A 2-year prospective evaluation of the Prostate Health Index in guiding biopsy decisions in a large cohort.

OBJECTIVES: To prospectively evaluate how the Prostate Health Index (PHI) impacts on clinical decision in a real-life setting for men with a prostate-specific antigen (PSA) level between 4 and 10 ng/mL and normal digital rectal examination. PATIENTS AND METHODS: Since 2016, the PHI has been available at no cost to eligible men in all Hong Kong public hospitals. All eligible patients who received PHI testing in all public Urology units (n = 16) in Hong Kong between May 2016 and August 2017 were prospectively included and followed up. All included men had a PHI test, with its result and implications explained; the subsequent follow-up plan was then decided via shared decision-making with urologists. Patients were followed up for 2 years, with outcomes including prostate biopsy rates and biopsy findings analysed in relation to the initial PHI measurements. RESULTS: A total of 2828 patients were followed up for 2 years. The majority (82%) had PHI results in the lower risk range (score <35). Knowing the PHI findings, 83% of the patients with elevated PSA decided not to undergo biopsy. In all, 11% and 45% opted for biopsy in the PHI score <35 and ≥35 groups, respectively. The initial detection rate of International Society of Urological Pathology (ISUP) Grade Group (GG) ≥2 cancer was higher in the PHI score ≥35 group (23%) than in the PHI score <35 group (7.9%). Amongst patients with no initial positive biopsy findings, the subsequent positive biopsy rate for ISUP GG ≥2 cancer was higher in the PHI score ≥35 group (34%) than the PHI score <35 group (13%) with a median follow-up of 2.4 years. CONCLUSION: In a real-life setting, with the PHI incorporated into the routine clinical pathway, 83% of the patients with elevated PSA level decided not to undergo prostate biopsy. The PHI pathway also improved the high-grade prostate cancer detection rate when compared to PSA-driven strategies. Higher baseline PHI predicted subsequent biopsy outcome at 2 years. The PHI can serve as a tool to individualise biopsy decisions and frequency of follow-up visits.

Effects of ibuprofen in the ZDF rat model of type 2 diabetes.

We aimed to investigate the therapeutic potential of ibuprofen against type 2 diabetes (T2D) using obese Zucker diabetic fatty (ZDF) rats as type 2 diabetes model. ZDF rats were hyperglycemic, dyslipidemic and expressed proinflammatory markers in contrast to lean controls, thus reflecting the relationship between obesity and chronic inflammation promoting T2D. Chronic treatment with ibuprofen (2-(4-Isobutylphenyl)propanoic acid) was used to study the impact on pathological T2D conditions as compared to metformin (1,1-dimethylbiguanide) treated ZDF as well as lean controls. Ibuprofen decreased A1c but induced a high insulin release with improved glucose tolerance only after early time points (i.g., 15 and 30 min) resulting in a non-significant decline of AUC values and translating into a high HOMA-IR. In addition, ibuprofen significantly lowered cholesterol, free fatty acids and HDL-C. Some of these effects by ibuprofen might be based on its anti-inflammatory effects through inhibition of cytokine/chemokine signaling (i.g., COX-2, ICAM-1 and TNF-α) as measured in whole blood and epididymal adipose tissue by TaqMan and/or upregulation of anti-inflammatory cytokines (i.g., IL-4 and IL-13) by ELISA analysis in blood. In conclusion, our ZDF animal study showed positive effects of ibuprofen against diabetic complications such as inflammation and dyslipidemia but also demonstrated the risk of causing insulin resistance.

Hepatoprotective effect of dietary pterostilbene against high-fat-diet-induced lipid accumulation exacerbated by chronic jet lag via SIRT1 and SIRT3 activation.

