Search Results (892)

Chemotherapy- and/or radiotherapy-induced oral mucositis (CRIOM) is a common complication in patients with head and neck cancer, driven largely by excessive proinflammatory cytokine signalling and treatment-associated bacterial dysbiosis. This narrative review synthesizes current mechanistic evidence and summarizes emerging therapeutic strategies targeting these pathways. Research indicates that elevated levels of IL-1β, IL-6, TNF, iNOS, and nitric oxide amplify tissue injury and ulceration, while disruption of oral and gut microbial communities, characterized by loss of beneficial commensals and enrichment of pathogenic taxa, further exacerbates mucosal inflammation. Anti-inflammatory agents, including pentoxifylline, atorvastatin, trans-caryophyllene, azilsartan, recombinant human IL-11, and low-level laser therapy have been shown in preclinical models to reduce cytokine levels and promote mucosal healing. Similarly, microbiome-targeted approaches, such as oral microbiota transplantation and multi-strain probiotic formulations, have demonstrated potential in restoring microbial balance and attenuating CRIOM severity, with current evidence including both preclinical and clinical studies. Overall, current findings highlight cytokine toxicity and dysbiosis as synergistic drivers of CRIOM and support anti-inflammatory and microbiome-modulating strategies as promising adjunctive approaches; however, further well-designed clinical studies are required to validate their efficacy and guide clinical translation. Full article

Emerging evidence indicates that non-coding RNAs (ncRNAs) play important regulatory roles in honeybee social behavior and development. However, the regulatory roles of ncRNAs in honeybees remain largely elusive. To systematically identify ncRNAs associated with queen-regulated ovary activation, we conducted whole-transcriptome sequencing on the heads of Apis mellifera workers from queenright and queenless colonies. Subsequent bioinformatics analyses were conducted to profile differentially expressed (DE) RNAs and construct potential regulatory networks. High-quality sequencing data provided a foundation for subsequent analyses. This transcriptome data yielded 3968 lncRNA transcripts, comprising 3146 known and 822 novel candidates, all of which exhibited typical structural features of lncRNAs. Comparative expression analyses revealed that 246 lncRNAs, 1439 mRNAs, and 10 miRNAs were differentially expressed. Comprehensive functional analyses indicated that the identified DElncRNAs potentially regulate sensory perception-related target mRNAs via cis-regulation, and coordinate metabolic and proteostatic reprogramming via trans-regulation to support the transition to reproductive activation in workers. Furthermore, a competing endogenous RNA network was constructed which integrated 74 DElncRNAs, 5 DEmiRNAs, and 36 DEmRNAs to predict their potential post-transcriptional interactions. Our findings highlight a comprehensive analysis of ncRNAs and mRNAs in worker heads, providing a foundation for functional validation of their roles in honeybee ovary development. Full article

Botanical insecticides containing a mixture of plant essential oils (EOs) are considered suitable for the management of houseflies (M. domestica). The adulticidal efficacies of single EOs and mixtures of EOs, including lemongrass (C. citratus), star anise (I. verum), nutmeg (M. fragrans), and their components (geranial, trans-anethole, and α-pinene), against houseflies were determined in comparison to 2% (w/v) α-cypermethrin as the positive control and distilled water as the negative control. The mixture of star anise EO (1%) + geranial (1%) was the most effective adulticide, superseding single EOs, other combinations of EOs, and its active component, α-cypermethrin, and distilled water. This mixture was highly synergistic and was found to be over 74% more toxic than all single EOs and almost 2.6 times more toxic than α-cypermethrin. Furthermore, the tested EOs did not cause mortality in guppies (P. reticulata) or earthworms (E. fetida), and caused a maximum of 48% mortality in honeybees (A. mellifera) at 24 h; by contrast, α-cypermethrin led to 100% mortality in honeybees within 0.5 h and in guppies and earthworms within 24 h, although it had low toxicity toward houseflies. Thus, a mixture of star anise EO + geranial is a promising source of EO-derived insecticides for housefly control that is also safe for important non-target species. Full article

