Fenfuro®-mediated arrest in the formation of protein-methyl glyoxal adducts: a new dimension in the anti-hyperglycemic potential of a novel fenugreek seed extract.

The fenugreek plant (Trigonella foenum-graecum) is traditionally known for its anti-diabetic properties owing to its high content of furostanolic saponins, which can synergistically treat many human ailments. Non-enzymatic protein glycation leading to the formation of Advanced Glycation End products (AGE) is a common pathophysiology observed in diabetic or prediabetic individuals, which can initiate the development of neurodegenerative disorders. A potent cellular source of glycation is Methyl Glyoxal, a highly reactive dicarbonyl formed as a glycolytic byproduct. We demonstrate the in vitro glycation arresting potential of Fenfuro®, a novel patented formulation of Fenugreek seed extract with clinically proven anti-diabetic properties, in Methyl-Glyoxal (MGO) adducts of three abundant amyloidogenic cellular proteins, alpha-synuclein, Serum albumin, and Lysozyme. A 0.25% w/v Fenfuro® was able to effectively arrest glycation by more than 50% in all three proteins, as evidenced by AGE fluorescence. Glycation-induced amyloid formation was also arrested by more than 36%, 14% and 15% for BSA, Alpha-synuclein and Lysozyme respectively. An increase in MW by attachment of MGO was also partially prevented by Fenfuro® as confirmed by SDS-PAGE analysis. Glycation resulted in enhanced aggregation of the three proteins as revealed by Native PAGE and Dynamic Light Scattering. However, in the presence of Fenfuro®, aggregation was arrested substantially, and the normal size distribution was restored. The results cumulatively indicated the lesser explored potential of direct inhibition of glycation by fenugreek seed in addition to its proven role in alleviating insulin resistance. Fenfuro® boosts its therapeutic potential as an effective phytotherapeutic to arrest Type 2 diabetes.

Fenfuro^® is a novel patented formulation of Fenugreek seed extract with more than 45% furostanolic saponins and anti-diabetic property free from any side effect as established through clinical study.In the present study, the role of Fenfuro® in arresting in vitro AGE formation and glycation-induced amyloid formation has been demonstrated with the help of three amyloidogenic proteins, namely Human Lysozyme, Human alpha-synuclein and Bovine Serum Albumin using Methyl Glyoxal as the glycating agent.A 0.25% (w/v) ethanolic solution of Fenfuro® resulted in more than 50% arrest in glycation with simultaneous prevention of aggregation as demonstrated by native PAGE, DLS and inhibition of development of Thio-T positive amyloid like entities.The studies collectively aim toward the development of a safe therapeutic method for arresting protein glycation through direct physical intervention.

Glyceraldehyde metabolism in mouse brain and the entry of blood-borne glyceraldehyde into the brain.

D-Glyceraldehyde, a reactive aldehyde metabolite of fructose and glucose, is neurotoxic in vitro by forming advanced glycation end products (AGEs) with neuronal proteins. In Alzheimer's disease brains, glyceraldehyde-containing AGEs have been detected intracellularly and in extracellular plaques. However, little information exists on how the brain handles D-glyceraldehyde metabolically or if glyceraldehyde crosses the blood-brain barrier from the circulation into the brain. We injected [U-13C]-D-glyceraldehyde intravenously into awake mice and analyzed extracts of serum and brain by 13C nuclear magnetic resonance spectroscopy. 13C-Labeling of brain lactate and glutamate indicated passage of D-glyceraldehyde from blood to brain and glycolytic and oxidative D-glyceraldehyde metabolism in brain cells. 13C-Labeling of serum glucose and lactate through hepatic metabolism of [U-13C]-D-glyceraldehyde could not explain the formation of 13C-labeled lactate and glutamate in the brain. Cerebral glyceraldehyde dehydrogenase and reductase activities, leading to the formation of D-glycerate and glycerol, respectively, were 0.27-0.28 nmol/mg/min; triokinase, which phosphorylates D-glyceraldehyde to D-glyceraldehyde-3-phosphate, has been demonstrated previously at low levels. Thus, D-glyceraldehyde metabolism toward glycolysis could proceed both through D-glycerate, glycerol, and D-glyceraldehyde-3-phosphate. The aldehyde group of D-glyceraldehyde was overwhelmingly hydrated into a diol in aqueous solution, but the diol dehydration rate greatly exceeded glyceraldehyde metabolism and did not restrict it. We conclude that (1) D-glyceraldehyde crosses the blood-brain barrier, and so blood-borne glyceraldehyde could contribute to AGE formation in the brain, (2) glyceraldehyde is taken up and metabolized by brain cells. Metabolism thus constitutes a detoxification mechanism for this reactive aldehyde, a mechanism that may be compromised in disease states.

