Anti-Inflammatory Effects of Anthocyanin-Enriched Black Soybean Seed Coat (BSSC) Crude Extract on LPS-Induced Acute Liver Injury in Mice.

Soybeans rank among the top five globally produced crops. Black soybeans contain anthocyanins in their seed coat, offering strong antioxidant and anti-inflammatory benefits. This study explores the protective effects of black soybean seed coat (BSSC) against acute liver injury (ALI) in mice. Mice pretreated with BSSC crude extract showed reduced liver damage, inflammation, and apoptosis. High doses (300 mg/kg) of the extract decreased levels of proinflammatory cytokines (IL-6, IFN-γ) and increased levels of anti-inflammatory ones (IL-4, IL-10), alongside mitigating liver pathological damage. Additionally, it influenced the Nrf2/HO-1 pathway and reduced levels of apoptosis-related proteins. In vitro, the compounds delphinidin-3-O-glucoside (D3G) and cyanidin-3-O-glucoside (C3G) in BSSC were found to modulate cytokine levels, suggesting their role in ALI protection. The study concludes that BSSC extract, particularly due to D3G and C3G, effectively protects against LPS-induced ALI in mice by inhibiting inflammation, oxidative stress, and apoptosis.

Djulis Hull Enhances the Efficacy of Ferric Citrate Supplementation via Restoring Normal Iron Efflux through the IL-6-Hepcidin-Ferroportin Pathway in High-Fat-Diet-Induced Obese Rats.

Obesity-related functional iron disorder remains a major nutritional challenge. We evaluated the effects of djulis hull (DH) on iron metabolism in 50% high-fat-diet-induced obese rats supplemented with ferric citrate (2 g iron/kg diet) for 12 weeks. DH supplementation (5, 10, 15% dry weight/kg diet) significantly increased serum and hepatic iron but decreased appetite hormones, body weight, hepcidin, and liver inflammation (all p < 0.05). The Spearman correlation showed that appetite hormones were negatively associated with iron but positively correlated with liver hepcidin (all p < 0.05). A Western blot analysis showed that DH significantly downregulated hepatic hepcidin through the IL-6-JAK-STAT3 and enhanced ferroportin (Fpn) via the Keap1-Nrf2 and PHD2-HIF-2α. An in vitro study revealed that major bioactive compounds of DH, hexacosanol, and squalene suppressed LPS-induced IL-6 and hepcidin but enhanced Fpn expression in activated THP-1 cells. In conclusion, DH may exert nutraceutical properties for the treatment of functional iron disorder and restoration of iron efflux may have beneficial effects on weight control.

Effects of dietary adjustment of n-3:n-6 fatty-acid ratio to 1:2 on anti-inflammatory and insulin-signaling pathways in ovariectomized mice with high fat diet-induced obesity.

Estrogen deficiency increases the secretion of inflammatory mediators and can lead to obesity. Consequently, estrogen deficiency can cause metabolic syndrome, particularly insulin resistance during menopause. Both fish oil and perilla oil contain n-3 fatty acids, which may regulate several inflammatory cytokines. Additionally, adjusting the dietary n-3:n-6 fatty-acid ratio to 1:2 may help treat or prevent chronic diseases. Therefore, we investigated the effect of anti-inflammatory and insulin-signaling pathways, not solely in relation to the (n-3:n-6 fatty-acid ratio at 1:2), but also considering the origin of n-3 fatty acids found in fish oil and perilla oil, in a mouse model of estrogen deficiency induced by ovariectomy and obesity induced by a high-fat diet (HFD). Female C57BL/6J mice were divided into five groups: sham mice on a normal diet; ovariectomized (OVX) mice on a normal diet (OC); OVX mice on a HFD plus lard oil (OL), fish oil (OF), or perilla oil (OP). The dietary n-3:n-6 ratio in the OF and OP groups was adjusted to 1:2. The results showed OF group exhibited significantly lower abdominal adipose tissue weight, fewer liver lipid droplets, and smaller uterine adipocytes, compared with the OL group. Compared with the OL group, the OF and OP groups exhibited higher oral glucose tolerance and lower serum alanine aminotransferase activity, triacylglycerol levels, and total cholesterol levels. Hepatic JAK2, STAT3, and SOCS3 mRNA expression and p-NF-κB p65 and IL-6 levels were significantly lower in the OF and OP groups than in the OL group. Only the OF group exhibited an increase in PI3K and Akt mRNA expression, decrease in GLUT2 mRNA expression, and considerable elevation of p-Akt. Both fish and perilla oil reduced inflammatory signaling markers. However, only fish oil improved insulin signaling (PI3K, Akt, and GLUT2). Our data suggest that fish oil can alleviate insulin signaling through activating the PI3K-Akt-GLUT2 cascade signaling pathway.

