아밀라제

Several studies have evaluated the effects of the dietary application of exogenous alpha-amylase preparations (AMA) as a strategy to increase total tract starch digestibility (TTSD) and milk yield (MY) in dairy cows, but the results have been inconsistent. Thus, the objective of this study was to evaluate the effects of the dietary application of AMA on the performance, digestibility, and rumen fermentation of lactating dairy cows using a meta-analytic method. A total of 18 peer-reviewed manuscripts (N = 32 treatment comparisons) from 2003 to 2019 were systematically identified following the PRISMA method. The weighted raw mean differences between dietary AMA and control treatments were compared with a robust variance estimation. Likewise, diet characteristics like crude protein (CP) content, NDF content, starch content, days in milk (DIM), experimental design (Latin square and continuous), and AMA dose (0 to 732 Kilo Novo units [KNU]/kg TMR) were used as covariates in a meta-regression, subgrouping, and dose-response analysis. Compared to the control, dietary AMA increased (P < 0.05) DM digestibility (69.32% vs. 68.30%), TTSD (94.62% vs. 94.10%), milk protein concentration and yield (3.11% vs. 3.08%; 1.14 vs. 1.10 kg/d) and tended to increase (P = 0.09) fat-corrected milk (35.96 vs. 35.10 kg/d), but no effects were observed on DM intake (22.99 vs. 22.90 kg/d) and feed efficiency (1.50 vs. 1.48). Dietary AMA tended (P = 0.10) to reduce rumen pH (6.27 vs. 6.30). Both the enzyme dose and DIM strongly influenced (P < 0.05) the effects of AMA on digestibility and performance. The dose-response analysis revealed that feeding 600 KNU/kg to high-producing early lactation (< 70 DIM) dairy cows increased FCM and milk protein. Accounting for the type of experimental design was associated with a lower between-studies-variance among comparisons. Overall, this meta-analysis supports the hypothesis that dietary AMA supplementation is associated with a better lactational performance in dairy cows. However, these effects are only suitable for high-producing early lactation dairy cows. Plain Language Summary: For more than a decade, starch-degrading enzymes (amylolytic enzymes)

BACKGROUND: Retrospective evaluations of multidisciplinary team (MDT) review of pancreatic cystic lesions (PCL) demonstrate improved PCL management. Endoscopic ultrasound (EUS) evaluates PCL for worrisome features; however, its influence on MDT is unclear and may be attenuated by anchoring/confirmation bias. We aimed to evaluate the impact of EUS and the overall performance of MDT evaluation of PCL. METHODS: Four mock MDT sessions at two institutions were presented imaging from 40 consecutive PCL cases (20 "high-risk" with advanced neoplasia, 20 "low-risk" with pathologic low-grade dysplasia or ≥ 3 years of non-progression on surveillance), with and without upfront EUS/FNA (cytology, CEA, Amylase), in a randomized, crossover design. Group 1 adjudicated without EUS, Group 2 adjudicated with EUS, and Group 3 adjudicated with EUS after initially adjudicating without it. RESULTS: The cohort included branch-duct (n = 20), mixed type (n = 6), and main duct (n = 4) IPMN, MCN (n = 5), and non-mucinous PCL (n = 5). Group 2 (EUS) correctly identified mucinous PCL with 97% sensitivity and 70% specificity, significantly higher than Group 1 (No EUS) (Sensitivity 91%, Specificity 20%; p = 0.04). Group 3 (Unblinded to EUS) performed significantly worse in mucinous PCL identification compared with Group 2, indicating cognitive bias (Sensitivity 97%, Specificity 10% (p = 0.0003)). Group 2 correctly identified high-risk PCL that required surgical intervention with 85% sensitivity and 85% specificity, significantly higher than Group 1 (Sensitivity 60%, Specificity 75%; p = 0.0016) and Group 3 (Sensitivity 73%, Specificity 80%, p = 0.0485). CONCLUSION: While susceptible to cognitive bias, EUS significantly improves MDT assessment of PCL. MDT establishes a high bar for iterative additions of biomarkers to PCL analysis. © 2026 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.

BACKGROUND: Wellness tourism increasingly incorporates short yoga sessions for stress management, yet evidence on their immediate physiological and emotional responses remains limited. OBJECTIVE: This exploratory pilot study aimed to generate preliminary data on acute physiological and emotional responses to a single 24-minute yoga session (breathing, postures, and meditation) compared with quiet sitting in novice practitioners. METHODS: In this single-center, randomized waitlist-controlled exploratory pilot study (1:1 allocation), 19 university-affiliated adults with self-reported daily stress and no prior guided yoga experience were allocated to an immediate 24-minute yoga session (n=10) or quiet sitting (n=9). The primary outcome was change in salivary cortisol from baseline to postintervention. Secondary outcomes included salivary alpha-amylase, heart rate (Apple Watch [Apple Inc], subset n=12), and real-time emotional indices (stress, calmness, and concentration) measured by a commercial single-channel electroencephalogram (EEG) device (Kansei Analyzer [Dentsu ScienceJAM], subset n=8). Data were analyzed using change scores relative to the breathing phase, with between-group comparison performed by independent t tests or multivariable linear regression adjusted for age, sex, and baseline values as appropriate. RESULTS: No significant between-group differences were observed for salivary cortisol or alpha-amylase. In the yoga group, heart rate increased during postures and remained mildly elevated during meditation relative to the breathing phase, consistent with mild physical exertion. Exploratory individual EEG analyses suggested reduced stress and increased concentration during breathing and meditation phases in some participants. CONCLUSIONS: In this small exploratory pilot study, a single 24-minute yoga session did not significantly alter salivary stress biomarkers at the group level. However, it induced measurable cardiovascular activation and heterogeneous EEG-derived emotional responses. These hypothesis-generating findings demonstrate marked interindividual variability, suggesting the need for larger validation studies with improved control condition

