Piperine had synergistic effects with other natural products in treating lung cancer. The synergistic effects of piperine combined with luteolin on anti-non-small cell lung cancer activity and their mechanism of action are studied using network pharmacology and molecular docking. Cell viability, wound-healing, colony-formation, cell-apoptosis, and cell-cycle tests on A549 cells were used to detect the in vitro synergistic effects. Tumour growth and hematoxylin and eosin (HE) staining were used to verify the synergistic effects in Lewis lung carcinoma (LLC) tumour-bearing mice. Their combination indexes ranged from 0.3 to 0.8 across different concentrations, and the combination of 175.3 µmol L-1 piperine and 87.32 µmol L-1 luteolin showed synergistic inhibition of A549 cell viability. Moreover, the combination induced a higher apoptosis rate (75.60 %) than luteolin (24.56 %) or piperine (17.53 %). It arrested more cells in the G0/G1 phase than luteolin or piperine did. The combination achieved a tumour inhibition rate of 75.28 %, with lower tumour density and more obvious apoptosis. Network pharmacology identified AKT1, EGFR, SRC, and MMP9 as core targets regulating the PI3K/AKT pathway. Multi-software molecular docking confirmed binding of both compounds to these targets, with MMP9 as the common primary target. In conclusion, piperine and luteolin acted synergistically against non-small cell lung cancer.
Chimeric RNA molecules-formed from nucleotide sequences of multiple genes-can arise through chromosomal rearrangements, transcriptional read-through events, or trans-splicing between distinct transcripts. These chimeric RNAs have been shown to play functional roles in both disease states and normal physiological processes, underscoring their biological relevance. Despite this, there are currently a limited number of tools available that aim to quantify chimeric RNA expression. Here, we introduce a metric called the Relative Index of Chimeric Expression (RICE), which assesses the expression of chimeric transcripts relative to their corresponding wild-type parental transcript, and we describe an easy-to-use bioinformatic tool called FusionBlaster for calculating RICE values from RNA sequencing data. After following this guide, users can apply the FusionBlaster pipeline to perform differential RICE analysis on their own RNA sequencing data by applying the appropriate statistical methods.
Grapevine trunk diseases (GTDs) are major constraints to vineyard longevity and productivity worldwide, and pruning wounds are recognized as key infection courts for their causal fungi. However, the dynamics of natural infection after pruning under field conditions remain insufficiently defined. This study evaluated natural infection of grapevine pruning wounds by GTD pathogens in three commercial vineyards in Spain and France over two growing seasons. At each site, vines were pruned in the dormant season either early (November-December) or late (February), and wounds were sampled weekly for 8 weeks. Recovery-based disease severity was quantified using the percentage of wood pieces yielding GTD pathogens after isolation. A total of 11,230 fungal isolates were recovered, of which Botryosphaeriaceae accounted for 54.4%, followed by Diaporthe spp. (34.2%) and Cytospora spp. (11.4%). The dominant species identified was D. seriata. Recovery-based disease severity varied significantly over time in all site-disease combinations, and temporal trajectories differed with pruning time and season. Late pruning resulted in significantly greater recovery-based disease severity than early pruning in 6 of 9 site-disease combinations. The strongest effect was observed in Pyrénées-Atlantiques for Botryosphaeria dieback, where late pruning increased severity by 18.8%; Cytospora canker at the same site increased by 7.2%. Climatic analyses revealed site-specific associations, with relative humidity showing the strongest association with recovery-based disease severity in Pyrénées-Atlantiques and rainfall in Pyrénées-Orientales. These results indicate that GTD pathogens can be recovered from pruning wounds for at least 8 weeks after pruning and that the effect of pruning time is strongly site- and pathogen-dependent.
