concentration for process elongation, long-term cultured cells did not exhibit apparent process retraction or degenerative morphology. This mild but progressive impairment, without extensive cell death, is consistent with the cellular features of early-stage conditions rather than advanced Alzheimer's pathologies. Similar results were observed in primary cortical neurons. Aβ also decreased the level of GTP-bound Ras and phosphorylation of the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). Furthermore, treatment with hesperetin, a bioactive flavonoid compound, recovered the Aβ-induced inhibition of neuronal process elongation. Hesperetin also restored Ras and MAPK/ERK states, suggesting that its effects are associated, at least in part, with modulation of signaling through Ras and MAPK/ERK. Our findings suggest that hesperetin may serve as a useful molecular probe for modulating early cellular responses associated with Alzheimer's disease-related pathology. This in vitro model might serve as a useful platform for investigating the molecular target candidates involved in recovery from nervous system disorders.
Protective Effects of Selective β-Adrenoceptor Blockade on Renal Pathophysiology in a Catecholamine Storm of Rat.
Chen BH, Liu TH, Lin GH … +4 more , Chen HH, Chu YT, Yang CC, Lu WH
Int J Mol Sci · 2026 Jun · PMID 42353196 · Full text
Excessive administration of epinephrine and norepinephrine in critically ill patients may trigger a catecholamine storm and contribute to acute kidney injury (AKI) through activation of β-adrenoceptor signaling. Although...
Excessive administration of epinephrine and norepinephrine in critically ill patients may trigger a catecholamine storm and contribute to acute kidney injury (AKI) through activation of β-adrenoceptor signaling. Although clinical observations link high-dose catecholamine exposure to increased AKI risk, experimental models and mechanistic studies remain limited. We established a rodent model of combined epinephrine and norepinephrine infusion to investigate the renoprotective effects of subtype-selective β-adrenoceptor blockers. Animals received the β1-selective blockers metoprolol or atenolol, or the β2-selective blocker ICI 118,551. β1-adrenoceptor blockade, particularly with metoprolol, significantly attenuated renal histopathological injury and improved biochemical markers of kidney dysfunction. These protective effects were associated with suppression of ferroptosis-related pathways in the renal cortex. Atenolol partially improved biochemical parameters but did not significantly reduce tubulointerstitial damage, whereas β2-adrenoceptor blockade conferred limited functional benefit despite modest morphological improvement. Collectively, our findings indicate that β1-adrenoceptor activation plays a critical role in catecholamine-induced AKI by promoting ferroptosis. Targeting β1-adrenoceptors, especially with metoprolol, may represent a potential therapeutic strategy for preventing renal injury during catecholamine storms.
Genome-Wide Analysis Reveals the Roles of Genes in × Under Abiotic/Biotic Stresses and Highlights Their Potential Functions in Anthocyanin Biosynthesis During Fruit Development.
Ren R, Xu Y, Cheng Y … +4 more , Li Q, Ding W, Shen L, Chen L
Int J Mol Sci · 2026 Jun · PMID 42353195 · Full text
transcription factors are key regulators of plant growth and development, but their identification and functions in strawberries ( × ) remain largely unexplored. In this study, 47 genes in cultivated strawberries were s...
transcription factors are key regulators of plant growth and development, but their identification and functions in strawberries ( × ) remain largely unexplored. In this study, 47 genes in cultivated strawberries were systematically identified, which were categorized into six subfamilies and randomly distributed across 15 chromosomes, with segmental duplication as the main driver of the expansion of this gene family. Integration of phylogenetic relationships, gene structure, and conserved motif composition uncovered distinct divergences among the subfamilies. A -acting element analysis of promoters and gene expression profiles showed that these genes responded to various abiotic and biotic stresses, phytohormones, and far-red light signals, with and strongly responding to multiple stresses, including temperature, drought, and pathogen infection. Additionally, and exhibited positive correlations with anthocyanin accumulation and the expression of key anthocyanin biosynthesis genes during fruit development. Dual-luciferase reporter assays further confirmed that FaFAR1-12 and FaFAR1-18 significantly activated the promoters of key structural genes related to anthocyanin biosynthesis, indicating that these two TFs exert vital regulatory functions in anthocyanin accumulation during strawberry fruit development. This study comprehensively identifies and characterizes the genes in cultivated strawberries, laying a foundation for their functional analysis and for screening out the key regulatory genes for strawberry fruit quality improvement.
