Gut microbiota promotes stem cell differentiation through macrophage and mesenchymal niches in early postnatal development.

Intestinal stem cell maturation and development coincide with gut microbiota exposure after birth. Here, we investigated how early life microbial exposure, and disruption of this process, impacts the intestinal stem cell niche and development. Single-cell transcriptional analysis revealed impaired stem cell differentiation into Paneth cells and macrophage specification upon antibiotic treatment in early life. Mouse genetic and organoid co-culture experiments demonstrated that a CD206+ subset of intestinal macrophages secreted Wnt ligands, which maintained the mesenchymal niche cells important for Paneth cell differentiation. Antibiotics and reduced numbers of Paneth cells are associated with the deadly infant disease, necrotizing enterocolitis (NEC). We showed that colonization with Lactobacillus or transfer of CD206+ macrophages promoted Paneth cell differentiation and reduced NEC severity. Together, our work defines the gut microbiota-mediated regulation of stem cell niches during early postnatal development.

The multiple roles of enteric glial cells in intestinal homeostasis and regeneration.

The gastrointestinal tract is innervated by the enteric nervous system (ENS), a complex network of neurons and glial cells, also called the "second brain". Enteric glial cells, one of the major cell types in the ENS, are located throughout the entire gut wall. Accumulating evidence has demonstrated their critical requirement for gut physiology. Notably, recent studies have shown that enteric glial cells control new aspects of gut function such as regulation of intestinal stem cell behavior and immunity. In addition, the emergence of single-cell genomics technologies has revealed enteric glial cell heterogeneity and plasticity. In this review, we discuss established and emerging concepts regarding the roles of mammalian enteric glial cells and their heterogeneity in gut development, homeostasis, and regeneration.

Pamidronate-induced irreversible symptomatic hypocalcemia in a dog with hypercalcemia after glucocorticoid withdrawal: a case report.

BACKGROUND: Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an unusual case of severe, irreversible hypocalcemia after a single injection of pamidronate for the treatment of hypercalcemia due to glucocorticoid withdrawal in a dog. CASE PRESENTATION: An 11-year-old castrated male Maltese dog presented with anorexia, vomiting, and diarrhea (day 0). The patient had calcinosis cutis throughout the body, calcification of intraabdominal organs, mild azotemia, and severe hypercalcemia. The severe calcification was attributed to long-term glucocorticoid administration, which was discontinued 1 month before presentation. Fluid therapy, diuretics, calcitonin, and a single intravenous injection of pamidronate were used for the treatment of hypercalcemia. On day 14, normocalcemia was achieved, but renal failure occurred. On day 20, severe and irreversible hypocalcemia occurred, and on day 42, the patient was euthanized at the owner's request because of worsened hypocalcemia and renal failure. CONCLUSIONS: Although hypocalcemia is an extremely rare adverse event of bisphosphonate treatment, bisphosphonates like pamidronate can result in potentially life-threatening conditions according to the patient's underlying conditions. Therefore, the patient's condition should be closely monitored and any underlying conditions should be carefully evaluated before initiating the treatment for hypercalcemia using pamidronate.

Capturing anatomy in computed tomography scans for genital pathology.

PURPOSE: In this cross-sectional study, we aimed to characterize how frequently the anatomy of interest (AOI) was excluded when evaluating genital pathology using the current CT pelvis protocol recommended by the American College of Radiology and evaluate how AOI exclusion affects patient management. METHODS: We retrospectively reviewed medical records, using diagnosis and CPT codes, of patients admitted with genital pathology who obtained a CT scan at our institution from July 1, 2020-April 30, 2023. Baseline patient demographics were included. Data about each index CT scan (scan obtained at our institution) were recorded and assessed for exclusion of the AOI. Statistical analysis was performed to determine the rate of AOI exclusion and to compare patient management between patients with AOI excluded versus those without AOI exclusion. RESULTS: 113 presentations for genital pathology included an index CT scan and were included for analysis. Patients were primarily men (98%) with a mean age of 53.1 years (SD 13.9). The most common diagnoses were Fournier's gangrene (35%), scrotal abscess (22%) and unspecified infection (19%). 26/113 scans (23%) did not capture the entire AOI. When the AOI was missed during the index scan, there was a higher rate of obtaining additional scans (38% vs. 21%), but a similar rate of intervention (77% vs. 63%) when compared to index scans that captured the entire AOI. 35 scans (31%) had protocol-extending instructions; index scans that captured the entire AOI were more likely to have specific protocol-extending instructions (38% vs. 8% p < 0.01). CONCLUSIONS: Creating a specific CT protocol for genital pathology could decrease the amount of inappropriate irradiation and improve AOI capture rates without relying on specific request for protocol deviation.