The high incidence of thrombosis in lymphoma is largely due to chronic inflammation and endothelial dysfunction. To elucidate the mechanisms underlying thrombus formation and fibrinolysis, we investigated interactions between circulating endothelial cells and peripheral blood mononuclear cells (MNCs), along with inflammatory signaling pathways, in patients with follicular lymphoma (FL), Hodgkin lymphoma (HL), and diffuse large B-cell lymphoma (DLBCL), independent of the presence of thrombosis, compared to healthy controls by flow cytometry, immunoblotting, and fluorometric assays. We observed increased tissue factor (TF) expression on CD31+ endothelial cells in DLBCL and FL. In DLBCL, inducible nitric oxide synthase expression was elevated in MNCs, while reduced nitrite levels correlated with an advanced clinical stage in patients with thrombosis. In lymphoma, nuclear factor kappa B (NFκB) signaling was activated in MNCs, while signal transducer and activator of transcription 3 (STAT3) activation was increased in DLBCL with thrombosis. Trans-endothelial migration of MNC was enhanced in HL, FL and DLBCL with thrombosis and reduced by inflammatory cytokine tumor necrosis factor alpha (TNF-α) that promoted platelet aggregation like interleukin-6 (IL-6) in HL and FL. Fibrinolytic analyses showed reduced tissue type plasminogen activator in lymphoma, whereas increased urokinase-type plasminogen activator (uPA) was linked to poorer total survival in DLBCL with thrombosis, suggesting a compensatory role in early thrombus resolution. These findings indicate that chronic inflammation promotes endothelial activation, dysregulated fibrinolysis, and increased vascular permeability, contributing to heightened thrombotic risk. This study provides mechanistic insight into lymphoma-associated thrombosis and identifies TF, uPA, and the inflammatory signaling pathways as potential biomarkers and therapeutic targets. Full article

Apple (Malus domestica Borkh.) is the most widely cultivated deciduous fruit tree with the largest industrial scale and the highest economic value in China. Fruit surface glossiness and plant stress tolerance are two core traits that determine the economic benefits and sustainable development of the apple industry. The plant epidermal cuticle is not only the core material basis for determining fruit glossiness but also the first barrier for plants to resist abiotic and biotic stresses. Glycosylphosphatidylinositol-anchored lipid transfer proteins (LTPGs) are the core functional factors mediating trans-cell wall lipid transport in plants. At present, the functions and action mechanisms of LTPG family members that simultaneously regulate fruit appearance quality and stress tolerance in apple remain largely unclear. In this study, we took the MdLTPG17 gene as the research object, clarified its biological function of stress resistance under drought stress, and dissected the molecular mechanism by which it mediates fruit glossiness formation via regulating fruit cuticle thickening. The results of this study provide important genetic resources and a theoretical basis for molecular breeding of stress resistance and targeted improvement of fruit appearance quality in apple. Full article

The anticancer ruthenium complex indazolium trans-[tetrachlorobis(1H-indazole) ruthenate (III)—also known as KP1019—inhibits cancer cell proliferation in vitro, causes tumor regression in animal models, and showed no dose-limiting toxicity in a phase I clinical trial. Previous studies found that KP1019 damages DNA in both cancer cells and the budding yeast Saccharomyces cerevisiae. To identify other potential targets of KP1019 along with pathways that modulate the drug’s cellular effects, we screened the yeast gene deletion strain library by quantitative high-throughput cell array phenotyping (Q-HTCP). Fitness differences, as judged by growth curve analysis, identified genes for which loss of function (gene deletion) interacts with (enhances or suppresses) KP1019 effects. Drug-enhancing deletions were enriched for DNA repair functions, consistent with DNA damage being a primary target of KP1019 in yeast. pH homeostasis also modified the effects of KP1019. Drug-suppressing deletions prominently involved ribosomal proteins. A mechanistic link between ribosomal protein function and KP1019 toxicity was supported by dose-dependent accumulation of Rpl7a-GFP in the nucleolus, which is a hallmark of ribosomal biogenesis stress. Furthermore, KP1019 acted synergistically with the TOR pathway inhibitor everolimus to inhibit cell proliferation. The resulting model, wherein KP1019 perturbs ribosome assembly, can inform the design of future combination therapies. Full article