Hepatic lipid metabolism is modulated by the circadian rhythm; therefore, circadian disruption may promote obesity and hepatic lipid accumulation. This study aims to investigate dietary pterostilbene (PSB) 's protective effect against high-fat-diet (HFD)-induced lipid accumulation exacerbated by chronic jet lag and the potential role of gut microbiota therein. Mice were treated with a HFD and chronic jet lag for 14 weeks. The experimental group was supplemented with 0.25% (w/w) PSB in its diet to evaluate whether PSB had a beneficial effect. Our study found that chronic jet lag exacerbates HFD-induced obesity and hepatic lipid accumulation, but these adverse effects were significantly mitigated by PSB supplementation. Specifically, PSB promoted hepatic lipolysis and ß-oxidation by upregulating SIRT1 expression, which indirectly reduced oxidative stress caused by lipid accumulation. Additionally, the PSB-induced elevation of SIRT1 and SIRT3 expression helped prevent excessive autophagy and mitochondrial fission by activating Nrf2-mediated antioxidant enzymes. The result was evidenced by the use of SIRT1 and SIRT3 inhibitors in in vitro studies, which demonstrated that activation of SIRT1 and SIRT3 by PSB is crucial for the translocation of PGC-1α and Nrf2, respectively. Moreover, the analysis of gut microbiota suggested that PSB's beneficial effects were partly due to its positive modulation of gut microbial composition and functionality. The findings of this study suggest the potential of dietary PSB as a candidate to improve hepatic lipid metabolism via several mechanisms. It may be developed as a treatment adjuvant in the future.

Common dietary emulsifiers promote metabolic disorders and intestinal microbiota dysbiosis in mice.

Dietary emulsifiers are linked to various diseases. The recent discovery of the role of gut microbiota-host interactions on health and disease warrants the safety reassessment of dietary emulsifiers through the lens of gut microbiota. Lecithin, sucrose fatty acid esters, carboxymethylcellulose (CMC), and mono- and diglycerides (MDG) emulsifiers are common dietary emulsifiers with high exposure levels in the population. This study demonstrates that sucrose fatty acid esters and carboxymethylcellulose induce hyperglycemia and hyperinsulinemia in a mouse model. Lecithin, sucrose fatty acid esters, and CMC disrupt glucose homeostasis in the in vitro insulin-resistance model. MDG impairs circulating lipid and glucose metabolism. All emulsifiers change the intestinal microbiota diversity and induce gut microbiota dysbiosis. Lecithin, sucrose fatty acid esters, and CMC do not impact mucus-bacterial interactions, whereas MDG tends to cause bacterial encroachment into the inner mucus layer and enhance inflammation potential by raising circulating lipopolysaccharide. Our findings demonstrate the safety concerns associated with using dietary emulsifiers, suggesting that they could lead to metabolic syndromes.

PyFaceWipe: a new defacing tool for almost any MRI contrast.

RATIONALE AND OBJECTIVES: Defacing research MRI brain scans is often a mandatory step. With current defacing software, there are issues with Windows compatibility and researcher doubt regarding the adequacy of preservation of brain voxels in non-T1w scans. To address this, we developed PyFaceWipe, a multiplatform software for multiple MRI contrasts, which was evaluated based on its anonymisation ability and effect on downstream processing. MATERIALS AND METHODS: Multiple MRI brain scan contrasts from the OASIS-3 dataset were defaced with PyFaceWipe and PyDeface and manually assessed for brain voxel preservation, remnant facial features and effect on automated face detection. Original and PyFaceWipe-defaced data from locally acquired T1w structural scans underwent volumetry with FastSurfer and brain atlas generation with ANTS. RESULTS: 214 MRI scans of several contrasts from OASIS-3 were successfully processed with both PyFaceWipe and PyDeface. PyFaceWipe maintained complete brain voxel preservation in all tested contrasts except ASL (45%) and DWI (90%), and PyDeface in all tested contrasts except ASL (95%), BOLD (25%), DWI (40%) and T2* (25%). Manual review of PyFaceWipe showed no failures of facial feature removal. Pinna removal was less successful (6% of T1 scans showed residual complete pinna). PyDeface achieved 5.1% failure rate. Automated detection found no faces in PyFaceWipe-defaced scans, 19 faces in PyDeface scans compared with 78 from the 224 original scans. Brain atlas generation showed no significant difference between atlases created from original and defaced data in both young adulthood and late elderly cohorts. Structural volumetry dice scores were ≥ 0.98 for all structures except for grey matter which had 0.93. PyFaceWipe output was identical across the tested operating systems. CONCLUSION: PyFaceWipe is a promising multiplatform defacing tool, demonstrating excellent brain voxel preservation and competitive defacing in multiple MRI contrasts, performing favourably against PyDeface. ASL, BOLD, DWI and T2* scans did not produce recognisable 3D renders and hence should not require defacing. Structural volumetry dice scores (≥ 0.98) were higher than previously published FreeSurfer results, except for grey matter which were comparable. The effect is measurable and care should be exercised during studies. ANTS atlas creation showed no significant effect from PyFaceWipe defacing.

