Obesity is a growing global concern, and pancreatic lipase inhibitors have emerged as potential targets for antiobesity strategies. This study evaluates the potential of Perilla frutescens (L.) Britton var. frutescens le...Obesity is a growing global concern, and pancreatic lipase inhibitors have emerged as potential targets for antiobesity strategies. This study evaluates the potential of Perilla frutescens (L.) Britton var. frutescens leaf tea as a pancreatic lipase inhibitor for managing dietary fat absorption. Perilla leaf tea significantly inhibited the pancreatic lipase-mediated hydrolysis of emulsified triglycerides, depending on its polyphenol and rosmarinic acid (RA) contents. However, the inhibitory effect diminished at higher concentrations, which coincided with the increased emulsion particle size. Perilla leaf tea did not inhibit the hydrolysis of solubilized p-nitrophenyl palmitate, whereas authentic RA reduced lipase activity against both substrate types. These findings suggest that perilla leaf tea and RA have different lipase inhibition mechanisms. This study implies that RA contributes to the lipase-inhibiting properties of perilla leaf tea and emulsion structure plays a pivotal role in modulating the ability of the tea to inhibit lipase activity.
The mammary circulatory system supports mammary growth and lactation by supplying oxygen and nutrients. Insulin-like growth factor 1 (IGF1) is essential for mammary gland development, yet its involvement in angiogenic re...The mammary circulatory system supports mammary growth and lactation by supplying oxygen and nutrients. Insulin-like growth factor 1 (IGF1) is essential for mammary gland development, yet its involvement in angiogenic regulation remains unclear. This study investigated whether IGF1 stimulates vascular endothelial growth factor (VEGF) production in mammary epithelial cells and explored the underlying signaling pathways. IGF1 increased VEGF mRNA expression in a bovine mammary epithelial cell line and in HC11 cells, and enhanced VEGF promoter activity and secretion in HC11 cells in a dose-dependent manner. Conditioned medium from IGF1-stimulated HC11 cells promoted tube formation in HUVECs, which was attenuated by a VEGFR inhibitor. IGF1 rapidly induced ERK1/2 and Akt phosphorylation, and inhibitors of these pathways suppressed VEGF secretion. These findings suggest that IGF1 upregulates VEGF via the MEK-ERK1/2 and PI3K-Akt pathways, thereby promoting mammary angiogenesis and contributing to mammary gland development and lactation efficiency.
Acetic acid bacteria (AAB) produce phosphatidylcholine (PC) as a major membrane component. PC has long been considered important for acetic acid tolerance in AAB, yet direct experimental support remains limited, and its...Acetic acid bacteria (AAB) produce phosphatidylcholine (PC) as a major membrane component. PC has long been considered important for acetic acid tolerance in AAB, yet direct experimental support remains limited, and its physiological roles under diverse environmental stresses are not well defined. In this study, we constructed PC-deficient mutants of Acetobacter pasteurianus by deleting the phosphatidylethanolamine N-methyltransferase gene. PC deficiency resulted in phosphatidylglycerol accumulation and a tendency toward acyl-chain shortening. Phenotypic analysis showed that PC deficiency impaired growth under ionic, heat, and acidic stresses, indicating that PC supports membrane integrity under these stress conditions. Heterologous expression of PC synthase from Pseudomonas aeruginosa enabled choline-dependent regulation of PC biosynthesis. This system revealed that even low PC levels are sufficient to restore normal growth and acetic acid fermentation. These findings suggest that PC has diverse physiological roles in AAB and its function does not necessarily depend on its abundance in the membrane.
Osteoarthritis (OA) is a progressive joint disorder characterized by inflammation and metabolic imbalance. Schisandrin A (Sch-A), a bioactive compound from Schisandra sphenanthera, is known for its anti-inflammatory and...Osteoarthritis (OA) is a progressive joint disorder characterized by inflammation and metabolic imbalance. Schisandrin A (Sch-A), a bioactive compound from Schisandra sphenanthera, is known for its anti-inflammatory and protective properties. This study investigated the effects of Sch-A on chondrocyte senescence and metabolism using IL-1β-stimulated CHON-001 cells as an in vitro OA model. Sch-A showed no cytotoxicity up to 100 μm and alleviated IL-1β-induced chondrocyte injury. It restored anabolic metabolism, suppressed catabolic activity, and reduced inflammatory and fibrotic responses. Bioinformatics indicated links between Sch-A, cellular senescence, and the PI3K/Akt pathway. Functional assays confirmed that Sch-A suppressed senescence-associated secretory phenotype factors, senescence markers, SA-β-galactosidase activity, and PI3K/Akt activation, while PI3K inhibition enhanced its anti-senescent effects. These findings suggest that Sch-A mitigates chondrocyte senescence and metabolic dysregulation by modulating PI3K/Akt signaling, supporting its therapeutic potential for OA.
