High-sugar Diet Research Articles

Obesogenic diet in pregnancy disrupts placental iron handling and ferroptosis and stress signalling in association with fetal growth alterations

Obesity and gestational diabetes (GDM) impact fetal growth during pregnancy. Iron is an essential micronutrient needed for energy-intense feto-placental development, but if mis-handled can lead to oxidative stress and ferroptosis (iron-dependent cell death). In a mouse model showing maternal obesity and glucose intolerance, we investigated the association of materno-fetal iron handling and placental ferroptosis, oxidative damage and stress signalling activation with fetal growth. Female mice were fed a standard chow or high fat, high sugar (HFHS) diet during pregnancy and outcomes were measured at day (d)16 or d19 of pregnancy. In HFHS-fed mice, maternal hepcidin was reduced and iron status maintained (tissue iron levels) at both d16 and d19. However, fetal weight, placental iron transfer capacity, iron deposition, TFR1 expression and ERK2-mediated signalling were reduced and oxidative damage-related lipofuscin accumulation in the placenta was increased in HFHS-fed mice. At d19, whilst TFR1 remained decreased, fetal weight was normal and placental weight, iron content and iron transporter genes (Dmt1, Zip14, and Fpn1) were reduced in HFHS-fed mice. Furthermore, there was stress kinase activation (increased phosphorylated p38MAPK, total ERK and JNK) in the placenta from HFHS-fed mice at d19. In summary, a maternal HFHS diet during pregnancy impacts fetal growth trajectory in association with changes in placental iron handling, ferroptosis and stress signalling. Downregulation of placental iron transporters in HFHS mice may protect the fetus from excessive oxidative iron. These findings suggest a role for alterations in placental iron homeostasis in determining perinatal outcomes of pregnancies associated with GDM and/or maternal obesity.Graphical

Effects of electroacupuncture on the PI3K/Akt/CREB signaling pathway and hippocampal neuronal apoptosis in diabetic cognitive impairment rats.

To observe the effects of electroacupuncture (EA) on the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/cAMP response element binding protein (CREB) signaling pathway-related proteins and hippocampal neuron apoptosis in diabetic cognitive impairment (DCI) rats, and to explore the mechanisms of EA in treating DCI. Adult male SD rats were randomly divided into normal, model, and EA groups, with 12 rats in each group. The animal model of DCI was replicated using a high-fat, high-sugar diet combined with low-dose streptozotocin. The EA group received EA stimulation at "Yishu" (EX-B6), "Zusanli" (ST36), "Baihui" (GV20), and "Dazhui" (GV14). Blood glucose contents of the rats in each group were measured. The Morris water maze test was used to assess the learning and memory abilities of rats. Transmission electron microscopy was used to observe the ultrastructure of hippocampal CA1 neurons. Nissl staining was used to observe the pathological changes in hippocampal CA1 neurons. TUNEL staining was used to detect the apoptosis in hippocampal CA1 neurons. Western blot was used to detect the protein expression levels of p-PI3K/PI3K and p-Akt/Akt, as well as CREB, p-CREB, cysteine aspartate pro-tease (Caspase)-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2 related X protein (Bax) in the hippocampal tissue of rats. Compared with the normal group, the rats' random blood glucose contents were significantly increased (P<0.01), the escape latency prolonged (P<0.01), and the original platform crossing counts reduced (P<0.01) in the model group. Significant damage to hippocampal CA1 neurons, a significantly increased neuronal apoptosis index (P<0.01), decreased ratio of p-PI3K/PI3K and p-Akt/Akt and expression of CREB, p-CREB and Bcl-2 proteins, increased expression of Caspase-3 and Bax proteins (P<0.01) were observed in the hippocampal tissue of rats in the model group. Compared with the model group, the rats in the EA group showed decreased random blood glucose content (P<0.01), shortened escape latency (P<0.01), increased original platform crossing counts (P<0.01), improved quantity and pathological morphology and ultrastructure of hippocampal CA1 neurons, reduced neuronal apoptosis index (P<0.01), increased ratio of p-PI3K/PI3K and p-Akt/Akt, and expression of CREB, p-CREB and Bcl-2 proteins (P<0.05, P<0.01) in the hippocampal tissue, and decreased expression of Caspase-3 and Bax proteins (P<0.01). EA can improve the learning and memory abilities of rats with DCI, and the mechanism may be related to the regulation of the expression of PI3K/Akt/CREB signaling pathway-related proteins, which attenuates the neuronal apoptosis in the hippocampus of rats, and improves the neural function.