Familial thoracic aortic aneurysm and dissection (FTAAD), caused by the pathogenic Myh11 K1256del variant, is characterized by impaired aortic contractility; however, how reduced contractility predisposes the aorta to dissection remains incompletely understood. In this study, we performed a data-driven trans-omic upstream analysis using Genome Enhancer to identify key regulatory mechanisms in aortas from Myh11 K1256del mice under baseline conditions, without exposure to exogenous pathological stimuli. Transcriptome analysis revealed enrichment of genes related to smooth muscle contraction and regulation of myosin light chain phosphatase activity. Upstream computational analysis of regulatory regions identified nuclear factor of activated T cells 1 and lymphoid enhancer-binding factor 1 as major transcription factors, and further highlighted Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) as a predicted central regulator of the dysregulated transcriptional network. Druggability analysis suggested ROCK1 and the JunB proto-oncogene AP-1 transcription factor subunit as potential therapeutic targets. Furthermore, it predicted 51 candidate therapeutants, including atorvastatin, GSK-269962A, and atovaquone. These findings indicate that even in the absence of overt pathological stimulation, aortic tissue carrying the Myh11 K1256del variant exhibits a transcriptional program centered on ROCK signaling, which may prime the aorta for maladaptive responses to additional stress and may enhance susceptibility to dissection. This computational analysis requires experimental validation, but may provide a hypothesis-generating framework for development of preventive pharmacological interventions against FTAAD. Full article

Resveratrol is a promising polyphenolic bioactive compound found in peanuts. However, the distribution of cis- and trans-resveratrol and their glycosides varies significantly among cultivars, and their correlations with other quality traits remain unclear. In this study, Ultra-Performance Liquid Chromatography (UPLC) combined with high-throughput spectral analysis was employed to systematically evaluate 42 main cultivated peanut varieties from seven series across China’s three major production regions. The results indicated that trans-piceid (trans-resveratrol glycoside) was the predominant component, accounting for over 85% of the total content. Significant variation was observed in the total content of resveratrol and its glycosides among cultivars (4.61–88.79 mg/kg), with the Weihua series (represented by Weihua 23) exhibiting the strongest resveratrol enrichment ability. Multidimensional correlation analysis systematically revealed, for the first time, distinct association patterns: trans-piceid was positively correlated with sucrose, cis-resveratrol was positively correlated with fatty acids such as oleic acid, and trans-resveratrol showed a specific association with linoleic acid. Based on these findings, seven specialized high-resveratrol cultivars suitable for processing, including Weihua 23 and Kainong 301, were identified. Furthermore, a specific correlation system between “resveratrol and key quality indicators” was established. This study provides important theoretical support for the targeted breeding of novel functional peanut varieties that combine a high resveratrol content with traits such as high oleic acid or sugar content, thereby promoting the high-value industrial utilization of high-quality peanuts. Full article

(1) Background: The search for new polymodal antioxidants to correct oxidative stress of various origins and its consequences remains one of the most pressing and rapidly developing areas of biomedical research. (2) Methods: Hydrogen peroxide and hydroxyl radical detection, induced luminescence assay, ELISA for 8-oxoguanine detection, animal survival, blood cell count, micronucleus test, and PCR were used. (3) Results: 2R,3R-trans-dihydroquercetin (DHQ) was shown to reduce the amount of hydrogen peroxide and hydroxyl radicals formed during water radiolysis, leading to reduced damage to biomolecules. DHQ is a radioprotector, most effective at a dose of 300 mg/kg administered 15 min before radiation exposure. The dose reduction factor is 1.22. DHQ administration reduces the severity of radiation-induced leukopenia and thrombopenia by protecting red bone marrow cells. The mechanism of DHQ’s radioprotective action is fundamentally different from that of classical stress response inducers and is based on the normalization of the target cell transcriptional profile, rather than its hyperstimulation. (4) Conclusions: DHQ’s ability to restore the expression of antioxidant defense, DNA repair, and apoptotic genes to physiological levels under radiation exposure allows it to be considered a promising pharmacological agent for the correction of radiation-induced damage to normal tissues. Full article

Aquaporins (AQPs) are increasingly recognized as key regulators of tumor progression, influencing key hallmarks of cancer progression and cellular homeostasis. Their frequent overexpression in malignancies highlights their potential as therapeutic targets, yet the development of selective synthetic inhibitors remains challenging due to structural conservation and off-target toxicity. Natural compounds have recently emerged as promising modulators of AQP expression and function, offering greater molecular diversity and generally favorable safety profiles. This review synthesizes current evidence on phytochemicals, including bacopaside II, curcumin, resveratrol, quercetin, EGCG, all-trans retinoic acid, chrysin, and rottlerin, that interact with AQP isoforms relevant to cancer biology. These agents regulate AQPs through transcriptional control, redox modulation, signaling-pathway interference, or direct pore blockade, thereby attenuating oncogenic processes such as migration, angiogenesis, inflammation, and metabolic adaptation. Several compounds, notably bacopaside II and rottlerin, display isoform-selective inhibitory properties that directly impair AQP1- and AQP3-mediated permeability. Collectively, available evidence positions natural AQP modulators as promising lead compounds providing scaffolds for further drug development in oncology. Continued structural, mechanistic, and preclinical research is required to optimize isoform specificity and therapeutic efficacy, paving the way for their integration into future anticancer strategies. Full article

