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1.
BMC Pediatr ; 24(1): 203, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38519924

ABSTRACT

Langerhans cell histiocytosis (LCH) involving the gastrointestinal tract is a rare condition for which clinical experience is limited. We describe the cases of two patients who initially presented with chronic diarrhoea, hypoproteinaemia, and intermittent fever. These findings suggest that in cases of refractory diarrhoea accompanied by recurrent hypoalbuminaemia, especially with abdominal rash, LCH should be considered. Gastrointestinal endoscopy, biopsy, and imaging studies are essential for obtaining a definitive diagnosis. This approach might be helpful for the early recognition of gastrointestinal tract involvement in LCH.


Subject(s)
Histiocytosis, Langerhans-Cell , Hypoalbuminemia , Child , Humans , Hypoalbuminemia/complications , Hypoalbuminemia/pathology , Histiocytosis, Langerhans-Cell/complications , Histiocytosis, Langerhans-Cell/diagnosis , Histiocytosis, Langerhans-Cell/pathology , Gastrointestinal Tract/pathology , Biopsy , Diarrhea/complications
2.
Front Endocrinol (Lausanne) ; 14: 1131993, 2023.
Article in English | MEDLINE | ID: mdl-37334311

ABSTRACT

Objective: To study the differences in blood cellular communication network factor 1 (CCN1) levels between patients with diabetes mellitus (DM) and healthy individuals and to explore the relationship between CCN1 and diabetic retinopathy (DR). Methods: Plasma CCN1 levels were detected using ELISA in 50 healthy controls, 74 patients with diabetes without diabetic retinopathy (DM group), and 69 patients with diabetic retinopathy (DR group). Correlations between CCN1 levels and age, body mass index, mean arterial pressure, hemoglobin A1c, and other factors were analyzed. The relationship between CCN1 expression and DR was explored using logistic regression after adjusting for confounding factors. Blood mRNA sequencing analysis was performed for all subjects, and the molecular changes that may be related to CCN1 were explored. The retinal vasculature of streptozotocin-induced diabetic rats was examined using fundus fluorescein angiography; in addition, retinal protein expression was examined using western blotting. Results: Plasma CCN1 levels in patients with DR were significantly higher than in the control and DM groups; however, no significant differences were observed between healthy controls and patients with DM. CCN1 levels negatively correlated with body mass index and positively correlated with the duration of diabetes and urea levels. It was observed that high (OR 4.72, 95% CI: 1.10-20.25) and very high (OR 8.54, 95% CI: 2.00-36.51) levels of CCN1 were risk factors for DR. Blood mRNA sequencing analysis revealed that CCN1-related pathways were significantly altered in the DR group. The expression of hypoxia-, oxidative stress-, and dephosphorylation-related proteins were elevated, while that of tight junction proteins were reduced in the retinas of diabetic rats. Conclusion: Blood CCN1 levels are significantly elevated in patients with DR. High and very high levels of plasma CCN1 are risk factors for DR. Blood CCN1 level may be a potential biomarker for diagnosis of DR. The effects of CCN1 on DR may be related to hypoxia, oxidative stress, and dephosphorylation.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Retinopathy , Animals , Rats , Diabetes Mellitus, Experimental/metabolism , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/etiology , Diabetic Retinopathy/metabolism , Retina/metabolism , Risk Factors , RNA, Messenger/metabolism
3.
World J Pediatr ; 18(4): 271-277, 2022 04.
Article in English | MEDLINE | ID: mdl-35211921