Deletion of Glyoxalase 1 Exacerbates Acetaminophen-Induced Hepatotoxicity in Mice.

Acetaminophen (APAP) overdose triggers a cascade of intracellular oxidative stress events, culminating in acute liver injury. The clinically used antidote, N-acetylcysteine (NAC), has a narrow therapeutic window, and early treatment is essential for a satisfactory therapeutic outcome. For more versatile therapies that can be effective even at late presentation, the intricacies of APAP-induced hepatotoxicity must be better understood. Accumulation of advanced glycation end products (AGEs) and the consequent activation of the receptor for AGEs (RAGE) are considered one of the key mechanistic features of APAP toxicity. Glyoxalase 1 (Glo-1) regulates AGE formation by limiting the levels of methylglyoxal (MEG). In this study, we studied the relevance of Glo-1 in the APAP-mediated activation of RAGE and downstream cell death cascades. Constitutive Glo-1-knockout mice (GKO) and a cofactor of Glo-1, ψ-GSH, were used as tools. Our findings showed elevated oxidative stress resulting from the activation of RAGE and hepatocyte necrosis through steatosis in GKO mice treated with high-dose APAP compared to wild-type controls. A unique feature of the hepatic necrosis in GKO mice was the appearance of microvesicular steatosis as a result of centrilobular necrosis, rather than the inflammation seen in the wild type. The GSH surrogate and general antioxidant ψ-GSH alleviated APAP toxicity irrespective of the Glo-1 status, suggesting that oxidative stress is the primary driver of APAP toxicity. Overall, the exacerbation of APAP hepatotoxicity in GKO mice suggests the importance of this enzyme system in antioxidant defense against the initial stages of APAP overdose.

Soluble receptor of advanced glycation end product as a biomarker in neurocognitive and neuropsychiatric disorders: A meta-analysis of controlled studies.

BACKGROUND & OBJECTIVES: Currently, there is a significant focus on the decrease of soluble receptor of advanced glycation end products (sRAGE) in neurocognitive and neuropsychiatric disorders. sRAGE plays a decoy role against the inflammatory response of advanced glycation end products (AGE), which has led to increased interest in its role in these disorders. This meta-analysis aimed to investigate the significant differences in sRAGE levels between neurocognitive and neuropsychiatric disorders compared to control groups. METHOD: A systematic review was conducted using the PUBMED, Scopus and Embase databases up to October 2023. Two reviewers assessed agreement for selecting papers based on titles and abstracts, with kappa used to measure agreement and finally publications were scanned according to controlled studies. Effect sizes were calculated as weighted mean differences (WMD) and pooled using a random effects model. Heterogeneity was assessed using I2, followed by subgroup analysis and meta-regression tests. Quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: In total, 16 studies were included in the present meta-analysis. Subjects with neurocognitive (n = 1444) and neuropsychiatric (n = 444) disorders had lower sRAGE levels in case-control (WMD: -0.21, 95% CI: -0.33, -0.10; p <.001) and cross-sectional (WMD: -0.29, 95% CI = -0.44, -0.13, p <.001) studies with high heterogeneity and no publication bias. In subgroup analysis, subjects with cognitive impairment (WMD: -0.87, 95% CI: -1.61, -0.13, p =.000), and age >50 years (WMD: -0.39, 95% CI: -0.74, -0.05, p =.000), had lower sRAGE levels in case-control studies. Also, dementia patients (WMD: -0.41, 95% CI: -0.72, -0.10, p =.014) with age >50 years (WMD: -0.33, 95% CI: -0.54, -0.13, p = 0.000) and in Asian countries (WMD: -0.28, 95% CI: -0.42, -0.13, p =.141) had lower sRAGE levels in cross-sectional studies. CONCLUSION: This meta-analysis revealed a significant reduction in sRAGE in neurocognitive and neuropsychiatric disorders particularly in Asians and moderate age.

