A circuit for secretion-coupled cellular autonomy in multicellular eukaryotic cells.

Cancers represent complex autonomous systems, displaying self-sufficiency in growth signaling. Autonomous growth is fueled by a cancer cell's ability to "secrete-and-sense" growth factors (GFs): a poorly understood phenomenon. Using an integrated computational and experimental approach, here we dissect the impact of a feedback-coupled GTPase circuit within the secretory pathway that imparts secretion-coupled autonomy. The circuit is assembled when the Ras-superfamily monomeric GTPase Arf1, and the heterotrimeric GTPase Giαßγ and their corresponding GAPs and GEFs are coupled by GIV/Girdin, a protein that is known to fuel aggressive traits in diverse cancers. One forward and two key negative feedback loops within the circuit create closed-loop control, allow the two GTPases to coregulate each other, and convert the expected switch-like behavior of Arf1-dependent secretion into an unexpected dose-response alignment behavior of sensing and secretion. Such behavior translates into cell survival that is self-sustained by stimulus-proportionate secretion. Proteomic studies and protein-protein interaction network analyses pinpoint GFs (e.g., the epidermal GF) as key stimuli for such self-sustenance. Findings highlight how the enhanced coupling of two biological switches in cancer cells is critical for multiscale feedback control to achieve secretion-coupled autonomy of growth factors.

Dual-task improvement of older adults after treadmill walking combined with blood flow restriction of low occlusion pressure: the effect on the heart-brain axis.

OBJECTIVE: This study explored the impact of one session of low-pressure leg blood flow restriction (BFR) during treadmill walking on dual-task performance in older adults using the neurovisceral integration model framework. METHODS: Twenty-seven older adults participated in 20-min treadmill sessions, either with BFR (100 mmHg cuff pressure on both thighs) or without it (NBFR). Dual-task performance, measured through light-pod tapping while standing on foam, and heart rate variability during treadmill walking were compared. RESULTS: Following BFR treadmill walking, the reaction time (p = 0.002) and sway area (p = 0.012) of the posture dual-task were significantly reduced. Participants exhibited a lower mean heart rate (p < 0.001) and higher heart rate variability (p = 0.038) during BFR treadmill walking. Notably, BFR also led to band-specific reductions in regional brain activities (theta, alpha, and beta bands, p < 0.05). The topology of the EEG network in the theta and alpha bands became more star-like in the post-test after BFR treadmill walking (p < 0.005). CONCLUSION: BFR treadmill walking improves dual-task performance in older adults via vagally-mediated network integration with superior neural economy. This approach has the potential to prevent age-related falls by promoting cognitive reserves.

Comparing the Outcomes of Suture Anchor Repair and Rein-Type Capsular Suture for Triangular Fibrocartilage Complex Foveal Tears With a Minimum 2-Year Follow-Up.

PURPOSE: Recent biomechanical studies have highlighted the importance of foveal reinsertion when repairing triangular fibrocartilage complex (TFCC) injury with foveal tears. However, clinical studies comparing different repair techniques are scarce. We compared the clinical outcomes of suture anchor repair and rein-type capsular suture in patients with TFCC palmer 1B foveal tears with a minimum of 2-year follow-up. METHODS: This was a single-surgeon, single-center, retrospective, comparative study. We included patients who underwent TFCC repair surgery due to a foveal tear from December 2013 to October 2018 with a minimum follow-up of 24 months. Postoperative Quick Disabilities of Arm, Shoulder, and Hand (QuickDASH) score, Modified Mayo Wrist Score, visual analogue scale for pain, wrist range of motion, and grip strength were compared. We also measured the maximal ulnar head displacement with dynamic ultrasound to quantify distal radioulnar joint stability. RESULTS: In total, 103 patients were in the suture anchor group (group A) and 84 patients in the rein-type capsular suture group (group B). The mean follow-up time exceeded three years for both groups. There was a minimal difference regarding QuickDASH score, visual analogue scale for pain, and grip strength ratio between the two groups. The rein-type group had significantly better Modified Mayo Wrist Score. The suture anchor group showed better distal radioulnar joint stability with dynamic ultrasound, but was more limited in ulnar deviation. However, these differences are most likely clinically insignificant. CONCLUSIONS: Both suture anchor repair and rein-type capsular suture yielded satisfactory results for TFCC 1B foveal tear in a minimum of 2-year follow-up. The functional scores were similar, and no major complications or recurrent instability were noted in either group. TYPE OF STUDY/LEVEL OF EVIDENCE: Retrospective Therapeutic Comparative Investigation IV.