ABSTRACT

BACKGROUND: Children with intestinal failure (IF) have frequent catheter-related bloodstream infections (CRBSIs). This study aimed to analyze the clinical presentation and laboratory parameters of CRBSIs in children with IF. METHODS: This 6-year retrospective study was conducted among IF children with CRBSIs at an intestinal rehabilitation center in China. Clinical data were collected, including data of temperature and gastrointestinal symptoms. Blood/catheter culture, fecal tests, and calculation of inflammatory index were performed, which were obtained within 1 week since CRBSI onset. RESULTS: Fifty children with 87 CRBSIs were identified, of which there were 17 suspected and 70 confirmed cases. Seventy-two pathogens were cultured from 70 positive blood cultures: 63% were Gram-positive organisms, 23% were Gram-negative organisms, and 11% were fungal organisms. Overall, 48.6% were enteric organisms; 47.2% of bacterial pathogens were consistent between fecal and blood cultures. Moreover, 46.3% fecal routines showed abnormalities including increased white blood cells, occult blood positive and the presence of fat droplets. The consistent symptom at onset of CRBSIs was fever and gastrointestinal symptoms including increased stool output, abdominal distension, or both. C-reactive protein (CRP) and procalcitonin (PCT) were elevated, i.e., 16.5 mg/L [interquartile range (IQR) 8.7-44.7] and 0.48 ng/mL (IQR 0.2-1.76), respectively. CONCLUSIONS: IF children had a high rate of CRBSIs, of which larger proportions were due to Gram-positive and enteric organisms. Fever and/or gastrointestinal symptoms, combined with elevated CRP and PCT, is conducive to the early diagnosis of CRBSIs in IF patients.


Subject(s)
Bacteremia , Catheter-Related Infections , Intestinal Failure , Bacteremia/diagnosis , Bacteremia/epidemiology , Catheter-Related Infections/diagnosis , Catheter-Related Infections/epidemiology , Catheters , Child , Fever , Humans , Rehabilitation Centers , Retrospective Studies
4.
Anal Methods ; 13(39): 4538-4556, 2021 10 14.
Article in English | MEDLINE | ID: mdl-34570126

ABSTRACT

Molecular imprinting technology for the preparation of polymers with specific molecular recognition function had become one of the current research hotspots. It has been widely applied in chromatographic separation, antibody and receptor mimetics, solid-phase extraction, bio-sensors, and other fields in the last decades. In this study, molecular imprinting technology was summarized from the points of templates and dummy templates, and four typical target analytes were selected to compare the differences between templates and dummy templates. The current status and prospects of molecular imprinting technology were also proposed.


Subject(s)
Molecular Imprinting , Polymers , Solid Phase Extraction
5.
Int J Ophthalmol ; 14(7): 1066-1072, 2021.
Article in English | MEDLINE | ID: mdl-34282393

ABSTRACT

AIM: To investigate the prevalence of diabetic retinopathy (DR) in residents of Shanghai and analyze the risk factors of DR. METHODS: This study involved 7233 patients with diabetes in 2016. The demographic data of the participants were collected using a questionnaire survey. Physical examination, laboratory tests, and ophthalmological examinations were conducted. Two professional ophthalmologists diagnosed and graded DR by fundus examination and then combined the results with fundus images. The unconditional multivariate Logistic regression analysis was used to determine the risk factors. RESULTS: In total, 6978 patients with type 2 diabetes in Shanghai with a mean age of 68.33±8.40y were recruited, including 2975 males (42.6%) and 4003 females (57.4%). Overall, 1184 patients were diagnosed with DR, with a prevalence rate of 16.97%. Regression analysis showed that duration of diabetes (OR 1.061, 95%CI 1.049-1.073), high systolic blood pressure (SBP; OR 1.071, 95%CI 1.037-1.106), increased glycosylated hemoglobin level (OR 1.234, 95%CI 1.162-1.311), high blood glucose level (OR 1.061, 95%CI 1.023-1.099), increased neutrophil-to-lymphocyte ratio (NLR; OR 1.132, 95%CI 1.053-1.217) and mean platelet volume (MPV; OR 1.077, 95%CI 1.016-1.142) were risk factors of DR. Conversely, hematocrit (HCT; OR 0.971, 95%CI 0.954-0.988) and mean corpuscular volume (MCV; OR 0.980, 95%CI 0.965-0.994) were protective factors. CONCLUSION: The prevalence rate of DR in Shanghai is 16.97%. The duration of diabetes, high SBP, increased glycosylated hemoglobin, NLR, and MPV were determined as risk factors of DR.

6.
Chem Commun (Camb) ; 56(75): 11038-11041, 2020 Sep 25.
Article in English | MEDLINE | ID: mdl-32808605

ABSTRACT

Achieving a profound understanding of the reaction kinetics of a catalyst by modulating its electronic structure is significant. Herein, we present a scalable approach to achieving a spatially partial substitution of S into NiMoO4. The increase in active components in a true Ni3+ oxidation state as a result of optimizing the coordination environment greatly improved urea oxidation activity.