Apigenin and baicalein ameliorate thoracic aortic structural deterioration and cognitive deficit via inhibiting AGEs/RAGE/NF-κB pathway in D-galactose-induced aging rats.

Apigenin and baicalein are structurally related flavonoids that have been reported to have multiple pharmacological activities. The aim of this study was to investigate the protective effects and potential mechanisms of apigenin and baicalein in D-galactose-induced aging rats. First, apigenin and baicalein showed remarkable antioxidant activity and anti-glycation activity in vitro. Secondly, the protective effects of apigenin and baicalein on aging rats were investigated. We found that apigenin and baicalein supplementation significantly ameliorated aging-related changes such as declines in the spatial learning and memory and histopathological damage of the hippocampus and thoracic aorta. In addition, our data showed that apigenin and baicalein alleviated oxidative stress as illustrated by decreasing MDA level, increasing SOD activity and GSH level. Further data showed that they significantly reduced the accumulation of advanced glycation end products (AGEs), inhibited the expression of RAGE, down-regulated phosphorylated nuclear factor (p-NF-κB (p65)). Our results suggested that the protective effects of apigenin and baicalein on aging rats were at least partially related to the inhibition of AGEs/RAGE/NF-κB pathway and the improvement of oxidative damage. Overall, apigenin and baicalein showed almost equal anti-aging efficacy. Our results provided an experimental basis for the application of apigenin and baicalein to delay the aging process.

Interactions between Age-Related Type 2 Diabetes and the Small Intestine.

The number of patients with type 2 diabetes is increasing worldwide. The mechanisms leading to type 2 diabetes and its complications is being researched; however, the pathological mechanisms of diabetes in the small intestine remain unclear. Therefore, we examined these pathological mechanisms in the small intestine using a mouse model of type 2 diabetes (KK-Ay/TaJcl) aged 10 and 50 weeks. The results showed that diabetes worsened with age in the mice with type 2 diabetes. In these mice, advanced glycation end products (AGEs) in the small intestine and mast cell expression increased, whereas diamine oxidase (DAO) decreased; increased tumor necrosis factor (TNF)-α and histamine levels in the plasma and small intestine were also detected. Additionally, the expression of zonula occludens (ZO)-1 and Claudin1 and cell adhesion molecules in the small intestine reduced. These results exacerbated with age. These findings indicate that type 2 diabetes causes AGE/mast cell/histamine and TNF-α signal transmission in the small intestine and decreases small intestinal wall cell adhesion molecules cause TNF-α and histamine to flow into the body, worsening the diabetic condition. In addition, this sequence of events is suggested to be strengthened in aged mice with type 2 diabetes, thus exacerbating the disease. These findings of this study may facilitate the elucidation of the pathological mechanisms of type 2 diabetes and its associated complications.

High-mobility group box 1 and its related receptors: potential therapeutic targets for contrast-induced acute kidney injury.

Percutaneous coronary intervention (PCI) is a crucial diagnostic and therapeutic approach for coronary heart disease. Contrast agents' exposure during PCI is associated with a risk of contrast-induced acute kidney injury (CI-AKI). CI-AKI is characterized by a sudden decline in renal function occurring as a result of exposure to intravascular contrast agents, which is associated with an increased risk of poor prognosis. The pathophysiological mechanisms underlying CI-AKI involve renal medullary hypoxia, direct cytotoxic effects, endoplasmic reticulum stress, inflammation, oxidative stress, and apoptosis. To date, there is no effective therapy for CI-AKI. High-mobility group box 1 (HMGB1), as a damage-associated molecular pattern molecule, is released extracellularly by damaged cells or activated immune cells and binds to related receptors, including toll-like receptors and receptor for advanced glycation end product. In renal injury, HMGB1 is expressed in renal tubular epithelial cells, macrophages, endothelial cells, and glomerular cells, involved in the pathogenesis of various kidney diseases by activating its receptors. Therefore, this review provides a theoretical basis for HMGB1 as a therapeutic intervention target for CI-AKI.