Selectively Enhanced Electrocatalytic Oxygen Evolution within Nanoscopic Channels Fitting a Specific Reaction Intermediate for Seawater Splitting.

Abundant availability of seawater grants economic and resource-rich benefits to water electrolysis technology requiring high-purity water if undesired reactions such as chlorine evolution reaction (CER) competitive to oxygen evolution reaction (OER) are suppressed. Inspired by a conceptual computational work suggesting that OER is kinetically improved via a double activation within 7 Å-gap nanochannels, RuO2 catalysts are realized to have nanoscopic channels at 7, 11, and 14 Å gap in average (dgap ), and preferential activity improvement of OER over CER in seawater by using nanochanneled RuO2 is demonstrated. When the channels are developed to have 7 Å gap, the OER current is maximized with the overpotential required for triggering OER minimized. The gap value guaranteeing the highest OER activity is identical to the value expected from the computational work. The improved OER activity significantly increases the selectivity of OER over CER in seawater since the double activation by the 7 Å-nanoconfined environments to allow an OER intermediate (*OOH) to be doubly anchored to Ru and O active sites does not work on the CER intermediate (*Cl). Successful operation of direct seawater electrolysis with improved hydrogen production is demonstrated by employing the 7 Å-nanochanneled RuO2 as the OER electrocatalyst.

Intrarectal Foley catheter-assisted high-intensity focused ultrasound ablation for benign uterine diseases beyond the treatment region.

OBJECTIVE: To evaluate the feasibility of using an intrarectal Foley catheter during ultrasound-guided high-intensity focused ultrasound (US-HIFU) in patients with benign uterine diseases of the posterior wall beyond the HIFU therapeutic range. METHODS: Patients were treated with US-HIFU and lesion changes were monitored using contrast-enhanced MRI from June 2020 to September 2021. A Foley catheter was inserted into the rectum to facilitate a successful US-HIFU ablation. Complications and lesion responses were recorded during the treatment and follow-up. RESULTS: Thirteen patients with 14 lesions beyond the device's treatable area were enrolled. The average placement time and insertion depth of the intrarectal Foley catheter was 7.6 ± 2.7 min and 23.2 ± 7.6 cm, respectively. A median of 50 mL degassed water was injected into the Foley catheter balloon. All 14 lesions were successfully pushed into a treatable area and subjected to HIFU. The average treatment time, irradiation time, and total therapeutic energy of HIFU were 44.2 ± 17.3 min, 394.4 ± 295.7 s, and 73.3 ± 46.6 kJ, respectively. The mean non-perfusion volume (NPV) in all treated lesions was 23.2 ± 19.2 cm3, and the mean NPV ratio was 57.8 ± 16.9%. Major complications were not observed. CONCLUSION: Intrarectal Foley catheter-assisted US-HIFU is effective and safe. Its clinical application could benefit patients with benign uterine diseases outside the HIFU therapeutic range.

Subcutaneous emphysema and pneumomediastinum following orbital blowout pathological fracture in a cat with nasal lymphoma: a case report.

BACKGROUND: Subcutaneous emphysema and pneumomediastinum are rare complications associated with orbital blowout pathological fracture. CASE PRESENTATION: A 7-year old, castrated male Abbysinian cat presented with anorexia, lethargy, nausea, eyelid swelling, nasal discharge, and sneezing. Based on the clinical and diagnostic work-up, the cat was diagnosed with T cell high-grade nasal lymphoma associated with orbital pathological fracture due to the tumour invasion. After chemotherapy, the cat showed massive subcutaneous emphysema from frontal region to abdomen and pneumomediastinum due to orbital blowout pathological fracture. As the nasal mass decreased in volume; the air had moved from the maxillary sinus to the subcutaneous region and the mediastinum through fascial planes in the head and neck region. CONCLUSIONS: This is a first case report of a massive subcutaneous emphysema and pneumomediastinum due to an orbital blowout pathological fracture following chemotherapy in feline nasal lymphoma in veterinary medicine.

Retrospective evaluation of prognosis and survival with various immunosuppressants in 82 dogs diagnosed with meningoencephalitis of unknown etiology (2010-2021).