Abstract 2184: A high-fat diet accelerates early-stage murine pancreatic carcinogenesis by influencing, in part, mesenteric adipose tissue metabolism

Abstract Increased adiposity represents a modifiable risk factor of pancreatic cancer. Multiple preclinical studies have shown that a high-fat and high-sugar diets on the acceleration of pancreatic carcinogenesis, in the context of obesity. However, the impact of diets resembling the omega-6 to omega-3 fatty acid (FA) ratio in a Western-style diet, remains unclear. Furthermore, the role of the mesenteric adipose tissue (MAT) in pancreatic carcinogenesis is poorly characterized. Thus, we aimed to determine the impact of a high-fat diet with a ratio of 9 parts omega-6 FA to each omega-3 FA, on early stages of pancreatic carcinogenesis in a genetically engineered LSL- KrasLSL-G12D; Ptf1aCre/+ (KC) model of pancreatic cancer, with an emphasis on evaluating the contribution of the MAT within the pancreatic microenvironment. For this purpose, cohorts of male and female KC mice (6-8 males and females per diet group) were randomly assigned to either a control diet (CD) group (9:1 of omega-6 FAs to omega-3 FAs) or a high-fat diet (HFD) group (9:1 of omega-6 FAs to omega-3 FAs) and fed their respective diets until three months of age. After eight weeks on their diets, HFD-fed mice had significantly increased body weight, fat mass, and elevated serum leptin levels. Furthermore, HFD-fed mice had increased acinar-to-ductal metaplasia, associated with increased PCNA expression, ERK and STAT3 phosphorylation and elevated pro-tumorigenic immune cell expression compared to CD-fed mice. Although no significant differences in MAT weight or adipocyte size were observed after 8 weeks between the groups, metabolomics analysis of the MAT revealed that HFD-fed mice had significant upregulation of many key metabolites linked to proliferative and inflammatory pathways. For instance, HFD-fed female KC mice had significant differences in α-linolenic acid metabolism and the biosynthesis of unsaturated fatty acids, while male mice had significant differences in arginine biosynthesis, amino acid metabolism, linoleic acid metabolism, and α-linolenic acid metabolism. HFD-fed female mice had a significant increase in α-linolenic acid and linoleic acid in MAT, concurrent with a reduction in inosine 5-monophosphate and α-tocopherol compared to female CD-fed mice. HFD-fed male mice displayed a more pronounced difference in metabolites, including an increase in α-linolenic acid, linoleic acid, malic acid, glutamine, isoleucine, and several other amino acids, with a concurrent reduction in lauric acid and palmitoleic acid compared to male CD-fed mice. In summary, a HFD accelerates pancreatic carcinogenesis through multifaceted mechanisms, including effects on the tumor and surrounding adipose depots. A HFD increases affects MAT metabolism in a sex-dependent manner, that might ultimately promote early-stage progression of pancreatic carcinogenesis. Citation Format: Aya Ead, Joanna Wirkus, Gerardo G. Mackenzie. A high-fat diet accelerates early-stage murine pancreatic carcinogenesis by influencing, in part, mesenteric adipose tissue metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2184.

Effects of Sjogren’s syndrome and high sugar diet on oral microbiome in patients with rampant caries: a clinical study

ObjectiveThe purpose of this study was to assess the composition of the oral microbial flora of adults with rampant caries in China to provide guidance for treatment.Patients and methodsSixty human salivary and supragingival plaque samples were collected. They were characterized into four groups: patients with rampant caries with Sjogren’s syndrome (RC-SS) or high-sugar diet (RC-HD), common dental caries (DC), and healthy individuals (HP). The 16S rRNA V3-V4 region of the bacterial DNA was detected by Illumina sequencing. PCoA based on OTU with Bray–Curtis algorithm, the abundance of each level, LEfSe analysis, network analysis, and PICRUSt analysis were carried out between the four groups and two sample types. Clinical and demographic data were compared using analysis of variance (ANOVA) or the nonparametric Kruskal–Wallis rank-sum test, depending on the normality of the data, using GraphPad Prism 8 (P < 0.05).ResultsOTU principal component analysis revealed a significant difference between healthy individuals and those with RC-SS. In the saliva of patients with rampant caries, the relative abundance of Firmicutes increased significantly at the phylum level. Further, Streptocpccus, Veillonella, Prevotella, and Dialister increased, while Neisseria and Haemophilus decreased at the genus level. Veillonella increased in the plaque samples of patients with rampant caries.ConclusionBoth salivary and dental plaque composition were significantly different between healthy individuals and patients with rampant caries. This study provides a microbiological basis for exploring the etiology of rampant caries.Clinical relevanceThis study provides basic information on the flora of the oral cavity in adults with rampant caries in China. These findings could serve as a reference for the treatment of this disease.