Development of piperine nanoparticles stabilized by OSA modified starch through wet-media milling technique with enhanced anti-adipogenic effect in 3T3-L1 adipocytes.

Piperine (PIP) has been known for its pharmacological activities with low water solubility and poor dissolution, which limits its nutritional application. The purpose of this research was to enhance PIP stability, dispersibility and biological activity by preparing PIP nanoparticles using the wet-media milling approach combined with nanosuspension solidification methods of spray/freeze drying. Octenyl succinic anhydride (OSA)-modified waxy maize starch was applied as the stabilizer to suppress aggregation of PIP nanoparticles. The particle size, redispersibility, storage stability and in vitro release behavior of PIP nanoparticles were measured. The regulating effect on adipocyte differentiation was evaluated using 3T3-L1 cell model. Results showed that PIP nanoparticles had a reduced particle size of 60 ± 1 nm, increased release rate in the simulated gastric (SGF) and intestinal fluids (SIF) and enhanced inhibition effect on adipogenesis in 3T3-L1 cells compared with free PIP, indicating that PIP-loaded nanoparticles with improved stability and anti-adipogenic property were developed successfully by combining wet-media milling and drying methods.

Structural Variances in Curcumin Degradants: Impact on Obesity in Mice.

Some thermal degradants of curcuminoids have demonstrated moderate health benefits in previous studies. Feruloyl acetone (FER), recently identified as a thermal degradant of curcumin, has been previously associated with anticancer and antioxidative effects, yet its other capabilities remain unexplored. Moreover, earlier reports suggest that methoxy groups on the aromatic ring may influence the functionality of the curcuminoids. To address these gaps, an animal study was conducted to investigate the antiobesity effects of both FER and its demethoxy counterpart (DFER) on mice subjected to a high-fat diet. The results demonstrated the significant prevention of weight gain and enlargement of the liver and various adipose tissues by both samples. Furthermore, these supplements exhibited a lipid regulatory effect in the liver through the adiponectin/AMPK/SIRT1 pathway, promoted thermogenesis via AMPK/PGC-1α activation, and positively influenced gut-microbial-produced short-chain fatty acid (SCFA) levels. Notably, DFER demonstrated superior overall efficacy in combating obesity, while FER displayed a significant effect in modulating inflammatory responses. It is considered that SCFA may be responsible for the distinct effects of FER and DFER in the animal study. Future studies are anticipated to delve into the efficacy of curcuminoid degradants, encompassing toxicity and pharmacokinetic evaluations.

Calebin A attenuated inflammation in RAW264.7 macrophages and adipose tissue to improve hepatic glucose metabolism and hyperglycemia in high-fat diet-fed obese mice.

The increased incidence of obesity, which become a global health problem, requires more functional food products with minor side and excellent effects. Calebin A (CbA) is a non-curcuminoid compound, which is reported to be an effective treatment for lipid metabolism and thermogenesis. However, its ability and mechanism of action in improving obesity-associated hyperglycemia remain unclear. This study was designed to explore the effect and mechanism of CbA in hyperglycemia via improvement of inflammation and glucose metabolism in the adipose tissue and liver in high-fat diet (HFD)-fed mice. After 10 weeks fed HFD, obese mice supplemented with CbA (25 and 100 mg/kg) for another 10 weeks showed a remarkable reducing adiposity and blood glucose. CbA modulated M1/M2 macrophage polarization, ameliorated inflammatory cytokines, and restored adiponectin as well as Glut 4 expression in the adipose tissue. In the in vitro study, CbA attenuated pro-inflammatory markers while upregulated anti-inflammatory IL-10 in LPS + IFNγ-generated M1 phenotype macrophages. In the liver, CbA attenuated steatosis, inflammatory infiltration, and protein levels of inflammatory TNF-α and IL-6. Moreover, CbA markedly upregulated Adiponectin receptor 1, AMPK, and insulin downstream Akt signaling to improve glycogen content and increase Glut2 protein. These findings indicated that CbA may be a novel therapeutic approach to treat obesity and hyperglycemia phenotype targeting on adipose inflammation and hepatic insulin signaling.