Total serum pentosidine quantification using liquid chromatography-tandem mass spectrometry.

Pentosidine (PEN) is an Advanced Glycation End-product (AGE) that is known to accumulate in bone collagen with aging and contribute to fracture risk. The PEN content in bone is correlated with serum PEN, making it an attractive, potential osteoporosis biomarker. We sought to develop a method for quantifying PEN in stored serum. After conducting a systematic narrative review of PEN quantification methodologies, we developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantifying total serum PEN. Our method is both sensitive and precise (LOD 2 nM, LOQ 5 nM, %CV < 6.5 % and recovery 91.2-100.7 %). Our method is also equivalent or better than other methods identified in our review. Additionally, LC-MS/MS avoids the pitfalls and limitations of using fluorescence as a means of detection and could be adapted to investigate a broad range of AGE compounds.

Targeting the heparan sulfate-binding site of RAGE with monoclonal antibodies.

Heparan sulfate (HS) plays its biological functions by interacting with hundreds of secreted extracellular and transmembrane proteins. Interaction with HS has been shown to be required for the normal function of many HS-binding proteins. Receptor for advanced glycation end-product (RAGE) is such a protein, whose activation requires HS-induced oligomerization. Using RAGE as an exemplary protein, we show here the workflow of a simple method of developing and characterizing mAbs that targets the HS-binding site. We found that HS-binding site of RAGE is quite immunogenic as 18 out of 94 anti-RAGE mAbs target various epitopes within the HS-binding site. Sequence analysis found that a common feature of anti-HS-binding site mAbs is the presence of abundant acidic residues (range between 6 to 11) in the complementarity determining region, suggesting electrostatic interaction plays an important role in promoting antigen-antibody interaction. Interestingly, mAbs targeting different epitopes within the HS-binding site blocks HS-RAGE interaction to different degrees, and the inhibitory effect is highly consistent among mAbs that target the same epitope. Functional assay revealed that anti-HS-binding site mAbs show different potency in inhibiting osteoclastogenesis, and the inhibitory potency does not have a simple correlation with the affinity and the epitope. Our study demonstrates that developing HS-binding site targeting mAbs should be applicable to most HS-binding proteins. By targeting this unique functional site, these mAbs might find therapeutic applications in treating various human diseases.

Trichosanthin alleviates streptozotocin-induced type 1 diabetes mellitus in mice by regulating the balance between bone marrow-derived IL6+ and IL10+ MDSCs.

Myeloid-derived suppressor cells (MDSCs) occupy a pivotal role in the intricate pathogenesis of the autoimmune disorder, Type 1 diabetes mellitus (T1DM). Since our previous work demonstrated that trichosanthin (TCS), an active compound of Chinese herb medicine Tian Hua Fen, regulated immune response, we aimed to clarify the efficacy and molecular mechanism of TCS in the treatment of T1DM. To this end, T1DM mouse model was established by streptozotocin (STZ) induction. The mice were randomly divided into normal control group (Ctl), T1DM group (STZ), TCS treated diabetic group (STZ + TCS) and insulin-treated diabetic group (STZ + insulin). Our comprehensive evaluation encompassed variables such as blood glucose, glycosylated hemoglobin, body weight, pertinent biochemical markers, pancreatic histopathology, and the distribution of immune cell populations. Furthermore, we meticulously isolated MDSCs from the bone marrow of T1DM mice, probing into the expressions of genes pertaining to the advanced glycation end product receptor (RAGE)/NF-κB signaling pathway through RT-qPCR. Evidently, TCS exhibited a substantial capacity to effectively counteract the T1DM-induced elevation in random blood glucose, glycosylated hemoglobin, and IL-6 levels in plasma. Pathological scrutiny underscored the ability of TCS to mitigate the damage incurred by islets. Intriguingly, TCS interventions engendered a reduction in the proportion of MDSCs within the bone marrow, particularly within the IL-6+ MDSC subset. In contrast, IL-10+ MDSCs exhibited an elevation following TCS treatment. Moreover, we observed a significant down-regulation of relative mRNA of pro-inflammatory genes, including arginase 1 (Arg1), inducible nitric oxide synthase (iNOS), RAGE and NF-κB, within MDSCs due to the influence of TCS. It decreases total MDSCs and regulates the balance between IL-6+ and IL-10+ MDSCs thus alleviating the symptoms of T1DM. TCS also down-regulates the RAGE/NF-κB signaling pathway, making it a promising alternative therapeutic treatment for T1DM. Collectively, our study offered novel insights into the underlying mechanism by which TCS serves as a promising therapeutic intervention for T1DM.