Hypercaloric low-carbohydrate high-fat diet protects against the development of nonalcoholic fatty liver disease in obese mice in contrast to isocaloric Western diet.

Obesity and metabolic complications, such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD), are one of the greatest public health challenges of the 21st century. The major role of high sugar and carbohydrate consumption rather than caloric intake in obesity and NAFLD pathophysiology remains a subject of debate. A low-carbohydrate but high-fat diet (LCHFD) has shown promising results in obesity management, but its effects in preventing NAFLD need to be detailed. This study aims to compare the effects of a LCHFD with a high-fat high-sugar obesogenic Western diet (WD) on the progression of obesity, type 2 diabetes, and nonalcoholic fatty liver disease. Male C57BL/6J mice were initially fed a WD for 10 weeks. Subsequently, they were either switched to a LCHFD or maintained on the WD for an additional 6 weeks. Hepatic effects of the diet were explored by histological staining and RT-qPCR. After the initial 10 weeks WD feeding, LCHF diet demonstrated effectiveness in halting weight gain, maintaining a normal glucose tolerance and insulin levels, in comparison to the WD-fed mice, which developed obesity, glucose intolerance, increased insulin levels and induced NAFLD. In the liver, LCHFD mitigated the accumulation of hepatic triglycerides and the increase in Fasn relative gene expression compared to the WD mice. Beneficial effects of the LCHFD occurred despite a similar calorie intake compared to the WD mice. Our results emphasize the negative impact of a high sugar/carbohydrate and lipid association for obesity progression and NAFLD development. LCHFD has shown beneficial effects for NAFLD management, notably improving weight management, and maintaining a normal glucose tolerance and liver health.

Unveiling the mechanism of high sugar diet induced advanced glycosylation end products damage skin structure via extracellular matrix-receptor interaction pathway.

AGEs accumulate in the skin as a result of a high-sugar diet and play an important role in the skin aging process. The aim of this study was to characterize the mechanism underlying the effect of a high-sugar diet on skin aging damage at a holistic level. We established a high-sugar diet mouse model to compare and analyze differences in physiological indexes. The effect of a high-sugar diet on skin aging damage was analyzed by means of a transcriptome study and staining of pathological sections. Furthermore, the differences in the protein expression of AGEs and ECM components between the HSD and control groups were further verified by immunohistochemistry. The skin in the HSD group mice tended toward a red, yellow, dark, and deep color. In addition, the epidermis was irregular with anomalous phenomena, the epidermis was thinned, and the dermis lost its normal structure and showed vacuolated changes. Transcriptomics results revealed significant downregulation of the ECM-receptor interaction pathway, significant upregulation of the expression of AGEs and significant downregulation of the expression levels of COLI, FN1, LM5, and TNC, among others ECM proteins and ECM receptors. High-sugar diets cause skin aging damage by inducing the accumulation of AGEs, disrupting the expression of ECM proteins and their receptors, and downregulating the ECM-receptor interaction pathway, which affects cellular behavioral functions such as cell proliferation, migration, and adhesion, as well as normal skin tissue structure.

Hepatic Effects of Low-Carbohydrate Diet Associated with Different Lipid Sources: Insights into Oxidative Stress, Cytotoxicity, and Epigenetic Markers in a mouse Model of Obesity

BackgroundLow-carbohydrate and high-fat diet (LCHF) models have been widely explored as alternatives for treating obesity and promoting weight loss. Their effect is attributed to the change in energy substrate that stimulates ketogenic pathways that can metabolically overload the liver. However, little has been studied about the impact of lipid sources prioritized in the LCHF diet. ObjectivesThis study aims to evaluate the impact of different fat sources in the LCHF diet on markers of liver injury, oxidative stress, and epigenetics in obesity. MethodsAdult male mice were initially induced to obesity by a high-fat and high-sugar diet for 10 wk. Subsequently, they underwent a weight-loss treatment intervention involving an LCHF diet with various sources of fats, including saturated, omega-3 (ω-3) (n–3), omega-6 (ω-6) (n–6), and omega-9 (ω-9) (n–9). At the end of the treatment, markers of liver injury, oxidative stress, and epigenetics were evaluated. ResultsThe LCHF diet was effective in inducing weight loss. However, unsaturated lipid sources (omegas) exhibited superior outcomes. Specifically, the ω-9 group displayed diminished oxidative stress concentrations and decreased markers of liver injury. The ω-3 group demonstrated efficacy in modulating epigenetic markers, thereby reducing oxidative stress, mutagenicity, and markers of liver injury. Correlation tests demonstrated that there was an interaction between the activity of antioxidants and epigenetic enzymes. ConclusionsOur results suggest that LCHF diets associated with ω-3 and ω-9 have the potential for weight loss and liver health recovery in obesity through antioxidant and epigenetic mechanisms.

