[Endoscopic ultrasonography features of benign esophageal stenosis in children]. / å„¿ç«¥é£Ÿç®¡è‰¯æ€§ç‹­çª„çš„è¶ å£°å† é•œç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the endoscopic ultrasonography (EUS) features of benign esophageal stenosis in children. METHODS: A retrospective analysis was conducted on the medical data of the children who were diagnosed with benign esophageal stenosis from February 2019 to February 2022. The clinical manifestations, EUS findings, and treatment outcome were analyzed to summarize the EUS features of benign esophageal stenosis in children. RESULTS: A total of 42 children with benign esophageal stenosis were included. Among these children, 19 (45%) had anastomotic stenosis after surgery for esophageal atresia, with unclear echogenic boundary of the esophageal walls and uneven thicknesses of the surrounding wall on EUS, and had 0-12 sessions of endoscopic treatment (average 2.1 sessions); 5 children (12%) had corrosive esophageal stenosis and 1 child (2%) had physical esophageal stenosis, with unclear stratification of the esophageal walls on EUS, and they had 2-9 sessions of endoscopic treatment (average 5.3 sessions); 1 child (2%) had patchy irregular hypoechoic areas of the esophageal walls on EUS and was diagnosed with tracheobronchial remnants with reference to pathology; 16 children (38%) had unexplained esophageal stenosis and unclear stratification of the esophageal walls on EUS, among whom 6 received endoscopic treatment. During follow-up, 95% (40/42) of the children had significant alleviation of the symptoms such as vomiting and dysphagia. CONCLUSIONS: For benign esophageal stenosis in children, EUS can help to evaluate the degree of esophageal wall involvement in esophageal stenosis lesions, possible etiologies, and the relationship between the esophagus and the lesion and provide an important basis for selecting treatment modality and avoiding complications, thereby helping to optimize the treatment regimen.

Preparation of Enzyme-Soluble Swim Bladder Collagen from Sea Eel (Muraenesox cinereus) and Evaluation Its Wound Healing Capacity.

In the present research, the enzyme-facilitated collagen from sea eel (Muraenesox cinereus) swim bladder was isolated, and the collagen characteristics were analyzed. Then, the collagen sponge was prepared and its potential mechanism in promoting skin wound healing in mice was further investigated. Collagen was obtained from the swim bladder of sea eels employing the pepsin extraction technique. Single-factor experiments served as the basis for the response surface method (RSM) to optimize pepsin concentration, solid-liquid ratio, and hydrolysis period. With a pepsin concentration of 2067 U/g, a solid-liquid ratio of 1:83 g/mL, and a hydrolysis period of 10 h, collagen extraction achieved a yield of 93.76%. The physicochemical analysis revealed that the extracted collagen belonged to type I collagen, and the collagen sponge displayed a fibrous structure under electron microscopy. Furthermore, in comparison to the control group, mice treated with collagen sponge dressing exhibited elevated activities of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px), and decreased levels of malondialdehyde (MDA), interleukin (IL)-1ß, interleukin (IL)-6, and tumor necrosis factor (TNF)-α. The collagen sponge dressing effectively alleviated inflammation in the wound area, facilitating efficient repair and rapid healing of the skin tissue. During the initial phase of wound healing, the group treated with collagen sponge dressing exhibited an enhancement in the expressions of cluster of differentiation (CD)31, epidermal growth factor (EGF), transforming growth factor (TGF)-ß1, and type I collagen, leading to an accelerated rate of wound healing. In addition, this collagen sponge dressing could also downregulate the expressions of CD31, EGF, and type I collagen to prevent scar formation in the later stage. Moreover, this collagen treatment minimized oxidative damage and inflammation during skin wound healing and facilitated blood vessel formation in the wound. Consequently, it exhibits significant potential as an ideal material for the development of a skin wound dressing.

Investigation of the potential ameliorative effects of DHA-enriched phosphatidylserine on bisphenol A-induced murine nephrotoxicity.