Effect of Anagliptin on Vascular Injury in the Femoral Artery of Type 2 Diabetic Rats.

Patients with diabetes mellitus (DM) often experience complications such as peripheral arterial disease (PAD), which is thought to be caused by vascular damage resulting from increased oxidative stress. Dipeptidyl peptidase-4 inhibitors have been reported to reduce oxidative stress, although the exact mechanism remains unclear. This study aimed to investigate the impact of long-term (6 weeks) anagliptin treatment at a dose of 200 mg/kg/d against oxidative stress in the femoral artery of Otsuka Long-Evans Tokushima Fatty (OLETF) rats using a well-established animal model for type 2 DM. Serum toxic advanced glycation end-products concentrations and blood glucose levels after glucose loading were significantly elevated in OLETF rats compared to Long-Evans Tokushima Otsuka (LETO) rats but were significantly suppressed by anagliptin administration. Plasma glucagon-like peptide-1 concentrations after glucose loading were significantly increased in anagliptin-treated rats. Superoxide production and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in femoral arteries were significantly increased in OLETF rats compared to LETO rats but were significantly decreased by anagliptin administration. The expressions of NADPH oxidase components (p22phox in the intima region and p22phox and gp91phox in the media region) in the femoral artery were significantly increased in OLETF rats compared to LETO rats but were significantly suppressed by anagliptin administration. Furthermore, the femoral artery showed increased wall thickness in OLETF rats compared to LETO rats, but anagliptin administration reduced the thickening. This study suggests that long-term anagliptin administration can reduce oxidative stress in femoral arteries and improve vascular injury.

Unlocking the Therapeutic Potential of Stevia rebaudiana Bertoni: A Natural Antiglycating Agent and Non-Toxic Support for HDF Cell Health.

Sugar carbonyl groups interact with protein amino groups, forming toxic components referred to as advanced glycation end products (AGEs). The glycation system (BSA, a model protein, and fructose) was incubated for five weeks at 37 °C in the presence and absence of Stevia leaf extract. The results indicated that the leaf extract (0.5 mg/mL) decreased the incidence of browning (70.84 ± 0.08%), fructosamine (67.27 ± 0.08%), and carbonyl content (64.04 ± 0.09%). Moreover, we observed an 81 ± 8.49% reduction in total AGEs. The inhibition of individual AGE (argpyrimidine, vesper lysine, and pentosidine) was ~80%. The decrease in the protein aggregation was observed with Congo red (46.88 ± 0.078%) and the Thioflavin T (31.25 ± 1.18%) methods in the presence of Stevia leaf extract. The repercussion of Stevia leaf extract on DNA glycation was examined using agarose gel electrophoresis, wherein the DNA damage was reversed in the presence of 1 mg/mL of leaf extract. When the HDF cell line was treated with 0.5 mg/mL of extract, the viability of cells decreased by only ~20% along with the same cytokine IL-10 production, and glucose uptake decreased by 28 ± 1.90% compared to the control. In conclusion, Stevia extract emerges as a promising natural agent for mitigating glycation-associated challenges, holding potential for novel therapeutic interventions and enhanced management of its related conditions.

Impact of intense physical activity in athletes on intestinal mucosal integrity and its role in acute gastric hemorrhage and postoperative infection risks