Analysis of Knowledge Level, Consumption Habits, Sugar and Calories Content in Ice Cream on the Nutritional Status of Depok Students

Background: Obesity is a nutritional problem in Indonesia. A factor that influences the incidence of obesity is a high-sugar diet (ex., ice cream products). The consumption rate of ice cream increases every year and is also accompanied by an increasing number of outlets providing ice cream products. Added sugar in ice cream contributes to an increased intake of high-calorie foods that leads to obesity.&#x0D; Objectives: To analyze level of knowledge, consumption habits, sugar and calorie content of ice cream on the nutritional status of Depok students.&#x0D; Methods: Observational research with cross-sectional design, analyzed with frequency distribution and chi-square test. Data were obtained using online questionnaire. The research was conducted in the city of Depok, involving 939 samples of Depok students selected with purposive sampling methods.&#x0D; Results: 667 (71,0%) students have a good level of nutritional knowledge and 578 (61,6%) students unusually eat ice cream. There is no relationship between the level of nutritional knowledge (p-value: 0,609) and ice cream consumption habits (p-value: 0,211) on the nutritional status of students. Vanilla ice cream cup with cookies and cream topping is the most preferred ice cream, containing 13,28 grams of sugar and 154,11 kcal calories.&#x0D; Conclusions: Depok students have good nutritional knowledge and unusually eat ice cream. The sugar and calorie content of the ice cream are high.

A single-cell atlas of Drosophila trachea reveals glycosylation-mediated Notch signaling in cell fate specification

The Drosophila tracheal system is a favorable model for investigating the program of tubular morphogenesis. This system is established in the embryo by post-mitotic cells, but also undergoes remodeling by adult stem cells. Here, we provide a comprehensive cell atlas of Drosophila trachea using the single-cell RNA-sequencing (scRNA-seq) technique. The atlas documents transcriptional profiles of tracheoblasts within the Drosophila airway, delineating 9 major subtypes. Further evidence gained from in silico as well as genetic investigations highlight a set of transcription factors characterized by their capacity to switch cell fate. Notably, the transcription factors Pebbled, Blistered, Knirps, Spalt and Cut are influenced by Notch signaling and determine tracheal cell identity. Moreover, Notch signaling orchestrates transcriptional activities essential for tracheoblast differentiation and responds to protein glycosylation that is induced by high sugar diet. Therefore, our study yields a single-cell transcriptomic atlas of tracheal development and regeneration, and suggests a glycosylation-responsive Notch signaling in cell fate determination.

Association between dental caries and adherence to the Mediterranean diet, dietary intake, and body mass index in children

BackgroundChildren with healthier nutritional status are less likely to develop severe caries than those with a high-sugar content diet. Studies evaluating dental caries and nutritional status in school-age children have generally focused on dietary intake, diet quality, or anthropometric measures, and the number of studies evaluating them together is limited.ObjectiveIt was aimed to evaluate the relationship between dental caries adherence to the Mediterranean Diet (MD), dietary intake, and Body Mass Index (BMI) in school-age children.Materials and methodsThis study was conducted with 300 healthy children (52.0% boys, 48.0% girls) aged between 6 and 12 years. The data collection forms included sociodemographic characteristics, oral health practices of children, Mediterranean Diet Quality Index for children and adolescents (KIDMED), and food consumption records. Anthropometric measurements (body weight and height) of the children were taken. Dental examinations were performed by a pediatric dentist.ResultsWhile the DMFT mean score of the children was 1.7 ± 2.09, the mean dft score was 2.9 ± 3.29. The mean of KIDMED scores was 5.9 ± 3.32. DMFT and dft scores decreased statistically as maternal education increased (p < 0.05). DMFT and dft scores were not statistically different between BMI groups according to gender and age (p > 0.05). DMFT scores differed statistically between KIDMED groups (p < 0.05). This difference was between low-optimal and low-improvement-needed groups. While there was a low negative correlation (r=-0.169) between calcium intake and DMFT score, a low positive correlation was found between glucose (r = 0.172) and fructose (r = 0.149) intake and dft score (p < 0.05). In regression analysis, while the children’s age related DMFT scores positively, maternal education and KIDMED scores related DMFT scores negatively. Also, children’s age and maternal education related dft scores negatively.ConclusionIn this study, adherence to the MD rather than nutrients was found to be important in dental caries. Also maternal education level was also found to be a determinant factor in dental caries in children. DMFT and dft did not differ between BMI groups.Further studies should be conducted to assess the impact of the MD on dental caries in children to develop dietary interventions for preventative purposes.