In order to investigate the amelioration of docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on bisphenol A (BPA)-induced nephrotoxicity, the murine nephrotoxicity model was established by intragastric administration of BPA (5 mg/kg/B.W.) for 6 weeks. The biochemical indices, hematoxylin-eosin (H&E) staining, kidney metabolomics, and related protein expression levels of SIRT1-AMPK pathway were then determined. Our results indicated that DHA-PS (100 mg/kg/B.W.) ameliorated the BPA-induced nephrotoxicity after 6 weeks of intragastric administration, primarily by decreasing the serum creatinine (CRE) and blood urea nitrogen (BUN), renal inflammatory cytokines and lipid levels, and increasing the antioxidant enzyme activities. In addition, the untargeted metabolomics of the kidney indicated that BPA perturbed the tryptophan metabolism, pyridine metabolism, and valine, leucine, and isoleucine biosynthesis, while DHA-PS administration significantly affected the glycerophospholipid metabolism, valine, leucine, and isoleucine biosynthesis to ameliorate the BPA-induced metabolic disorder. Moreover, DHA-PS administration could ameliorate the BPA-induced lipid disturbance by upregulating the expressions of AMPKα1, SIRT1, and PPARα while downregulating the expression of SREBP-1c through the SIRT1-AMPK pathway. This is the first time that the amelioration effects of DHA-PS on BPA-induced nephrotoxicity have been investigated from multiple perspectives, suggesting that DHA-PS might be a potential dietary supplement for reducing BPA-induced nephrotoxicity.

Effects of Low Molecular Weight Peptides from Red Shrimp (Solenocera crassicornis) Head on Immune Response in Immunosuppressed Mice.

This study aimed to investigate the immunoenhancement effects of low molecular weight peptides (SCHPs-F1) from red shrimp (Solenocera crassicornis) head against cyclophosphamide (CTX)-induced immunosuppressed mice. ICR mice were intraperitoneally injected with 80 mg/kg CTX for 5 consecutive days to establish the immunosuppressive model and then intragastrically administered with SCHPs-F1 (100 mg/kg, 200 mg/kg, and 400 mg/kg) to investigate its improving effect on immunosuppressed mice and explore its potential mechanism using Western blot. SCHPs-F1 could effectively improve the spleen and thymus index, promoting serum cytokines and immunoglobulins production and upregulating the proliferative activity of splenic lymphocytes and peritoneal macrophages of the CTX-treated mice. Moreover, SCHPs-F1 could significantly promote the expression levels of related proteins in the NF-κB and MAPK pathways in the spleen tissues. Overall, the results suggested that SCHPs-F1 could effectively ameliorate the immune deficiency caused by CTX and had the potential to explore as an immunomodulator in functional foods or dietary supplements.

Investigation of nephrotoxicity on mice exposed to polystyrene nanoplastics and the potential amelioration effects of DHA-enriched phosphatidylserine.

Nanoplastics (NPs) induce nephrotoxicity in mammals, but an understanding of the potential mechanism or amelioration strategies is lacking. Herein, we established the polystyrene nanoplastics (PS-NPs, 100 nm)-induced nephrotoxicity murine model, and investigated the potential molecular mechanism of docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) alleviating effects. Based on the biochemical indices, H&E staining and kidney metabolomics, we found that PS-NPs did cause murine nephrotoxicity, mainly due to inflammation, oxidative stress, and lipid disturbance. DHA-PS administration alleviated these effects, mainly by decreasing renal levels of IL-6, IL-1ß, TNF-α and MDA, increasing the level of IL-10, increasing the activities of SOD, GSH-Px, CAT, and alleviating lipid disturbance, mainly by modulating kidney glycerophospholipid metabolism, linoleic acid metabolism and the SIRT1-AMPK pathway. This is the first time that the amelioration effects of DHA-PS on PS-NPs-induced nephrotoxicity have been investigated from multiple perspectives, providing a potential mechanism of nephrotoxicity caused by PS-NPs.