Difference comparison of characteristic aroma compounds between braised pork cooked by traditional open-fire and induction cooker and the potential formation cause under electromagnetic cooking.

The characteristic aroma compounds of braised pork were identified through molecular sensory science and PLSR analysis, and the difference between two cooking methods, traditional open-fire (BPF) and induction cooker (BPC), was compared. Seventeen aroma compounds with odor activity values (OAVs) > 1 were identified in both samples. BPF revealed higher OAVs for most of the aroma compounds compared to BPC, and the higher aroma quality. Aroma recombination and omission experiments confirmed that twelve aroma compounds significantly contributed to the characteristic aroma of braised pork, and eight compounds such as hexanal, (E)-2-octenal, and methanethiol were further confirmed as important contributors by PLSR analysis. Furthermore, PLSR analysis clarified the role of aldehydes such as hexanal, (E)-2-octenal, and (E,E)-2,4-decadienal in contributing to fatty attribute, whereas methanethiol was responsible for the meaty aroma. These characteristic aroma compounds mainly derived from lean meat due to its high content of phospholipids, and the exogenous seasonings contributed to the balanced characteristic aroma profile of braised pork by altering the distribution of these characteristic aroma compounds. Variations in heating parameters affected the formation of lipid oxidation and Strecker degradation products, which might explain aroma discrepancy between braised pork cooked by two methods with different heat transfer efficiencies.

Biological fate, functional properties, and design strategies for oral delivery systems for cinnamaldehyde.

Cinnamaldehyde (CA) is the main bioactive component extracted from the internal bark of cinnamon trees with many health benefits. In this paper, the bioavailability and biological activities of cinnamaldehyde, and the underlying molecular mechanism are reviewed and discussed, including antioxidant, cardioprotective, anti-inflammatory, anti-obesity, anticancer, and antibacterial properties. Common delivery systems that could improve the stability and bioavailability of CA are also summarized and evaluated, such as micelles, microcapsules, liposomes, nanoparticles, and nanoemulsions. This work provides a comprehensive understanding of the beneficial functions and delivery strategies of CA, which is useful for the future application of CA in the functional food industry.

Berry anthocyanins prevent α-dicarbonyls and advanced glycation end product formation in phosphate-buffered saline-based model systems, cookie and ground pork.

α-Dicarbonyls and advanced glycation end products (AGEs) are the heat-induced potential toxicants commonly found in thermally processed foods due to the Maillard reaction. Research has shown that both α-dicarbonyls and AGEs can cause oxidative stress and inflammation and have a positive link with several chronic diseases, such as diabetes. This study found that commonly consumed berry fruits exhibited excellent methylglyoxal (MGO)-trapping and antiglycative activities, positively associated with their total phenolic and flavonoid contents. Blackcurrant exhibited the strongest MGO-trapping and antiglycative activities among the tested berry fruits. In addition, we demonstrated that fortification with blackcurrant significantly reduced α-dicarbonyls and AGEs formation in the chocolate cookies and marinated ground pork. Delphinidin and cyanidin glycosides were identified as the primary bioactive compounds of blackcurrant that trapped MGO to form the corresponding mono- and di-MGO adducts. This study suggested that blackcurrant anthocyanins might serve as a novel additive to reduce the consumption of dietary reactive carbonyl species and AGEs from both animal- and plant-derived processed foods. PRACTICAL APPLICATION: The levels of α-dicarbonyls and advanced glycation end products in ground pork and cookies were significantly reduced when fortified with blackcurrant. The blackcurrant anthocyanins might be a novel agent inhibiting α-dicarbonyls and dietary advanced glycation end products formation in thermally processed foods.