Real-time PCR-based quantitative microbiome profiling elucidates the microbial dynamic succession in backslopping fermentation of Taiwanese pickled cabbage.

BACKGROUND: Microbiota succession determines the flavor and quality of fermented foods. Quantitative PCR-based quantitative microbiome profiling (QMP) has been applied broadly for microbial analysis from absolute abundance perspectives, transforming microbiota ratios into counts by normalizing 16S ribosomal RNA (16S rRNA) gene sequencing data with gene copies quantified by quantitative PCR. However, the application of QMP in fermented foods is still limited. RESULTS: QMP elucidated microbial succession of Taiwanese pickled cabbage. In the spontaneous first-round fermentation (FR), the 16S rRNA gene copies of total bacteria increased from 6.1 to 10 log copies mL-1. The dominant lactic acid bacteria genera were successively Lactococcus, Leuconostoc and Lactiplantibacillus. Despite the decrease in the proportion of Lactococcus during the succession, the absolute abundance of Lactococcus still increased. In the backslopping second-round fermentation (SR), the total bacteria 16S rRNA gene copies increased from 7.6 to 9.9 log copies mL-1. The addition of backslopping starter and vinegar rapidly led to a homogenous microbial community dominated by Lactiplantibacillus. The proportion of Lactiplantibacillus remained consistently around 90% during SR, whereas its absolute abundance exhibited a continuous increase. In SR without vinegar, Leuconostoc consistently dominated the fermentation. CONCLUSION: The present study highlights that compositional analysis would misinterpret microbial dynamics, whereas QMP reflected the real succession profiles and unveiled the essential role of vinegar in promoting Lactiplantibacillus dominance in backslopping fermentation of Taiwanese pickled cabbage. Quantitative microbiome profiling (QMP) was found to be a more promising approach for the detailed observation of microbiome succession in food fermentation compared to compositional analysis. © 2024 Society of Chemical Industry.

Potential natural product 3,4-seco-schitriterpenoids from Kadsura japonica L. as anti-neuroinflammatory agents.

In the present study, the undescribed schitriterpenoids, kadsujanonols A-I (1-9), and eleven reported compounds (10-20) were isolated from K. japonica L. vines. Their structures of 3,4-seco-schitriterpenoids were elucidated mainly by spectroscopic analyses including 1H-, 13C-, and 2D-NMR, IR, HRESIMS spectra. The spatial configurations were determined by the single-crystal X-ray diffraction analysis of kadsujapnonol A (1), 15, 17, and 18, CD data and computational analysis. Furthermore, all isolates were evaluated for the anti-neuroinflammatory activity on LPS-stimulated NO production in BV2 microglial cells and compounds 2, 4, 5, 7, 9, 11, 13-16, and 18 exposed better or comparable suppression abilities than PDTC. Among them, kadlongilactone B (14) showed the best significant inhibiting ability (IC50 = 0.87 µg/mL) and the effect is through the attenuation of the inflammatory transcription factor p65NF-κB. Preliminary structure-activity relationship revealed that δ-lactone at the side chain and 7-member lactone at C-3/C-4, and 3,4:9,10 ring opening are important.

Evaluation of cytosine base editing and adenine base editing as a potential treatment for alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin deficiency (AATD) is a rare autosomal codominant disease caused by mutations within the SERPINA1 gene. The most prevalent variant in patients is PiZ SERPINA1, containing a single G > A transition mutation. PiZ alpha-1 antitrypsin (AAT) is prone to misfolding, leading to the accumulation of toxic aggregates within hepatocytes. In addition, the abnormally low level of AAT secreted into circulation provides insufficient inhibition of neutrophil elastase within the lungs, eventually causing emphysema. Cytosine and adenine base editors enable the programmable conversion of C⋅G to T⋅A and A⋅T to G⋅C base pairs, respectively. In this study, two different base editing approaches were developed: use of a cytosine base editor to install a compensatory mutation (p.Met374Ile) and use of an adenine base editor to mediate the correction of the pathogenic PiZ mutation. After treatment with lipid nanoparticles formulated with base editing reagents, PiZ-transgenic mice exhibited durable editing of SERPINA1 in the liver, increased serum AAT, and improved liver histology. These results indicate that base editing has the potential to address both lung and liver disease in AATD.