Steroid-resistant nephrotic syndrome (SRNS) in childhood frequently reflects monogenic podocytopathies in which immunosuppression is ineffective. Biallelic variants in MYO1E, encoding the class I myosin Myo1E, cause a distinctive form of focal segmental glomerulosclerosis (FSGS) often accompanied by “Alport-like” multilamination of the glomerular basement membrane (GBM). Early recognition has therapeutic and prognostic implications. A previously healthy 4-year-old boy presented with generalized edema and nephrotic-range proteinuria. Glucocorticoids induced no remission; sequential calcineurin inhibition (cyclosporine, then tacrolimus) and a single dose of ofatumumab yielded only transient, partial reductions in proteinuria. A first biopsy elsewhere showed FSGS with nonspecific IgM/C3 trapping; electron microscopy (EM) was not performed. At age 10, repeat biopsy with EM revealed ~30% segmental foot-process effacement, focal GBM thickening (to 1740 nm), irregular lamina densa multilamination, and lamellar duplications without immune-complex deposits—features highly suggestive of hereditary GBM disease. Targeted sequencing identified compound-heterozygous MYO1E variants segregating in trans: a canonical splice-donor change (c.2785+1G>A) and a frameshift (c.3094_3097del; p.Thr1032Profs*73). Each parent was an unaffected heterozygous carrier; the sibling was negative. Supportive therapy with ramipril was continued. At last follow-up (January 2025), renal function was normal (serum creatinine 0.5 mg/dL; creatinine clearance 122 mL/min) with stable sub-nephrotic proteinuria (0.52 g/day; 16 mg/m² per hour) and normotension. This case broadens clinicopathologic recognition of MYO1E-associated nephropathy and highlights the teaching point that Alport-like GBM changes are not pathognomonic for type IV collagen disorders but may signal defects in podocyte cytoskeletal anchoring. Full article

Stem cells, also known as progenitor cells, can differentiate into specialized cells for specific tissues. Genetic mutations and epigenetic changes may cause normal stem cells to become cancer-initiating cells. Research indicates that cells acquiring a mutation for myeloproliferative neoplasm (MPN) are likely to be long-term hematopoietic stem cells (LT-HSCs) at the top of the hematopoietic hierarchy. Natural killer (NK) cells play a crucial role in combating cancer by targeting and eliminating cancer stem cells (CSCs) while promoting their maturation. NK cells do this through direct lysis of CSCs or by releasing cytokines like interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), which inhibit tumor growth and metastasis by driving differentiation of CSCs. Interleukin-2 (IL-2) enhances the activity of CD4+ and CD8+ T cells and boosts NK cell cytotoxicity. This study highlights a case of MPN with a more clinically aggressive Type 1 calreticulin (CALR) mutation, where a combination of low-dose IL-2 immunotherapy and targeted therapy with oral tretinoin (all-trans retinoic acid, ATRA, a vitamin A derivative) improved immune cells, particularly NK-cell-mediated destruction of malignant cells, reduced CALR mutation levels to undetectable, and alleviated disease symptoms. The aim is to offer a new, low-toxicity personalized treatment strategy that eradicates cancer-initiating stem cells, reduces side effects, and provides an option for patients with limited conventional therapy alternatives. Full article

An anti-inflammatory dietary pattern represents a key component of non-pharmacological management in obesity and metabolic syndrome (MetS), as it targets chronic low-grade inflammation, adipose tissue dysfunction, insulin resistance, and disturbances of the gut–metabolic axis. In the present work, we outline a framework for an “omics-based” approach that integrates data on gut microbiota composition and function (metagenomics), adipokine profiles, nutrigenomics, epigenetics, and related transcriptomic and metabolomic layers in order to enable more precise characterization of the metabolic phenotype and to support precision nutrition strategies. The proposed dietary model emphasizes the quality rather than merely the quantity of macronutrients, with particular focus on lipid profile optimization. Specifically, total fat intake is recommended to remain below 30% of total energy through the reduction in saturated fatty acids (SFA), trans fats, and excessive omega-6 fatty acids, alongside increased consumption of omega-3 PUFA (EPA/DHA) and plant-based sources of α-linolenic acid (ALA). Concurrently, greater intake of lean protein sources and low-glycemic-index carbohydrates rich in dietary fibre—particularly fermentable fractions—is recommended. The model also highlights the importance of polyphenols with antioxidant and immunomodulatory properties. To enhance feasibility and long-term adherence, recommendations are structured as flexible food substitutions rather than rigid prescriptions. Further well-designed interventional studies are required to confirm the impact of a multi-omics-based anti-inflammatory diet on both molecular and clinical endpoints. Full article