Molecular Characterization of Viruses Revealed by Japanese Flowering Cherry () Virome Analysis.
Sheveleva A, Sharko F, Motsar E … +2 more , Karpun N, Chirkov S
Int J Mol Sci · 2026 Jun · PMID 42353194 · Full text
Japanese flowering cherry ( Lindl.) is a deciduous tree with great decorative value due to its splendid spring bloom. Flowering cherry is native to East Asia and is cultivated in many other parts of the world. Two trees...
Japanese flowering cherry ( Lindl.) is a deciduous tree with great decorative value due to its splendid spring bloom. Flowering cherry is native to East Asia and is cultivated in many other parts of the world. Two trees with virus-like symptoms on leaves, denoted by S14 and S27, were found in the town of Sochi, Russia. Virome analysis of these trees using high-throughput sequencing revealed the presence of several viruses, including little cherry virus 2 (LChV-2), American plum line pattern virus (APLPV), and cherry virus A (CVA) in the S14 tree, as well as CVA, prune dwarf virus (PDV), and alfalfa mosaic virus (AMV) in the S27 tree. Nearly complete genomes of the detected viruses have been recovered and characterized. In the S14 tree, CVA was represented by three diverse genotypes sharing 80.8-83.5% nt identity. The complete APLPV genome from flowering cherry has been first sequenced. AMV was detected on species for the first time. This is the first report of LChV-2 from Russia. Thus, PDV, APLPV, AMV, LChV-2, and CVA were first found on from Russia, adding to the information on their genetic diversity, host range, and global geographical distribution.
20(S/R)-Ginsenoside Rh1 Alleviates AOM/DSS-Induced Colorectal Cancer: Gut-Microbiota Modulation and Tryptophan-Metabolism-Mediated AhR/PXR Activation and IDO1.
Lu L, Min J, Gao Y … +6 more , Yang G, Zhao Z, Kang Y, Zhao Y, Zhao L, Li S
Int J Mol Sci · 2026 Jun · PMID 42353193 · Full text
Colorectal cancer (CRC) is intricately linked to gut microbiota dysbiosis and tryptophan (Trp) metabolic dysregulation. This study aimed to clarify the role and mechanisms of 20(S/R)-ginsenoside Rh1 in suppressing colore...
Colorectal cancer (CRC) is intricately linked to gut microbiota dysbiosis and tryptophan (Trp) metabolic dysregulation. This study aimed to clarify the role and mechanisms of 20(S/R)-ginsenoside Rh1 in suppressing colorectal cancer through the regulation of gut microbiota and Trp metabolism. Azoxymethane/dextran sulfate sodium (AOM/DSS)was employed to induce a CRC mouse model, followed by treatment with 20(S/R)-ginsenoside Rh1 at 100 mg·kg·day for 6 weeks. 20(S/R)-ginsenoside Rh1 significantly reduced the disease activity index (DAI) score, restored colon length, and decreased tumor count. 20(S/R)-Ginsenoside Rh1 ameliorated gut dysbiosis by increasing gut microbial diversity and elevating the prevalence of beneficial bacteria, including , and stimulated the production of indole derivatives, including indole-3-propionic acid (IPA), indole-3-acetic acid (IAA), and indole-3-lactic acid (ILA) by enriching Trp -metabolizing bacteria such as . These changes further activated the AhR/CYP1A1/IL-22 and PXR/TLR4 pathways, upregulated the expression of intestinal tight junction proteins, suppressed the secretion of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IFN-γ, and elevated the levels of the anti-inflammatory cytokine IL-10. Furthermore, 20(S/R)-ginsenoside Rh1 reduces the serum kynurenine (Kyn)/Trp ratio, downregulates the expression of forkhead box P3 (FoxP3), a marker of regulatory T (Treg) cells, and increases the number of CD8 T cells by inhibiting the expression of indoleamine 2,3-dioxygenase 1 (IDO1) in colonic tissue. In conclusion, 20(S/R)-ginsenoside Rh1 showed potential anti-CRC activity, with our study observing links between its action and gut microbiota structure regulation, Trp metabolism modulation, AhR/PXR-mediated intestinal barrier activation, and IDO1-related immune suppression reversal.
Integrated Metabolomics and Transcriptomics Analysis of Exogenous Arginine-Mediated Sucrose Accumulation in Sugarcane.