Subject(s)
Electrochemical Techniques , Molybdenum/chemistry , Nickel/chemistry , Oxides/chemistry , Urea/chemistry , Catalysis , Kinetics , Models, Molecular , Oxidation-Reduction , Particle Size , Surface Properties
7.
Zhen Ci Yan Jiu ; 45(7): 578-82, 2020 Jul 25.
Article in Chinese | MEDLINE | ID: mdl-32705834

ABSTRACT

OBJECTIVE: To observe the clinical effect of electroacupuncture combined with moxibustion in the treatment of urinary incontinence after stroke due to deficiency of kidney-yang. METHODS: Sixty patients with urinary incontinence after stroke due to kidney-yang deficiency were randomly divided into a control group and an observation group,with 30 cases in each group. The patients in the control group were given oral administration of Jingui Shenqi pills and Suoquan capsules. On the basis of the treatment in the control group, the patients in the observation group were given electroacupuncture treatment at the Foot Motor sensory Area on the head, Shenshu(BL23) and Huiyang(BL35), together with moxibustion at Guanyuan(CV4) and Qihai(CV6) once daily. The treatment was conducted 6 times per week and for 2 successive weeks. The average number of daily urinary incontinence and night urinary incontinence, maximum bladder volume, residual bladder urine volume, degree of urinary incontinence and clinical symptoms score of the two groups before and after treatment were observed. And the clinical efficacy of the two groups were compared. RESULTS: After the treatment, compared with those before the treatment, the average numbers of daily and night urinary incontinence of the two groups were significantly reduced (P<0.01), the maximum bladder volume was significantly increased (P<0.05), and the residual urine volume of the bladder was significantly reduced (P<0.05). The number of cases with urinary incontinence degree Ⅰ and Ⅱ increased (P<0.05), and the score of clinical symptoms of urinary incontinence was significantly reduced (P<0.05). After the treatment, compared with the control group, the number of daily and night urinary incontinence in the observation group decreased (P<0.05), the maximum bladder volume increased (P<0.05), the residual bladder urine volume decreased (P<0.05), and the number of cases with urinary incontinence degree Ⅰ and Ⅱ increased (P<0.05), the clinical symptom score of urinary incontinence was significantly reduced (P<0.05). The total effective rates of the control group and the observation group were 73.3% (22/30) and 93.3% (28/30) respectively, and the effective rate of the observation group was higher than that of the control group (P<0.05). CONCLUSION: The combination of electroacupuncture, moxibustion and traditional Chinese medicine is effective in treating urinary incontinence after stroke due to deficiency of kidney-yang.


Subject(s)
Electroacupuncture , Moxibustion , Stroke , Urinary Incontinence , Humans , Yang Deficiency
8.
Biosci Biotechnol Biochem ; 83(3): 417-428, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30458666

ABSTRACT

Wounding increased the extracellular Adenosine 5'-triphosphate (eATP) level of kidney bean leaves. Treatment with wounding or exogenous ATP increased the hydrogen peroxide (H2O2) content, activities of catalase and polyphenol oxidase, and malondialdehyde content in both the treated and systemic leaves. Pre-treatment with ATP-degrading enzyme, apyrase, to the wounded leaves reduced the wound-induced local and systemic increases in H2O2 content, activities of catalase and polyphenol oxidase, and malondialdehyde content. Application of dimethylthiourea (DMTU) and diphenylene iodonium (DPI) to the wounded and ATP-treated leaves, respectively, reduced the wound- and ATP-induced local and systemic increases in H2O2 content, activities of catalase and polyphenol oxidase, and malondialdehyde content. Moreover, the wound- and ATP-induced systemic increases of these physiological parameters were suppressed when DMTU or DPI applied to leaf petiole of the wounded and ATP-treated leaves. These results suggest that eATP at wounded sites could mediate the wound-induced local and systemic responses by H2O2-dependent signal transduction.