Genetic and Biochemical Characterization of Halogenation and Drug Transportation Genes Encoded in the Albofungin Biosynthetic Gene Cluster.

Albofungin, a hexacyclic aromatic natural product, exhibits broad-spectrum antimicrobial activity. Its biosynthesis, regulation, and resistance remain elusive. Here, we report the albofungin (abf) biosynthetic gene cluster (BGC) from its producing strain Streptomyces tumemacerans JCM5050. The nascent abf BGC encodes 70 putative genes, including regulators, transporters, type II polyketide synthases (PKSs), oxidoreductase, and tailoring enzymes. To validate the intactness and functionality of the BGC, we developed an Escherichia coli-Streptomyces shuttle bacterial artificial chromosome system, whereby the abf BGC was integrated into the genome of a nonproducing host via heterologous conjugation, wherefrom albofungin can be produced, confirming that the BGC is in effect. We then delimited the boundaries of the BGC by means of in vitro CRISPR-Cas9 DNA editing, concluding a minimal but essential 60-kb abf BGC ranging from orfL to abf58. The orfA gene encoding a reduced flavin adenine dinucleotide (FADH2)-dependent halogenase was examined and is capable of transforming albofungin to halogen-substituted congeners in vivo and in vitro. The orfL gene encoding a transporter was examined in vivo. The presence/absence of orfA or orfL demonstrated that the MIC of albofungin is subject to alteration when an extracellular polysaccharide intercellular adhesin was formed. Despite that halogenation of albofungin somewhat increases binding affinity to transglycosylase (TGase), albofungin with/without a halogen substituent manifests similar in vitro antimicrobial activity. Halogenation, however, limits overall dissemination and effectiveness given a high secretion rate, weak membrane permeability, and high hydrophobicity of the resulting products, whereby the functions of orfA and orfL are correlated with drug detoxification/resistance for the first time. IMPORTANCE Albofungin, a natural product produced from Streptomycetes, exhibits bioactivities against bacteria, fungi, and tumor cells. The biosynthetic logic, regulations, and resistance of albofungin remain yet to be addressed. Herein, the minimal albofungin (abf) biosynthetic gene cluster (BGC) from the producing strain Streptomyces tumemacerans JCM5050 was precisely delimited using the Escherichia coli-Streptomyces shuttle bacterial artificial chromosome system, of which the gene essentiality was established in vivo and in vitro. Next, we characterized two genes orfA and orfL encoded in the abf BGC, which act as a reduced flavin adenine dinucleotide (FADH2)-dependent halogenase and an albofungin-congeners transporter, respectively. While each testing microorganism exhibited different sensitivities to albofungins, the MIC values of albofungins against testing strains with/without orfA and/or orfL were subject to considerable changes. Halogen-substituted albofungins mediated by OrfA manifested overall compromised dissemination and effectiveness, revealing for the first time that two functionally distinct proteins OrfA and OrfL are associated together, exerting a novel "belt and braces" mechanism in antimicrobial detoxification/resistance.

GIV/Girdin activates Gαi and inhibits Gαs via the same motif.

We previously showed that guanine nucleotide-binding (G) protein α subunit (Gα)-interacting vesicle-associated protein (GIV), a guanine-nucleotide exchange factor (GEF), transactivates Gα activity-inhibiting polypeptide 1 (Gαi) proteins in response to growth factors, such as EGF, using a short C-terminal motif. Subsequent work demonstrated that GIV also binds Gαs and that inactive Gαs promotes maturation of endosomes and shuts down mitogenic MAPK-ERK1/2 signals from endosomes. However, the mechanism and consequences of dual coupling of GIV to two G proteins, Gαi and Gαs, remained unknown. Here we report that GIV is a bifunctional modulator of G proteins; it serves as a guanine nucleotide dissociation inhibitor (GDI) for Gαs using the same motif that allows it to serve as a GEF for Gαi. Upon EGF stimulation, GIV modulates Gαi and Gαs sequentially: first, a key phosphomodification favors the assembly of GIV-Gαi complexes and activates GIV's GEF function; then a second phosphomodification terminates GIV's GEF function, triggers the assembly of GIV-Gαs complexes, and activates GIV's GDI function. By comparing WT and GIV mutants, we demonstrate that GIV inhibits Gαs activity in cells responding to EGF. Consequently, the cAMP→PKA→cAMP response element-binding protein signaling axis is inhibited, the transit time of EGF receptor through early endosomes are accelerated, mitogenic MAPK-ERK1/2 signals are rapidly terminated, and proliferation is suppressed. These insights define a paradigm in G-protein signaling in which a pleiotropically acting modulator uses the same motif both to activate and to inhibit G proteins. Our findings also illuminate how such modulation of two opposing Gα proteins integrates downstream signals and cellular responses.