In the context of rising gastric disease prevalence, acute gastric hemorrhage presents a significant clinical challenge, particularly among athletes who engage in intense physical activity. This demographic may have unique vulnerabilities due to the stress and strain of their rigorous training and performance routines. Acute gastric bleeding can arise from various sources, including gastritis from Helicobacter pylori infection, gastric ulcers, or vascular abnormalities exacerbated by lifestyle factors like excessive alcohol consumption. However, the impact of high-intensity physical exertion, common in athletes, on these conditions remains underexplored. In athletes, the management of acute gastric bleeding often involves conservative drug therapy post-hemodilation, with proton pump inhibitors like omeprazole offering both anti-inflammatory and acid-inhibiting effects. Surgical intervention is reserved for severe cases, considering the heightened risk of postoperative abdominal infections due to the stomach's unique physiology and its microbial population. This study focuses on the intestinal mucosal barrier's function postoperatively in athletes who have undergone treatment for acute gastric bleeding. We explore how intense physical activity influences intestinal mucosal integrity and its subsequent role in postoperative infection risks. The role of high-mobility group box1 (HMGB1) and the receptor for advanced glycation end products (RAGE) in this context is also examined. HMGB1, a crucial pro-inflammatory cytokine and late inflammatory mediator, and RAGE, a significant HMGB1 receptor, are believed to play pivotal roles in the inflammatory response following acute gastric bleeding (AU)

Implications of receptor for advanced glycation end products for progression from obesity to diabetes and from diabetes to cancer.

Obesity and type 2 diabetes mellitus (T2DM) are chronic pathologies with a high incidence worldwide. They share some pathological mechanisms, including hyperinsulinemia, the production and release of hormones, and hyperglycemia. The above, over time, affects other systems of the human body by causing tissue hypoxia, low-grade inflammation, and oxidative stress, which lay the pathophysiological groundwork for cancer. The leading causes of death globally are T2DM and cancer. Other main alterations of this pathological triad include the accumulation of advanced glycation end products and the release of endogenous alarmins due to cell death (i.e., damage-associated molecular patterns) such as the intracellular proteins high-mobility group box protein 1 and protein S100 that bind to the receptor for advanced glycation products (RAGE) - a multiligand receptor involved in inflammatory and metabolic and neoplastic processes. This review analyzes the latest advanced reports on the role of RAGE in the development of obesity, T2DM, and cancer, with an aim to understand the intracellular signaling mechanisms linked with cancer initiation. This review also explores inflammation, oxidative stress, hypoxia, cellular senescence, RAGE ligands, tumor microenvironment changes, and the "cancer hallmarks" of the leading tumors associated with T2DM. The assimilation of this information could aid in the development of diagnostic and therapeutic approaches to lower the morbidity and mortality associated with these diseases.

Extrusion of lupines with or without addition of reducing sugars: Effects on the formation of Maillard reaction compounds, partition of nitrogen and Nε-carboxymethyl-lysine, and performance of dairy cows.

The extrusion of leguminous seeds induces the formation of Maillard reaction compounds (MRC) as a product of protein advanced glycation and oxidation, which lowers protein degradability in the rumen. However, the quantitative relationship between the parameters of pretreatment (i.e., addition of reducing sugars) and extrusion, and the formation of MRC has not been established yet. Moreover, the fate of the main stable MRC, Nε-carboxymethyl-lysine (CML), in the excretory routes has never been investigated in ruminants. We aimed to test the effects of the temperature of extrusion of white lupines with or without addition of reducing sugars on the formation of MRC, crude protein (CP) degradability in the rumen, N use efficiency for milk production (milk N/N intake), and performance of dairy cows. Two experiments with a replicated 4 × 4 Latin square design were conducted simultaneously with 16 (3 rumen-cannulated) multiparous Holstein cows to measure indicators of ruminal CP degradability (ruminal NH3 concentration, branched-chain volatile fatty acids), metabolizable protein supply (plasma essential AA concentration), N use efficiency (N isotopic discrimination), and dairy performance. In parallel, apparent total-tract digestibility of dry matter, organic matter, neutral detergent fibers, N, total Lys and CML, and partition of N and CML were measured with 4 cows in both experiments. The diets consisted on a DM basis of 20% raw or extruded lupines and 80% basal mixed ration of corn silage, silage and hay from permanent grasslands, pelleted concentrate, and a vitaminized mineral mix. Expected output temperatures of lupine extrusion were 115°C, 135°C, and 150°C, without and with the addition of reducing sugars before extrusion. The extrusion numerically reduced the in vitro ruminal CP degradability of the lupines, and consequently increased the predicted supply of CP to the small intestine. Nitrogen balance and urinary N excretion did not differ among dietary treatments in either experiment. Milk yield and N use efficiency for milk production increased with extrusion of lupines at 150°C without addition of reducing sugars compared with raw lupines. Nitrogen isotopic discrimination between dietary and animal proteins (the difference between δ15N in plasma and δ15N in the diet) were lower with lupines extruded at 150°C without and with addition of reducing sugars. Regardless of sugar addition, milk true protein yield was not affected, but milk urea concentration and fat:protein ratio were lower with lupines extruded at 150°C than with raw lupines. In the CML partition study, we observed that on average 26% of the apparently digested CML was excreted in urine, and a much lower proportion (0.63% on average) of the apparently digested CML was secreted in milk, with no differences among dietary treatments. In conclusion, we showed that the extrusion of white lupines without or with addition of reducing sugars numerically reduced enzymatic CP degradability, with limited effects on N partition, but increased milk yield and N use efficiency at the highest temperature of extrusion without addition of reducing sugars.