Subject(s)
Adenosine Triphosphate/metabolism , Extracellular Space/metabolism , Phaseolus/cytology , Phaseolus/metabolism , Plant Leaves/cytology , Plant Leaves/metabolism , Apyrase/metabolism , Catalase/metabolism , Catechol Oxidase/metabolism , Hydrogen Peroxide/metabolism , Malondialdehyde/metabolism , Phaseolus/physiology , Plant Leaves/physiology
10.
J Asian Nat Prod Res ; 20(4): 306-312, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28581822

ABSTRACT

Three new sesquiterpenes of canusesnol K (1), canusesnol L (2) and 12, 15-dihydroxycurcumene (3), along with five known ones (4-8), were isolated from the heartwood extract of Pterocarpus santalinus. Their structures were established by extensive analyses of 1D and 2D NMR spectroscopy, including 1H NMR, 13C NMR, HSQC, HMBC and NOESY, and HRESI-MS. The absolute configurations of the new compounds were established with Modified Mosher's method. The cytotoxic activities of all these compounds against HepG2 (human liver cancer), MCF-7 (human breast cancer), MDA-MB-231 (human breast cancer), and Hela (human cervical carcinoma) cancer cell lines were evaluated. Compound 1 exhibited moderate cytotoxic activity toward MDA-MB-231 cell lines.


Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Drugs, Chinese Herbal/isolation & purification , Pterocarpus/chemistry , Sesquiterpenes/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , HeLa Cells , Hep G2 Cells , Humans , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology
11.
Zhongguo Zhong Yao Za Zhi ; 42(8): 1532-1538, 2017 Apr.
Article in Chinese | MEDLINE | ID: mdl-29071858

ABSTRACT

Biopharmaceutics classification system of Chinese materia medica (CMMBCS) emphasizes characteristic of the multi-component environment based on the drug solubility and permeability. In this study, the in situ closed-loop method combined with LC-MS technique was utilized to study the intestinal absorption and metabolism of Puerariae Lobatae Radix decoction (PLRD), providing selection basis for intestinal permeability components in CMMBCS. A total of 36 components were identified from PLRD. Among them, 17 components could be detected in the plasma sample, indicating that 17 components could be absorbed into blood, so these 17 components could be used as intestinal permeability evaluation components in CMMBCS. The other 19 components were not detected in the plasma sample, suggesting that they may not be absorbed or metabolized by the gut wall enzymes.


Subject(s)
Drugs, Chinese Herbal/pharmacokinetics , Intestinal Absorption , Pueraria/chemistry , Humans , Plant Roots/chemistry
12.
Mol Neurobiol ; 54(7): 5213-5224, 2017 09.
Article in English | MEDLINE | ID: mdl-27578012

ABSTRACT

Iron accumulates progressively in the brain with age; however, the cause is unknown. We hypothesized that iron accumulation may be associated with the age-induced changes in the expression of iron metabolism proteins in the brain. Here, we systematically investigated iron content and the expression of two major iron importers, transferrin receptor 1 (TfR1) and divalent metal transporter (DMT1), two iron exporters, ferroportin 1 (Fpn1) and ceruloplasmin (CP), and hepcidin, along with the pathological hallmarks of Parkinson's (PD) and Alzheimer's diseases (AD) in the brain of young (3 months), adult (12 months), and aged (24 months) rats. We demonstrated that age has a region-specific effect on iron transport proteins along with iron content in the cortex, striatum, hippocampus, and substantia nigra. We also found an age-dependent increase in hyperphosphorylated tau, total beta-amyloid, and neurotoxic oligomeric aggregates in the cortex and hippocampus as well as an increase in α-synuclein and a decrease in tyrosine hydroxylase positive neurons in the substantia nigra. Our findings suggest that the age-dependent increase in brain iron may be partly due to the age-induced increase in DMT1 expression, rather than TfR1 and Fpn1 expression, and also imply that the increased brain iron is associated with expression of the pathological hallmarks of AD and PD.