Although Telenomus remus is an important parasitoid of Spodoptera frugiperda, the chemical basis for its host selection behavior remains unclear. To elucidate the chemical basis of this behavior, this study combined behavioral ecology and chemical ecology methods to systematically investigate the host location and recognition behaviors of this wasp, as well as the semiochemicals that regulate these behaviors. In Y-tube olfactometer assays, T. remus exhibited a significantly stronger olfactory preference for eggs of S. frugiperda over those of S. litura (p < 0.05) or the non-host Ostrinia furnacalis. A total of 759 metabolites belonging to 11 categories were identified via metabolomics analysis, and principal component analysis (PCA) clearly distinguished between host eggs and non-host eggs. Analysis of differential metabolites revealed that the significantly upregulated metabolites in host eggs mainly included aldehydes, ketones and esters, followed by hydrocarbons, alcohols and amines. Subsequently, we screened and verified the effects of the significantly upregulated metabolites in host eggs compared with non-host eggs on the host-selection behavior of T. remus, including indole, 2-hexanol, and trans-1,2-dimethylcyclohexane, as well as 2-heptadecanone and n-nonadecane—two alkane compounds which are specifically upregulated on the surface of S. frugiperda eggs. Behavioral validation demonstrated that 2-hexanol exerted a significant repellent effect on T. remus, whereas trans-1,2-dimethylcyclohexane exhibited a significant attractive effect on the parasitoid wasp. Among the metabolites specifically upregulated in S. frugiperda eggs, 2-heptadecanone exhibited significant attractive activity at concentrations ranging from 0.1 to 1.0 mg/mL. This study is the first to report that the cycloalkane compound trans-1,2-dimethylcyclohexane acts as a potential broad-spectrum chemical marker for T. remus to recognize the eggs of host species belonging to the family Noctuidae, while 2-heptadecanone may further enhance its preference for the optimal host S. frugiperda. These findings provide novel candidate molecular targets for the development of behavioral regulators targeting egg parasitoids against S. frugiperda. Full article

Pollen development is a complex process that is highly sensitive to environmental stresses. Abscisic acid (ABA), a key hormone mediating plant growth and stress responses, has been implicated in the regulation of sexual reproduction, especially pollen development, yet its precise regulatory role remains unclear. This study investigated the effects of exogenous ABA on Arabidopsis thaliana pollen development and function through integrated phenotypic, cytological, and transcriptomic approaches. ABA treatment specifically impaired pollen function by reducing germination rates and inhibiting pollen tube elongation, which resulted in shortened siliques and decreased seed set, without affecting pollen morphology or viability. Transcriptome analysis of mature anthers revealed a transient and time-dependent transcriptional response, with the number of differentially expressed genes (DEGs) peaking at 8 h post-ABA treatment and markedly declining by 22 h. These DEGs were enriched in stress-response pathways (e.g., salt, cold, and dehydration), hormone signaling, and carbohydrate metabolism. Moreover, we identified 25 differentially expressed transcription factors and 16 pollen development and function-related genes, highlighting their key roles in ABA-mediated regulation. In parallel, 146 differentially expressed lncRNAs (DELs) were identified, which formed 144 cis-regulatory pairs with genes involved in ABA response and pollen tube growth, with their predicted targets enriched in pathways such as hormone and MAPK signaling, carbohydrate metabolism and stress response. Trans-regulatory analysis further revealed that these DELs co-expressed with DEGs in modules enriched for stress response, pollen development, and tube growth pathways. Notably, key pollen function genes showed strong co-expression with DELs, indicating that lncRNAs participate in ABA-induced transcriptional reprogramming that shifts metabolic resources from growth to defense, thereby suppressing pollen germination and tube elongation. Together, these findings elucidate a coordinated regulatory network involving mRNAs, lncRNAs and transcription factors roles in modulating ABA responses during pollen/anther development. Full article