We prepared nanovesicles (NVs) derived from broccoli using ultracentrifugation and evaluated their anti-inflammatory properties. Two distinct NV populations were isolated as precipitates from broccoli homogenates followi...We prepared nanovesicles (NVs) derived from broccoli using ultracentrifugation and evaluated their anti-inflammatory properties. Two distinct NV populations were isolated as precipitates from broccoli homogenates following centrifugation at 20 000 × g and 200 000 × g. These NVs contained RNAs, proteins, isothiocyanates, and chlorophylls. Dynamic light scattering analysis confirmed their nanoscale size. The NVs were internalized by RAW264 cells and significantly inhibited nitric oxide production and NF-κB pathway activation under lipopolysaccharide (LPS) stimulation. Comprehensive analysis of inflammatory cytokine expression revealed strong suppression of interleukin-6 (IL-6) by both NV types, which was further validated by ELISA. Additionally, IL-1β and tumor necrosis factor-α production were also reduced. Notably, the anti-inflammatory effects were partially attributed to small RNAs (<200 nt) present within the NVs. Collectively, these findings suggest that broccoli-derived NVs possess potent anti-inflammatory activity.
This study aimed to determine the changes in polyphenols associated with autumn coloration of Acer palmatum leaves. Acer palmatum leaves harvested in July (before autumn coloration: BAC) and November (after autumn colora...This study aimed to determine the changes in polyphenols associated with autumn coloration of Acer palmatum leaves. Acer palmatum leaves harvested in July (before autumn coloration: BAC) and November (after autumn coloration: AAC) were boiled in water. The AAC extract showed higher antioxidant activity than the BAC extract in assays measuring 2,2-diphenyl-1-picrylhydrazyl radical scavenging and superoxide dismutase-like activity. High-performance liquid chromatography analysis showed that the 2 extracts exhibited similar peak patterns for major polyphenols, with AAC extract exhibiting a large peak for compound I. After the 2 extracts were fractionated, the compound I-rich fraction (AAC Fr. 2) showed the strongest antioxidant activity among the obtained fractions. Finally, compound I was identified as mallotinic acid by liquid chromatography-mass spectrometry and nuclear magnetic resonance analyses. Our study revealed that the antioxidant activity of A. palmatum leaves is enhanced and mallotinic acid is accumulated during autumn coloration.
Poly-γ-glutamic acid (γ-PGA) occurs in three stereochemical forms-L-, DL-, and D-polymers-and the D/L ratio profoundly affects crystallinity, degradability, and materials performance. Bacillus subtilis and related secret...Poly-γ-glutamic acid (γ-PGA) occurs in three stereochemical forms-L-, DL-, and D-polymers-and the D/L ratio profoundly affects crystallinity, degradability, and materials performance. Bacillus subtilis and related secretors typically produce DL-PGA, whereas halophilic archaea yield stereoregular L-PGA and Bacillus anthracis forms a covalently anchored D-PGA capsule. Recent work has clarified how the PgsBCA/CapBCA modules access these outputs: PgsB and PgsC build and export a purely L-Glu polymer, while the MslH-like enzyme PgsA/CapA introduces D-Glu, establishing the D/L ratio. In the extracellular space, the D/L composition of γ-PGA is shaped by stereoselective hydrolases-PgdS, NlpC/P60 DL-endopeptidases, phage-derived Pgh enzymes, and GGT-family proteins. We integrate these biosynthetic and degradative pathways into a stereochemical framework and outline how tuning epimerase activity and controlling these hydrolases may enable high-molecular-weight, L-rich γ-PGA in Bacillus for coatings, absorbents, biomedical applications, and personal-care formulations where L-PGA surpasses DL-PGA in moisture retention and stability.
Molybdenum and tungsten are essential trace metals whose biological utilization requires strict and selective control of their uptake and intracellular availability. Prokaryotes achieve this through highly specialized sy...Molybdenum and tungsten are essential trace metals whose biological utilization requires strict and selective control of their uptake and intracellular availability. Prokaryotes achieve this through highly specialized systems, involving the oxyanion-specific ATP-binding cassette transporters (ModABC, WtpABC, and TupABC), which discriminate between molybdate and tungstate via distinct periplasmic-binding mechanisms. Following molybdenum import, the molybdenum storage proteins store up to ∼130 molybdate ions as polyoxometalate clusters within a protein cage via an ATP-dependent sequestration mechanism. These transport and storage strategies maintain metal homeostasis even under nutrient-limiting conditions, allowing sustained biosynthesis of molybdoenzymes and illustrating an advanced paradigm for microbial trace metal regulation.