Subject(s)
Alzheimer Disease/metabolism , Brain/metabolism , Cation Transport Proteins/metabolism , Hepcidins/metabolism , Parkinson Disease/metabolism , Aging , Alzheimer Disease/pathology , Animals , Astrocytes/metabolism , Iron/metabolism , Male , Neurons/metabolism , Parkinson Disease/pathology , Parkinsonian Disorders/metabolism , Rats, Sprague-Dawley
13.
Sci Rep ; 6: 39264, 2016 12 15.
Article in English | MEDLINE | ID: mdl-27976737

ABSTRACT

Intestinal failure (IF)-associated liver disease (IFALD), as a major complication, contributes to significant morbidity in pediatric IF patients. However, the pathogenesis of IFALD is still uncertain. We here investigate the roles of bile acid (BA) dysmetabolism in the unclear pathogenesis of IFALD. It found that the histological evidence of pediatric IF patients exhibited liver injury, which was characterized by liver bile duct proliferation, inflammatory infiltration, hepatocyte apoptosis and different stages of fibrosis. The BA compositions were altered in serum and liver of pediatric IF patients, as reflected by a primary BA dominant composition. In IF patients, the serum FGF19 levels decreased significantly, and were conversely correlated with ileal inflammation grades (r = -0.50, p < 0.05). In ileum, the inflammation grades were inversely associated with farnesoid X receptor (FXR) expression (r = -0.55, p < 0.05). In liver, the expression of induction of the rate-limiting enzyme in bile salt synthesis, cytochrome P450 7a1 (CYP7A1) increased evidently. In conclusion, ileum inflammation decreases FXR expression corresponding to reduce serum FGF19 concentration, along with increased hepatic bile acid synthesis, leading to liver damages in IF patients.


Subject(s)
Bile Acids and Salts/metabolism , Intestinal Diseases/pathology , Liver Diseases/pathology , Bile Acids and Salts/blood , Child, Preschool , Cholesterol 7-alpha-Hydroxylase/metabolism , Female , Fibroblast Growth Factors/blood , Humans , Ileal Diseases/pathology , Infant , Interleukin-6 , Intestinal Diseases/complications , Liver/metabolism , Liver Diseases/etiology , Liver Diseases/metabolism , Male , Receptors, Cytoplasmic and Nuclear/metabolism , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism , Up-Regulation
14.
Medicine (Baltimore) ; 95(36): e4604, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27603351

ABSTRACT

BACKGROUND: Hereditary pancreatitis (HP) is quite rare and is distinguished by incomplete penetrance presentation as early-onset relapsing pancreatitis, usually beginning in childhood. HP is now known to be commonly relevant to mutations in the PRSS1 (gene-encoding cationic trypsinogen), SPINK1 (serine protease inhibitor, Kazal type 1), CFTR (cystic fibrosis), carboxypeptidase A1 (CPA1), and chymotrypsin C (CTRC) genes as reported in some Caucasian studies. HP has a variable spectrum of severity and may develop complications. METHODS & RESULTS: We describe the clinical course of 3 preschool children, hospitalized with postprandial abdominal pain, whose laboratory tests showed high serum amylase. Similar episodes of abdominal pain led to readmission, and the patients recovered quickly after using symptomatic therapy. The condition of the first boy, who developed a pancreatic tail pseudocyst and splenic infarction, was especially complicated. The boy underwent 2 endoscopic retrograde cholangiopancreatographies and stenting, along with a surgical procedure that completely relieved his symptoms for 3 months. The 3 patients and their parents were given genetic testing. All of the patients carried 1 or more gene mutations inherited from their mothers, fathers, or both parents; however, none of the parents were affected. CONCLUSION: For children with repeated pancreatitis, clinicians should consider HP in the differential diagnosis. It is reliable to perform gene sequencing on suspicious patients and their parents. Multidisciplinary and comprehensive treatment should be recommended to manage HP and its complications. Cholangiopancreatography and stenting is a relatively minimally invasive approach when compared with surgery and can be tried as an early intervention. Surgical procedures should be reserved for patients with complications.