Mechanism of ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix regulates HIF-1α signaling pathway mediated by renal hypoxia to ameliorate renal fibrosis in DKD rats

This study explored the mechanism of the ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix in ameliorating renal fibrosis in the rat model of diabetic kidney disease(DKD) based on the expression of hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF) and HIF-1α/platelet-derived growth factor(PDGF)/platelet-derived growth factor receptor(PDGFR) signaling pathways in the DKD rats. After 1 week of adaptive feeding, 50 male SPF-grade Wistar rats were randomized into a blank group(n=7) and a modeling group. After 24 h of fasting, the rats in the modeling group were subjected to intraperitoneal injection of streptozocin and fed with a high-sugar and high-fat diet to establish a DKD model. After modeling, the rats were randomly assigned into model(n=7), low-dose ultrafiltration extract(n=7), medium-dose ultrafiltration extract(n=7), irbesartan(n=8), and high-dose ultrafiltration extract(n=8) groups. After intervention by corresponding drugs for 12 weeks, the general conditions of the rats were observed. The body weights and blood glucose levels of the rats were measured weekly, and the 24 h urinary protein(24hUP) was measured at the 6th and 12th weeks of drug administration. After the last drug administration, the renal function indicators were determined. Masson staining was employed to observe the pathological changes of the renal tissue. The expression of prolyl hydroxylase domain 2(PHD2) and HIF-1α in the renal tissue was detected by immunohistochemistry(IHC). Real-time qPCR was employed to determine the mRNA levels of PHD2, VEGF, PDGF, and PDGFR in the renal tissue. Western blot was employed to determine the protein levels of HIF-1α, VEGF, PDGF, and PDGFR in the renal tissue. The results showed that compared with the model group, drug administration lowered the levels of glycosylated serum protein(GSP), aerum creatinine(Scr), and blood urea nitrogen(BUN) in a dose-dependent manner(P&lt;0.05 or P&lt;0.01) and mitigated the pathological changes in the renal tissue. Furthermore, drug administration up-regulated mRNA level of PHD2(P&lt;0.05 or P&lt;0.01), down-regulated the mRNA levels of VEGF, PDGF, and PDGFR(P&lt;0.05 or P&lt;0.01) and the protein levels of HIF-1α, VEGF, PDGF, and PDGFR(P&lt;0.01) in the renal tissue, and increased the rate of PHD2-positive cells(P&lt;0.01). In conclusion, the ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix effectively alleviated the renal fibrosis in DKD rats by inhibiting the expression of key proteins in the HIF-1α signaling pathway mediated by renal hypoxia and reducing extracellular matrix(ECM) deposition.

Pharmacokinetics of 11 active components of Psoraleae Fructus in normal and diabetic rats

A total of 11 active ingredients including psoralen, isopsoralen, bakuchiol, bavachalcone, bavachinin, corylin, coryfolin, isobavachalcone, neobavaisoflavone, bakuchalcone, and corylifol A from Psoraleae Fructus in the plasma samples of diabetic and normal rats were simultaneously determined by UHPLC-MS/MS. The pharmacokinetic parameters were calculated to elucidate the pharmacokinetic profiles of coumarins, flavonoids, and monoterpene phenols in normal and diabetic rats. The rat model of type 2 diabetes mellitus(T2DM) was induced by a high-sugar and high-fat diet combined with injection of 1% streptozotocin every two days. The plasma samples were collected at different time points after the rats were administrated with Psoraleae Fructus. The proteins in the plasma samples were precipitated by ethyl acetate, and the plasma concentrations of the 11 components of Psoraleae Fructus were determined by UHPLC-MS/MS. The pharmacokinetic parameters were calculated by DAS 3.0. The results showed that the pharmacokinetic beha-viors of 8 components including psoralen, isopsoralen, bakuchiol, and bavachinin from Psoraleae Fructus in both female and male mo-del rats were significantly different from those in normal rats. Among them, the coumarins including psoralen, isopsoralen, and corylin showed lowered levels in the blood of both female and male model rats. The flavonoids(bavachinin, corylifol A, and bakuchalcone) and the monoterpene phenol bakuchiol showed decreased levels in the female model rats but elevated levels in the male model rats. It is suggested that the dosage of Psoraleae Fructus should be reasonably adjusted for the patients of different genders at the time of clinical administration.

The Tao Hong Si Wu Decoction ameliorates diabetes-associated cognitive dysfunction by inhibiting the formation of amyloid plaques.