Laggera alata is a traditional medicinal herb used for inflammatory and infectious diseases, but its mechanisms against endotoxin‑induced systemic inflammation remain unclear. The present study investigated the protective effects of total phenolics from Laggera alata (TPLA) on lipopolysaccharide (LPS)‑induced inflammatory injury and explored the involvement of PTEN‑induced putative kinase 1 (PINK1)/Parkin‑associated mitophagy and macrophage polarization. LPS‑induced inflammatory models were established in RAW264.7 macrophages and C57BL/6 mice. Cell viability, apoptosis, mitochondrial membrane potential (MMP), cytokine production, macrophage polarization and mitophagy‑related protein expression were evaluated. Mdivi‑1 was used to assess the involvement of mitophagy‑related signaling. In vivo, core body temperature, serum cytokines, and lung and liver histopathology were examined. TPLA improved the viability of LPS‑stimulated macrophages, reduced apoptosis, restored MMP, decreased p62 expression, and increased PINK1, Parkin and the LC3‑II/LC3‑I ratio. TPLA also suppressed M1‑associated indicators, including inducible nitric oxide synthase, IL‑12 and CD80/CD86, while enhancing M2‑associated indicators, including arginase 1, IL‑10 and CD206/CD163. In addition, TPLA reduced IL‑1β, IL‑6 and TNF‑α release. Mdivi‑1 partially reversed the effects of high‑dose TPLA on mitophagy‑related protein expression and macrophage polarization. In LPS‑challenged mice, TPLA alleviated hypothermia, reduced systemic cytokine levels, and attenuated hepatic and pulmonary injury. These findings suggest that TPLA protects against LPS‑induced systemic inflammation and hepatic‑pulmonary injury by modulating PINK1/Parkin‑associated mitophagy‑related signaling and macrophage polarization.
Phospholipid flippases (P4-ATPases) are central to the establishment of membrane lipid asymmetry, a property underlying membrane trafficking and polarized growth in eukaryotic cells. However, the specific contribution of individual flippases to hyphal morphogenesis in filamentous fungi remains poorly defined. Here, we characterize DNF-4, a putative P4-ATPase in Neurospora crassa with high sequence identity to the essential flippase Neo1 of Saccharomyces cerevisiae. Using endogenous tagging and live-cell imaging, we show that DNF-4 localizes to highly dynamic punctate structures associated with endoplasmic reticulum- and Golgi-related compartments, supported by quantitative co-localization analyses with the ER marker CSE-7-mChFP and the Golgi-associated Rab GTPase YPT-1-mChFP. FRAP experiments revealed partial fluorescence recovery, indicating dynamic exchange of DNF-4-associated compartments. These structures undergo bidirectional movement along the hypha, and their motility is strongly dependent on an intact microtubule cytoskeleton. Deletion of dnf-4 results in pronounced defects in hyphal growth and development, including reduced hyphal elongation, decreased biomass accumulation, smaller conidia, and a severe reduction in conidiation. These defects are accompanied by increased branching frequency, abnormal hyphal morphology, and altered Spitzenkörper positioning and dynamics, indicating impaired coordination of polarized growth. Our results demonstrate that DNF-4 contributes to membrane trafficking processes required for the maintenance of hyphal polarity and normal developmental progression in N. crassa. These findings provide new evidence that P4-ATPases play an important role in the spatial organization of membrane trafficking pathways underlying fungal morphogenesis.
The taxonomy of the crickets of the genus Rhicnogryllus Chopard, 1925 is reviewed, with a focus on species from the Philippines. Previously, only two species were known from the Philippines: the type species Rhicnogryllus fascipes Chopard, 1925 and Rhicnogryllus? paetensis Tan, Yap & Baroga-Barbecho, 2020. Based on new material collected from Mindanao and Visayas regions, we describe three new species from Mindanao: Rhicnogryllus olivaceus Tan & Alo, sp. nov., Rhicnogryllus pictus Tan & Daguplo, sp. nov. and Rhicnogryllus vittatus Tan & Daguplo, sp. nov. We also record a new locality for Rhicnogryllus bipunctatus Ingrisch, 1987 in Negros Island, having previously been known only from Borneo. Consequently, six species presently exist in the Philippines.