Unrinsed Nemipterus virgatus surimi provides more nutrients than rinsed surimi and helps recover immunosuppressed mice treated with cyclophosphamide.

BACKGROUND: The rinsing process in the production of surimi can cause the loss of some important nutrients. To investigate the differences in nutritional properties between rinsed surimi (RS) and unrinsed surimi (US), this study compared the elemental composition, amino acid composition, fatty acid composition, proteomics, and an immunosuppression mouse model of surimi before and after rinsing, and analyzed the nutritional and immunological properties of RS and US. RESULTS: The results showed that the protein, fat, and ash contents of RS were decreased compared with those of US; specifically, the contents of essential amino acids, semi-essential amino acids, non-essential amino acids, saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids were decreased. In the non-labeled quantitative proteomics analysis, three high-abundance quantifiable protein contents and 68 low-abundance quantifiable protein contents were found in RS (P-values < 0.05, ratio > 2). Immune function experiments in mice revealed that both RS and US contributed to the recovery of immunity in immunocompromised mice. The effect of US was better than that of RS. CONCLUSION: The rinsing process in surimi processing leads to the loss of nutrients in surimi. US promotes the recovery of immunity in immunocompromised mice more effectively than RS. © 2023 Society of Chemical Industry.

DHA-enriched phosphatidylserine alleviates high fat diet-induced jejunum injury in mice by modulating gut microbiota.

A long-term high-fat diet (HFD) is one of the high-risk factors for intestinal barrier damage. Docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) has multiple biological activities, while its protective effect on HFD-caused jejunum injury remains unknown. Thus, the present study investigated the protective effect of DHA-PS on HFD-induced jejunum injury in mice. Our results showed that DHA-PS (100 mg per kg per d) could protect against HFD-caused jejunum injury by decreasing the levels of inflammatory factors such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) in the serum and jejunum tissues, with histological analysis confirming this injury amelioration. Additionally, DHA-PS alleviated the HFD-caused oxidative stress by decreasing malondialdehyde (MDA) and increasing total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) levels in the jejunum. Moreover, DHA-PS significantly increased the expression of tight junction proteins (ZO-1, occludin, and claudin-4) in the jejunum, and modulated the HFD-induced gut microbiota disorder by decreasing the Firmicutes and Bacteroidetes ratio, and reducing the relative abundance of Lachnoclostridium, Coriobacteriaceae, Desulfovibrionaceae, and Helicobacter, while increasing the relative abundance of Lachnospiraceae_NK4A136_group, Alistipes, norank_f__Muribaculaceae, and Bacteroides. Overall, these results support that DHA-PS can alleviate the HFD-caused jejunum injury.

Small Peptides from Periplaneta americana Inhibits Oxidative Stress-Induced KGN Cell Apoptosis by Regulating Mitochondrial Function Through Bcl2L13.

This study examined the protective effects of small peptides from Periplaneta americana against H2O2-induced mitochondrial injury in human ovarian granulosa cells. The ATP level and mitochondrial membrane potential as well as the quantity and ultrastructure of mitochondria in cells were detected. Mitochondrial DNA copy number and expression levels of Bcl2L13, LC3B, and p62 were tested. Targeted silencing of Bcl2L13 expression in KGN cells. The expression levels of Bcl2L13 and LC3B as well as interaction were evaluated. The ATP level, mtDNA-CN, and MMP of the H2O2 group were significantly lower than those of the normal control group (P < 0.05), accompanied by a reduction in mitochondrial mass and mitochondrial fluorescence intensity (P < 0.05). However, the ATP level, mtDNA, and MMP in KGN cells were increased after SPPA treatment (P < 0.05). Scanning electron microscopy shows that SPPA ameliorates H2O2-induced structural damage to mitochondria. Moreover, the expression levels of Bcl2L13 and p62 in the H2O2 group were downregulated significantly compared with those of the normal control group (P < 0.05), while LC3B was upregulated (P < 0.05). After SPPA treatment, the expression levels of Bcl2L13 and p62 were upregulated (P < 0.05), while LC3B was downregulated (P < 0.05). The Co-IP results indicated that Bcl2L13 and LC3B interacted, and this interaction was weakened after cell treatment with H2O2, and dissociation between Bcl2L13 and LC3B declined after SPPA treatment. SPPA inhibits KGN cell apoptosis induced by oxidative stress via inhibition of mitochondrial injury Bcl2L13-mediated mitochondrial autophagy might participate in the regulation process.