Subject(s)
Carboxypeptidases A/genetics , Carrier Proteins/genetics , Pancreatitis, Chronic/genetics , Trypsin/genetics , Child, Preschool , Humans , Male , Trypsin Inhibitor, Kazal Pancreatic
15.
JPEN J Parenter Enteral Nutr ; 40(6): 842-50, 2016 08.
Article in English | MEDLINE | ID: mdl-25560678

ABSTRACT

BACKGROUND: The pathogenesis of parenteral nutrition (PN)-associated liver dysfunction is multifactorial. Lipid emulsions may be one of the putative mechanisms. Our aim was to comparatively assess the effect of parenteral olive oil- and soybean oil-based lipid emulsions on liver chemistry and bile acid composition in preterm infants. METHODS: We performed a double-blind, randomized clinical study in which 103 preterm infants were randomly assigned to PN using either soybean oil-based lipid emulsion (SO; n = 51) or olive oil (OO)-based lipid emulsion (OO; n = 52). The primary end point was liver chemistry. The secondary end point was the plasma bile acid composition. RESULTS: One hundred infants completed this study. In the SO group, the serum direct bilirubin was significantly higher after PN for 7 days compared with the OO group. Bile acids increased over time in both treatment groups. However, specific differences in the change in bile acid composition over time were noted between groups. CONCLUSIONS: Differences in direct bilirubin and bile acid composition were observed over time between the 2 groups. Considering the long-term use of lipid emulsions in higher risk babies, these findings might be useful for understanding the pathogenesis of PN-associated liver dysfunction.


Subject(s)
Bile Acids and Salts/chemistry , Infant, Premature/metabolism , Liver/chemistry , Olive Oil , Parenteral Nutrition/adverse effects , Soybean Oil , Cholestasis/etiology , Double-Blind Method , Fat Emulsions, Intravenous , Female , Humans , Infant, Newborn , Liver Diseases/etiology , Male , Parenteral Nutrition/methods
16.
Clin Nutr ; 35(5): 1023-31, 2016 10.
Article in English | MEDLINE | ID: mdl-26561301

ABSTRACT

BACKGROUND & AIMS: Olive oil (OO), medium-chain triglycerides (MCT)/long-chain triglycerides (LCT) mixture and soybean oil (SO) lipid emulsions are currently used for preterm infants in China. The aim of our study was to compare the lipid profile, fatty acid composition, and antioxidant capacity of preterm infants administered OO, MCT/LCT, or SO lipid emulsions. METHODS: In this study, 156 preterm infants (birth weight < 2000 g and gestational age < 37 weeks) received parenteral nutrition (PN) containing OO, MCT/LCT, or SO lipid emulsions for a minimum of 14 d. On days 0, 7, and 14, the lipid profile, fatty acid composition and antioxidant capacity were analyzed. RESULTS: On day 7, HDL levels in the MCT/LCT group were significantly lower than in the OO (1.06 ± 0.40 mmol/L) or SO groups. LDL levels were higher in the OO group than in the MCT/LCT or SO groups on day 7. A-I/B was higher in MCT/LCT than in OO or SO groups. Myristic acid (C14:0) levels on days 7 and 14 increased in MCT/LCT compared to the OO and SO groups. The OO group had higher oleic acid (C18:1n9) levels than the two other groups. Linoleic acid (C18:2n6), linolenic acid (C18:3n3), and eicosapentaenoic acid (20:5n3) were significantly lower in the OO group than in MCT/LCT or SO groups. Monounsaturated fatty acid levels decreased, and ω-6 polyunsaturated fatty acid and essential fatty acids levels increased in MCT/LCT and SO groups. No significant differences were obtained in SOD, MDA, GSH-Px, and T-AOC among the groups. CONCLUSION: The three lipid emulsions were safe and well tolerated in preterm infants. Oleic acid (C18:1n9) levels increased and LA (C18:2n6), ALA (C18:3n3), and EPA (C20:5n23) levels decreased in OO compared to MCT/LCT or SO. CLINICAL TRIAL REGISTRATION NUMBER: NCT01683162, https://register.clinicaltrials.gov/.


Subject(s)
Fat Emulsions, Intravenous/chemistry , Infant, Premature/growth & development , Parenteral Nutrition , Antioxidants/administration & dosage , Antioxidants/analysis , China , Double-Blind Method , Eicosapentaenoic Acid/administration & dosage , Eicosapentaenoic Acid/analysis , Fat Emulsions, Intravenous/administration & dosage , Fatty Acids, Essential/administration & dosage , Fatty Acids, Essential/analysis , Fatty Acids, Omega-6/administration & dosage , Fatty Acids, Omega-6/analysis , Female , Humans , Infant, Newborn , Linoleic Acid/administration & dosage , Linoleic Acid/analysis , Male , Oleic Acid/administration & dosage , Oleic Acid/analysis , Olive Oil/administration & dosage , Olive Oil/chemistry , Soybean Oil/administration & dosage , Soybean Oil/chemistry , Triglycerides/administration & dosage , Triglycerides/analysis , alpha-Linolenic Acid/administration & dosage , alpha-Linolenic Acid/analysis
17.
Mol Neurobiol ; 50(3): 811-20, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24659348