Butterflies exhibit seasonal dynamics in diversity and population in response to bioclimatic factors. However, their seasonal diversity remains poorly understood in urban landscapes. Therefore, we examined how butterfly diversity varies across seasons in the urban forests of Pokhara City, located in Nepal's subtropical region. We selected three urban forests-Banpale, Bhadrakali, and Shanti Ban Batika-to sample butterflies. We employed the Pollard Walk Survey method to collect data across all four seasons and analyzed various diversity indices, community composition, and indicator species. We also applied generalized linear mixed models (GLMMs) to assess the effects of precipitation and temperature on species richness and abundance. In total, 197 butterfly species, comprising 3344 individuals from six families, were recorded. The diversity and community composition differed significantly across seasons, with richness, Shannon, and Simpson diversities peaking during the monsoon and abundance peaking in the pre-monsoon. Winter recorded the lowest species richness, diversity, and abundance. Species like Pieris canidia, Eurema hecabe, Ypthima baldus, and Junonia iphita contributed most to the differences across seasons. Anthene emolus was associated with the pre-monsoon season, Lethe kansa and Athyma ranga were confined to winter, and several other species served as seasonal indicators. The family Nymphalidae dominated the butterfly community, with different families exhibiting notable seasonal variation in richness and abundance. Additionally, GLMMs found that precipitation alone has a significant positive effect on species richness, while the combined effect of precipitation and temperature negatively impacts both richness and abundance. This study highlights the importance of seasonality in shaping butterfly diversity and community composition in urban forests, offering essential insights for their conservation in urban landscapes.
The impact of climate change induced habitat fragmentation on plant species and populations has been studied in numerous systems, but far less is known about how these processes shaped the population structure and demographic history of fungal symbionts. Here, we investigate the population structure and demographic history of ectomycorrhizal fungus Rhizopogon salebrosus, a symbiont of Pinus species, across the Madrean Sky Islands Archipelago (MSIA) of southern Arizona and northern Sonora. Rhizopogon salebrosus produces truffle-like sporocarps and depends on small mammals for spore dispersal. Using genome-wide data from sporocarps and bioassay-derived root tips sampled across seven mountain ranges, we assessed patterns of genetic structure, divergence, and connectivity across this fragmented landscape. We identified strong geographic structuring consistent with island-like population differentiation, accompanied by rare signals of admixture. Genetic divergence among populations increased with geographic distance, and demographic inference supports long-term isolation associated with historical habitat fragmentation, with limited recent gene flow among islands. Together, these results highlight the lasting influence of past climate-driven landscape dynamics on fungal population structure and emphasize the role of geographic isolation in shaping the evolutionary history of symbiotic fungi in montane systems.
Fea's muntjac (Muntiacus feae) is a poorly known cervid restricted to forested regions along the Thai-Myanmar border, and its ex-situ population in Thailand has declined to critically low numbers. Limited founder size and incomplete pedigree records raise concerns about inbreeding and the loss of genetic diversity, underscoring the need for genome-based assessments to support effective conservation management. In this study, restriction site-associated DNA sequencing (RADseq) was applied to investigate genetic diversity, relatedness, and population structure among the remaining ex-situ Fea's muntjac individuals in Thailand, including one putative hybrid. Genome-wide single-nucleotide polymorphisms (SNPs) were generated and analyzed using phylogenetic reconstruction, Bayesian clustering, multidimensional scaling (MDS), and identity-by-descent (IBD) approaches. Phylogenetic, ADMIXTURE, and MDS analyses consistently revealed clear genetic structuring corresponding to institution of origin, whereas the putative hybrid formed a distinct genetic lineage. IBD analyses identified both first- and second-degree relationships among individuals, largely corroborating available pedigree records, while also revealing previously undocumented relatedness, emphasizing the limitations of pedigree-based management in small ex-situ populations. Notably, one individual exhibited no detectable genetic relatedness to the others and consistently formed an independent lineage across analyses, indicating the presence of unique genetic variation with high conservation value. Collectively, these results demonstrate the utility of RADseq-derived genomic data for resolving kinship, validating pedigrees, and detecting hybridization in extremely small ex-situ populations. This study represents the first comprehensive genome-wide genetic assessment of ex-situ Fea's muntjac in Thailand and establishes an essential genomic baseline to inform breeding decisions and support long-term conservation planning for this highly threatened cervid.