Dyspnea is the symptom that conveys the upsetting or distressing awareness of respiratory sensations. It is part of an ensemble of respiratory, neurovegetative, and behavioral manifestations resulting from the brain's reaction to abnormal respiratory-related afferents. This attests to a systemic phenomenon and suggests the existence of measurable biological changes. Different types of experimental respiratory challenges evoke different perceptual, physiological, and psychological responses, suggesting distinct mechanisms and the possibility of varied systemic biological responses. We investigated this hypothesis in 34 healthy volunteers (17 women) exposed to inspiratory threshold loading (ITL) and carbon dioxide stimulation with restricted ventilation (CO2-rv), in a randomized cross-over design. Blood and saliva samples were collected at baseline (T0), at the end of a 5-min dyspnea challenge (T1), and at 30 and 60 min postchallenge (T2 and T3). They were analyzed for neuromodulators and inflammatory biomarkers. Substance P levels rose at all time points during both challenges, but were significantly higher after CO2-rv than after ITL. β-Endorphin levels rose similarly after both challenges, with a correlation to affective dyspnea ratings during ITL only (R = 0.527, P = 0.0023). Brain-derived neurotrophic factor (BDNF) decreased after both stimuli, with lower values following ITL. There were no significant changes in salivary α-amylase, FGF-2, TNF-α, IL-1β, IL-8, or indoleamine/tryptophan 2,3-dioxygenase (IDO/TDO) activity, and salivary cortisol decreased. These results provide a biological substrate for the differences between responses to respiratory challenges. They open new avenues toward biology-guided research into respiratory-related brain suffering.NEW & NOTEWORTHY Dyspnea can be induced through different types of respiratory challenges, including inspiratory loading and carbon dioxide stimulation with restricted ventilation. These paradigms elicit different physiological, perceptual, and psychological responses, suggesting distinct modes of engagement of respiratory-related brain suffering. This study shows that the associated biological responses also d

Stress is frequently reported as a trigger for binge episodes, yet it remains unclear how subjective and physiological stress responses interact with cognitive and affective mechanisms to increase binge eating risk. The present study investigated the effects of acute psychosocial stress on binge urges, focusing on the role of state- and trait-level vulnerabilities. Twenty-eight individuals with BED were randomized to either a Stress condition (n = 14) or No-Stress condition (n = 14). Following an acute psychosocial stressor, participants completed the Stop-Signal Task to behaviourally assess inhibitory control. Self-reported mood, binge urge ratings and saliva samples for stress biomarker detection were collected at three timepoints throughout the experimental session. Results demonstrated that acute psychosocial stress elicited marked increases in total mood disturbance, without corresponding physiological stress responses and significantly impaired inhibitory control. Notably, only subjective stress responses were associated with greater binge urges, whereas physiological stress responses were not. This dissociation highlights subjective stress reactivity as a clinically meaningful mechanism of risk in BED, underscoring the potential value of interventions that target stress perception and regulation to reduce binge eating vulnerability.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute Pancreatitis (AP) is a pancreatic inflammatory disease lacking specific therapeutics. Da-Cheng-Qi Decoction (DCQD) has been proven to alleviate the severity and mortality of AP. However, its underlying mechanisms remain to be fully elucidated. AIM OF THE STUDY: This study aimed to explore DCQD's dynamic metabolic regulatory effects on AP patients and potential pharmacodynamic substances via serum metabolomics and serum pharmacochemistry analysis, with validation in animal models. MATERIALS AND METHODS: AP patients were randomized into conventional therapy (Con) and Con + DCQD groups. Fasting venous blood samples were collected at four time points (admission, 24 h/96 h post-admission, pre-discharge) for biochemical assays and UHPLC-Q-Exactive-Orbitrap-MS analysis. Metabolomics was used to screen AP-related biomarkers, evaluate the two regimens' reversal effects, and compare inter-group differences in metabolic recovery trajectories. Prototypes and metabolites of DCQD were identified, with potential pharmacodynamic substances screened via correlation analysis with AP biomarkers. L-arginine-induced SAP mouse model was used for validation. RESULTS: Serum amylase normalization and C-reactive protein decline were accelerated in Con + DCQD group. Both regimens reversed AP-related energy, amino acid, and lipid metabolic disorders. Adjuvant DCQD therapy accelerated inflammation alleviation and energy homeostasis restoration in early stage, and improved lipid metabolism more comprehensively in middle-to-late stage, with efficacy validated in SAP mice. Forty-eight and 35 blood-migrated components were identified in patients and mice, respectively, with 8 key pharmacodynamic substances screened. CONCLUSIONS: Integrating serum metabolomics and multi-time-point monitoring, this study delineated AP's metabolic recovery trajectory and clarified DCQD's efficacy and dynamic metabolic regulation, providing guidance for its clinical application.

OBJECTIVE: Rumination-the repetitive negative thinking about stressful events-impairs biological stress system activity. However, its impact on the habituation of stress responses, particularly of the sympathetic nervous system (SNS) and hypothalamus-pituitary-adrenal (HPA) axis, remains understudied. This study examined how post-event rumination affects the habituation of biological responses to repeated stress. METHODS: In this randomized experimental study, 47 participants were assigned to a rumination or control condition and exposed to two consecutive stress tasks. After the first stress exposure, the rumination group engaged in guided post-event rumination, while the control group reflected on a neutral everyday topic. Biological markers of HPA axis (cortisol) and SNS activity (salivary alpha-amylase, sAA), as well as psychological variables (positive and negative affect, state rumination), were assessed before and after each stressor. RESULTS: Compared with the control group, participants in the rumination condition showed reduced habituation of HPA axis activity ( t(45) =-2.01, p =.025) and increased SNS activation over time, as indicated by rising sAA levels ( t(45) =-2.03, p =.024). No significant group differences were observed in self-reported affect or state rumination. CONCLUSIONS: Post-event rumination impairs biological habituation to repeated stress. These findings suggest that rumination disrupts physiological stress adaptation, which may contribute to prolonged stress responses and increased risk for stress-related health problems. Interventions targeting rumination may support more adaptive stress regulation and promote better health outcomes.