Mycosporine-like amino acids (MAAs) are natural compounds widely studied for their photoprotective and antioxidant properties. Typical MAAs consist of one or two amino acids attached to a cyclohexenone or cyclohexenimine...Mycosporine-like amino acids (MAAs) are natural compounds widely studied for their photoprotective and antioxidant properties. Typical MAAs consist of one or two amino acids attached to a cyclohexenone or cyclohexenimine ring, whereas atypical MAAs possess unique chemical modifications such as glycosylation and methylation. Recently, we identified an atypical MAA, GlcHMS326, from the cyanobacterium Gloeocapsa sp. BRSZ, characterized by glycosylation, methylation, and hydroxylation. In this study, we compared the chemical stability and biological activities of GlcHMS326 with those of a typical di-substituted MAA, porphyra-334. GlcHMS326 was less stable under high-temperature conditions but showed a slightly higher residual rate than porphyra-334 under the present visible-light exposure conditions. Functionally, GlcHMS326 showed stronger antioxidant and collagenase inhibitory activities but weaker antiglycative activity. Neither compound inhibited hyaluronidase activity. Both MAAs inhibited angiotensin-converting enzyme, with porphyra-334 showing stronger inhibition. These results provide insights into how chemical modifications influence the functional properties of MAAs.
Jasmonate is a plant hormone that regulates development and defense responses. Jasmonoyl-l-isoleucine (JA-Ile) is a ligand for the most studied jasmonate co-receptor, COI1-JAZ, in seed plants. 12-Oxygenation to 12-hydrox...Jasmonate is a plant hormone that regulates development and defense responses. Jasmonoyl-l-isoleucine (JA-Ile) is a ligand for the most studied jasmonate co-receptor, COI1-JAZ, in seed plants. 12-Oxygenation to 12-hydroxyjasmonoyl-l-isoleucine (12-OH-JA-Ile) is a major metabolic pathway of JA-Ile. Moreover, 12-OH-JA-Ile is a selective ligand for some COI1-JAZ pairs in Arabidopsis thaliana. However, few studies have reported on the activity of 12-OH-JA-Ile in rice (Oryza sativa L.). In this study, we synthesized 12-OH-JA-Ile and its isomers, and evaluated their biological activities against rice. 12-OH-JA-Ile inhibited root elongation but did not induce the biosynthesis of momilactone A, a phytoalexin. These results suggested that 12-OH-JA-Ile selectively induced a jasmonate response in rice. The bioactivity of the E-isomer of 12-OH-JA-Ile revealed that the Z-olefin was necessary for root inhibitory activity.
We identify a novel effect in which dietary purple nonsulfur bacteria Cereibacter sphaeroides increase body size in Caenorhabditis elegans. This response requires the Toll-like receptor homolog TOL-1 and the TIR-domain a...We identify a novel effect in which dietary purple nonsulfur bacteria Cereibacter sphaeroides increase body size in Caenorhabditis elegans. This response requires the Toll-like receptor homolog TOL-1 and the TIR-domain adaptor TIR-1, but not the p38 MAP kinase PMK-1. Components of the DBL-1/BMP pathway, including LON-1, also contribute, revealing a new interaction between a beneficial bacterium and host growth regulation.
We developed a simple and effective method for distinguishing mature spores (MSs) of Bacillus subtilis 168 from mixed cell population using Auramine O (AuO) staining combined with flow cytometry (FCM) analysis. AuO prefe...We developed a simple and effective method for distinguishing mature spores (MSs) of Bacillus subtilis 168 from mixed cell population using Auramine O (AuO) staining combined with flow cytometry (FCM) analysis. AuO preferentially stains MSs, enabling fluorescence-based discrimination. To optimize the method, B. subtilis 168 was stained with AuO and heated at different temperatures (25, 40, 55, or 70 °C) before FCM analysis. Among the tested conditions, heating for 30 min at 55 °C yielded the most distinct separation between MSs and other cell types based on fluorescence intensity. This approach combines the high-throughput capability of FCM with temperature-enhanced fluorescent staining to achieve efficient and accurate spore identification. This method is simple, rapid, and scalable, with potential applications in food safety testing and probiotic product manufacturing, where fast and reliable bacterial enumeration is essential.