BACKGROUND: Meningoencephalomyelitis of unknown etiology (MUE) is a comprehensive term for non-infectious inflammatory brain diseases of the central nervous system (CNS) caused by abnormal autoimmune responses. This study aims to compare the differences in survival and clinical response of MUE according to the adjuvant immunosuppressant use. Medical records of 82 dogs diagnosed with MUE were reviewed retrospectively. RESULTS: The overall survival time was 769 days (range 14-2687 days). The median survival time for each adjunctive was: leflunomide 1035 days (range 126-2163 days), mycophenolate mofetil 865 days (range 39-2191 days), cyclosporin 441 days (range 11-2176 days), cytosine arabinoside 754 days (range 6-1898 days) and a combination of mycophenolate mofetil and cytosine arabinoside 132 days (range 23-1227 days). There was no significant difference in the incidence rate of adverse events according to the immunosuppressants, but moderate to severe anemia was confirmed in 3 patients (18.7%) in the leflunomide group. CONCLUSIONS: The survival time and response rate of MUE dogs differed depending on which adjunctive immunosuppressants were used. Leflunomide showed a long survival time and a relatively good response rate in dogs with MUE. However, a large-scale further study with standardized doses of immunosuppressants and supportive treatment and constant monitoring interval is needed.

Anti-inflammatory effect of polydeoxyribonucleotides (PDRN) extracted from red alga (Porphyra sp.) (Ps-PDRN) in RAW 264.7 macrophages stimulated with Escherichia coli lipopolysaccharides: A comparative study with commercial PDRN.

Polydeoxyribonucleotide (PDRN) is a DNA-derived drug extracted from the sperm cells of Oncorhynchus mykiss or O. keta. PDRN exhibits wound healing and anti-inflammatory activities by activating adenosine A2A receptor and salvage pathways. However, commercial PDRN products (e.g., Placentex, Rejuvenex, and HiDr) have limitations as they are exclusively extracted O. mykiss and O. keta, which are expensive and can only be used as extraction sources during a specific period when their sperm cells are activated. Therefore, this study aimed to extract PDRN from Porphyra sp. (Ps-PDRN) and investigate whether it has anti-inflammatory activity through a comparative study with commercial product. The results indicated that Ps-PDRN had an anti-inflammatory effect on Escherichia coli lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophages. It inhibited nitric oxide production and inducible nitric oxygen synthase protein expression by suppressing phosphorylation of p38 and ERK, without cytotoxicity. Furthermore, Ps-PDRN promoted cell proliferation and collagen production in human dermal fibroblast. In conclusion, our study confirms that Ps-PDRN exhibits both anti-inflammatory and cell proliferative effects. These results indicated that Ps-PDRN has the potential as a bioactive drug for tissue engineering.

What we need to know about uncertainty in illness among people with primary malignant brain tumours: A mixed-methods systematic review.

AIMS AND OBJECTIVES: To identify the characteristics of uncertainty in illness (UI) among people with primary malignant brain tumours (PMBT). BACKGROUND: High recurrence rates and complex symptoms cause uncertainty in people with PMBT. Given the characteristics of PMBT, reviewing UI among people with PMBT will benefit future research and clinical intervention development. DESIGN: A mixed-methods systematic review. METHODS: We performed a mixed-methods systematic review (PubMed, CINAHL, Embase, PsycINFO, Scopus and Cochrane Library), including studies on UI among people with PMBT, searched from the databases' inception to the search date. The initial search was conducted in July 2021, with an additional search in March 2022. The major search terms were PMBT and UI, and no limitations were placed on the study design. The Cochrane tool was used to evaluate the risk of bias in randomised controlled trials, and JBI checklists were used to evaluate quasi-experimental studies, survey methodology studies and a case study. This review was reported using the PRISMA 2020 checklist. Both quantitative and qualitative research data were extracted, analysed and then integrated in three stages of a mixed-methods systematic review. RESULTS: Eleven studies were included. Due to physical, psychological and social risk factors, the UI progression of people with PMBT was complex and ambiguous, although they adapted to the PMBT diagnosis and treatment process. Subsequently, we proposed a model of UI among people with PMBT. CONCLUSIONS: UI has multidimensional characteristics, and healthcare providers need to consider these aspects for people with PMBT. RELEVANCE TO CLINICAL PRACTICE: The proposed model provides directions for nursing practice and future research. Nurses caring for people with PMBT should comprehend their UI and intervene accordingly. PATIENT OR PUBLIC CONTRIBUTION: This review incorporated data including people with PMBT in hospitals and communities. This analysis contributes to the clinical-to-community nursing transition process for people with PMBT.