BACKGROUND: Harmful alcohol use and alcohol use disorders (AUD) are major public health issues. Alcohol craving plays a central role in AUD by increasing the likelihood of consumption. While stress is a known trigger for craving, most evidence comes from observational or clinical studies. This study aimed to investigate the causal effect of experimentally induced stress on alcohol craving. METHODS: Two hundred and eighty-eight healthy young men were randomized to either the Trier Social Stress Test or a control condition. Alcohol craving was assessed before and immediately after the task. Stress reactivity was measured via mood scales and biological (salivary cortisol and alpha-amylase) markers. Latent mixture modeling explored variability in the effect of stress exposure on craving, and latent group differences were examined in relation to habitual alcohol use, self-control, anxiety, depression, and emotion dysregulation. RESULTS: Participants exposed to the stressor reported higher poststress craving compared with controls (b = 2.35, 95% CI [0.54, 4.16], p = 0.011). Within the stress group, greater mood changes (b = -0.53, 95% CI [-0.82, -0.24], p < 0.001) and biological (alpha-amylase) stress reactivity (b = 0.01, 95% CI [-0.02, 0.04], p = 0.391) were associated with increased craving. Two latent classes emerged: one (51.4% class membership) showed a positive effect of stress on craving (stress-related craving increase class [SCI]) (b = 5.37, p = 0.002), while the other (49.6%) showed a negative effect (stress-related craving decrease class [SCD]) (b = -2.70, p = 0.012). The SCI class was characterized by higher anxiety and depressive symptoms, greater emotion dysregulation, and lower self-control compared with the SCD class. CONCLUSIONS: Experimental stress can increase alcohol craving, particularly in individuals with certain psychological profiles. Craving was linked to subjective and biological stress reactivity. These findings highlight the importance of individual differences in stress responses and provide targets for more personalized studies on stress-related craving and alcohol use. © 2026 The Author(s). Alcohol, Clinical and Experimental Research

PURPOSE: Cancer-related fatigue (CRF) is a common and debilitating symptom in palliative care, with limited effective treatments. This study evaluated the efficacy and safety of K-style contact needle technique (CNT), a non-invasive form of traditional Japanese acupuncture, for alleviating CRF. METHODS: In this multicenter, single-blind randomized controlled trial, 119 patients with stage III or IV cancer and moderate to severe fatigue (≥ 4 on a Numerical Rating Scale [NRS]) were randomized to receive either CNT or sham CNT weekly for 4 weeks. The primary outcome was change in fatigue NRS scores. Secondary outcomes included the Cancer Fatigue Scale (CFS), Support Team Assessment Schedule-Japanese version (STAS-J), Palliative Prognostic Index (PPI), Palliative Performance Scale (PPS), salivary amylase activity (SAA), and adverse events. RESULTS: Although no significant difference was observed in the primary outcome between groups by t test, multiple regression analysis at Week 4 revealed a significant treatment effect for CNT (β = 1.548, p = 0.029). CNT also improved STAS-J scores (β = 1.758, p = 0.044) and reduced SAA at Week 2 and final evaluation (p < 0.05). No serious adverse events occurred. CONCLUSIONS: CNT may be a safe, gentle, and potentially effective intervention for managing fatigue and distress in palliative care patients with advanced cancer. Further research is warranted to confirm these findings and assess long-term outcomes. TRIAL REGISTRATION: UMIN000028304, registered on July 21st, 2017; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000032401. © 2026. The Author(s).

Glossodynia-related pain refers to persistent, chronic pain occurring on the oral mucosal surface. Various medications are prescribed depending on symptom profiles and have demonstrated therapeutic benefits; however, these agents are often associated with adverse effects such as drowsiness or dizziness. Goreisan, a traditional Japanese Kampo medicine, has long been used empirically for glossodynia-related pain, particularly in patients reporting symptom fluctuation associated with weather changes. Nevertheless, high-quality clinical evidence supporting its efficacy remains limited. This multicenter, randomized, open-label preliminary exploratory study enrolled patients receiving treatment for glossodynia-related pain. Participants were assigned to receive either Goreisan (7.5 g/day for 12 weeks) in addition to standard therapy or standard therapy alone. Pain intensity was assessed using the visual analog scale (VAS) at baseline and at 4, 8, and 12 weeks. Salivary amylase activity was measured as an exploratory stress-related biomarker, and atmospheric pressure was recorded at each outpatient visit. Owing to insufficient enrollment, all analyses were descriptive and exploratory. Pain intensity improved from baseline in both groups. However, the proportion of patients achieving ≥ 20% improvement in VAS at week 12 was not higher in the Goreisan group than in the control group. Weak negative correlations between VAS scores and barometric pressure were observed in both groups (r ≈ - 0.2). No clinically relevant adverse events or hepatic dysfunction related to Goreisan were identified. This preliminary exploratory study did not confirm a clear analgesic efficacy of Goreisan for glossodynia. However, the findings provide descriptive data on pain trajectories, safety, and potential meteorological associations, supporting the need for future large-scale, double-blind, placebo-controlled trials.

BACKGROUND: Age-related decline in digestive function increases malnutrition risk. Supplementing meals with digestive enzymes may improve macronutrient digestion and bioavailability in adults reaching older ages. OBJECTIVES: To assess postprandial plasma nutrient concentrations after co-ingestion of a mixed meal and a mixture of 6 enzyme preparations (ENZ), including proteases, lipase, amylase, and glucoamylase. METHODS: Thirty middle-aged and older adults (56 ± 11 y; 18 females, 12 males) ingested chicken, peas, potatoes, and butter (435 kcal; 34 g protein, 51 g carbohydrate, 11 g fat) with either ENZ or placebo (PLA) in a randomized crossover fashion. Blood samples were collected at baseline and throughout a 0-5 h postprandial period for measurement of plasma amino acid, insulin, glucose, and nonesterified fatty acid (NEFA) concentrations. Clustering of postprandial amino acid responses was conducted in MFuzz, and logistic regression for response groups was conducted in JMP 18.2.0 (JMP Statistical Discovery LLC). RESULTS: Plasma amino acid concentrations were not statistically different between treatments (PLA compared with ENZ) over the postprandial period (all P > 0.05). Leucine time to maximum concentration was significantly faster (P = 0.047) with ENZ (121.2 ± 55.9 min) compared with PLA (141.0 ± 49.2 min). Postprandial plasma glucose concentrations (P = 0.04) and total NEFA (P = 0.001) were higher with ENZ compared with PLA. Three distinct response patterns (clusters) were detected within and across all postprandial amino acid categories. Differences in habitual macronutrient intake and interactions between sex, lean mass, and BMI distinguished participants with an earlier time to maximum postprandial leucine concentration when consuming ENZ compared with PLA from those with stable responses. CONCLUSIONS: Multienzyme supplementation improved macronutrient digestion of a mixed meal in middle-aged and older adults. For plasma amino acids, this benefit was most pronounced in adults with lower BMI and higher lean mass, and the effect was sex-dependent. This study was registered at clinicaltrials.gov as NCT05211440.