Selenate and tellurate are toxic chalcogen oxyanions that can be reduced by several bacteria to the less-toxic elemental forms. In Escherichia coli, the ynfEFGH gene cluster encodes two complex iron-sulfur molybdoenzymes...Selenate and tellurate are toxic chalcogen oxyanions that can be reduced by several bacteria to the less-toxic elemental forms. In Escherichia coli, the ynfEFGH gene cluster encodes two complex iron-sulfur molybdoenzymes, YnfEGH and YnfFGH, involved in this reduction. This study investigated the functional relationship between the two catalytic subunits, YnfE and YnfF. Phylogenetic analysis revealed that their homologs were divided into three major clades, with YnfE and YnfF belonging to different subclades within the same clade. Reductase assays using gene-disruption strains revealed that selenate was mainly reduced by YnfE, whereas tellurate was reduced by both YnfE and YnfF. Analysis of the reaction product indicated that YnfE and YnfF catalyzed the two-electron reduction of selenate/tellurate to selenite/tellurite. These findings suggest that selenate and tellurate are initially reduced to selenite and tellurite, which are subsequently converted to elemental selenium and tellurium by intracellular thiols in E. coli.
The need for eco-friendly pest control has grown with increasing concerns over toxicity of synthetic pesticides. Repellents offer a nonlethal alternative for crop protection. Here, we report the identification of natural...The need for eco-friendly pest control has grown with increasing concerns over toxicity of synthetic pesticides. Repellents offer a nonlethal alternative for crop protection. Here, we report the identification of naturally occurring organic acids as repellents for agricultural pests. We evaluated the repellent activity of methanolic extracts of 12 Persicaria species against pillbug. All extracts showed significant activity, with that from P. chinensis being the most effective. Bioassay-guided isolation from P. chinensis shoots revealed oxalic acid as the principal active compound. Oxalic acid and related dicarboxylic acids exhibited concentration-dependent repellency, indicative of the influence of both acidity and molecular structure on the activity. Oxalic acid was detected in all species and was generally more abundant in the shoots, partially correlating with the repellent strength. This study reveals a previously unrecognized defensive role of plant organic acids and highlights their potential as safe, biodegradable agents for pest management.
We showed that several phytochemicals, but not nutrients, significantly decreased intracellular ATP levels in HT-29 human colon adenocarcinoma cells. Curcumin, one of the active compounds, markedly inhibited the prolifer...We showed that several phytochemicals, but not nutrients, significantly decreased intracellular ATP levels in HT-29 human colon adenocarcinoma cells. Curcumin, one of the active compounds, markedly inhibited the proliferation of HT-29 cells, which was exaggerated in low-glucose media and lipase-downregulated cells as well. In addition, curcumin significantly induced lipolysis. Collectively, curcumin may inhibit cancer cell growth by inducing energy starvation.
The stringent response is a conserved stress-adaptation program in bacteria, mediated by the alarmones (p)ppGpp that reprogram transcription, translation, and metabolism. This mini-review surveys mechanistic, physiologic...The stringent response is a conserved stress-adaptation program in bacteria, mediated by the alarmones (p)ppGpp that reprogram transcription, translation, and metabolism. This mini-review surveys mechanistic, physiological, and evolutionary facets of alarmone singnaling across two classes of RelA/SpoT homologue (RSH) enzymes: multidomain-containing long RSHs and small alarmone synthetases/hydrolases (SAS/SAH). We first outline how activation is ribosome-centered: in Escherichia coli, synthesis-only RelA is activated only when bound to a starved ("hungry") ribosome, while SpoT is hydrolase-biased; in Bacillus subtilis, a single bifunctional Rel shifts from hydrolysis- to synthesis-state when locked on a starved ribosome. Beyond (p)ppGpp, SAS enzymes diversify outputs by producing adenosine alarmones such as (p)ppApp and, in toxic SAS (toxSAS) modules, by pyrophosphorylating the tRNA 3'-CCA end. Finally, we discuss evolutionary trajectories-from SAH-SAS operons to fused, ribosome-regulated long RSHs-and argue that pseudo-ZFD motifs in some toxSAS likely represent independent acquisitions.