Dizziness associated with central neurological disorders-broadly defined as dizziness or vertigo attributable to central nervous system pathology affecting central vestibular processing-is a clinically challenging and heterogeneous condition with limited treatment options. Ginkgo biloba extract-through its microcirculatory, neuroprotective, and anti-inflammatory mechanisms-represents a biologically plausible intervention. However, its efficacy in this setting has not been comprehensively established. We evaluated the efficacy and safety of Ginkgo biloba extract through a systematic review and meta-analysis of randomized controlled trials (RCTs). Nine international and Korean databases were searched from January 1974 through November 2025. Studies were eligible if they were RCTs enrolling adults aged 18 years or older with cerebrovascular disease, neurodegenerative disease, or central vestibular dysfunction who had dizziness, vertigo, or balance-related symptoms or relevant outcome assessments. Cochrane RoB 2.0 tool and certainty of evidence was rated using the Assessment, Development and Evaluations (GRADE) approach. Prespecified subgroup analyses by underlying etiology and intervention type, together with leave-one-out sensitivity analyses, were performed to explore heterogeneity. Nine RCTs (N = 2,394) were included; participants were predominantly drawn from dementia populations (71.6%), with smaller contributions from cerebral arteriosclerosis (23.0%) and vertebrobasilar or posterior circulation disorders (5.4%). Ginkgo biloba significantly reduced dizziness/vertigo severity on the 11-point box scale (MD - 0.76, 95% CI - 1.35 to -0.18; p = 0.01) and VAS (SMD - 0.38, 95% CI - 0.58 to -0.19; p = 0.0001). Moderate-certainty evidence suggested improvements in functional outcomes and quality of life, including the Alzheimer's Disease Activities of Daily Living International Scale (MD = -0.17, 95% CI: -0.22 to -0.13) and the Dementia Quality of Life - Proxy (MD = 2.00, 95% CI: 0.85 to 3.15). The intervention was generally well tolerated, with significantly lower risks of angina pectoris (OR 0.51, 95% CI 0.31 to 0.85) and tinnitus (OR 0.37, 95% CI 0.22 to 0.63) and no significant increase in other adverse events. Ginkgo biloba extract may reduce dizziness severity and improve daily functioning in patients with central neurological disorders accompanied by dizziness or vertigo, with a favorable safety profile. However, given the small number of eligible trials, substantial clinical and statistical heterogeneity, and the predominance of dementia-derived data, these findings should be interpreted with caution. Well-designed RCTs in clearly defined central vestibular populations, ideally confirmed by neuroimaging or vestibular testing, are needed to confirm these results. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251229692, PROSPERO: CRD420251229692.
The shapes and material properties of cotton (Gossypium spp.) seed coat trichoblasts form the basis of a multibillion-dollar natural fiber industry. As such, these highly specialized cells are low-hanging fruit for intentional trait engineering. However, broad success will require more mechanistic knowledge of their systems-level cellular controls. This time-series study integrates daily measurements of purified fiber transcriptomes and proteomes with multiscale fiber phenotyping datasets that span the same developmental interval. Abundance profiles of the subcellular proteomes are the foundation of the analyses. This resource article provides direct information about which homoeologs operate and offers informative depictions of how compartmentalized cellular systems change during developmental transitions. Prediction accuracy was partially validated by analyzing protein expression group 11, which contained multiple known secondary cell wall (CW) cellulose synthases together with dozens of unknown proteins, and displayed an averaged expression profile that strongly correlated with a sharp state transition in cellulose microfibril alignment and increased cellulose content. The dataset as a whole can serve as a hypothesis-generating tool to guide future experiments related to CW glycome remodeling, morphogenesis, reversible tissue formation, and growth rate control. Integration of mRNA and protein abundance revealed widespread evidence of post-transcriptional control. In addition, there were hundreds of transcriptionally controlled genes with different time points of transition. This latter gene set can be used to more reliably analyze transcriptional control networks and to generate collections of gene expression drivers for cotton fiber research. The protein and transcript abundance profiles are organized into user-friendly tables and a web interface that can be searched using any plant ortholog of interest based on developmental time, abundance, annotations, or phenotypic association.