Gut Microbiota Mediate the Neuroprotective Effect of Oolong Tea Polyphenols in Cognitive Impairment Induced by Circadian Rhythm Disorder.

Oolong tea polyphenols (OTP) have attracted wide attention due to their ability to reduce inflammatory response, regulate gut microbiota, and improve cognitive function. However, exactly how the gut microbiota modulates nervous system activity is still an open question. We previously expounded that supplementing with OTP alleviated neuroinflammation in circadian rhythm disorder (CRD) mice. Here, we showed that OTP can relieve microglia activation by reducing harmful microbial metabolites lipopolysaccharide (LPS) that alleviate CRD-induced cognitive decline. Mechanistically, OTP suppressed the inflammation response by regulating the gut microbiota composition, including upregulating the relative abundance of Muribaculaceae and Clostridia_UCG-014 and downregulating Desulfovibrio, promoting the production of short-chain fatty acids (SCFAs). Moreover, the use of OTP alleviated intestinal barrier damage and decreased the LPS transport to the serum. These results further inhibited the activation of microglia, thus alleviating cognitive impairment by inhibiting neuroinflammation, neuron damage, and neurotoxicity metabolite glutamate elevation. Meanwhile, OTP upregulated the expression of synaptic plasticity-related protein postsynaptic density protein 95 (PSD-95) and synaptophysin (SYN) by elevating the brain-derived neurotrophic factor (BDNF) level. Taken together, our findings suggest that the OTP has the potential to prevent CRD-induced cognition decline by modulating gut microbiota and microbial metabolites.

Urbanization and renewable energy consumption in the emerging ASEAN markets: A comparison between short and long-run effects.

The emerging markets in the ASEAN region, such as Indonesia, Malaysia, the Philippines, Thailand and Vietnam, have put great effort into achieving dual objectives: (i) supporting economic growth and (ii) combating environmental degradation simultaneously. These objectively depend on the fast urbanization taking place in these countries. While increased energy consumption from urbanization supports economic growth, urbanization is a key driver of environmental degradation. This paper examines a potential link between urbanization and renewable energy consumption, primarily ignored in current literature, particularly in the ASEAN-5 countries. Findings from this paper indicate that, despite the adverse effect of urbanization on renewable energy consumption in the short run, a positive effect is found in the long run for these emerging ASEAN markets, except Malaysia. The Philippines appears to balance well between urbanization and renewable energy consumption in the short and long run. Policy implications have emerged based on the findings of this paper.

Natural product nobiletin-loaded Pickering emulsion stabilized by bovine serum albumin/carboxymethyl inulin complexes: preparation and digestive characteristics.

To expand the application of nobiletin (NOB) in semi-solid functional foods, bovine serum albumin (BSA)/carboxymethyl inulin (CMI) complexes-stabilized Pickering emulsion (BCPE) (φoil = 60%, v/v) was fabricated, and the swallowing index and bioavailability of the NOB-loaded Pickering emulsion was evaluated. Confocal laser scanning microscope (CLSM) and cryo-scanning electron microscopy (cryo-SEM) images revealed that BSA/CMI complexes attached to the oil-water interface. NOB-loaded BCPE exhibited a viscoelastic and shear-thinning behavior. Fork drip test results suggested that the textural value of unloaded and NOB-loaded emulsions was International Dysphagia Diet Standardisation Initiative Level 4, which could be swallowed directly without chewing. The in vitro lipolysis model suggested that NOB had a faster digestive profile and a higher bioaccessibility in the BCPE than in the oil suspension. The in vivo rat model revealed that the oral bioavailability of NOB was increased by 2.07 folds in BCPE compared to its bioavailability in unformulated oil. Moreover, BCPE led to a higher plasma concentration of the major demethylated metabolite of NOB (4'-demethylnobiletin) than the unformulated oil. Accordingly, BCPE enhanced the oral bioavailability of NOB by improving bioaccessibility, absorption, and biotransformation.

Formation of Volatile Pyrazinones in the Asparagine Maillard Reaction Systems and Novel Pyrazinone Formation Pathways in the Amidated-Alanine Maillard Reaction Systems.