Acute sleep deprivation exacerbates systemic inflammation and psychiatry disorders through gut microbiota dysbiosis and disruption of circadian rhythms.

Acute sleep deprivation (ASD) is often observed in shift workers and characterized by drowsiness and unrelenting exhaustion. The physiological and psychological effects of ASD include anxiety, depression, cognitive impairment, systemic inflammation, stress responses, and disruptions of gut microbiota. However, the mechanisms involved in the ASD-associated circadian dysregulations with regard to gut dysbiosis, systemic inflammation, physiological modulation, and psychiatry disorders remain unclear. The aim of this study was to investigate whether central nervous system disorders induced by ASD are related to inflammation, barrier dysfunction, and circadian dysregulation. We also assessed impacts on microbiota succession. Male C57BL/6 mice were randomly allocated to the control and sleep deprivation (SD) groups. Mice in the SD group were subjected to 72 h of paradoxical SD using the modified multiple-platform method for ASD induction (72 h rapid eye movement-SD). The effects of ASD on dietary consumption, behaviors, cytokines, microbiota, and functional genes were determined. The appetite of the SD group was significantly higher than that of the control group, but the body weight was significantly lower than that of the control group. The anxiety-like behaviors were found in the SD group. Alpha and beta diversity of microbiota showed significant decrease after ASD induction; the relative abundance of Candidatus_Arthromitus and Enterobacter was increased, whereas that abundance of Lactobacillus, Muribaculum, Monoglobus, Parasutterella, and others was decreased in the SD group. These effects were accompanied by reduction in fecal propionic acid. In the proximal colon, the SD group exhibited significantly higher inflammation (tumor necrosis factor-α [TNF-α]) and dysregulation of the circadian rhythms (brain and muscle ARNT-like 1 [BMAL1] and cryptochrome circadian regulator 1 [CRY1]) and tight junction genes (occludin [OCLN]) than the control group. Gut barrier dysfunction slightly increased the plasma concentration of lipopolysaccharide and significantly elevated TNF-α. Inflammatory signals might be transduced through the brain via TNF receptor superfamily member 1 A (TNFRSF1A), which significantly increased the levels of microglia activation marker (ionized calcium-binding adapter molecule 1 [IBA1]) and chemokine (intercellular adhesion molecule 1 [ICAM1]) in the cerebral cortex. The serotonin receptor (5-hydroxytryptamine 1A receptor [5-HT1AR]) was significantly downregulated in the hippocampus. In summary, 72 h of rapid eye movement-SD induced physiological and psychological stress, which led to disruption of the circadian rhythms and gut microbiota dysbiosis; these effects were related to decrement of short chain fatty acids, gut inflammation, and hyperpermeability. The microbiota may be utilized as preventive and therapeutic strategies for ASD from the perspectives of medicine and nutrition.

Ascophyllum nodosum and Fucus vesiculosus Extracts Improved Lipid Metabolism and Inflammation in High-Energy Diet-Induced Hyperlipidemia Rats.

Ascophyllum nodosum and Fucus vesiculosus both contain unique polyphenols called phlorotannins. Phlorotannins reportedly possess various pharmacological activities. A previous study reported that the activity of phlorotannin is strongly correlated with the normalization of metabolic function, and phlorotannins are extremely promising nutrients for use in the treatment of metabolic syndrome. To date, no study has explored the antihyperlipidemic effects of phlorotannins from A. nodosum and F. vesiculosus in animal models. Therefore, in the present study, we investigated the effects of phlorotannins using a rat model of high-energy diet (HED)-induced hyperlipidemia. The results showed that the rats that were fed an HED and treated with phlorotannin-rich extract from A. nodosum and F. vesiculosus had significantly lower serum fasting blood sugar (FBS), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triacylglyceride (TG) and free fatty acids (FFAs) levels and hepatic TG level and had higher serum insulin, high-density lipoprotein cholesterol (HDL-C) levels and lipase activity in their fat tissues than in the case with the rats that were fed the HED alone. A histopathological analysis revealed that phlorotannin-rich extract could significantly reduce the size of adipocytes around the epididymis. In addition, the rats treated with phlorotannin-rich extract had significantly lowered interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels and increased superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities than did those in the HED group. These results suggested that the phlorotannin-rich extract stimulated lipid metabolism and may have promoted lipase activity in rats with HED-induced hyperlipidemia. Our results indicated that A. nodosum and F. vesiculosus, marine algae typically used as health foods, have strong antihyperlipidemic effects and may, therefore, be useful for preventing atherosclerosis. These algae may be incorporated into antihyperlipidemia pharmaceuticals and functional foods.