The chondroitin sulfate moiety mediates thrombomodulin-enhanced adhesion and migration of vascular smooth muscle cells.

BACKGROUND: Thrombomodulin (TM), a transmembrane glycoprotein highly expressed in endothelial cells (ECs), is a potent anticoagulant maintaining circulation homeostasis. Under inflammatory states, TM expression is drastically reduced in ECs while vascular smooth muscle cells (VSMCs) show a robust expression of TM. The functional role of TM in VSMCs remains elusive. METHODS: We examined the role of TM in VSMCs activities in human aortic VSMCs stimulated with platelet-derived growth factor-BB (PDGF-BB). Using rat embryonic aorta-derived A7r5 VSMCs which do not express TM, the role of the chondroitin sulfate (CS) moiety of TM in VSMCs was delineated with cells expressing wild-type TM and the CS-devoid TM mutant. RESULTS: Expression of TM enhanced cell migration and adhesion/spreading onto type I collagen, but had no effect on cell proliferation. Knocking down TM with short hairpin RNA reduced PDGF-stimulated adhesion and migration of human aortic VSMCs. In A7r5 cells, TM-mediated cell adhesion was eradicated by pretreatment with chondroitinase ABC which degrades CS moiety. Furthermore, the TM mutant (TMS490, 492A) devoid of CS moiety failed to increase cell adhesion, spreading or migration. Wild-type TM, but not TMS490, 492A, increased focal adhesion kinase (FAK) activation during cell adhesion, and TM-enhanced cell migration was abolished by a function-blocking anti-integrin ß1 antibody. CONCLUSION: Chondroitin sulfate modification is required for TM-mediated activation of ß1-integrin and FAK, thereby enhancing adhesion and migration activity of VSMCs.

Cyclin-dependent kinase 5 activates guanine nucleotide exchange factor GIV/Girdin to orchestrate migration-proliferation dichotomy.

Signals propagated by receptor tyrosine kinases (RTKs) can drive cell migration and proliferation, two cellular processes that do not occur simultaneously--a phenomenon called "migration-proliferation dichotomy." We previously showed that epidermal growth factor (EGF) signaling is skewed to favor migration over proliferation via noncanonical transactivation of Gαi proteins by the guanine exchange factor (GEF) GIV. However, what turns on GIV-GEF downstream of growth factor RTKs remained unknown. Here we reveal the molecular mechanism by which phosphorylation of GIV by cyclin-dependent kinase 5 (CDK5) triggers GIV's ability to bind and activate Gαi in response to growth factors and modulate downstream signals to establish a dichotomy between migration and proliferation. We show that CDK5 binds and phosphorylates GIV at Ser1674 near its GEF motif. When Ser1674 is phosphorylated, GIV activates Gαi and enhances promigratory Akt signals. Phosphorylated GIV also binds Gαs and enhances endosomal maturation, which shortens the transit time of EGFR through early endosomes, thereby limiting mitogenic MAPK signals. Consequently, this phosphoevent triggers cells to preferentially migrate during wound healing and transmigration of cancer cells. When Ser1674 cannot be phosphorylated, GIV cannot bind either Gαi or Gαs, Akt signaling is suppressed, mitogenic signals are enhanced due to delayed transit time of EGFR through early endosomes, and cells preferentially proliferate. These results illuminate how GIV-GEF is turned on upon receptor activation, adds GIV to the repertoire of CDK5 substrates, and defines a mechanism by which this unusual CDK orchestrates migration-proliferation dichotomy during cancer invasion, wound healing, and development.

Genetic profile and clinical application of chromosomal microarray in children with intellectual disability in Hong Kong.