Effects of low molecular weight peptides from monkfish (Lophius litulon) roe on immune response in immunosuppressed mice.

This study aimed to investigate the immunomodulatory activation of low-molecular-weight peptides from monkfish (Lophius litulon) roe (named MRP) on cyclophosphamide (CTX)-induced immunosuppressed mice. Our results indicated that MRP (100 mg/kg/d BW) could significantly increase the body weight and immune organ index, and improve the morphological changes in the spleen and thymus of mice. These effects subsequently enhance the serum levels of interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, and immunoglobulin (Ig) A, IgM, and IgG. Furthermore, MRP could also improve CTX-induced oxidative stress, and activate the NF-κB and MAPK pathways in the spleen tissues. The findings reported herein indicate that MRP has a good immunomodulatory activation toward immunosuppressed mice, hence can potentially be developed as an immune adjuvant or functional food.

DHA-enriched phosphatidylcholine from Clupea harengus roes regulates the gut-liver axis to ameliorate high-fat diet-induced non-alcoholic fatty liver disease.

In this study, the protective effect of DHA-enriched phosphatidylcholine (DHA-PC) from Clupea harengus roes against high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) was investigated. Our results indicated that DHA-PC significantly decreased the murine body weights, liver indexes, serum ALT, AST, and LPS levels, improved the serum lipid levels (TG, TC, LDL-C, HDL-C, NEFA), relieved the hepatic levels of the pro-inflammatory cytokines (IL-6, IL-1ß, and TNF-α), and hepatic oxidative stress (MDA, SOD, GSH-Px, and CAT) in mice fed on HFD. DHA-PC significantly decreased protein expression levels of TLR4, MyD88, IKKß, p-P65, and p-IκBα in the liver and upregulated the protein expression levels of ZO-1, occludin, and claudin-4 in the jejunum. Moreover, DHA-PC treatment alleviated intestinal dysbiosis caused by HFD. At the genus level, DHA-PC promoted the relative abundances of unclassified Muribaculaceae, Lachnospiraceae NK4A136 group, Blautia, and unclassified Clostridia UCG-014, while reducing the abundance of Allobaculum, unclassified Atopobiaceae, Alistipes, Faecalibaculum, Lachnoclostridium, and Tuzzerella. Our findings suggest that DHA-PC alleviated HFD-induced NAFLD by regulating lipid metabolism and dysbiosis via the gut-liver axis.

Immunoenhancing Effects of Cyclina sinensis Pentadecapeptide through Modulation of Signaling Pathways in Mice with Cyclophosphamide-Induced Immunosuppression.

Our study aimed to investigate the immune-enhancing mechanism of the pentadecapeptide (RVAPEEHPVEGRYLV) from Cyclina sinensis (SCSP) in a cyclophosphamide (CTX)-induced murine model of immunosuppression. Our results showed that SCSP treatment significantly increased mouse body weight, immune organ indices, and the production of serum IL-6, IL-1ß, and tumor necrosis factor (TNF)-α in CTX-treated mice. In addition, SCSP treatment enhanced the proliferation of splenic lymphocytes and peritoneal macrophages, as well as phagocytosis of the latter in a dose-dependent manner. Moreover, SCSP elevated the phosphorylation levels of p38, ERK, JNK, PI3K and Akt, and up-regulated IKKα, IKKß, p50 NF-κB and p65 NF-κB protein levels, while down-regulating IκBα protein levels. Our results indicate that SCSP has immune-enhancing activities, and that it can activate the MAPK/NF-κB and PI3K/Akt pathways to enhance immunity in CTX-induced immunosuppressed mice.