Effects of the Water Extract of Fermented Rice Bran on Liver Damage and Intestinal Injury in Aged Rats with High-Fat Diet Feeding.

The purpose of this study was to investigate the protective effects of the water extract of fermented rice bran (FRB) on liver damage and intestinal injury in old rats fed a high-fat (HF) diet. Rice bran (RB) was fermented with Aspergillus kawachii, and FRB was produced based on a previous study. Male Sprague Dawley rats at 36 weeks of age were allowed free access to a standard rodent diet and water for 8 weeks of acclimation then randomly divided into four groups (six rats/group), including a normal control (NC) group (normal diet), HF group (HF diet; 60% of total calories from fat), HF + 1% FRB group (HF diet + 1% FRB w/w), and HF + 5% FRB group (HF diet + 5% FRB w/w). It was found that the antioxidant ability of FRB was significantly increased when compared to RB. After 8 weeks of feeding, the HF group exhibited liver damage including an increased non-alcoholic fatty liver disease score (hepatic steatosis and inflammation) and higher interleukin (IL)-1ß levels, while these were attenuated in the FRB-treated groups. Elevated plasma leptin levels were also found in the HF group, but the level was down-regulated by FRB treatment. An altered gut microbiotic composition was observed in the HF group, while beneficial bacteria including of the Lactobacillaceae and Lachnospiraceae had increased after FRB supplementation. In conclusion, it was found that FRB had higher anti-oxidative ability and showed the potential for preventing liver damage induced by a HF diet, which might be achieved through regulating imbalanced adipokines and maintaining a healthier microbiotic composition.

Endurance exercise ameliorates Western diet-induced atherosclerosis through modulation of microbiota and its metabolites.

The World Health Organization determined cardiovascular disease to be the leading cause of death globally; atherosclerosis is the primary cause of the high morbidity and mortality rates. Regular physical activity is an effective strategy for maintaining endothelial health and function to prevent the development of atherosclerosis. Obesity is also a crucial risk factor for atherosclerotic progression in combination with various complications and systemic inflammation. Physiological homeostasis is modulated by the intestinal microbiota, but the mechanisms through which exercise attenuates atherosclerosis through the microbiota have not been elucidated. Therefore, we investigated the effects of endurance exercise on atherosclerosis induced by a Western diet (WD) and apolipoprotein E (ApoE) knockout in terms of microbiota parameters and metabolites. Genetically modified ApoE knockout mice (C57BL/6-Apoeem1Narl/Narl, ApoEKO) and wild-type mice (C57BL6/J) were divided into the following four groups (n = 6), namely, wild-type mice fed a chow diet (WT CD), ApoEKO mice fed a chow diet (ApoE CD), ApoEKO mice fed a WD (ApoE WD), and ApoEKO mice fed a WD and performing endurance exercise (ApoE WD EX), for a 12-week intervention. The WD significantly induced obesity and atherosclerotic syndrome in the ApoE WD group. Severe atherosclerotic lesions and arterial thickness were significantly elevated and accompanied by increases in VCAM-1, MCP-1, TNF-α, and IL-1ß for immune cell chemotaxis and inflammation during atherosclerotic pathogenesis in the ApoE WD group. In addition, dysbiosis in the ApoE WD group resulted in the lowest short-chain fatty acid (SCFA) production. Endurance exercise intervention (ApoE WD EX) significantly alleviated atherosclerotic syndrome by reducing obesity, significantly inhibiting VCAM-1, MCP-1, TNF-α, and IL-1ß expression, and increasing the production of SCFAs. Modulation of the microbiota associated with inflammation, such as Desulfovibrio, Tyzzerella, and Lachnospiraceae_ge, and increased SCFA production, particularly through an abundance of Rikenellaceae and Dubosiella, were also observed after exercise intervention. Endurance exercise can alleviate WD-induced atherosclerosis through the amelioration of obesity, inflammation, and chemotaxis signaling, which are modulated by the microbiota and derived SCFAs.