INTRODUCTION: Chromosomal microarray (CMA) is recommended as a first-tier genetic investigation for intellectual disability (ID), developmental delay, or autism spectrum disorder due to its higher diagnostic yield with respect to conventional karyotyping. The aim of the present study was to investigate the genetic profile and diagnostic yield of CMA in children with moderate, severe and profound ID. METHODS: A pilot cross-sectional study was performed by the Child Assessment Service and the Clinical Genetic Service in Hong Kong from July 2016 to June 2017. Children with unexplained ID were recruited for CMA testing by an expedited referral pathway. Children who were existing clients of the Clinical Genetic Service were also recruited. RESULTS: Of 225 children included in this study, 68 (30.2%) had genetic diagnoses. Among the 138 children who underwent CMA testing, 53 (38%) children were referred to the Clinical Genetic Service by the expedited referral pathway. The respective diagnostic yields of CMA in moderate, severe, and profound ID were 8.7%, 17.6%, and 23.5% (P<0.05). Children with dysmorphic features demonstrated a much higher yield from CMA (45.8% vs 4.4%, P<0.05). CONCLUSTION. The overall diagnostic yield (11.6%) of CMA in this cohort is comparable with that of other international cohorts. This further supports the use of CMA as a first-tier genetic investigation for children with ID, developmental delay, or autism spectrum disorder, particularly for those with severe disease.

Novel 11-norbetaenone isolated from an entomopathogenic fungus Lecanicillium antillanum.

A novel nor-betaenone compound, 11-norbetaenone (1), was isolated from the culture broth of an entomopathogenic fungus Lecanicillium antillanum. The structure was determined on the basis of 1D and 2D NMR spectroscopic data. The absolute stereochemistry of 1 was further confirmed by X-ray single crystallography analysis. It is the first secondary metabolite reported from the species Lecanicillium antillanum. And it is also the first time that a betaenone-type compound was isolated from the genus Lecanicillium. Furthermore, 11-norbetaenone (1) displayed significant anti-angiogenic effect by suppressing tube formation.

Inflammation Modulatory Phorbol Esters from the Seeds of Aquilaria malaccensis.

The tree Aquilaria malaccensis is a valuable source of agarwood, which is used in herbal medicinal preparations. Phytochemical research on A. malaccensis seeds has led to the isolation of four new phorbol esters (1-4), two known phorbol esters (5, isolated from Nature for the first time, and 6), and two known glycerides (7 and 8). The structures of these isolates were elucidated by means of spectroscopic data interpretation. The inflammation-modulatory activities of the isolates on elastase release and superoxide anion generation in human neutrophils were evaluated. Interestingly, phorbol esters 1, 5, and 6 showed potent inhibitory activity on elastase release in human neutrophils, with IC50 values of 2.7, 0.8, and 2.1 µM, respectively. All isolated phorbol esters exerted enhancing activity on superoxide anion generation. The results indicated that phorbol esters may play a bilateral modulatory role in the processes of inflammation. In addition, the compounds were evaluated for their cytotoxic properties against HepG2 (hepatoma), MDA-MB-231 (breast), and A549 (lung) cancer cells, but all compounds were inactive for all cell lines used (IC50 > 10 µM).

Biosynthesis of Complex Indole Alkaloids: Elucidation of the Concise Pathway of Okaramines.

The okaramines are a class of complex indole alkaloids isolated from Penicillium and Aspergillus species. Their potent insecticidal activity arises from selectively activating glutamate-gated chloride channels (GluCls) in invertebrates, not affecting human ligand-gated anion channels. Okaramines B (1) and D (2) contain a polycyclic skeleton, including an azocine ring and an unprecedented 2-dimethyl-3-methyl-azetidine ring. Owing to their complex scaffold, okaramines have inspired many total synthesis efforts, but the enzymology of the okaramine biosynthetic pathway remains unexplored. Here, we identified and characterized the biosynthetic gene cluster (oka) of 1 and 2, then elucidated the pathway with target gene inactivation, heterologous reconstitution, and biochemical characterization. Notably, we characterized an α-ketoglutarate-dependent non-heme FeII dioxygenase that forged the azetidine ring on the okaramine skeleton.

Ecdysones from Zoanthus spp. with inhibitory activity against dengue virus 2.

Bioassay-guided fractionation of an ethanolic extract of Zoanthus spp. collected in Taiwan has resulted in the isolation of one new ecdysone, zoanthone A (1), along with thirteen known compounds (2-14). The structures of these compounds were determined by spectroscopic methods, especially 2D NMR analyses. The in vitro antiviral activities of all isolated ecdysones (1-14) against dengue virus type 2 (DENV-2) were evaluated using DENV infectious system. New compound (1) exhibited potent antiviral activity (EC50=19.61 ± 2.46 µM) with a selectivity index (CC50/EC50) value of 36.7. The structure-activity relationships of isolated ecdysones against DENV-2 were concluded. Molecular docking information of 3 and NS5 polymerase was performed either.