12. Neotrop Entomol. 2026 Apr 15;55(1):29. doi: 10.1007/s13744-026-01377-8. Synergistic Action of Alpha-cypermethrin, Propolis Nanoemulsions and Other Activator Adjuvants for Peach Fruit Fly, Bactrcera zonata Management. Romeh AA(1), El-Nagar HM(2), Romeh ZAA(1), Ismail AM(3), Al-Kahtani SN(4),

Background: This study aimed to explore the synergistic hypoglycemic effect and mechanism of 1-deoxynojirimycin (DNJ) in mulberry leaves and theaflavins (TFs) in black tea. Methods: The synergistic inhibition of α-glucosidase and α-amylase by DNJ-TFs was evaluated using enzyme assays and the Chou-Talalay model. Insulin-resistant (IR) HepG2 cells and high-fat diet (HFD)-induced type 2 diabetes mellitus mice were treated with DNJ, TFs, or DNJ-TFs, determining the efficacy of drug combinations by measuring glycolipids and inflammatory factors. Network pharmacology and molecular docking were used to identify key target genes and signaling pathways, and CETSA experiments were used to verify the binding of drugs to targets. Key genes were further verified by immunofluorescence, Western blot, and Real-time PCR. Results: DNJ-TFs synergistically suppressed α-glucosidase (CI = 0.85) and α-amylase (CI = 0.76). In HepG2 cells, DNJ-TFs ameliorated palmitic acid-induced IR by promoting glucose uptake, attenuating lipid accumulation, and regulating glycolipid metabolism. In HFD mice, DNJ-TFs counteracted hyperglycemia, dyslipidemia, systemic inflammation and oxidative stress, elevated HOMA-IR, and hepatic steatosis. Network pharmacology integrated with experimental validation identified PTGS2 and MMP9 as key binding targets of DNJ and TFs. Furthermore, DNJ-TFs could inhibit the increase in liver TNFα protein and the decrease in p-AKT, p-GSKα, p-GSKβ, and GLUT2 protein caused by high fat, both in vivo and in vitro. Conclusions: DNJ and TFs exert synergistic glucose-lowering effects by targeting PTGS2/MMP9 and regulating the TNFα/AKT/GSK3/GLUT2 axis, providing a promising natural therapeutic strategy for diabetes management.

Starch digestion induces postprandial hyperglycemia, which can be modulated by polyphenols and polysaccharides via α-amylase inhibition. Current research focuses on individual α-amylase inhibitors, neglecting the activity changes of combined compounds induced by structural differences. This study explored the inhibitory effect and mechanism of the epigallocatechin gallate (EGCG) and exopolysaccharides from Bacillus subtilis STB22 (BS-EPS) complex on porcine pancreatic α-amylase (PPA). The results showed that EGCG (30 mg/mL) and BS-EPS (0.1 mg/mL) individually inhibited PPA by 44.47 % and 21.55 %, respectively, while their complex exhibited enhanced inhibition (72.95 %). The combination index ≤1 confirmed a synergistic and additive inhibitory effect. Mechanistic studies revealed that EGCG and BS-EPS acted as non-competitive and mixed-type inhibitors of PPA, respectively. When combined, they formed a monolayer adsorption complex that exhibited mixed-type inhibition on PPA and statically quenched PPA fluorescence via ternary complex formation. These findings provide a theoretical foundation for developing novel α-amylase inhibitors.

Recently, essential oils (EOs) have garnered attention for their biological properties as a source of natural compounds with anticancer and antioxidant effects. Artemisia herba alba grows commonly on the dry steppes of the Mediterranean regions in Northern Africa, Western Asia, and Southwestern Europe. This species is native to Palestine and the western region of Jordan, known as Sheeh. It is employed by the Bedouins for the remedy of many diseases. Recently, essential oils (EOs) have been booming with a growing interest in their use as palliative treatments to conventional medicine due to their biological qualities. The objective of this study is to identify the chemical composition of EO extracted from the dry leaves of A. herba alba and to evaluate their in vitro antioxidant, anticancer, and α-amylase and lipase inhibitory activity. The EO was extracted via hydrodistillation and examined using gas chromatography-mass (GC-MS) spectrometry to determine its chemical composition. The primary components included 1,8-cineole (28.67%), followed by trans-thujone (24.00%), cis-thujone (17.69%), camphor (12.76%), and concluding with terpinen-4-ol (8.34%). Biologically, the EO performed high antioxidant activity against 1,1-diphenyl-2-picrylhydrzyl (DPPH) with 22.17 ± 1.11 µg/mL and modest lipase and α-amylase activity. The EO displayed significant anticancer properties against B16F10 and MCF-7 with IC50 values of 12.39 and 13.60 µg/mL, respectively. A 1:1 combination of Artemisia herba alba and Teucrium polium EOs improved the anticancer activities against B16F10 and MCF-7 cell lines, with IC50 values of 6.184 and 9.427, respectively. Adding 25-50 µg/mL to Taxol (10 ng) caused a remarkable increase in the inhibition of cancer cells. This enhancement in cancer cell inhibition suggests a potential synergistic effect between the essential oil and Taxol, warranting further investigation into their combinatory use in therapeutic applications. Future studies may explore the underlying mechanisms of this synergy to optimize treatment strategies for cancer patients. © 2025. The Author(s).