Effects of exercise on high-fat diet-induced non-alcoholic fatty liver disease and lipid metabolism in ApoE knockout mice.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), which is growing more common in the Western world, has become the main cause of chronic liver disease and is strongly associated with metabolism syndromes. NAFLD can indicate a wide spectrum of hepatic pathologies, ranging from simple hepatic steatosis and inflammatory non-alcoholic steatohepatitis to more severe stages of fibrosis and cirrhosis. Moreover, evidence has demonstrated that physical inactivity and westernized dietary habits may facilitate the development of NAFLD. Lipid modulation and metabolism could be important factors in the development of steatosis. Lipid species, characterized using a lipidomic approach with untargeted analysis, could provide potential biomarkers for the pathogenesis of NAFLD or therapeutic applications. Thus, in this study, the effects of exercise on the improvement of NAFLD were further investigated from a lipidomic perspective through the aspects of lipid regulation and metabolism. METHODS: Wild type (WT) C57BL/6 J and C57BL/6-ApoEem1Narl/Narl mice were assigned to one of four groups: WT mice fed a normal chow diet (CD), apolipoprotein E (ApoE) knockout mice fed a normal CD, ApoE knockout mice fed a high-fat diet (HFD), and ApoE knockout mice fed a HFD and provided with swimming exercise. The treatments (e.g., normal diet, HFD, and exercise) were provided for 12 consecutive weeks before the growth curves, biochemistry, fat composition, pathological syndromes, and lipid profiles were determined. RESULTS: Exercise significantly reduced the HFD-induced obesity (weight and fat composition), adipocyte hypertrophy, liver lipid accumulation, and pathological steatosis. In addition, exercise ameliorated HFD-induced steatosis in the process of NAFLD. The lipidomic analysis revealed that the changes in plasma triglyceride (14:0/16:0/22:2), phosphatidic acid (18:0/17:2), and phosphatidylglycerol (16:0/20:2) induced by the administration of the HFD could be reversed significantly by exercise. CONCLUSIONS: The 12-week regular exercise intervention significantly alleviated HFD-induced NAFLD through modulation of specific lipid species in plasma. This finding could elucidate the lipids effects behind the hepatic pathogenesis with exercise.

Plasma Proteomic Changes of Atherosclerosis after Exercise in ApoE Knockout Mice.

Atherosclerosis is the preliminary cause of coronary artery disease, one of the diseases that account for the largest number of fatal mortalities. Physical activity is an effective strategy to restrain atherosclerosis from deterioration. Evidence indicated that changes in the proteomic profile are highly associated with atherosclerosis development, but the mechanism behind exercise for atherosclerosis amelioration has not yet been investigated from a proteomics perspective. Hence, the proteomic profiles could further elucidate the systematic effects of exercise intervention on ApoE knockout atherosclerotic model and high-fat-diet intervention. In the current study, Apoeem1Narl/Narl mice were randomly allocated into a normal diet (ND), Western diet (WD), and WD with 12-week exercise intervention (WD EX) groups. The plasma proteome between WD and WD EX groups demonstrate the significant difference, and ten major pathways, including cardiovascular disease (CVD)-hematological disease, inflammatory disease, infectious diseases, inflammatory response, cell-to-cell signaling and interaction, connective tissue disorders_inflammatory disease, metabolic disease_organismal injury and abnormalities, cell-to-cell signaling and interaction, connective tissue disorders_inflammatory disease, and endocrine system disorders_gastrointestinal disease, etc., were generated by the IPA analysis. The 15 proteins (MYOCD, PROS1, C2, SERPINA10, CRP, F5, C5, CFB, FGG, CFH, F12, PRDX2, PROZ, PPIA, and HABP2) critically involved in CVD-hematological disease pathway showed significant difference between WD and WD EX groups. In current study, exercise could significantly alleviate the significantly elevated C5 and inflammation induced by the WD group in accordance with amelioration of atherosclerosis. Therefore, exercise could mitigate chemotaxis through the modulation of the C5 level and innate immunity, thereby alleviating the pathogenesis of atherosclerosis in Western-diet-induced obese mice.

Anti-NAFLD Effect of Djulis Hull and Its Major Compound, Rutin, in Mice with High-Fat Diet (HFD)-Induced Obesity.