Liu HB, Kumar T, Lin XQ … +12 more , Xu CH, Mao J, Kong CY, Li XJ, Tian CY, Khan W, Nur-Ul-Haq, Yao L, Zhao PF, Liu JY, Wang JG, Lu X
Int J Mol Sci · 2026 Jun · PMID 42353192 · Full text
The improvement of sucrose yield in sugarcane is impeded by the crop's complex polyploid genome and slow progress in breeding. To clarify how arginine (Arg) regulates sugar metabolism and identify key genes associated wi...
The improvement of sucrose yield in sugarcane is impeded by the crop's complex polyploid genome and slow progress in breeding. To clarify how arginine (Arg) regulates sugar metabolism and identify key genes associated with sucrose transport and accumulation in sugarcane, a screening experiment was performed by spraying L-arginine hydrochloride on the leaves and leaf sheaths of three sugarcane varieties (YZ05-51, YZ08-1609, and YT93-159), which differ in growth vigor, leaf morphology and other phenotypic traits. YZ05-51 exhibited the most prominent sugar-increasing effect, and subsequent optimization experiments on its leaf sheaths revealed that 20 g/mu L-arginine hydrochloride at pH 7.0 was optimal, significantly enhancing stem sucrose content. Transcriptomic analysis revealed the upregulation of genes related to sucrose synthesis and transport, with candidate genes enriched in pathways such as starch-sucrose metabolism, glycolysis/gluconeogenesis, and ATP-binding cassette (ABC) transporters. Metabolomic analysis detected 32 sugar metabolites across three categories, of which 24 were differentially abundant (e.g., glucose, galactose, fructose, and mannose). Integrated multi-omics analysis identified key regulatory genes, including and (sucrose synthesis and carbon flux regulation), , , (starch breakdown, glycolysis, and sugar mobilization), ABC transporters, , and / (sucrose transporter). Collectively, these analyses demonstrate enhanced activity of genes and metabolites involved in sucrose synthesis/transport in leaf sheaths, accompanied by reduced synthesis of other monosaccharides and oligosaccharides. Vigorously metabolizing leaf sheaths is more conducive to sucrose transport. This study provides valuable insights into the molecular mechanisms underlying Arg-mediated sucrose accumulation specifically in the sugarcane YZ05-51 sugarcane, highlighting its critical regulatory roles.
Alleviates -Exacerbated Alcoholic Liver Injury by Modulating Gut Microbiota and Barrier Function.
Sui X, Feng S, Wang W … +3 more , Zhang X, Liu Y, Peng N
Int J Mol Sci · 2026 Jun · PMID 42353191 · Full text
Cytolysin-positive is a key pathogen in severe alcoholic hepatitis, yet the mechanisms through which it worsens disease and possible therapeutic strategies remain poorly understood. This study aimed to clarify the patho...
Cytolysin-positive is a key pathogen in severe alcoholic hepatitis, yet the mechanisms through which it worsens disease and possible therapeutic strategies remain poorly understood. This study aimed to clarify the pathogenic effects of in acute alcohol-associated liver disease (ALD) and to assess the protective potential of (Akk11) against this pathogen. Using a mouse model of acute ethanol gavage, animals received and/or Akk11 under prophylactic or therapeutic regimens. Assessments included liver injury markers, histopathology, lipid profiles, inflammatory cytokines, gut barrier integrity, and gut microbiota composition. exacerbated ethanol-induced hepatic steatosis and injury, showing a paradoxical effect: it increased histological damage while lowering circulating LPS and transaminases. This was linked to upregulated hepatic autophagy (increased Atg7) and reduced cholesterol, yet it promoted neutral lipid accumulation. Importantly, aggravated gut dysbiosis by markedly enriching the pro-inflammatory pathobiont and impairing colonic barrier function. Intervention with Akk11 alleviated liver injury, reduced lipid accumulation and oxidative stress, and restored cytokine balance. Akk11 also strengthened gut barrier integrity, lowered serum endotoxin, and beneficially reshaped the microbiota. Prophylactic administration was particularly effective, normalizing the / ratio, suppressing , and enriching beneficial . This study confirms the pathogenic role of in acute ALD and establishes (Akk11) as a promising microbiota-targeted therapy, which protects against liver injury by reinforcing the gut barrier, selectively modulating microbiota, and reducing inflammation, with prophylactic administration showing superior efficacy.