Anti-Cancer Effect of Chlorophyllin-Assisted Photodynamic Therapy to Induce Apoptosis through Oxidative Stress on Human Cervical Cancer.

Photodynamic therapy is an alternative approach to treating tumors that utilizes photochemical reactions between a photosensitizer and laser irradiation for the generation of reactive oxygen species. Currently, natural photosensitive compounds are being promised to replace synthetic photosensitizers used in photodynamic therapy because of their low toxicity, lesser side effects, and high solubility in water. Therefore, the present study investigated the anti-cancer efficacy of chlorophyllin-assisted photodynamic therapy on human cervical cancer by inducing apoptotic response through oxidative stress. The chlorophyllin-assisted photodynamic therapy significantly induced cytotoxicity, and the optimal conditions were determined based on the results, including laser irradiation time, laser power density, and chlorophyllin concentration. In addition, reactive oxygen species generation and Annexin V expression level were detected on the photodynamic reaction-treated HeLa cells under the optimized conditions to evaluate apoptosis using a fluorescence microscope. In the Western blotting analysis, the photodynamic therapy group showed the increased protein expression level of the cleaved caspase 8, caspase 9, Bax, and cytochrome C, and the suppressed protein expression level of Bcl-2, pro-caspase 8, and pro-caspase 9. Moreover, the proposed photodynamic therapy downregulated the phosphorylation of AKT1 in the HeLa cells. Therefore, our results suggest that the chlorophyllin-assisted photodynamic therapy has potential as an antitumor therapy for cervical cancer.

Evaluation of endothelial cell-specific molecule-1 as a biomarker of glycocalyx damage in canine myxomatous mitral valve disease.

BACKGROUND: Endothelial cell-specific molecule-1 (ESM-1) has emerged as a potential biomarker for cardiovascular disease in humans. Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs, and we hypothesized that MMVD causes chronic inflammation that increases susceptibility to endothelial glycocalyx (eGCX) damage. In this study, we measured the concentration of ESM-1 in a group of dogs with MMVD and evaluated factors affecting eGCX damage. RESULTS: Sixty-four dogs (control, n = 6; MMVD, n = 58) were enrolled in this study. There was no significant difference in serum ESM-1 concentrations among the MMVD stages. The serum ESM-1 concentration was significantly higher in the death group than in the alive group in MMVD dogs. (p = 0.006). In five dogs with MMVD, serum ESM-1 concentrations tended to decrease when the cardiac drug (pimobendan, furosemide, and digoxin) dose was increased. CONCLUSIONS: In cases where MMVD progressed to decompensated heart failure with clinical symptoms and resulted in death, the concentration of serum ESM-1 increased significantly. Therefore, ESM-1 could be utilized as a new potential negative prognostic factor in patients with MMVD.

Impact of BRCA mutations and hormone receptor status on reproductive potential in breast cancer patients undergoing fertility preservation.

OBJECTIVE: To identify whether the BRCA mutations and hormone receptor status affect the ovarian reserve and ovarian stimulation outcomes in breast cancer patients undergoing fertility preservation. METHODS: A total of 117 women diagnosed with breast cancer who were referred to the fertility preservation clinics at Seoul National University Bundang Hospital and Seoul National University Hospital between September 2012 and July 2019 undergone ovarian stimulation for oocyte retrieval. Basal characteristics including age, BMI, basal AMH, basal FSH, and fertility preservation outcomes such as the number of retrieved oocytes and mature oocytes were compared retrospectively. RESULTS: BRCA1 mutation was noted in 25 women, and BRCA2 mutation was observed in 35 women. Positive estrogen receptor status was noted in 87 women, and positive progesterone receptor status was noted in 69 women. HER2 was positive in 55 women, and 19 women were diagnosed with triple-negative breast cancers. The number of total oocytes retrieved was lower in patients with BRCA mutation (8.3 ± 5.4 vs. 15.3 ± 8.7, p = .002). The number of mature oocytes retrieved was also lower in BRCA carriers (4.7 ± 4.2 vs. 8.7 ± 7.9, p = .025). Triple-negative breast cancer (TNBC) patients were younger than non-TNBC patients (30.3 ± 4.8 vs. 33.9 ± 5.0, p = .007). The rate of mature oocyte rate was higher in TNBC patients (68.6%±20.6 vs. 52.5%±29.7, p = .037). CONCLUSIONS: Our study demonstrated that BRCA carriers with breast cancer had comparable ovarian reserve to non-carriers but the response to ovarian stimulation was lower. We also observed that oocyte maturity was higher in TNBC patients, however age might be a confounding factor of this result.