Nonalcoholic fatty liver disease (NAFLD) has become the main cause of chronic liver disease worldwide, and the increasing trend of NAFLD has burdened the healthcare system. NAFLD encompasses a wide range of liver pathologies, from simple benign hepatocyte steatosis to more severe inflammatory nonalcoholic steatohepatitis. Djulis (Chenopodium formosanum Koidz.) is traditionally used as a native cereal and a food supplement that promotes human health through its antioxidant, hepatoprotection, skin protection, hypolipidemic, hypoglycemic, and antitumor effects. Djulis hull, regarded as agricultural waste, is usually removed during food processing and contains high rutin content. The present study evaluated the anti-NAFLD effect of Djulis hull and its major compound, rutin, in mice with high-fat diet (HFD)-induced obesity. Male C57BL/6J mice were randomly divided into one of five diet groups (n = 6 per group) and fed the following for 16 weeks: (1) normal diet group (ND), (2) HFD group (HFD), (3) HFD and oral gavage of low dose (50 mg/kg) of Djulis hull crude extract group (HFD/LCE), (4) HFD and oral gavage of high dose (250 mg/kg) of Djulis hull crude extract group (HFD/HCE), or (5) HFD and oral gavage (50 mg/kg) of rutin (HFD/R) group. We found that Djulis hull crude extract markedly reduced HFD-induced elevation in body weight and fat around the kidney weights, hepatic injury indicators (AST and ALT), and steatosis and hypertrophy. Furthermore, Djulis hull crude extract administration significantly affected DG(20:4/18:1), PA(22:0/17:1), PC(10:0/17:0), and PA(18:4/20:5) in HFD-induced obese mice. In addition, treating HFD-induced obese rats with Djulis hull crude extract significantly increased fatty acid oxidation by increasing the protein expression of phosphorylated AMP-activated protein kinase, peroxisome proliferator-activated receptor-α, and hepatic carnitine palmitoyltransferase-1 in the liver. Moreover, the administration of Djulis hull crude extract significantly decreased the inflammatory response (PPARγ, IL-6, and TNF-α) to modulate oxidative damage. Therefore, Djulis hull crude extract attenuated the progression of NAFLD by reducing inflammation mediated by PPARγ and enhancing the expression levels of genes involved in fatty acid oxidation mediated by AMPK signaling.

The Gastroprotective Effect of Naringenin against Ethanol-Induced Gastric Ulcers in Mice through Inhibiting Oxidative and Inflammatory Responses.

Naringenin is a major flavanone found in grapes, tangelos, blood oranges, lemons, pummelo, and tangerines. It is known to have anti-inflammatory, antioxidant, anticancer, antimutagenic, antifibrogenic, and antiatherogenic pharmacological properties. This study aims to investigate the anti-inflammatory effects of naringenin in ethanol-induced gastric damage in vivo and ethanol-stimulated KATO III cells in vitro. Our results showed that pretreatment with naringenin significantly protected mice from ethanol-induced hemorrhagic damage, epithelial cell loss, and edema with leucocytes. It reduced gastric ulcers (GU) by suppressing ethanol-induced nuclear factor-κB (NF-κB) activity and decreasing the levels of nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and myeloperoxidase (MPO). In addition, pretreatment with naringenin might inhibit the secretion of TNF-α, IL-6, and IL-8, as well as the proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) via the suppression of NF-κB and mitogen-activated protein kinase (MAPK) signaling in ethanol-stimulated stomach epithelial KATO III cells. Together, the results of this study highlight the gastroprotective effect of naringenin in GU of mice by inhibiting gastric secretion and acidity, reducing inflammation and oxidative stress, suppressing NF-κB activity, and restoring the histological architecture. These findings suggested that naringenin has therapeutic potential in the alleviation of ethanol-induced GU.

KFP-1, a Novel Calcium-Binding Peptide Isolated from Kefir, Promotes Calcium Influx Through TRPV6 Channels.