DHA-enriched phosphatidylserine ameliorates high-fat diet-induced kidney injury in mice possibly by regulating TLR4/NF-κB and AMPK pathways.

The present study sought to investigate the amelioration effects of enzymatically synthesized docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on the high-fat diet (HFD)-induced kidney injury in mice. After 6 weeks of DHA-PS intervention, the mice's body weight in the 20 and 40 mg/kg DHA-PS groups decreased by 7.09% and 9.71%, respectively, compared to the HFD group. Especially, compared to the HFD group, 40 mg/kg DHA-PS treatment effectively reduced the levels of serum urea nitrogen by 68.48%, creatinine by 38.98%, kidney lipid accumulation (total cholesterol, triglycerides, and nonesterified fatty acids levels by 26.19%, 51.00%, and 26.11%), kidney or serum proinflammatory cytokines and enhanced the levels of kidney or serum oxidative stress parameters, except for malondialdehyde (MDA). Moreover, 40 mg/kg DHA-PS treatment decreased the expression levels of toll-like receptor 4 (TLR4) by 18.63%, IKKα by 31.81%, and p-p65 by 40.73% in the nuclear factor kappa-B pathway, thereby upregulating the expression levels of p-AMPKα by 64.93%, HSL by 99.60%, ATGL by 344.50%, PPARα by 162.02%, CPT1 by 167.95%, p-ACC1 by 144.92%, and p-SREBP1 by 1172.95%, and downregulating the expression levels of SREBP1 by 38.80%, ACC1 by 18.10%, and FAS by 82.28% in the AMPK pathway. Furthermore, our results also suggested that improving serum or kidney parameters and regulating intestinal microbial could affect each other after DHA-PS treatment. These results elucidated that DHA-PS could be a potential dietary supplement to alleviate HFD-induced kidney injury. PRACTICAL APPLICATION: Our results elucidated that DHA-PS could be a potential dietary supplement to alleviate HFD-induced kidney injury.

Effects of Fucoidan Isolated From Laminaria japonica on Immune Response and Gut Microbiota in Cyclophosphamide-Treated Mice.

The effects of Laminaria japonica fucoidan (LF) on immune regulation and intestinal microflora in cyclophosphamide (CTX)-treated mice were investigated in this work. Results indicated that LF significantly enhanced the spleen and thymus indices, promoted spleen lymphocyte and peritoneal macrophages proliferation, and increased the immune-related cytokines production in serum. Moreover, LF could regulate intestinal flora composition, increasing the abundance of Lactobacillaceae and Alistipes, and inhibiting Erysipelotrichia, Turicibacter, Romboutsia, Peptostreptococcaceae, and Faecalibaculum. These results were positively correlated with immune characteristics. Overall, LF could be useful as a new potential strategy to mitigate CTX immunosuppression and intestinal microbiota disorders.

Pyrroloquinoline quinone ameliorates liver injury in mice induced by cyclophosphamide.