The herbs in Tao Hong Si Wu Decoction (THSWD) are beneficial in the treatment of cognitive impairment. However, the underlying mechanisms of THSWD in treating diabetes-associated cognitive dysfunction (DACD) are not entirely explored. This study is aimed to investigate the therapeutic effects of THSWD in DACD model rats and the underlying mechanism. Ultra-high-phase liquid chromatography was employed to identify the main compounds contained in the THSWD extract. DACD rat model was induced by feeding with a high-sugar and high-fat diet and injecting streptozotocin (35mg/kg). DACD rats were gavaged with THSWD for 1week. The learning and memory abilities of the rats were measured by using the Morris water maze. Western blotting was used to detect the changes in DACD rat targets. Statistical methods were used to evaluate the correlation between proteins. The results show that THSWD effectively reduced the escape latency, hippocampal neuron damage, glycosylated hemoglobin, type A1C, and blood lipid levels in DACD rats. Furthermore, DACD rats showed significantly increased amyloid precursor protein, β-secretase, Aβ1-40 , Aβ1-42 , Tau phosphorylation, and advanced glycation end products (AGEs) expression. However, THSWD treatment can reverse this phenomenon. THSWD can improve the learning and memory abilities of DACD rats by inhibiting the expression of AEGs-AGE receptors pathway, which provides an experimental basis for the clinical application of THSWD. In addition, the experiment combines pharmacological and statistical methods, which offers a new perspective for the study of Chinese herbal medicine.

Ziyin Bushen Fang improves Diabetic Osteoporosis by Inhibiting Autophagy and Oxidative Stress In vitro and In vivo.

Diabetic osteoporosis (DOP) belongs to the group of diabetes-induced secondary osteoporosis and is the main cause of bone fragility and fractures in many patients with diabetes. The aim of this study was to determine whether Ziyin Bushen Fang (ZYBSF) can improve DOP by inhibiting autophagy and oxidative stress. Type 1 diabetes mellitus (T1DM) was induced in rats using a high-fat high-sugar diet combined with streptozotocin. Micro-CT scanning was used to quantitatively observe changes in the bone microstructure in each group. Changes in the serum metabolites of DOP rats were analyzed using UHPLC-QTOF-MS. The DOP mouse embryonic osteoblast precursor cell model (MC3T3-E1) was induced using high glucose levels. After ZYBSF treatment, bone microstructure significantly improved. The bone mineral density, trabecular number, and trabecular thickness in the ZYBSF-M and ZYBSF-H groups significantly increased. After ZYBSF treatment, the femur structure of the rats was relatively intact, collagen fibers were significantly increased, and osteoporosis was significantly improved. A total of 1239 metabolites were upregulated and 1527 were downregulated in the serum of T1DM and ZYBSF-treated rats. A total of 20 metabolic pathways were identified. In cellular experiments, ZYBSF reduced ROS levels and inhibited the protein expression of LC3II / I, Beclin-1, and p-ERK. ZYBSF may improve DOP by inhibiting the ROS/ERK-induced autophagy signaling pathway.

Use of Callistemon citrinus as a gastroprotective and anti-inflammatory agent on indomethacin-induced gastric ulcers in obese rats.

Obesity leads to an elevated risk of developing gastrointestinal disease such as gastric ulcers. Callistemon citrinus leaf extract has shown antioxidant, antimicrobial, hepatoprotective, and chemoprotective effects against colon cancer. The aim of this study is to evaluate the gastroprotective effect of C. citrinus leaf extract on indomethacin-induced gastric ulcers in obese rats. Gastric ulcers were induced in female obese Wistar rats using a single oral dose of indomethacin (IND). In the first stage, the rats were fed with a high fat sugar diet (HFSD) for 15 weeks to induce obesity and, at the same time, the diet of the other group of animals included daily administration of ethanolic C. citrinus leaf extract (250 mg/kg) in addition to HFSD. In the second stage, gastric ulcers were induced with IND (30 mg/kg). The gastroprotective activity of C. citrinus, the inflammatory enzyme activities, and cytokines in the stomach were determined. C. citrinus produced a reduction of gastric lesions caused by IND. Myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX) activities also decreased. Although inflammatory biomarkers such as TNFα, IL-6, AOPP, and leptin were significantly decreased by C. citrinus, adiponectin levels increased. Moreover, C. citrinus decreased weight gain and morphological and biochemical parameters. The use of indomethacin in rats fed with a high fat-sugar diet increased gastric ulcers. Gastroprotective effect of C. citrinus in obese rats is attributed to the reduction of pro-inflammatory cytokines and the inflammatory enzymes.