INTRODUCTION: Kefir is an acidic and alcoholic fermented milk product with multiple health-promoting benefits. A previous study demonstrated that kefir enhanced calcium absorption in intestinal Caco-2 cells. In this study, kefir-fermented peptide-1 (KFP-1) is isolated from the kefir peptide fraction, and its function as a calcium-binding peptide is characterized. METHODS AND RESULTS: KFP-1 was identified as a 17-residue peptide with a sequence identical to that of κ-casein (residues 138-154) in milk protein. KFP-1 is demonstrated to promote calcium influx in Caco-2 and IEC-6 small intestinal cells in a concentration-dependent manner. TRPV6, but not L-type voltage-gated calcium channels, is associated with the calcium influx induced by KFP-1. An in vitro calcium binding assay indicates that the full-length KFP-1 peptide has a higher calcium-binding capacity than the two truncated KFP-1 peptides, KFP-1∆C5 and KFP-1C5. Alexa Fluor 594 labeling shows that KFP-1 is taken up by Caco-2 cells and interacts with calcium ions and TRPV6 protein. Moreover, KFP-1 is found moderately resistant to pepsin and pancreatin digestions and enhanced calcium uptake by intestinal enterocytes in vivo. CONCLUSION: These data suggest that KFP-1, a novel calcium-binding peptide, binds extracellular calcium ions and enters Caco-2 and IEC-6 cells, and promotes calcium uptake through TRPV6 calcium channels. The present study is of great importance for developing kefir-derived metal ion-binding peptides as functional nutraceutical additives.

Alantolactone Suppresses Proliferation and the Inflammatory Response in Human HaCaT Keratinocytes and Ameliorates Imiquimod-Induced Skin Lesions in a Psoriasis-Like Mouse Model.

Psoriasis is an immune-mediated inflammatory disease that affects 2% to 3% of the world population. Alantolactone, a sesquiterpene lactone, was isolated from Inula helenium and Radix inulae and has several biological effects, including antifungal, anthelmintic, antimicrobial, anti-inflammatory, antitrypanosomal, and anticancer properties. This study aimed to evaluate the antipsoriatic potential of alantolactone in vitro and in vivo and to explore its underlying mechanisms. These results showed that alantolactone significantly attenuated IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) cytokine-induced hyperproliferation in HaCaT keratinocytes. Moreover, M5 cytokines significantly upregulated the mRNA levels of TNF-α, IL-6, IL-1ß, and IL-8. However, alantolactone attenuated the upregulation of these inflammatory cytokines. In addition, alantolactone was found to inhibit STAT3 phosphorylation and NF-κB p65 nuclear translocation in HaCaT keratinocytes. Furthermore, alantolactone treatment in mice significantly alleviated the severity of skin lesions (erythema, scaling and epidermal thickness, and inflammatory cell infiltration) and decreased the mRNA expression of inflammatory cytokines (e.g., TNF-α, IL-6, IL-1ß, IL-8, IL-17A, and IL-23) in an IMQ-induced-like mouse model. Therefore, our new findings revealed that alantolactone alleviates psoriatic skin lesions by inhibiting inflammation, making it an attractive candidate for future development as an antipsoriatic agent.

Effect of the Chinese Herbal Medicine SS-1 on a Sjögren's Syndrome-Like Disease in Mice.

Sjögren's syndrome (SS) is an inflammatory autoimmune disease primarily affecting the exocrine glands; it has a major impact on patients' lives. The Chinese herbal formula SS-1 is composed of Gan Lu Yin, Sang Ju Yin, and Xuefu Zhuyu decoction, which exerts anti-inflammatory, immunomodulatory, and antifibrotic effects. Our previous study demonstrated that SS-1 alleviates clinical SS. This study aimed to evaluate the efficacy and mechanism of the Chinese herbal formula SS-1 for salivary gland protein-induced experimental Sjögren's syndrome (ESS). These results showed that ESS treatment with the Chinese herbal formula SS-1 (1500 mg/kg) significantly alleviated the severity of ESS. We found that SS-1 substantially improved saliva flow rates in SS mice and ameliorated lymphocytic infiltrations in submandibular glands. In addition, salivary gland protein-induced SS in mice treated with SS-1 significantly lowered proinflammatory cytokines (including IFN-γ, IL-6, and IL-17A) in mouse salivary glands and decreased serum anti-M3R autoantibody levels. In addition, we found that CD4+ T cells isolated from SS-1-treated SS mice significantly reduced the percentages of IFN-γ-producing CD4+ T cells (Th1) and IL-17A-producing CD4+ T cells (Th17). Our data show that SS-1 alleviates ESS through anti-inflammatory and immunomodulatory effects, which provides new insight into the clinical treatment of SS.

Effects of Dietary Fatty Acid Composition on Lipid Metabolism and Body Fat Accumulation in Ovariectomized Rats.