Phytophthora cactorum is a versatile plant pathogen with a wide host spectrum causing substantial yield losses in various forest and agricultural systems, the most affected being apple, ginseng, and strawberry. This review synthesizes the current knowledge on the biology and epidemiology of P. cactorum and presents an extensive overview of the available management strategies, including preventive measures, cultural practices, detection tools, chemical and biological control. Beyond compiling existing data, this review also highlights emerging conceptual shifts in our understanding of P. cactorum, particularly the transition from viewing it as a single broadly infective generalist to recognizing the presence of partially specialized lineages with host- and organ-specific adaptations. We further link advances in molecular biology, including effector repertoire characterization, with practical implications for disease management in agricultural and nursery systems. By integrating insights across disciplines, we aim to establish a strong foundation for deciphering the mechanisms underlying pathogenicity and to support the development of more effective and sustainable management strategies.
Tomato spotted wilt virus (TSWV) and late leaf spot (LLS) are among the major constraints to peanut production. Cultivated peanut has narrow genetic bases and lacks strong sources of resistance. Wild species, on the other hand, harbor diverse and strong resistances to multiple pathogens. In this study, we evaluated advanced breeding lines carrying introgressions from multiple wild Arachis species (A. stenosperma, A. batizocoi, A. valida, and A. cardenasii) across three contrasting field environments and experimental designs in Georgia, USA using complementary incidence- and severity-based phenotyping. Genotype effects were highly significant for both diseases. Several wild-derived lines -particularly those from A. stenosperma ancestry- showed strong and stable TSWV resistance across environments. Interestingly, some lines lacking detectable wild segments also showed high resistance to TSWV, suggesting cryptic or undetected introgressions. LLS resistance was primarily associated with the characteristic A. cardenasii segments on A02 and A03, and lines stacking these introgressions consistently outperformed both cultivated parents and Georgia-06G, the most popular cultivar in the USA. Correlations between TSWV and LLS responses were weak, confirming genetic independence and emphasizing the need to screen both traits. A small subset of lines combined resistance to both diseases, and many also retained resistance loci to root-knot nematode (RKN), expanding their value as multi-trait donors. These findings demonstrate the power of wild introgression breeding for enhancing disease resistance and provide a foundation for deploying stacked alleles through marker-assisted and multi-environment selection.
Cryphodera lithocarpussp. nov., collected from roots and rhizospheric soil of Lithocarpus uvariifolius in Guangdong province, China. The new species was characterized by having the female nearly spherical, labial region offset, stylet length 38.9 (37.4-40.3) μm, vulval lips protruding, area between vulva and anus concave, vulva-anus distance 52.3 (31.1-62.7) μm; second stage juvenile with 2 lip annules, stylet length 30.7 (28.4-32.4) μm, lateral field areolated with 3 incisures, tail 60.5 (49.6-68.0) μm long, with narrow rounded terminus, hyaline region 31.7 (24.0-39.2) μm long and hyaline region approximately equal to stylet. The new species was close to C. guangdongensis, C. sinensis and C. japonicum. The phylogenetic trees based on the ITS-rRNA, 28S-rRNA D2-D3 region and the partial COI gene sequences showed that the new species clustered with Cryphodera species but with separate species status. A key to the species of the genus Cryphodera is also provided in this study.