Salmon milt extract (SME) is rich in deoxyribonucleic acids and has been suggested as a functional material. However, whether these components contribute to SME's functionality remains unclear, and data on their intestin...Salmon milt extract (SME) is rich in deoxyribonucleic acids and has been suggested as a functional material. However, whether these components contribute to SME's functionality remains unclear, and data on their intestinal absorption are limited. This study investigated absorption mechanisms of deoxyribonucleic acid components in SME using in-situ and in-vitro models. Ultra-performance liquid chromatography/tandem mass spectrometry was used to simultaneously quantify four deoxyribonucleosides (dNs). The in-situ rat intestinal loop study showed increased levels of 2'-deoxyadenosine (dAdo) and 2'-deoxyguanosine (dGuo) in the portal vein. In the transcellular transport assay, dAdo and dGuo levels on the receiver side increased in a time-dependent manner after SME treatment, particularly in human induced pluripotent stem cell-derived small intestinal epithelial cells. No increase in 2'-deoxycytidine or thymidine levels was observed under any experimental condition. These results indicate that purine dNs are absorbed into the portal vein after oral intake of SME, whereas intestinal absorption of pyrimidine dNs is limited.
Hyperglycemia activates the polyol pathway, producing fructose, which promotes glycation and denatures α-crystallin, ultimately leading to diabetic cataracts. This study compared the antiglycation effects of SMR and SBN,...Hyperglycemia activates the polyol pathway, producing fructose, which promotes glycation and denatures α-crystallin, ultimately leading to diabetic cataracts. This study compared the antiglycation effects of SMR and SBN, using a fructose-induced human αA-crystallin glycation model. Through fluorescence analysis, SDS-PAGE, and Western blotting methods, we found that glycation caused αA-crystallin to form fluorescent advanced glycation end products (AGEs), cross-linking AGEs, and Nε-carboxymethyllysine (CML). Results show that SMR (> 20 μg/mL) and SBN (> 100 μg/mL) effectively inhibited cross-linking AGEs and CML formation. At concentrations above 4 μg/mL, both significantly reduced fluorescent AGEs, with SMR showing 91.0 ± 0.8% inhibition and SBN 81.1 ± 1.7% at 100 μg/mL. SMR also outperformed aminoguanidine hydrochloride in reducing carbonyl content at 500 μg/mL. Therefore, SMR exhibited stronger antiglycation and antioxidation properties than SBN, showing potential as a natural health product to prevent diabetic cataract formation.
Transplanting allogeneic or even interspecies mitochondria to modulate cancer malignancy was investigated herein. Melanoma is a highly metastatic cancer that strongly relies on mitochondrial function. The mitochondrial m...Transplanting allogeneic or even interspecies mitochondria to modulate cancer malignancy was investigated herein. Melanoma is a highly metastatic cancer that strongly relies on mitochondrial function. The mitochondrial membrane potential (MMP) and ATP of human (A375) and mouse (B16F10) melanoma cells, and four donor cells, human and mouse (MPEK-BL6) keratinocytes, human (HUVEC) and mouse endothelial cells were compared. The mitochondrial transplantations between mouse and human were identified. HUVEC mitochondria could uniquely retard the migration of B16F10. HUVEC mitochondria could be substantially transplanted into B16F10 and were colocalized with endogenous B16F10 mitochondria, in which, the branched mitochondria were converted into globular mitochondria. The reduced DRP1 and LC3 II corresponded to the reduced MMP and ATP. The decreased TGF-β, NANOG, SOX2, SMAD2/3, AKT, ERK, N-cadherin, and MMP-9 corresponded to the attenuated invasion, elevated reactive oxygen species and impaired cell viability. In conclusion, the feasibility of interspecies mitochondrial transplantation was preliminarily validated.
Epithelial-mesenchymal transition (EMT) is an essential event during the initial steps of the cancer metastasis process. Resveratrol, a natural polyphenolic compound, has received considerable attention for its inhibitor...Epithelial-mesenchymal transition (EMT) is an essential event during the initial steps of the cancer metastasis process. Resveratrol, a natural polyphenolic compound, has received considerable attention for its inhibitory effects on cancer metastasis through the prevention of EMT, but the specific mechanisms have not yet been fully elucidated. To address this issue, we investigated the effects of resveratrol on the migration of SW480 cells using a high glucose-induced EMT model. The data revealed that resveratrol inhibited the high glucose-induced migration of SW480. Resveratrol also decreased the levels of heat shock factor 1 (HSF1), a modulator of EMT marker molecules, which is often overexpressed in cancer cells. Resveratrol-induced HSF1 suppression was linked to the inhibition of EMT-associated cell migration. Furthermore, resveratrol reduced HSF1 expression by inducing a proteasome-mediated degradation. Our results provide the first evidence that resveratrol inhibits the EMT of cancer cells, which might be involved in the suppression of HSF1.