Amine-Functionalized and Gold-Decorated Amine-Functionalized TiO Nanoparticles Modulate Breast Cancer Cell Viability.
Muñoz JP, Muñoz-Jaime K, Soto-Jiménez D … +3 more , Venkatesh N, Novoa N, Shanmugaraj K
Int J Mol Sci · 2026 Jun · PMID 42353190 · Full text
Surface engineering is a key strategy for modulating the biological behavior of TiO-based nanomaterials, with potential relevance for future localized or adjuvant approaches targeting residual cancer cells. This study ev...
Surface engineering is a key strategy for modulating the biological behavior of TiO-based nanomaterials, with potential relevance for future localized or adjuvant approaches targeting residual cancer cells. This study evaluated whether amine functionalization and subsequent gold decoration modify the effects of TiO nanoparticles (TiONPs) on MCF7 and MDA-MB-231 breast cancer cells. The synthesized materials preserved the anatase TiO framework, while surface modification altered their physicochemical and optical properties. After 24 h of exposure, pristine TiONPs produced minimal changes in cell viability, whereas NH-functionalized TiONPs (TiONPs-NH) and gold-decorated NH-functionalized TiONPs (Au@TiONPs-NH) reduced viability in a concentration-dependent and cell line-dependent manner. These effects were more evident in the MTT assay than in Trypan Blue exclusion counting, suggesting changes in metabolic activity before extensive membrane integrity loss. Overall, the findings indicate that surface modification, rather than the TiO core alone, is a major determinant of the cellular response to these nanomaterials. These results provide an initial in vitro basis for further mechanistic studies evaluating surface-engineered TiONPs as candidate platforms for future adjuvant breast cancer strategies.
Alterations in the Placenta Following Vaccination and Infection with SARS-CoV-2 During Pregnancy.
Hoymann N, Scholz L, Alboradi S … +10 more , Grabar V, Uehre GM, Khuankhunsathid JT, Taube ET, Toth G, Mészáros J, Gennari P, Tchaikovski S, Ignatov A, Busse M
Int J Mol Sci · 2026 Jun · PMID 42353189 · Full text
Despite the years that have passed since the pandemic, data regarding the effects of mild SARS-CoV-2 infection and vaccination during pregnancy remain limited. The current study investigated the expression of molecules t...
Despite the years that have passed since the pandemic, data regarding the effects of mild SARS-CoV-2 infection and vaccination during pregnancy remain limited. The current study investigated the expression of molecules that may be involved in the placental immune response using real-time PCR and Western blot analysis in a well-characterized cohort of 118 placentas collected between the 37th and 40th week of gestation. Secreted mediators were assessed in the supernatant of placental cell cultures, and histological examinations of the placental tissue were performed. Significant differences in the expression levels of , and were observed in control versus vaccinated and previously infected women, as determined by PCR. Acute SARS-CoV-2 infection decreased the expression of p38 MAPK and Bcl-2 compared to control patients. The secretion of G-CSF, IFN-α2, IL-2, and CXCL8 (IL-8) increased in women who were infected during pregnancy and/or vaccinated. However, histological analysis revealed only minor differences between the groups. In conclusion, SARS-CoV-2 infection or vaccination during pregnancy induced a measurable placental immune response that remained below the threshold of histologically detectable tissue injury.
Targeting the Warburg Effect in Anaplastic Thyroid Carcinoma: Metabolic Vulnerabilities and Therapeutic Opportunities.
Iova OM, Marin GE, Răzniceanu V … +4 more , Mocrei-Rebrean ȘM, Pintilie SR, Netea-Maier RT, Berindan-Neagoe I
Int J Mol Sci · 2026 Jun · PMID 42353188 · Full text
Anaplastic thyroid carcinoma (ATC) represents the most aggressive thyroid malignancy, characterized by rapid progression, therapeutic resistance, and poor prognosis. Conventional treatments remain largely ineffective, hi...