Age-related changes in scalp biophysical parameters: A comparative analysis of the 20s and 50s age groups.

BACKGROUND: Age-related changes in scalp parameters affect hair quality and scalp condition. However, detailed data on biophysical parameters of the scalp across age groups remain scarce. We aimed to investigate the differences in scalp parameters between individuals in their 20s and 50s and analyze their sex-specific variations. MATERIALS AND METHODS: Two hundred participants (160 women and 40 men) were equally divided into 20s and 50s age groups. Biophysical parameters of the scalp, including elasticity, pH, trans-epidermal water loss (TEWL), sebum production, desquamation, firmness, redness, and yellowness, were measured in the vertex, occipital, and temporal regions. Hair density and thickness were measured in the temporal region. The accumulation of advanced glycation end products (AGEs) in the skin was noninvasively measured in a subset of 60 women. RESULTS: Skin firmness and redness increased with age in women, whereas yellowness increased with age in both sexes. Sebum production and pH levels were significantly lower in the 50s age group than in the 20s age group, particularly in women. TEWL was lower in men in their 50s than in those in their 20s, particularly in the occipital region. A significant reduction in hair density was observed in the 50s age group in both sexes. AGE accumulation in the skin increased with age and was correlated with scalp skin yellowness. CONCLUSION: Age-related changes in scalp parameters have important implications for hair health and scalp condition. These findings emphasize the importance of considering age and sex when developing hair care strategies.

Serum and follicular fluid levels of soluble receptor for advanced glycation end-products in women with and without polycystic ovary syndrome.

BACKGROUND: Advanced glycation end products (AGEs) are known to associate with the pathogenesis of several chronic diseases via interaction with their corresponding receptor (RAGE). The soluble forms of RAGE (sRAGE) are considered as anti-inflammatory agents by inhibiting the consequent adverse effects of AGE. We aimed at comparing sRAGE levels in the follicular fluid (FF) and serum of women with or without Polycystic Ovary Syndrome (PCOS) who underwent controlled ovarian stimulation for in vitro fertilisation (IVF). METHODS: A total of forty-five eligible women (26 non-PCOS (control) and 19 patients with PCOS (case)) were included the study. sRAGEs in FF and blood serum were measured using ELISA kit. RESULTS: No statistically significant differences were found in FF and serum sRAGE between case and control groups. Correlation analysis showed a significant and positive relationship between serum levels of sRAGE and FF sRAGE in PCOS (r = 0.639; p = 0.004), in control participants (r = 0.481; p = 0.017), and in total participants (r = 0.552; p = 0.000). Data revealed a statistically significant difference in FF sRAGE concentration among all participants by body mass index (BMI) categories (p = 0.01) and in controls (p = 0.022). Significant differences were found for all the nutrients and AGEs consumption according to Food Frequency Questionnaire in both groups (p = 0.0001). A significant reverse relationship was found between FF levels of sRAGE and AGE in PCOS (r = -0.513; p = 0.025). The concentration of sRAGE in serum and FF is the same in PCOS and control. CONCLUSION: The present study revealed for the first time that there are no statistically significant differences between the concentration of serum sRAGE and FF sRAGE among Iranian women with and without PCOS. However, BMI and dietary intake of AGEs have more significant effects on sRAGE concentration in Iranian women. Future studies in developed and developing countries with larger sample sizes are required to determine the long-term consequences of chronic AGE over consumption and the optimal strategies for minimizing AGE-related pathology, specifically in low income and developing countries.