In this study, Alangium salvifolium and Ocimum sanctum extracts were investigated for their antioxidant, antidiabetic and hypolipidemic activities individually and in combined form. HPLC, LC-MS and UPLC phytochemicals profiling identified phenolics and flavonoids as major bioactives. Antioxidant assays showed significant DPPH and ABTS radical scavenging activities, with the combined formulation (1:1 ratio) 91.2 and 89.6% inhibition was achieved respectively. Antidiabetic activities were first investigated in vitro with the ability of the combination to inhibit both α-amylase (IC50 = 38.4 µg/mL) and α-glucosidase (IC50 = 45.2 µg/mL) having the strongest inhibitory effects. The hypolipidemic activity included inhibition of lipid peroxidation (78.5%); pancreatic lipase inhibition (70.2%). The bioactives were further molecular docked to find strong binding affinities with PPARγ, DPP-IV, and HMG-CoA reductase. Results were confirmed statistically different (p < 0.05) between treated and control groups. These results suggest that the extracts can exhibit synergy as natural therapeutics in diabetes and lipid disorders.

BACKGROUND: The inhibition of carbohydrate-digesting enzymes, α-glucosidase and α-amylase, is a key strategy in managing postprandial hyperglycemia in type 2 diabetes. Natural phenolic compounds isolated from olive mill by-product (alperujo), such as hydroxytyrosol (HT) and trans-p-coumaroyl secologanoside (comselogoside, COM), have shown potential in this regard. However, the individual effect of the 3,4-dihydroxyphenylglycol (DHPG), another potent phenolic antioxidant naturally found in olive fruit with the same ortho-diphenolic structure as HT, but with an additional hydroxyl group in the β position, and their combination with HT and COM on these enzymes remain underexplored. RESULTS: The present study evaluated the inhibitory effects of HT, DHPG and COM on α-glucosidase and α-amylase. DHPG exhibited the strongest inhibition of α-glucosidase (IC50 = 288.2 μm), comparable to the anti-diabetic drug acarbose (IC50 = 281.9 μm), whereas HT and COM showed moderate activity. Binary combinations of HT and DHPG (1:1) displayed synergistic inhibition of both enzymes, significantly enhancing their efficacy. Conversely, DHPG and COM combinations resulted in antagonistic effects on α-amylase inhibition, although they showed a significant inhibitory effect on α-glucosidase (IC50 = 100.7 μm). CONCLUSION: These findings highlight the potential of phenolic compounds derived from olive oil by-products as natural alternatives for postprandial glucose control. The synergistic interactions between specific compounds suggest an enhanced therapeutic effect that could be used for diabetes management. Further studies are needed to elucidate the mechanisms underlying these interactions and assess their in vivo efficacy. © 2025 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2025 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

With the increasing prevalence of diabetes, the search for natural compounds with potential anti-hyperglycemic effects has become a key focus in food and nutrition research. L-theanine (THE) and epigallocatechin gallate (EGCG) from tea are gaining attention due to their antioxidant and metabolic regulation properties. Although they have been shown to have an effect on glucose metabolism, their synergistic effect on starch digestive properties and the mechanism remain unclear. Here, we explored that THE and EGCG synergistically regulated starch digestive properties in ultrasound treatment through two different perspectives. At specific THE/EGCG ratios (THE/EGCG1:1), maize starch granules exhibited significant aggregation and densification. THE promoted the ordered arrangement of starch molecular chains through hydrogen bonding, and the polyphenolic structure of EGCG further stabilised this ordered structure, thus enhancing the crystallinity and short-range ordering of starch. It meant that THE and EGCG further reduced starch digestibility by synergistically modulating the multi-scale structure of starch. In addition, THE and EGCG exhibited significant synergistic inhibition of α-amylase activity (1.6 mM THE and 0.05 mg/mL EGCG). The multi-spectral results showed that the addition of THE and EGCG enhanced the conformational change of the enzyme, leading to the change of the secondary structure, and the synergistic effect might originate from the multiple interactions of THE and EGCG with different amino acid residues in the digestive enzyme (e.g., THR-163, GLN-63, ASP-197, etc), which strengthened the inhibition, and the molecular dynamics simulations further supported the findings. This work promotes the further development and utilisation of endogenous substances in tea and provides some references for the development of food ingredients with potential hypoglycaemic functions.

Coreopsin is a flavonoid from Coreopsis tinctoria. The inhibition of coreopsin and synergy with acarbose against α-amylase (PPA) or α-glucosidase (SCG) were explored. As a result, coreopsin exhibited stronger inhibition on PPA/SCG than that of acarbose. Combination of coreopsin (4.11 μM) with acarbose (132.77 μM) had significant synergistic effect on PPA, while combination of coreopsin (5.76 μM) and acarbose (121.7 μM) had significant synergy on SCG. Coreopsin, acarbose and acarbose-coreopsin inhibited PPA in mixed-type mode. Acarbose competitively inhibited SCG, whereas coreopsin and acarbose-coreopsin inhibited SCG in mixed-type mode. Fluorescence analysis conformed that coreopsin could synergize with acarbose by increasing the binding ability of acarbose to PPA/SCG. Compared with acarbose or coreopsin, acarbose-coreopsin complexes resulted in more conformational changes of PPA/SCG, revealing that the complexes had stronger inhibitory ability than acarbose or coreopsin alone. The detail binding information of coreopsin, acarbose or acarbose-coreopsin to PPA /SCG was revealed by computer simulation.