Bergamot by-product, a source of biogenic amines, reduces hypertension induced by high sugar-fat diet

The high-sugar fat diet (HSF) generates hypertension. Bergamot by-product (BBP) is a source of hydrophilic bioactive compounds. The aim was to test BBP administration against hypertension induced by the HSF. The 48 male Wistar rats were equally divided into 4 groups: control diet (C), C+BBP, HSF, and HSF+BBP. The BBP (250 mg/Kg) was administrated by gavage for 20 weeks. The total phenolic compounds, carotenoids, and antioxidant capacity of BBP were evaluated by spectrophotometry, and HPLC was used to evaluate the biogenic amines (BAs) profile. The animals' body weight (BW), caloric intake, glucose levels, superoxide dismutase activity, and systolic blood pressure (SBP) were measured at the final of the experiment. Results showed that BBP is a good source of bioactive compounds, such as phenolic compounds (15 ± 2.1 µg Gallic Acid Equivalents/mg, w-w) and flavonoids (5.09 ± 0.22 µg Quercetin Equivalents/mg, w-w), and has a high antioxidant capacity (5.35 ± 0.06 µg Trolox Equivalents (TE)/mg, w-w; 1.30 ± 0.14 µg TE/mg, and 2.54 ± 0.31 mM FeSO/mg), by three different methods). BBP contains the BA histamine (28.4 ± 3.1 µg/g, w-w), tyramine (6.39 ± 0.39 µg/g, w-w), tryptamine (186 ± 11 µg/g, w-w), putrescine (29.0 ± 4.4 µg/g, w-w), cadaverine (10.6 ± 0.8 µg/g, w-w), spermidine (34.8 ± 4.3 µg/g, w-w), spermine (2.28 ± 0.25 µg/g, w-w), serotonin (4.46 ± 0.77 µg/g, w-w), dopamine (2.50 ± 0.29 µg/g, w-w), and agmatine (140 ± 10 µg/g, w-w). BBP has remarkable levels of antioxidant BAs, such as spermidine (34.8 ± 4.3 µg/g, w-w) and agmatine (140 ± 10 µg/g, w-w). HSF increased BW (532 ± 72 g VS 474 ± 36 g (C), p<0.001), glucose levels (91.4 ± 6.2 mg/dL VS 80.9 ± 7.1 mg/dL (C), p<0.001) and SBP (146 ± 9 mmHg VS 121 ± 5 mmHg (C), p<0.001). BBP reduced hypertension generated by HSF (133 ± 9 mmHg VS 146 ± 9 mmHg, p<0.001), suggesting a direct hypotensive action. The synergy between the bioactive compounds identified in BBP demonstrates great potential for use to prevent and treat hypertension.

Beta cell specific cannabinoid 1 receptor deletion counteracts progression to hyperglycemia in non-obese diabetic mice

ObjectiveType 1 diabetes (T1D) occurs because of islet infiltration by autoreactive immune cells leading to destruction of beta cells and it is becoming evident that beta cell dysfunction partakes in this process. We previously reported that genetic deletion and pharmacological antagonism of the cannabinoid 1 receptor (CB1) in mice improves insulin synthesis and secretion, upregulates glucose sensing machinery, favors beta cell survival by reducing apoptosis, and enhances beta cell proliferation. Moreover, beta cell specific deletion of CB1 protected mice fed a high fat high sugar diet against islet inflammation and beta cell dysfunction. Therefore, we hypothesized that it would mitigate the dysfunction of beta cells in the precipitating events leading to T1D. MethodsWe genetically deleted CB1 specifically from beta cells in non-obese diabetic (NOD; NOD RIP Cre+ Cnr1fl/fl) mice. We evaluated female NOD RIP Cre+ Cnr1fl/fl mice and their NOD RIP Cre−Cnr1fl/fl and NOD RIP Cre+ Cnr1Wt/Wt littermates for onset of hyperglycemia over 26 weeks. We also examined islet morphology, islet infiltration by immune cells and beta cell function and proliferation. ResultsBeta cell specific deletion of CB1 in NOD mice significantly reduced the incidence of hyperglycemia by preserving beta cell function and mass. Deletion also prevented beta cell apoptosis and aggressive insulitis in NOD RIP Cre+ Cnr1fl/fl mice compared to wild-type littermates. NOD RIP Cre+ Cnr1fl/fl islets maintained normal morphology with no evidence of beta cell dedifferentiation or appearance of extra islet beta cells, indicating that protection from autoimmunity is inherent to genetic deletion of beta cell CB1. Pancreatic lymph node Treg cells were significantly higher in NOD RIP Cre+ Cnr1fl/flvs NOD RIP Cre−Cnr1fl/fl. ConclusionsCollectively these data demonstrate how protection of beta cells from metabolic stress during the active phase of T1D can ameliorate destructive insulitis and provides evidence for CB1 as a potential pharmacologic target in T1D.