Urinary pentosidine level is associated with the risk of fracture in community-dwelling older adults: a prospective observational study.

A history of fracture in adulthood and urinary pentosidine levels were independently and significantly associated with fracture occurrence in this prospective observational study of community-dwelling older adults. PURPOSE: This prospective observational study aimed to determine the factors associated with fragility fractures in community-dwelling older adults. METHODS: Overall, 254 older adults who were participants of the Good Aging and Intervention Against Nursing Care and Activity Decline study in 2016 were included in this study. Grip strength, muscle mass, gait speed, calcaneal bone density, and the levels of parathyroid hormone, osteocalcin, 25-hydroxyvitamin D, total procollagen type I N-terminal propeptide, insulin-like growth factor-1 (IGF-1), tartrate-resistant acid phosphatase-5b, and urinary pentosidine were measured at baseline. Participants were classified as fracture ( +) or fracture (-) based on the data collected during a 5-year follow-up period. RESULTS: Excluding those who were lost to follow-up during the observation period, 182 participants (64 men and 118 women, mean age: 74.2 years, range: 47-99 years) were included in the analysis. During the observation period, 23 patients experienced 24 new fractures. In univariate analysis, sex, height, weight, history of fracture in adulthood, baseline grip strength, muscle mass, bone density, and the levels of urinary pentosidine and IGF-1 at baseline were significantly different between patients who developed a fracture during follow-up and those who did not. In multivariate analysis, a history of fracture in adulthood and urinary pentosidine levels were independently and significantly associated with fracture occurrence. CONCLUSION: High urine pentosidine levels and a history of fracture in adulthood are independent risk factors for fracture occurrence in community-dwelling older adults.

Advanced Glycation End Products as a Potential Target for Restructuring the Ovarian Cancer Microenvironment: A Pilot Study.

Ovarian cancer is the sixth leading cause of cancer-related death in women, and both occurrence and mortality are increased in women over the age of 60. There are documented age-related changes in the ovarian cancer microenvironment that have been shown to create a permissive metastatic niche, including the formation of advanced glycation end products, or AGEs, that form crosslinks between collagen molecules. Small molecules that disrupt AGEs, known as AGE breakers, have been examined in other diseases, but their efficacy in ovarian cancer has not been evaluated. The goal of this pilot study is to target age-related changes in the tumor microenvironment with the long-term aim of improving response to therapy in older patients. Here, we show that AGE breakers have the potential to change the omental collagen structure and modulate the peritoneal immune landscape, suggesting a potential use for AGE breakers in the treatment of ovarian cancer.

Biochemical Markers of Bone Fragility in Patients With Diabetes.

CONTEXT: The risk of fragility fractures is increased in both type 1 and type 2 diabetes. Numerous biochemical markers reflecting bone and/or glucose metabolism have been evaluated in this context. OBJECTIVE: This review summarizes current data on biochemical markers in relation to bone fragility and fracture risk in diabetes. METHODS: A group of experts from the International Osteoporosis Foundation and European Calcified Tissue Society reviewed the literature focusing on biochemical markers, diabetes, diabetes treatments, and bone in adults. RESULTS: Although bone resorption and bone formation markers are low and poorly predictive of fracture risk in diabetes, osteoporosis drugs seem to change bone turnover markers (BTMs) in diabetics similarly to nondiabetics, with similar reductions in fracture risk. Several other biochemical markers related to bone and glucose metabolism have been correlated with bone mineral density and/or fracture risk in diabetes, including osteocyte-related markers such as sclerostin, glycated hemoglobin A1c (HbA1c) and advanced glycation end products, inflammatory markers, and adipokines, as well as insulin-like growth factor-1 and calciotropic hormones. CONCLUSION: Several biochemical markers and hormonal levels related to bone and/or glucose metabolism have been associated with skeletal parameters in diabetes. Currently, only HbA1c levels seem to provide a reliable estimate of fracture risk, while BTMs could be used to monitor the effects of antiosteoporosis therapy.