The current study aimed to investigate the potential ameliorative effects of pyrroloquinoline quinone (PQQ) on cyclophosphamide (CTX)-induced liver injury in mice. The liver injury model was established by injecting mice with CTX (80 mg/kg/day). Liver function indices, antioxidant enzyme activities, and inflammatory cytokines were evaluated. In addition, protein expression levels of the nuclear factor E2-related factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) pathways in the liver tissues were determined using western blot. The results indicated that PQQ decreased the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the malondialdehyde (MDA), interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α) levels in the liver tissues. Moreover, PQQ enhanced the activities of oxidative stress markers to alleviate CTX induced oxidative stress. Furthermore, the expression levels of heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H quinone oxidoreductase 1 (NQO1) were significantly increased, and the expression levels of NF-κB p50, NF-κB p65, and inhibitor of NF-κB kinase alpha (IKKα) were significantly decreased after PQQ administration, suggesting that PQQ alleviated CTX-induced liver injury via activating the Nrf2-mediated antioxidant response pathway, and inhibiting the NF-κB-mediated inflammation pathway. Therefore, PQQ can be potentially used as a dietary supplement or functional foods for alleviating the CTX-induced liver injury.

Laminaria japonica fucoidan ameliorates cyclophosphamide-induced liver and kidney injury possibly by regulating Nrf2/HO-1 and TLR4/NF-κB signaling pathways.

BACKGROUND: During clinical practice, cyclophosphamide (CTX) can lead to liver and kidney injury in vivo. In this study, we established a liver and kidney injury model by injecting CTX (80 mg kg-1 d-1 ) into male ICR mice, and then mice were treated with saline and fucoidan (20 or 40 mg kg-1 ), respectively. Subsequently, the liver and kidney toxicity indices, the expression levels of malonic dialdehyde (MDA), inflammatory factors, and the main protein levels of the Nrf2/HO-1 and TLR4/NF-κB pathways were determined. RESULTS: Our results indicated that fucoidan could significantly decrease serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CRE), and urea (BUN) in the test group compared to the model group. Fucoidan administration caused reductions in MDA, interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor alpha (TNF-α) levels and improved superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities in the liver and kidney of CTX-induced mice. Fucoidan up-regulated the Nrf2/HO-1 pathway and enhanced the protein levels of Nrf2, HO-1, GCLM, and NQO1. Moreover, fucoidan down-regulated the TLR4/NF-κB pathway, as indicated by decreased levels of TLR4, NF-κB p65, NF-κB p50, and increased IκBα level in liver and kidney tissues. CONCLUSION: Our studies suggest that fucoidan can ameliorate CTX-induced liver and kidney injury, potentially via up-regulating the Nrf2/HO-1 pathway and inhibiting the TLR4/NF-κB pathway. © 2021 Society of Chemical Industry.

A novel electro-Fenton process coupled with sulfite: Enhanced Fe3+ reduction and TOC removal.

To promote the reduction of Fe3+ and improve the mineralization of organic pollutants, a novel electro-Fenton coupled with sulfite (Fe3+-EF/sulfite) process was constructed, which was superior to Fe3+-EF process in terms of carbamazepine (CBZ) degradation and mineralization with 5.99 times enhancement in degradation rate constant and 15.7 times enhancement on TOC removal. The complexation of Fe3+ and sulfite prevented the precipitation of Fe3+, reduced Fe3+ to Fe2+, and accelerated the iron cycle, so that H2O2 utilization efficiency (0.051 mgTOC mgH2O2-1) was greatly improved and electric energy consumption was greatly reduced (0.081 kWh g-1 TOC). The quenching experiments and EPR test confirmed that the reactive species, such as SO3•-, SO4•-, •OH, O2•- and 1O2 were responsible for the degradation of CBZ. This process also expanded the pH application range from 3 to 9 with satisfactory CBZ removal efficiency. This work verified the suitability of the Fe3+-EF/sulfite process for different sulfites (sulfite and bisulfite), typical pollutants (atrazine, sulfamethazine, rhodamine B) and real wastewater with 2.1-18.7 folds enhancement in degradation rate. The Fe3+-EF/sulfite process can achieve deep mineralization with low cost and simple operation, which has a broad and cost-effective application prospect in removal of refractory organic pollutants.

DHA-enriched phosphatidylserine ameliorates non-alcoholic fatty liver disease and intestinal dysbacteriosis in mice induced by a high-fat diet.

Docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) has attracted increasing attention because of its unique health benefits. In this study, DHA-PS was biosynthesized from DHA-enriched phosphatidylcholine (DHA-PC), which was extracted from herring roe, Clupea harengus. The ameliorating effect of DHA-PS on high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) was investigated using a mouse model. The DHA-PS treatment ameliorated NAFLD and effectively decreased the serum total cholesterol, triglyceride, non-esterified fatty acid, and low-density lipoprotein cholesterol levels and considerably increased the serum high-density lipoprotein cholesterol levels. Moreover, the DHA-PS treatment reduced the levels of liver-function enzymes and pro-inflammatory cytokines and also the oxidative stress indices. Furthermore, DHA-PS increased the diversity and richness of the beneficial intestinal microorganisms, suggesting its potential as a dietary supplement and functional food to combat HFD-induced NAFLD.

Successful treatment of infantile oxysterol 7α-hydroxylase deficiency with oral chenodeoxycholic acid.

BACKGROUND: Deficiency of oxysterol 7α-hydroxylase, encoded by CYP7B1, is associated with fatal infantile progressive intrahepatic cholestasis and hereditary spastic paraplegia type 5. Most reported patients with CYP7B1 mutations presenting with liver disease in infancy have died of liver failure. However, it was recently reported that two patients treated with chenodeoxycholic acid survived. Correlations between the phenotype and genotype of CYP7B1 deficiency have not been clearly established. CASE PRESENTATION: A 5-month-7-day-old Chinese baby from non-consanguineous parents was referred for progressive cholestasis and prolonged prothrombin time from one month of age. Genetic testing revealed compound heterozygous mutations c.187C > T(p.R63X)/c.334C > T(p.R112X) in CYP7B1, and fast atom bombardment mass spectrometry analysis of the urinary bile acid confirmed the presence of atypical hepatotoxic 3ß-hydroxy-Δ5-bile acids. While awaiting liver transplantation she was orally administered chenodeoxycholic acid. Her liver function rapidly improved, urine atypical bile acids normalized, and she thrived well until the last follow-up at 23 months of age. Her 15-year-old brother, with no history of infantile cholestasis but harboring the same mutations in CYP7B1, had gait abnormality from 13 years of age. Neurological examination revealed hyper-reflexia and spasticity of the lower limbs. Brain MRI revealed enlarged perivascular space in the bilateral basal ganglia and white matter of frontal parietal. CONCLUSIONS: In summary, these findings highlight that the phenotype of CYP7B1 deficiency varies widely, even in siblings and that early administration of chenodeoxycholic acid may improve prognosis.

Anti-Hyperuricemic Effects of Astaxanthin by Regulating Xanthine Oxidase, Adenosine Deaminase and Urate Transporters in Rats.

This study was designed to investigate the effects and underlying mechanisms of Astaxanthin (AST) on high-fructose-induced hyperuricemia (HUA) from the perspectives of the uric acid (UA) synthesis and excretion in rat models. Following six weeks of a 10% fructose diet, the level of serum UA effectively decreased in the AST groups as compared to the model group. The enzymatic activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) were significantly inhibited, and the mRNA expression levels of XOD and ADA significantly decreased after the AST administration. These results suggested that the AST reduced UA synthesis by inhibiting the mRNA expressions and enzyme activities of XOD and ADA, thereby contributing to HUA improvement. On the hand, the relative expressions of the mRNA and protein of kidney reabsorption transport proteins (GLUT9 and URAT1) were significantly down-regulated by AST, while that of the kidney secretion proteins (OAT1, OAT3 and ABCG2) were significantly up-regulated by AST. These results indicated that the AST promoted UA excretion by regulating the urate transport proteins, and thus alleviated HUA. This study suggested that the AST could serve as an effective alternative to traditional medicinal drugs for the prevention of fructose-induced HUA.