Type 2 Diabetes Mellitus accounts for 90% of most diabetes cases. Many commercial drugs used to treat this disease come with adverse side effects and eventually fail to restore glucose homeostasis. Therefore, an effective, economical and safe antidiabetic remedy from dietary source is considered. Taraxacum officinale (L.) Weber ex F.H.Wigg and Momordica charantia L. were chosen since both are used for centuries as traditional medicine to treat various ailments and diseases. In this study, the antidiabetic properties of a polyherbal combination of T. officinale and M. charantia ethanol extracts are evaluated. The bioactive solvent extracts of the samples selected from in vitro antidiabetic assays; α-amylase, α-glucosidase, and dipeptidyl peptidase-4 (DPP-4) inhibition, and glucose-uptake in L6 muscle cells were combined (1:1) to form the polyherbal combination. The antidiabetic efficacy of polyherbal combination was evaluated employing the above stated in vitro antidiabetic assays and in vivo oral glucose tolerance test and streptozotocin-nicotinamide (STZ-NA) induced diabetic rat model. A quadrupole time-of-flight liquid chromatography-mass spectrometry (Q-TOF LCMS) analysis was done to identify active compounds. The polyherbal combination exerted improved antidiabetic properties; increased DPP-4, α-amylase, and α-glucosidase inhibition. The polyherbal combination tested in vivo on diabetic rats showed optimum blood glucose-lowering activity comparable to that of Glibenclamide and Metformin. This study confirms the polyherbal combination of T. officinale and M. charantia to be rich in various bioactive compounds, which exhibited antidiabetic properties. Therefore, this polyherbal combination has the potential to be further developed as complex phytotherapeutic remedy for the treatment of Type 2 Diabetes Mellitus.

INTRODUCTION: Acute pancreatitis associated with Pazopanib has been reported in the literature. Bitter Melon (Momordica Charantia) is traditionally used as a folk medicine in many regions. In this report, we describe a 65-year-old patient with a diagnosis of renal cell carcinoma, admitted to the hospital with symptoms of acute pancreatitis at the 8th year of pazopanib treatment. CASE REPORT: The patient diagnosed with renal cell carcinoma was admitted to the hospital with the complaint of abdominal pain, nausea, and vomiting in the 8th year of Pazopanib treatment. It was noticed from the patient's history that he had received Bitter Melon extract for 4 days prior to the beginning of his complaints (100-150 ml/day). Levels of serum amylase and lipase were measured as 9163 U/L and 14,206 U/L, respectively. MANAGEMENT & OUTCOME: Pazopanib drug was held. The patient was treated for acute pancreatitis. Pazopanib treatment was started again after the clinical condition of the patient had improved and levels of serum amylase and lipase had returned to normal levels. Levels of serum amylase and lipase did not increase again after re-administration of pazopanib treatment. DISCUSSION: It is thought that Bitter Melon extract and pazopanib interaction might have led to acute pancreatitis. To the best of our knowledge, this case is the first to highlight the interaction of Bitter Melon extract with pazopanib. The Drug Interaction Probability Scale indicates that there is a probable association between bitter melon and acute pancreatitis.

BACKGROUND: ALG-000184 (pevifoscorvir sodium) is a prodrug of the class-E (empty) capsid assembly modulator (CAM), ALG-001075. CAM-Es prevent hepatitis B virus (HBV) replication by inhibiting capsid assembly and pregenomic RNA encapsidation and preventing covalently closed circular DNA (cccDNA) establishment. This part of the study aimed to assess the safety, tolerability, pharmacokinetics and short-term antiviral activity of ALG-000184 in participants with HBeAg-negative and HBeAg-positive chronic HBV infection to determine the subsequent development pathway for this novel therapeutic. METHODS: ALG-000184-201 was a phase 1, multicentre, randomised, dose escalation trial designed to evaluate the safety and pharmacokinetics of ALG-000184 in healthy participants (parts 1-2, reported separately) and antiviral activity in treatment-naive or currently not treated participants with chronic HBV infection (part 3, presented here). Eligible participants were 18-65 years old with BMI 18·0-35·0 kg/m2, and HBeAg-negative or HBeAg-positive chronic HBV infection with serum HBV DNA concentration more than 2000 IU/mL and serum ALT concentrations less than 5 times the upper limit of normal. Eligible patients were randomly assigned (4:1) to receive 28 days of oral ALG-000184 (10 mg, 50 mg, 100 mg, or 300 mg) or matching placebo once per day. Randomisation was managed via an interactive web response system and other than knowing the dose being evaluated in each cohort, all investigational site personnel and study participants were unaware of treatment assignments. The primary objective of this study was to evaluate the safety and tolerability of ALG-000184 in all randomly assigned participants (intention to treat population) using safety data including all treatment emergence adverse events, physical exam and vital signs findings, 12-lead electrocardiogram, and clinical laboratory findings. This study was registered at ClinicalTrials.gov, NCT04536337, and is complete. FINDINGS: Between March 16, 2021, and Oct 13, 2022, 135 participants were screened for inclusion from seven clinical investigational sites in Hong Kong, China, Moldova, New Zealand, and the UK. 76 participants did no

BACKGROUND/AIMS: To assess the safety and efficacy of early oral refeeding (ERF) versus delayed refeeding (DRF) in patients with mild post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). METHODS: Eligible patients were randomly assigned in a 1:1 ratio to the ERF or DRF group. Eligible patients were randomly assigned in a 1:1 ratio to the ERF or DRF group. In the ERF group, feeding began 24 hours after the diagnosis of PEP; in the DRF group, feeding commenced once normal bowel sounds returned and pain had decreased to a visual analog scale score of <2. The diet was advanced from clear fluids to soft foods according to patient tolerance. Refeeding was temporarily halted if the visual analog scale score reached ≥5 points or if intake was refused due to pain. Resumption required normal amylase/lipase levels, pain relief, and bowel movement restoration. Discharge criteria included patient well-being >24 hours post-diet. The primary outcome was PEP hospitalization duration, and secondary outcomes were the incidence of severe acute pancreatitis, readmission rate (<30 days), and PEP-related mortality rate. RESULTS: A total of 80 patients (40 in each ERF and DRF group) were enrolled across nine referral centers. Baseline characteristics, procedural parameters and initial PEP severity were not significantly different between the two groups. Four ERF and three DRF patients had refeeding interruptions. ERF significantly reduced PEP hospitalization duration compared to DRF (2.93±1.59 days vs 3.78±1.97 days: relative risk, 0.75; 95% confidence interval, 0.59 to 0.97; p=0.026). Rates of severe acute pancreatitis, readmission, and mortality/morbidity related to PEP were similar between the two groups. CONCLUSIONS: ERF effectively shortens hospitalization in mild PEP patients without increasing safety risks (ClinicalTrials.gov identifier NCT04750044).