Zoanthamine-Type Alkaloids from the Zoanthid Zoanthus kuroshio Collected in Taiwan and Their Effects on Inflammation.

Zoanthus kuroshio is a colorful zoanthid with a fluorescent pink oral disc and brown tentacles, which dominates certain parts of the Taiwanese and Japanese coasts. This sea anemone is a rich source of biologically active alkaloids. In the current investigation, two novel halogenated zoanthamines [5α-iodozoanthenamine (1) and 11ß-chloro-11-deoxykuroshine A (2)], along with four new zoanthamines [18-epi-kuroshine A (3), 7α-hydroxykuroshine E (4), 5α-methoxykuroshine E (5), and 18-epi-kuroshine E (6)], and six known compounds were isolated from Z. kuroshio. Compounds 1 and 2 are the first examples of halogenated zoanthamine-type alkaloids isolated from nature. Compounds 3 and 6 are the first zoanthamine stereoisomers with a cis-junction of the A/B rings. All isolated compounds were evaluated for their anti-inflammatory activities by measuring their effects on superoxide anion generation and elastase release by human neutrophils in response to fMLP.

Silver-Russell syndrome in Hong Kong.

OBJECTIVES: To examine the molecular pathogenetic mechanisms, (epi)genotype-phenotype correlation, and the performance of the three clinical scoring systems-namely Netchine et al, Bartholdi et al, and Birmingham scores-for patients with Silver-Russell syndrome in Hong Kong. METHODS: This retrospective case series was conducted at two tertiary genetic clinics, the Clinical Genetic Service, Department of Health, and clinical genetic clinic in Queen Mary Hospital in Hong Kong. All records of patients with suspected Silver-Russell syndrome under the care of the two genetic clinics between January 2010 and September 2015 were retrieved from the computer database. RESULTS: Of the 28 live-birth patients with Silver-Russell syndrome, 35.7% had H19 loss of DNA methylation, 21.4% had maternal uniparental disomy of chromosome 7, 3.6% had mosaic maternal uniparental disomy of chromosome 11, and the remaining 39.3% were Silver-Russell syndrome of unexplained molecular origin. No significant correlation between (epi)genotype and phenotype could be identified between H19 loss of DNA methylation and maternal uniparental disomy of chromosome 7. Comparison of molecularly confirmed patients and patients with Silver-Russell syndrome of unexplained origin revealed that postnatal microcephaly and café-au-lait spots were more common in the latter group, and body and limb asymmetry was more common in the former group. Performance analysis showed the Netchine et al and Birmingham scoring systems had similar sensitivity in identifying Hong Kong Chinese subjects with Silver-Russell syndrome. CONCLUSION: This is the first territory-wide study of Silver-Russell syndrome in Hong Kong. The clinical features and the spectrum of underlying epigenetic defects were comparable to those reported in western populations.

Antiallergic Phorbol Ester from the Seeds of Aquilaria malaccensis.

The Aquilaria malaccensis (Thymelaeaceae) tree is a source of precious fragrant resin, called agarwood, which is widely used in traditional medicines in East Asia against diseases such as asthma. In our continuous search for active natural products, A. malaccensis seeds ethanolic extract demonstrated antiallergic effect with an IC50 value less than 1 µg/mL. Therefore, the present research aimed to purify and identify the antiallergic principle of A. malaccensis through a bioactivity-guided fractionation approach. We found that phorbol ester-rich fraction was responsible for the antiallergic activity of A. malaccensis seeds. One new active phorbol ester, 12-O-(2Z,4E,6E)-tetradeca-2,4,6-trienoylphorbol-13-acetate, aquimavitalin (1) was isolated. The structure of 1 was assigned by means of 1D and 2D NMR data and high-resolution mass spectrometry (HR-MS). Aquimavitalin (1) showed strong inhibitory activity in A23187- and antigen-induced degranulation assay with IC50 values of 1.7 and 11 nM, respectively, with a therapeutic index up to 71,000. The antiallergic activities of A. malaccensis seeds and aquimavitalin (1) have never been revealed before. The results indicated that A. malaccensis seeds and the pure compound have the potential for use in the treatment of allergy.