Marine Biological Macromolecules and Chemically Modified Macromolecules; Potential Anticoagulants.

Coagulation is a potential defense mechanism that involves activating a series of zymogens to convert soluble fibrinogen to insoluble fibrin clots to prevent bleeding and hemorrhagic complications. To prevent the extra formation and diffusion of clots, the counterbalance inhibitory mechanism is activated at levels of the coagulation pathway. Contrariwise, this system can evade normal control due to either inherited or acquired defects or aging which leads to unusual clots formation. The abnormal formations and deposition of excess fibrin trigger serious arterial and cardiovascular diseases. Although heparin and heparin-based anticoagulants are a widely prescribed class of anticoagulants, the clinical use of heparin has limitations due to the unpredictable anticoagulation, risk of bleeding, and other complications. Hence, significant interest has been established over the years to investigate alternative therapeutic anticoagulants from natural sources, especially from marine sources with good safety and potency due to their unique chemical structure and biological activity. This review summarizes the coagulation cascade and potential macromolecular anticoagulants derived from marine flora and fauna.

Vascular remodeling by placenta-derived mesenchymal stem cells restores ovarian function in ovariectomized rat model via the VEGF pathway.

Angiogenesis plays an important role in damaged organ or tissue and cell regeneration and ovarian development and function. Primary ovarian insufficiency (POI) is a prevalent pathology in women under 40. Conventional treatment for POI involves hormone therapy. However, due to its side effects, an alternative approach is desirable. Human mesenchymal stem cells (MSCs) from various sources restore ovarian function; however, they have many limitations as stem cell sources. Therefore, it is desirable to study the efficacy of placenta-derived MSCs (PD-MSCs), which possess many advantages over other MSCs, in a rat model of ovarian dysfunction. Here, we investigated the restorative effect of PD-MSCs on injured ovaries in ovariectomized (OVX) rats and the ability of intravenous transplantation (Tx) of PD-MSCs (5 × 105) to enhance ovarian vasculature and follicular development. ELISA analysis of serum revealed that compared to the non-transplantation (NTx) group, the Tx group showed significantly increased levels of anti-Müllerian hormone, follicle stimulating hormone, and estradiol (E2) (*P < 0.05). In addition, histological analysis showed more mature follicles and less atresia and restoration of expanded blood vessels in the ovaries of the OVX PD-MSC Tx group than those of the NTx group (*P < 0.05). Furthermore, folliculogenesis-related gene expression was also significantly increased in the PD-MSC Tx group (*P < 0.05). Vascular endothelial growth factor (VEGF) and VEGF receptor 2 expressions were increased in the ovaries of the OVX PD-MSC Tx group compared to the NTx group through PI3K/AKT/mTOR and GSK3ß/ß-catenin pathway activation. Interestingly, ex vivo cocultivation of damaged ovaries and PD-MSCs or treatment with recombinant VEGF (50 ng/ml) increased folliculogenic factors and VEGF signaling pathways. Notably, compared to recombinant VEGF, PD-MSCs significantly increased folliculogenesis and angiogenesis (*P < 0.05). These findings suggest that VEGF secreted by PD-MSCs promotes follicular development and ovarian function after OVX through vascular remodeling. Therefore, these results provide fundamental data for understanding the therapeutic effects and mechanism of stem cell therapy based on PD-MSCs and provide a theoretical foundation for their application for obstetrical and gynecological diseases, including infertility and menopause.

Applications of Marine Organism-Derived Polydeoxyribonucleotide: Its Potential in Biomedical Engineering.

Polydeoxyribonucleotides (PDRNs) are a family of DNA-derived drugs with a molecular weight ranging from 50 to 1500 kDa, which are mainly extracted from the sperm cells of salmon trout or chum salmon. Many pre-clinical and clinical studies have demonstrated the wound healing and anti-inflammatory properties of PDRN, which are mediated by the activation of adenosine A2A receptor and salvage pathways, in addition to promoting osteoblast activity, collagen synthesis, and angiogenesis. In fact, PDRN is already marketed due to its therapeutic properties against various wound healing- and inflammation-related diseases. Therefore, this review assessed the most recent trends in marine organism-derived PDRN using the Google Scholar search engine. Further, we summarized the current applications and pharmacological properties of PDRN to serve as a reference for the development of novel PDRN-based technologies.