BACKGROUND: Obesity is a state of excess energy storage resulting in body fat accumulation, and postmenopausal obesity is a rising issue. In this study using ovariectomized (OVX) rats, we mimicked low estrogen levels in a postmenopausal state in order to investigate the effects of different amounts and types of dietary fatty acids on body fat accumulation and body lipid metabolism. METHODS: At 9 weeks of age, rats (n = 40) were given an ovariectomy, eight of which were sham-operated to serve as a control group (S). We then divided OVX rats into four different intervention groups: diet with 5% soybean oil (C), and diet with 5% (L), 15% (M), and 20% (H) (w/w) experimental oil, containing 60% monounsaturated fatty acids (MUFAs) and with a polyunsaturated/saturated fatty acid (P/S) ratio of 5. RESULTS: After OVX, compared to the S group, the C group showed significantly higher body weight, and insulin and leptin levels. Compared to the C group, the H group had lower hepatic triglyceride level and FAS enzyme activity, and higher hepatic ACO and CPT-1 gene expressions and enzyme activities. CONCLUSIONS: An OVX leads to severe weight gain and lipid metabolism abnormalities, while according to previous studies, high fat diet may worsen the situation. However, during our experiment, we discovered that the experimental oil mixture with 60% MUFAs and P/S = 5 may ameliorate these imbalances.

A Novel Relative High-Density Lipoprotein Index to Predict the Structural Changes in High-Density Lipoprotein and Its Ability to Inhibit Endothelial-Mesenchymal Transition.

Therapeutic elevation of high-density lipoprotein (HDL) is thought to minimize atherogenesis in subjects with dyslipidemia. However, this is not the case in clinical practice. The function of HDL is not determined by its concentration in the plasma but by its specific structural components. We previously identified an index for the prediction of HDL functionality, relative HDL (rHDL) index, and preliminarily explored that dysfunctional HDL (rHDL index value > 2) failed to rescue the damage to endothelial progenitor cells (EPCs). To confirm the effectiveness of the rHDL index for predicting HDL functions, here we evaluated the effects of HDL from patients with different rHDL index values on the endothelial-mesenchymal transition (EndoMT) of EPCs. We also analyzed the lipid species in HDL with different rHDL index values and investigated the structural differences that affect HDL functions. The results indicate that HDL from healthy adults and subjects with an rHDL index value < 2 protected transforming growth factor (TGF)-ß1-stimulated EndoMT by modulating Smad2/3 and Snail activation. HDL from subjects with an rHDL index value > 2 failed to restore the functionality of TGF-ß1-treated EPCs. Lipidomic analysis demonstrated that HDL with different rHDL index values may differ in the composition of triglycerides, phosphatidylcholine, and phosphatidylinositol. In conclusion, we confirmed the applicability of the rHDL index value to predict HDL function and found structural differences that may affect the function of HDL, which warrants further in-depth studies.

Maternal Vegetable and Fruit Consumption during Pregnancy and Its Effects on Infant Gut Microbiome.

Maternal nutrition intake during pregnancy may affect the mother-to-child transmission of bacteria, resulting in gut microflora changes in the offspring, with long-term health consequences in later life. Longitudinal human studies are lacking, as only a small amount of studies showing the effect of nutrition intake during pregnancy on the gut microbiome of infants have been performed, and these studies have been mainly conducted on animals. This pilot study explores the effects of high or low fruit and vegetable gestational intake on the infant microbiome. We enrolled pregnant women with a complete 3-day dietary record and received postpartum follow-up. The 16S rRNA gene sequence was used to characterize the infant gut microbiome at 2 months (n = 39). Principal coordinate analysis ordination revealed that the infant gut microbiome clustered differently for high and low maternal fruit and vegetable consumption (p < 0.001). The linear discriminant analysis effect size and feature selection identified 6 and 17 taxa from both the high and low fruit and vegetable consumption groups. Among the 23 abundant taxa, we observed that six maternal intake nutrients were associated with nine taxa (e.g., Erysipelatoclostridium, Isobaculum, Lachnospiraceae, Betaproteobacteria, Burkholderiaceae, Sutterella, Clostridia, Clostridiales, and Lachnoclostridium). The amount of gestational fruit and vegetable consumption is associated with distinct changes in the infant gut microbiome at 2 months of age. Therefore, strategies involving increased fruit and vegetable consumption during pregnancy should be employed for modifying the gut microbiome early in life.

Bavachinin Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Small Cell Lung Cancer and Shows an Antitumor Effect in the Xenograft Model.