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The global rise in cancer occurrence, together with the spread of multidrug resistance, highlights the critical demand for innovative treatment strategies. Nano-delivery approaches have emerged as promising solutions that enhance bioavailability and facilitate targeted drug delivery. This study evaluated the anticancer efficacy of Nepeta glomerulosa extract and its silver-loaded nanoemulsion (Ag-N.g.Ext. NEs) against human lung (A549) and gastric (AGS) cells.MethodsNepeta glomerulosa was collected from the Binaloud Mountains, and a hydroalcoholic extract was obtained by maceration. Ag-N.g.Ext. NEs were prepared via high-energy emulsification and characterized by FTIR, SEM, DLS, ZP, and XRD. Cytotoxicity and apoptosis were assessed using MTT assay, DAPI staining, and Real-time PCR of TP53 and BAX genes.ResultsAg-N.g.Ext. NEs were spherical (confirmed by SEM) with a PSA (DLS) size of 269.5 nm, a negative zeta potential of -23.1 mV, and a non-crystalline structure. The IC₅₀ of the extract for A549 and AGS was 500 and 250 µg/mL, while the Ag-N.g.Ext. NEs showed enhanced potency with an IC₅₀ of 125 µg/mL. Apoptosis and gene expression were significantly higher in Ag-N.g.Ext. NEs-treated cells (p ≤ 0.05). TP53 expression increased 3.317-fold in A549 and 8.027-fold in AGS; BAX increased 3.877-fold in A549 and 2.351-fold in AGS.ConclusionsNanoemulsion-based delivery significantly enhances the anticancer efficacy of the extract by promoting apoptosis, offering a promising strategy for plant-derived therapeutics.
Plant systemic acquired resistance (SAR) requires generation and movement of mobile signals from local leaves in which plant disease resistance has been activated (effector-triggered immunity, ETI), to distal, uninfected regions, where they prime host defences. Although salicylic acid (SA) and N-hydroxypipecolic acid (NHP) are widely recognised as key regulators of SAR, the requirement for de novo synthesis implies the existence of upstream or parallel inducing signals. Recent studies using whole plant and confocal reporter imaging, electrical signalling, and single-cell transcriptomics have revealed how specific cell types and the temporal-spatial organisation of phytohormone networks contribute to immune signalling. We summarise these findings alongside previous knowledge to highlight the collective importance of jasmonates, calcium, reactive oxygen species, and electrical signals as early initiators, coordinators, and most likely propagators of long-distance signalling during ETI-induced SAR. We draw parallels with induced systemic resistance and highlight the coordinated roles of jasmonates, volatile compounds, and the microbiome in plant-to-plant communication. Furthermore, we also review environmental modulation of defence responses, a research area deriving further attention. Evidence points towards the coordinated activation of multiple signals, including jasmonates, driving systemic immunity across biological scales from the infected cell to entire plant communities.
To gain insights into the biology of bacteria of the genus Xylophilus, including the grapevine pathogen Xylophilus ampelinus, we scrutinized all available genome sequences of the genus for the presence of type III secretion and flagellar systems. We found three distinct flagellar systems within the genus, one of which was present in all 12 strains for which good-quality genome sequences were available. The other two flagellar systems were only detected in one or two strains. We also identified two sub-classes of type III secretion systems, likely under control of the AraC-type transcriptional activator HrpX. One system with resemblance to systems from plant-pathogenic bacteria was only found in the grapevine pathogen. The other system was found in three strains of Xylophilus, all isolated from plant material. We predicted which genes are co-regulated with the type III secretion systems, as supported by the presence of strongly conserved HrpX-binding promoter elements. We identified about 40 type III effectors in the grapevine pathogen with homologs in plant pathogenic bacteria. In contrast, a rhododendron flower isolate had only two type III effector gene candidates with conserved HrpX-binding promoter elements, but many genes without homologs beyond the species. Finally, we predicted and confirmed three novel effector candidates from X. ampelinus to contain a functional type III secretion signal using an AvrBs1 reporter approach. The presence of type III effectors suggests that effector-triggered immunity may exist in grapevine or non-host plants and that strategies targeting type III effectors for resistance engineering may contribute to suitable control measures.IMPORTANCEXylophilus species include poorly characterized plant-associated bacteria, among them the grapevine pathogen Xylophilus ampelinus, yet their molecular mechanisms of host interaction have remained largely unknown. By curating public genomes and performing a genus-wide comparative analysis, this study clarifies Xylophilus taxonomy, reveals the distribution and evolutionary history of flagellar and type III secretion systems (T3SS), and identifies two distinct Hrp2/Hrc2-class T3SS types within the genus. Importantly, we define the predicted effector repertoires associated with these systems and experimentally validate three previously unrecognized type III effectors from X. ampelinus. These findings provide the first comprehensive framework for understanding virulence and host interaction strategies in Xylophilus, offering molecular targets and genomic markers relevant to plant pathology, disease surveillance, and the management of bacterial grapevine diseases.