BACKGROUND: Axatilimab, an anti-colony-stimulating factor 1 receptor (CSF-1R) antibody, blocks colony-stimulating factor 1 (CSF-1) and interleukin-34 (IL-34) binding to CSF-1R on macrophages and monocytes. Axatilimab has demonstrated efficacy and safety in chronic graft-versus-host disease, and its safety, pharmacokinetics (PK), and pharmacodynamics (PD) were characterized in healthy Western participants. OBJECTIVE: The objective of this study was to evaluate the safety, PK, and PD of axatilimab among healthy Japanese men. METHODS: In this double-blind, randomized, dose-escalation study, eligible participants were healthy Japanese men aged 18-55 years, with a body weight of 50-100 kg, a body mass index of 18.0-30.0 kg/m2, and no clinically significant findings on screening evaluation (clinical, laboratory, electrocardiogram, and physical exam). Participants were randomized to receive axatilimab or placebo in a 3:1 ratio in a blinded manner. Safety (30 d follow-up; primary endpoint), PK, and PD were evaluated at a clinic in Japan following single-dose infusions of axatilimab 0.3 mg/kg (n = 6), axatilimab 1.0 mg/kg (n = 9), or placebo (n = 5). RESULTS: Three participants receiving axatilimab experienced a nonserious treatment-emergent adverse event (nasopharyngitis [0.3-mg/kg dose], amylase level increased [1.0-mg/kg dose], and headache [1.0-mg/kg dose]), with no clinically meaningful trends in hematology, urinalysis, physiologic, and most clinical chemistry measures. PK exposure increased with the 1.0 mg/kg versus 0.3 mg/kg dose, with greater than dose-proportional increases in area under the curve. CSF-1 and IL-34 levels had dose-dependent increases following axatilimab infusion. A transient increase in nonclassical monocytes was observed for 8 h following axatilimab infusion and then decreased below baseline until day 8 (0.3 mg/kg) or day 15 (1.0 mg/kg). The inverse effect was observed with classical monocytes. Intermediate monocytes had similar transient increases as nonclassical monocytes. CONCLUSIONS: A single dose of axatilimab 0.3 mg/kg and 1.0 mg/kg was generally well tolerated in healthy Japanese men. Safety, PK, and PD findings were consistent with thos

INTRODUCTION: Aggressive hydration using lactated Ringer's solution prevents postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Concerns of this strategy are large volume and lengthy hydration. Our study aimed to evaluate the efficacy of tailored aggressive hydration (TAH) for PEP prevention. METHODS: In this prospective, multicenter, double-blinded, randomized trial conducted across 3 tertiary Korean hospitals, patients who underwent ERCP for the first time were randomly assigned (1:1) to the tailored standard hydration (TSH) and TAH groups. The TSH group received 1.5 mL/kg/hr lactated Ringer's solution during and after ERCP, whereas the TAH group was administered a 20 mL/kg bolus post-ERCP and 3 mL/kg/hr during and after the procedure. Both groups were assessed for elevated serum amylase levels and pain 4-6 hours after ERCP. If both were absent, hydration was discontinued. If either was present, hydration was continued at the original rate until 8 hours. The primary end point was PEP development and was analyzed on an intention-to-treat analysis. RESULTS: A total of 344 patients were randomly assigned to treatment groups (171 to the TSH group and 172 to the TAH group). PEP was observed in 9.4% (16/171) in the TSH group and 3.5% (6/172) in the TAH group (relative risk 0.37, 95% confidence interval 0.15-0.93, P = 0.03). No difference was identified between the 2 groups in PEP severity ( P = 0.80) and complications related to volume overload ( P = 0.32). DISCUSSION: TAH according to the presence of abdominal pain or elevated serum amylase levels at 4-6 hours after ERCP is safe and prevents PEP development.

AIM: To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. MATERIALS AND METHODS: This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. RESULTS: At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. CONCLUSIONS: Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated. © 2024 John Wiley & Sons Ltd.

BACKGROUND: The phase 3 JAVELIN Bladder 100 trial showed significantly prolonged overall survival (OS) with avelumab first-line maintenance + best supportive care (BSC) vs. BSC alone in patients with advanced urothelial carcinoma (UC) that had not progressed with first-line platinum-containing chemotherapy. Here, efficacy and safety were assessed from the initial analysis of the JAVELIN Bladder 100 trial (data cutoff October 21, 2019) in patients enrolled in Asian countries. METHODS: Patients with locally advanced or metastatic UC that had not progressed with 4 to 6 cycles of first-line platinum-containing chemotherapy (gemcitabine + cisplatin or carboplatin) were randomized 1:1 to receive avelumab first-line maintenance + BSC or BSC alone, stratified by best response to first-line chemotherapy and visceral vs. nonvisceral disease when initiating first-line chemotherapy. The primary endpoint was OS assessed from randomization in all patients and patients with PD-L1+ tumors (Ventana SP263 assay). Secondary endpoints included progression-free survival (PFS) and safety. RESULTS: A total of 147 patients in JAVELIN Bladder 100 were enrolled in Asian countries (Hong Kong, India, Japan, South Korea, and Taiwan). In this Asian subgroup, 73 and 74 patients received avelumab + BSC or BSC alone, respectively. Median OS was 25.3 months (95% CI, 18.6 to not estimable [NE]) in the avelumab + BSC arm vs. 18.7 months (95% CI, 12.8-NE) in the BSC alone arm (hazard ratio [HR], 0.74 [95% CI, 0.43-1.26]); median PFS was 5.6 months (95% CI, 2.0-7.5) vs. 1.9 months (95% CI, 1.9-1.9), respectively (HR, 0.58 [95% CI, 0.38-0.86]). In the avelumab + BSC vs. BSC alone arms, grade ≥3 treatment-emergent adverse events (any causality) occurred in 44.4% vs. 16.2%, respectively. The most common grade ≥3 treatment-emergent adverse events in the avelumab + BSC arm were anemia (9.7%), amylase increased (5.6%), and urinary tract infection (4.2%). CONCLUSIONS: Efficacy and safety results for avelumab first-line maintenance in the Asian subgroup of JAVELIN Bladder 100 were generally consistent with those in the overall trial population. These data support the use of avelumab first-line maintenance a