Lung cancer is grouped into small cell lung cancer (SCLC) and non-SCLC (NSCLC). SCLC exhibits a poor prognosis, and the current anticancer treatment remains unsatisfactory. Bavachinin, present in the seed of Psoralea corylifolia, shows anti-inflammatory effects, immune modulation, and anticancer potency. This study aims to investigate the antitumor effect of bavachinin on SCLC and its underlying mechanism. The SCLC cell line H1688 was treated with different concentrations of bavachinin and showed decreased viability with arrested G2/M and sub-G1 phase cell accumulation at a concentration as low as 25 µM. Expression levels of caspase-3, -8, and -9, as well as Fas, FasL, and Bax, increased with the concentration of bavachinin. The accumulated sub-G1 cells and annexin V confirmed increasing apoptotic cancer cells after treatment. The accumulated G2/M phase cells with increasing levels of phosphorylated CDC25C, CDC2, ATM/ATR, and CHK2/CHK1 confirmed the arrested cell cycle caused by bavachinin via a dose-dependent manner. This phenomenon can be reversed by an ATM/ATR inhibitor, caffeine. Following the administration of bavachinin to xenograft mice with SCLC, the tumor burden decreased without impairing hematologic or hepatorenal functions. Bavachinin induces SCLC apoptosis via intrinsic and extrinsic pathways and causes cancer cell cycle arrest via the ATM/ATR signaling pathway.

Proteomics Reveals Octyl Gallate as an Environmentally Friendly Wood Preservative Leading to Reactive Oxygen Species-Driven Metabolic Inflexibility and Growth Inhibition in White-Rot Fungi (Lenzites betulina and Trametes versicolor).

The most commonly applied wood preservatives are based on creosote, pentachlorophenol, and waterborne chromate copper arsenate, which negatively affect the environment. Thus, environmentally friendly wood preservatives are required. This study investigated the antifungal activity and mechanism of several long-chain alkyl gallates (3,4,5-trihydroxybenzoates) against white-rot fungi, Lenzites betulina and Trametes versicolor. The results revealed that octyl gallate (OG) had the best antifungal activity. Additionally, OG may have a mechanism of action similar to surfactants and inhibit ATPase activity, causing mitochondrial dysfunction and endogenous reactive oxygen species (ROS) production. Upon exposure to endogenous ROS, cells rapidly inhibit the synthesis of 60S ribosomal subunits, thus reducing the mycelial growth rate. L. betulina and T. versicolor also remodeled their energy metabolism in response to low ATP levels and endogenous ROS. After OG treatment, ATP citrate synthase activity was downregulated and glycolytic activity was upregulated in L. betulina. However, the activity of aerobic pathways was decreased and the oxidative branch of the pentose phosphate pathway was redirected form nicotinamide adenine dinucleotide phosphate (NADPH) to minimize endogenous ROS-mediated damage in T. versicolor. Taken together, these observations reveal that OG is a potent inhibitor of white-rot fungus. Further structural optimization research and pharmacological investigations are warranted.

Kefir peptides exhibit antidepressant-like activity in mice through the BDNF/TrkB pathway.

Depression is a prevalent, stress-related mental disorder that can lead to serious psychiatric diseases with morbidity and high mortality. Although some functional fermented dairy drinks have promising anxiolytic and antidepressant effects, the mechanism is still not clear. To determine the antidepressant-like effect and the potential molecule mechanism of kefir peptides (KP), various behavioral tests, including the elevated plus maze test, open field test, forced swimming test, and tail suspension test, were used. Administration of 150 mg/kg KP in mice reduced the duration of immobility in the forced swimming test and tail suspension test, elevated the time spent in the open arm and center zone in the elevated plus maze test, and increased the total distance traveled, average speed, and time spent in the center zone in the open field test compared with the mock group. These results indicated that KP dramatically ameliorated the depression-like behaviors. Kefir peptides were further isolated and identified using high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry, from which 3 peptides were identified and designated KFP-1, KFP-3, and KFP-5. Among these peptides, administration of KFP-3 (15 AA residues) remarkably decreased immobility time in the forced swimming test and increased mobility time in the tail suspension test. Therefore, KFP-3 may be the major active peptide with antidepressant activity in KP. Overexpression of brain-derived neurotrophic factor, phosphorylated tropomyosin receptor kinase B, and phosphorylated ERK1/2 protein levels could be detected in the hippocampus under KP administration. Therefore, we suggest that KP improves depressive-like behaviors by activating the brain-derived neurotrophic factor-phosphorylated tropomyosin receptor kinase B signaling pathway. Kefir peptides may serve as a new type of antidepressant dairy product and may provide potent antidepressant effects for clinical use.