Anacyclus pyrethrum (L.) DC. is a herbaceous species of the Asteraceae family. This medicinal plant has been widely used in traditional medicine to treat diabetes and its associated complications. N-(4-Hydroxyphenethyl)-(4E)-decenamide (HPD) is a synthetic derivative of natural N-alkylamides extracted from its roots. To date, the therapeutic efficacy and molecular mechanisms of HPD against diabetic retinopathy (DR) have not been fully clarified. This study aimed to explore the therapeutic potential of HPD against DR and clarify its molecular mechanisms. HPD was chemically synthesized. Its anti-angiogenic efficacy was evaluated using both in vitro and in vivo assays. Proteomic analysis, combined with molecular docking and surface plasmon resonance (SPR), was employed to screen and validate the direct binding targets of HPD. Additionally, siRNA-mediated gene knockdown was performed to clarify the functional role of the identified target in DR pathology. In vitro and in vivo experiments demonstrated that HPD significantly inhibited pathological angiogenesis and restored retinal thickness in diabetic retinopathy (DR) model mice. Proteomics analysis, coupled with surface plasmon resonance (SPR) validation, revealed that HPD directly and exclusively bound to PARK7. Furthermore, knockdown of PARK7 exacerbated pathological angiogenesis, whereas intervention with HPD markedly reversed this phenotypic alteration. HPD directly targets PARK7 to attenuate diabetic retinopathy by suppressing pathological angiogenesis, preserving retinal structure, and maintaining blood-retinal barrier integrity.
A phytochemical investigation of the aqueous-MeOH extract of Allanblackia floribunda (Guttifereae) pods was conducted to isolate five compounds (1-5). The structures were established based on the interpretation of their HRMS-ES, HRMS-LD+ and NMR data. The absolute configurations of 1-3 were determined using DFT-based ECD (electronic circular dichroism) data. To explore the therapeutic potential of this plant for microbial diseases, the inhibitory and cytotoxic activities of the extract and the isolated compounds were evaluated against a panel of human pathogens. An in silico molecular docking study was performed on isolated compounds using the DNA gyrase-bound crystal structures 7C7N and 5CDP, enzymes implicated against E. coli and S. aureus resistance. Three unreported compounds i.e. (+)-nlongboflavone A (1), (+)-nlongboflavone B (2) and florinone (3), together with two known compounds: morelloflavone (4) and morelloflavone-7"-O-β-glucopyranoside (5) were identified. Potent activity against Staphylococcus aureus NR 46003 was observed for the crude extract, ethyl acetate and residual fractions, with MICs of 12.5, 10.60 and 16.34 μg/mL as well as (+)-nlongboflavone A (1), also exhibited activity at 17.5 μM. . Compound (1) exhibited a favorable binding energy (ΔG = -11.7 kcal/mol) against S. aureus DNA gyrase, suggesting that its antibacterial activity may be mediated through DNA gyrase inhibition. This research supports the traditional use of Allanblackia floribunda to treat microbial ailments.