Maillard reaction (MR) plays a pivotal role in the food flavor industry, including a cascade of reactions starting with the reaction between amino compounds and reducing sugars, and thus provides various colors and flavors. A new group of volatile compounds called pyrazinones found in MR are now getting more attention. In this study, eight volatile pyrazinones were found in the asparagine MR systems, in which 3,5-dimethyl- and 3,6-dimethyl-2(1H)-pyrazinones were reported for the first time. The major formation pathways were the reactions between asparagine and α-dicarbonyls, with decarboxylation as a critical step. Besides, novel alternative pathways involving alanine amidation and successive reactions with α-dicarbonyls were explored and successfully formed eight pyrazinones. The major differences between alanine-amidated pathways and decarboxylation pathways are the amidation step and absence of the decarboxylation step. For the alanine-amidated pathways, the higher the temperature, the better the amidation effect. The optimal amidation temperature was 200 °C in this study. The reaction between the alanine amide and α-dicarbonyls after amidation can happen at low temperatures, such as 35 and 50 °C, proposing the possibility of pyrazinone formation in real food systems. Further investigations should be conducted to investigate volatile pyrazinones in various food systems as well as the biological effects and kinetic formation differences of the volatile pyrazinones.

Chronic radiation proctitis refractory to steroid enema was successfully treated by metformin and sodium butyrate: a case report.

BACKGROUND: Radiation proctitis (RP) is a significant complication of pelvic radiation. Effective treatments for chronic RP are currently lacking. We report a case where chronic RP was successfully managed by metformin and butyrate (M-B) enema and suppository therapy. CASE PRESENTATION: A 70-year-old Asian male was diagnosed with prostate cancer of bilateral lobes, underwent definitive radiotherapy to the prostate of 76 Gy in 38 fractions and six months of androgen deprivation therapy. Despite a stable PSA nadir of 0.2 ng/mL for 10 months post-radiotherapy, he developed intermittent rectal bleeding, and was diagnosed as chronic RP. Symptoms persisted despite two months of oral mesalamine, mesalamine enema and hydrocortisone enema treatment. Transition to daily 2% metformin and butyrate (M-B) enema for one week led to significant improvement, followed by maintenance therapy with daily 2.0% M-B suppository for three weeks, resulting in continued reduction of rectal bleeding. Endoscopic examination and biopsy demonstrated a good therapeutic effect. CONCLUSIONS: M-B enema and suppository may be an effective treatment for chronic RP.

From foreign direct investment to environmental regulations: Does a feedback effect ever exist?

This study revisits the feedback effect from foreign direct investments (FDI) on environmental regulations under the presence of the host country's political structure. Such a relationship may encounter the endogeneity problem due to the omitted variable bias and reverse causality. As such, the two-step system generalized method of moments is employed. Using data from 21 OECD countries from 1990 to 2019, we confirm that FDI flows influence environmental regulations, but such an effect is conditional on the host country's political constraints. Specifically, FDI increases (decreases) the stringency of environmental regulations if domestic political constraints are sufficiently high (low). Understanding the mechanisms of how FDI flows can affect environmental regulations allows countries to revise their policies to attract more FDI flows to support economic growth while simultaneously minimising their negative effects on the environment.

Formation of Volatile Pyrazinones in Amadori Rearrangement Products and Maillard Reaction Systems and the Major Formation Pathways.