SIRT3 alleviates high glucose-induced chondrocyte injury through the promotion of autophagy and suppression of apoptosis in osteoarthritis progression

A growing amount of epidemiological evidence proposes diabetes mellitus (DM) to be an independent risk factor for osteoarthritis (OA). Sirtuin 3 (SIRT3), which is mainly located in mitochondria, belongs to the family of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases and is involved in the physiological and pathological processes of cell regulation. The aim of this study was to investigate the effects of SIRT3 on diabetic OA and underlying mechanisms in the prevention of type 2 DM (T2DM)-induced articular cartilage damage. High-fat and high-sugar diets combined with streptozotocin (STZ) injection were used for establishing an experimental T2DM rat model. The destabilization of medial meniscus (DMM) surgery was applied to induce the rat OA model. Primary rat chondrocytes were cultivated with a concentration of gradient glucose. Treatment with intra-articular injection of SIRT3 overexpression lentivirus was achieved in vivo, and intervention with SIRT3 knockdown was performed using siRNA transfection in vitro. High glucose content was found to activate inflammatory response, facilitate apoptosis, downregulate autophagy, and exacerbate mitochondrial dysfunction in a dose-dependent manner in rat chondrocytes, which can be deteriorated by SIRT3 knockdown. In addition, articular cartilage damage was found to be more severe in T2DM-OA rats than in DMM-induced OA rats, which can be mitigated by the intra-articular injection of SIRT3 overexpression lentivirus. Targeting SIRT3 is a potential therapeutic strategy for the alleviation of diabetic OA.

Adolescents with a Favorable Mediterranean-Style-Based Pattern Show Higher Cognitive and Academic Achievement: A Cluster Analysis-The Cogni-Action Project.

A Mediterranean diet (MedDiet) has emerged as a crucial dietary choice, not only in attenuating various adolescents' metabolic health issues but it has also been associated with improved cognitive and academic achievement. However, few studies have established patterns of food consumption linked to both cognitive and academic achievement in adolescents living in a developing country with non-Mediterranean-based food. Methods: This cross-sectional study included 1296 Chilean adolescents (50% girls) aged 10-14 years. The MedDiet Quality Index was used to assess adherence to the MedDiet in children and adolescents. Through cluster analysis, four distinct dietary patterns were identified: Western diet (WD = 4.3%); low fruit and vegetables, high-sugar diet (LFV-HSD = 28.2%); low fruit and vegetables, low-sugar diet (LFV-LSD = 42.2%); and the MedDiet (25.3%). A mixed-model analysis was conducted to compare these clusters and their relationships with cognitive and academic achievements. Principal component analysis was performed to identify four primary cognitive domains: working memory, cognitive flexibility, inhibitory control, and fluid reasoning. Academic achievement was determined with five school subjects (Language, English, Mathematics, Science, and History) and included the Academic-PISA score derived from the mean scores in Language, Mathematics, and Science. Results: A marked difference was observed between the four clusters, which was mainly related to the consumption of sugar, ultra-processed foods, fruits, and vegetables. According to cognitive performance, the MedDiet group showed higher performance across all domains than the LFV-HSD, LFV-LSD, and WD groups. Regarding academic achievement, the WD underperformed in all analyses compared to the other groups, while the MedDiet was the unique profile that achieved a positive difference in all academic subjects compared to the WD and LFV-HSD groups (p < 0.05). Conclusions: These findings suggest that higher adherence to Mediterranean-style-based patterns and better food quality choices are associated with improved cognitive and academic achievements.

PH-triggered chitosan-sodium caseinate nanocarriers with charge-switching property: Characterization and applications in dental care

As a typical biofilm disease, dental caries is a public healthcare problem and high sugar diets increase the risk of dental caries. Cationic nanomaterials play an important role in targeting and removing of biofilms, but their negative effects on normal cells have always caused widespread concern. In this work, pH-triggered charge-switching nanoparticles (SC&CS NPs) with selectable targeting were skillfully constructed by electrostatic adsorption and chemical cross-linking of sodium caseinate (SC) and chitosan (CS) to develop functional foods. SC&CS NPs were negatively charged and stable at pH 7.4. Once encountering in acidic microenvironment below pH 5.7, the potential of SC&CS NPs converted to positive. Based on this property, SC&CS NPs could identify the infected sites of biofilms to selectively target bacteria, while not interacting with cells in the normal physiological environment, thereby avoiding damage to normal cells. Besides, SC&CS NPs were excellent delivery systems that could effectively encapsulate bioactive ingredients with high loading efficiency (12.16 ± 0.04%) and release bioactive ingredients on demand. Moreover, after being encapsulated by SC&CS NPs, the antibacterial and anti-biofilm activities of bioactive ingredients were significantly improved. The charge-switching nanomaterials are expected to provide a safer, more effective, and smarter strategy for functional foods.