Anti-Allergic Effect of Low Molecular Weight Digest from Abalone Viscera on Atopic Dermatitis-Induced NC/Nga.

Abalone viscera (AV) is one of the byproducts of the seafood processing industry. The low molecular weight (<5 kDa) peptides (LMW-AV) obtained from gastrointestinal digestion of AV could suppress allergenic responses on activated HMC-1 human mast cells in our previous study. Regarding the allergenic response of LMW-AV, in the present study, we further investigated the potential of oral administration of LMW-AV against atopic dermatitis (AD) in a dermatitis-induced model stimulated with Dermatophagoides farinae. The results demonstrated that the LMW-AV reduced a number of clinical symptoms, such as the severity of the dermatitis and serum immunoglobulin E levels. Moreover, LMW-AV could inhibit the expression of chemokines and cytokines. The histological analysis indicated that the LMW-AV has suppressed the eosinophil count and the mast cell infiltration into the upper dermis. The results suggest that LMW-AV can be considered as a promising candidate for AD treatment.

Effects of Ethanol Extracts from Grateloupia elliptica, a Red Seaweed, and Its Chlorophyll Derivative on 3T3-L1 Adipocytes: Suppression of Lipid Accumulation through Downregulation of Adipogenic Protein Expression.

Grateloupia elliptica (G. elliptica) is a red seaweed with antioxidant, antidiabetic, anticancer, anti-inflammatory, and anticoagulant activities. However, the anti-obesity activity of G. elliptica has not been fully investigated. Therefore, the effect of G. elliptica ethanol extract on the suppression of intracellular lipid accumulation in 3T3-L1 cells by Oil Red O staining (ORO) was evaluated. Among the eight red seaweeds tested, G. elliptica 60% ethanol extract (GEE) exhibited the highest inhibition of lipid accumulation. GEE was the only extract to successfully suppress lipid accumulation among ethanol extracts from eight red seaweeds. In this study, we successfully isolated chlorophyll derivative (CD) from the ethyl acetate fraction (EA) of GEE by high-performance liquid chromatography and evaluated their inhibitory effect on intracellular lipid accumulation in 3T3-L1 adipocytes. CD significantly suppressed intracellular lipid accumulation. In addition, CD suppressed adipogenic protein expression such as sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (C/EBP-α), and fatty acid binding protein 4 (FABP4). Taken together, our results indicate that CD from GEE inhibits lipid accumulation by suppressing adipogenesis via the downregulation of adipogenic protein expressions in the differentiated adipocytes. Therefore, chlorophyll from G. elliptica has a beneficial effect on lipid metabolism and it could be utilized as a potential therapeutic agent for preventing obesity.

Synergistic Effect of Methyl Jasmonate and Abscisic Acid Co-Treatment on Avenanthramide Production in Germinating Oats.

The oat (Avena sativa L.) is a grain of the Poaceae grass family and contains many powerful anti-oxidants, including avenanthramides as phenolic alkaloids with anti-inflammatory, anti-oxidant, anti-itch, anti-irritant, and anti-atherogenic activities. Here, the treatment of germinating oats with methyl jasmonate (MeJA) or abscisic acid (ABA) resulted in 2.5-fold (582.9 mg/kg FW) and 2.8-fold (642.9 mg/kg FW) increase in avenanthramide content, respectively, relative to untreated controls (232.6 mg/kg FW). Moreover, MeJA and ABA co-treatment synergistically increased avenanthramide production in germinating oats to 1505 mg/kg FW. Individual or combined MeJA and ABA treatment increased the expression of genes encoding key catalytic enzymes in the avenanthramide-biosynthesis pathway, including hydroxycinnamoyl-CoA:hydrocyanthranilate N-hydroxycinnamoyl transferase (HHT). Further analyses showed that six AsHHT genes were effectively upregulated by MeJA or ABA treatment, especially AsHHT4 for MeJA and AsHHT5 for ABA, thereby enhancing the production of all three avenanthramides in germinating oats. Specifically, AsHHT5 exhibited the highest expression following MeJA and ABA co-treatment, indicating that AsHHT5 played a more crucial role in avenanthramide biosynthesis in response to MeJA and ABA co-treatment of germinating oats. These findings suggest that elicitor-mediated metabolite farming using MeJA and ABA could be a valuable method for avenanthramide production in germinating oats.