AIM: To report a Phase I study of subcutaneous glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R) dual agonist BI 456906 versus placebo in healthy Japanese men with overweight/obesity. MATERIALS AND METHODS: We investigated multiple rising doses of BI 456906 escalated over 16 weeks (maximum doses: 1.8 mg once weekly [dose group {DG} 1], 4.8 mg once weekly [DG 2] and 2.4 mg twice weekly [DG 3]) in Japanese men with a body mass index of 23 to 40 kg/m2 . RESULTS: Thirty-six participants were treated (n = 9 per DG and placebo). Overall, 10 participants (37.0%) treated with BI 456906 withdrew from dose escalation due to adverse events (amylase increase, n = 1; decreased appetite, n = 9), and the proportion of participants was higher in DG 2 (n = 6, 66.7%) versus DGs 1 and 3 (both n = 2, 22.2%). No participants receiving placebo withdrew from dose escalation. BI 456906 exposure increased with dose and dose escalation in each DG. Treatment with BI 456906 decreased placebo-corrected bodyweight after 16 weeks (placebo +1.06%): DG 1, -5.57%; DG 2, -12.37%; DG 3, -9.62%. Paracetamol absorption decreased in Week 1 for DGs 2 and 3, indicating transient delayed gastric emptying. BI 456906 reduced plasma alanine and glucagon levels, indicating indirect target engagement at GCGRs and GLP-1Rs. Drug-related adverse events were reported for all participants receiving BI 456906 and four receiving placebo, the most frequent being decreased appetite (n = 24, 66.7%). CONCLUSIONS: BI 456906 showed no unexpected tolerability concerns and it reduced placebo-corrected bodyweight by up to 12.37% in Japanese men with overweight/obesity after 16 weeks of treatment. © 2023 Boehringer Ingelheim and The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

BACKGROUND: The phase 3 CheckMate 274 trial demonstrated superiority of adjuvant nivolumab over placebo after radical surgery in patients with high-risk muscle-invasive urothelial carcinoma. However, the efficacy and safety of adjuvant nivolumab in Japanese patients with muscle-invasive urothelial carcinoma have not been clarified. METHODS: Patients with muscle-invasive urothelial carcinoma were randomized to adjuvant nivolumab 240 mg or placebo (every 2 weeks via intravenous infusion) up to 120 days after radical surgery in CheckMate 274. RESULTS: Of 49 patients in the Japanese subgroup, 27 and 22 patients were randomized to nivolumab and placebo, respectively. Eleven and 8 patients, respectively, had tumor PD-L1 expression level of 1% or more. The median disease-free survival times in the nivolumab and placebo groups were 29.67 months (95% confidence interval 7.79-not reached) and 9.72 months (95% confidence interval 4.73-not reached), respectively (hazard ratio 0.77, 95% confidence interval 0.35-1.69). The corresponding values in patients with tumor PD-L1 expression level of 1% or more were 29.67 months (95% confidence interval 2.63-not reached) and 25.95 months (95% confidence interval 5.59-not reached) (hazard ratio 1.10, 95% confidence interval 0.31-3.92), respectively. Treatment-related adverse events of Grade 3-4 occurred in 25.9 and 13.6% of patients in the nivolumab and placebo groups, respectively. The most common treatment-related adverse events in the nivolumab group were lipase increased, amylase increased and diarrhea. The changes in quality of life scores from baseline over time were similar in both groups. CONCLUSIONS: The efficacy and safety results in the Japanese subgroup were consistent with the overall population of CheckMate 274. © The Author(s) 2022. Published by Oxford University Press.

A 7-week feeding trial was conducted to evaluate the combined effects of propionic acid (PA, 5 or 10 g/kg) and a multi-strain Bacillus spp. (Bacillus subtilis IS02 (accession no. JN856456) and B. licheniformis IBRC-M 11,319) (1.7 × 107 CFU/g) probiotic in a plant protein source (PP)-rich diet (∼70% of dietary protein derived from PP sources) on performance of Asian sea bass (Lates calcarifer) fry (initial body weight 2.97 ± 0.11 g). In this regard, six isoproteic (∼48%) diets were formulated as follows: a control (without supplementation of the additives); probiotic (only contained Bacillus spp. mixture); 5 g PA/kg diet; 10 g PA/kg diet; probiotic + 5 g PA/kg diet, and probiotic + 10 g PA/kg diet. Specific growth rate in fish fed with 10 g PA/kg (2.84 ± 0.1%) and diets contained blends of probiotic and PA (2.76 ± 0.19% in probiotic + 5 g PA, and 2.79 ± 0.04% in probiotic + 10 g PA) was better than in the control (2.45 ± 0.1%) (P < 0.05). Feed conversion ratio in fish fed with 10 g PA/kg (0.92 ± 0.12) and diets contained blends of probiotic and PA (0.94 ± 0.06 in probiotic + 5 g PA and 0.91 ± 0.02 in probiotic + 10 g PA) was better than in the control (1.24 ± 0.08) (P < 0.05). Digestive enzymes including α-amylase, total alkaline proteases, and bile salt dependent lipase activities improved in fish fed diets contained additives. The activity of glutathione-S-transferase and glutathione reductase enhanced in the liver of fish fed diets contained additives. The relative abundance of lysozyme, interleukin 1β, and insulin-like growth factor-1 genes mRNA transcript showed multifold increase in the liver of fish fed with the 10 g PA/kg and diets contained blends of probiotic and PA (P < 0.05). By considering the above mentioned results, supplementing a PP-rich diet with 10 g PA/kg diet or combination of PA and a mixture of Bacillus spp. probiotic recommended for L. calcarifer. © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.