Amadori rearrangement products (ARPs) are gaining more attention for their potential usage in the food flavor industry. Peptide-ARPs have been studied, but pyrazinones that were theoretically found in the Maillard reaction (MR) have not been reported to be formed from small peptide-ARPs. This study found four pyrazinones: 1-methyl-, 1,5-dimethyl-, 1,6-dimethyl-, and 1,5,6-trimethyl-2(1H)-pyrazinones in both MR and ARP systems. It was the first time 1-methyl-2(1H)-pyrazinone was reported, along with 1,5-dimethyl- and 1,5,6-trimethyl-2(1H)-pyrazinones being purified and analyzed by nuclear magnetic resonance for the first time. The primary formation routes of the pyrazinones were also proven as the reaction between diglycine and α-dicarbonyls, including glyoxal, methylglyoxal, and diacetyl. The pyrazinones, especially 1,5-dimethyl-2(1H)-pyrazinone, have strong fluorescence intensity, which may be the reason for the increase of fluorescence intensity in MR besides α-dicarbonyls. Cytotoxicity analysis showed that both Gly-/Digly-/Trigly-ARP and the three pyrazinones [1-methyl-, 1,5-dimethyl-, and 1,5,6-trimethyl-2(1H)-pyrazinones] showed no prominent cytotoxicity in the HepG2 cell line below 100 µg/mL, further suggesting that ARPs or pyrazinones could be used as flavor additives in the future. Further research should be conducted to investigate pyrazinones in various systems, especially the peptide-ARPs, which are ubiquitous in real food systems.

Taste-Active Peptides from Triple-Enzymatically Hydrolyzed Straw Mushroom Proteins Enhance Salty Taste: An Elucidation of Their Effect on the T1R1/T1R3 Taste Receptor via Molecular Docking.

The objective of our study was to analyze and identify enzymatic peptides from straw mushrooms that can enhance salty taste with the aim of developing saltiness enhancement peptides to reduce salt intake and promote dietary health. We isolated taste-related peptides from the straw mushroom extract using ultrafiltration and identified them using UPLC-Q-TOF-MS/MS. The study found that the ultrafiltration fraction (500-2000 Da) of straw mushroom peptides had a saltiness enhancement effect, as revealed via subsequent E-tongue and sensory analyses. The ultrafiltration fractions (500-2000 Da) were found to contain 220 peptides, which were identified through UPLC-Q-TOF-MS/MS analysis. The interaction of these peptides with the T1R1/T1R3 receptor was also assessed. The investigation highlighted the significant involvement of Asp223, Gln243, Leu232, Asp251, and Pro254 in binding peptides from triple-enzymatically hydrolyzed straw mushrooms to T1R1/T1R3. Based on the binding energy and active site analysis, three peptides were selected for synthesis: DFNALPFK (-9.2 kcal/mol), YNEDNGIVK (-8.8 kcal/mol), and VPGGQEIKDR (-8.9 kcal/mol). Importantly, 3.2 mmol of VPGGQEIKDR increased the saltiness level of a 0.05% NaCl solution to that of a 0.15% NaCl solution. Additionally, the addition of 0.8 mmol of YNEDNGIVK to a 0.05% NaCl solution resulted in the same level of saltiness as a 0.1% NaCl solution.

Stool protein mass spectrometry identifies biomarkers for the early detection of diffuse-type gastric cancer.

There is a high unmet need for early detection approaches for diffuse gastric cancer (DGC). We examined whether the stool proteome of mouse models of GC or individuals with hereditary diffuse GC (HDGC) have utility as biomarkers for early detection. Proteomic mass spectrometry of stool from a genetically engineered mouse model driven by oncogenic KrasG12D and loss of p53 and Cdh1 in gastric parietal cells (known as TCON mice) identified differentially abundant proteins compared to littermate controls. Immunoblot assays validated a panel of proteins including actinin alpha 4 (ACTN4), N-acylsphingosine amidohydrolase 2 (ASAH2), dipeptidyl peptidase 4 (DPP4), and valosin-containing protein (VCP) as enriched in TCON stool compared to littermate control stool. Immunofluorescence analysis of these proteins in TCON stomach sections revealed increased protein expression as compared to littermate controls. Proteomic mass spectrometry of stool obtained from HDGC patients with CDH1 mutations identified increased expression of ASAH2, DPP4, VCP, lactotransferrin (LTF), and tropomyosin-2 (TPM2) relative to stool from healthy sex and age-matched donors. Chemical inhibition of ASAH2 using C6-urea ceramide was toxic to GC cell lines and patient derived-GC organoids. This toxicity was reversed by adding downstream products of the S1P synthesis pathway, suggesting a dependency on ASAH2 activity in GC. An exploratory analysis of the HDGC stool microbiome identified features which correlated with patient tumors. Here we provide evidence supporting the potential of analyzing stool biomarkers for the early detection of DGC.