Anaplastic thyroid carcinoma (ATC) represents the most aggressive thyroid malignancy, characterized by rapid progression, therapeutic resistance, and poor prognosis. Conventional treatments remain largely ineffective, highlighting the need for novel therapies. Metabolic reprogramming, particularly the Warburg effect (WE), has emerged as a promising area of investigation. This review synthesizes current evidence on the role of WE in ATC and PDTC, integrating data from molecular profiling, preclinical studies, and emerging therapeutic strategies. Oncogenic alterations frequently observed in ATC, including mutations in BRAF, RAS, TP53, and activation of PI3K/AKT/mTOR and HIF-1α signaling, converge to promote glycolytic reprogramming. This metabolic shift supports tumor proliferation, immune evasion, and metastasis through increased glucose uptake, lactate production, and microenvironmental remodeling. Key metabolic nodes, including glucose transporters, hexokinase, and monocarboxylate transporters, are regarded as promising targets. Preclinical studies suggest that pharmacological inhibition of these pathways reduces tumor growth, enhances radiosensitivity, and improves response to targeted therapies. Future efforts should focus on combination therapies, biomarker-driven patient stratification, and the development of targeted delivery systems to overcome toxicity and resistance. A deeper understanding of tumor metabolic heterogeneity will be essential for translating these approaches into clinical practice.
Overexpression of Protects Differentiated QM7 Cells from HO-Induced Oxidative Damage.
Choi S, Shin S
Int J Mol Sci · 2026 Jun · PMID 42353187 · Full text
Oxidative stress, caused by excessive reactive oxygen species (ROS) accumulation, is a major factor in muscle cell damage and muscle atrophy-related disorders. Although () is involved in cellular stress and exhibits cyt...
Oxidative stress, caused by excessive reactive oxygen species (ROS) accumulation, is a major factor in muscle cell damage and muscle atrophy-related disorders. Although () is involved in cellular stress and exhibits cytoprotective effects in various cell types, its role in skeletal muscle cells during oxidative stress is unclear. This study investigated the effects of overexpression in quail muscle (QM7) cells exposed to HO-induced oxidative stress. expression was upregulated in non-transfected QM7 cells following HO treatment. Stable -overexpressing cells were differentiated for 4 days, and then assessed for cell viability, ROS accumulation, cell death, and myotube morphology following HO treatment. Compared with control cells, -overexpressing cells exhibited higher cell viability, reduced ROS accumulation, and decreased cell death. overexpression also attenuated the HO-induced reduction in MyHC protein expression. Antioxidant-related genes, including , , , and , were significantly upregulated in -overexpressing cells. Compared with the control cells, nuclear factor erythroid 2-related factor 2 protein levels were not increased in -overexpressing cells under oxidative stress conditions. These findings suggest that overexpression alleviates oxidative stress-induced cellular damage and may contribute to protective antioxidant responses in muscle cells.
Genome-Wide Identification and Expression Profiling of the Gene Family During Seed Germination in Sesame ( L.) Under Abiotic Stresses.
Deng Y, Liang J, Zeng P … +4 more , Wang Z, Yan X, Wei W, Sun J
Int J Mol Sci · 2026 Jun · PMID 42353186 · Full text
Auxin response factors (ARFs) are pivotal regulators mediating plant growth, development, and abiotic stress responses, especially during seed germination under stressful conditions. However, the ARF gene family has not...
Auxin response factors (ARFs) are pivotal regulators mediating plant growth, development, and abiotic stress responses, especially during seed germination under stressful conditions. However, the ARF gene family has not been thoroughly studied or characterized in sesame. The identification and characterization of ARF family members in the sesame genome were analyzed by bioinformatics methods, and the expression patterns of sesame genes were assessed by quantitative real-time PCR. In this study, a total of 23 genes were identified in the sesame genome, distributed unevenly across 12 chromosomes. Additionally, 15 segmental duplication events were detected. Phylogenetic analysis classified the genes into four subfamilies, with members within each subgroup sharing conserved structural features and motif compositions. Promoter analysis revealed multiple cis-acting elements associated with plant growth, phytohormone responses, and stress responses. Expression profiling demonstrated distinct tissue-specific expression patterns among the genes. Notably, and showed predominant expression in seeds 5 days after pollination, whereas exhibited broad expression in roots, stems, leaves, and seeds germinated for 24 h. QRT-PCR analysis identified eight genes exhibiting biphasic expression patterns during seed germination under abiotic stresses, characterized by initial downregulation and subsequent upregulation. Among them, showed significant induction under all three stress conditions, while was specifically upregulated under salt stress, suggesting their critical roles in stress response regulation. These findings provide a foundation for further investigation into Auxin-mediated responses to abiotic stress during seed germination in sesame.
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