ABSTRACT

Neuroinflammation is closely related to brain iron homeostasis. Our previous study demonstrated that lipopolysaccharides (LPS) can regulate expression of iron-regulatory peptide hepcidin; however, the mechanism is undefined. Here, we demonstrated that intracerebroventricular injection of LPS in rat brain upregulated hepcidin and downregulated ferroportin 1 in the cortex and substantia nigra. LPS increased hepcidin expression in neurons only when they were co-cultured with BV-2 microglia, and the upregulation was suppressed by IL-6 neutralizing antibody in vitro. In addition, IL-6 but not IL-1α, IL-1ß, or tumor necrosis factor-alpha increased hepcidin expression and signal transducer and activator of transcription 3 (STAT3) phosphorylation in cortical neurons and MES23.5 dopaminergic neurons. These effects were blocked by the STAT3 inhibitor, stattic. Our results show that neurons are the major source of increased hepcidin expression in response to LPS challenge but microglia play a key mediator role by releasing IL-6 and recruiting the STAT3 pathway. We conclude that LPS upregulates hepcidin expression in neurons via microglia and the IL-6/STAT3 signaling pathway.


Subject(s)
Hepcidins/metabolism , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Microglia/metabolism , Neurons/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Up-Regulation/drug effects , Animals , Cerebral Cortex/cytology , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Male , Microglia/cytology , Microglia/drug effects , Neurons/cytology , Neurons/drug effects , Phosphorylation/drug effects , Rats , Rats, Sprague-Dawley
18.
Neurobiol Aging ; 35(5): 1045-54, 2014 May.
Article in English | MEDLINE | ID: mdl-24332448

ABSTRACT

Huperzine A (HupA), a natural inhibitor of acetylcholinesterase derived from a plant, is a licensed anti-Alzheimer's disease (AD) drug in China and a nutraceutical in the United States. In addition to acting as an acetylcholinesterase inhibitor, HupA possesses neuroprotective properties. However, the relevant mechanism is unknown. Here, we showed that the neuroprotective effect of HupA was derived from a novel action on brain iron regulation. HupA treatment reduced insoluble and soluble beta amyloid levels, ameliorated amyloid plaques formation, and hyperphosphorylated tau in the cortex and hippocampus of APPswe/PS1dE9 transgenic AD mice. Also, HupA decreased beta amyloid oligomers and amyloid precursor protein levels, and increased A Disintegrin And Metalloprotease Domain 10 (ADAM10) expression in these treated AD mice. However, these beneficial effects of HupA were largely abolished by feeding the animals with a high iron diet. In parallel, we found that HupA decreased iron content in the brain and demonstrated that HupA also has a role to reduce the expression of transferrin-receptor 1 as well as the transferrin-bound iron uptake in cultured neurons. The findings implied that reducing iron in the brain is a novel mechanism of HupA in the treatment of Alzheimer's disease.


Subject(s)
Alkaloids/pharmacology , Alkaloids/therapeutic use , Alzheimer Disease/drug therapy , Brain/metabolism , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/therapeutic use , Iron/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Phytotherapy , Sesquiterpenes/pharmacology , Sesquiterpenes/therapeutic use , ADAM Proteins/metabolism , ADAM10 Protein , Alzheimer Disease/metabolism , Amyloid Precursor Protein Secretases/metabolism , Amyloid beta-Peptides/metabolism , Animals , Disease Models, Animal , Membrane Proteins/metabolism , Mice , Mice, Transgenic , Phosphorylation/drug effects , Plaque, Amyloid/drug therapy , Receptors, Transferrin/metabolism , tau Proteins/metabolism
19.
Zhonghua Gan Zang Bing Za Zhi ; 21(9): 668-73, 2013 Sep.
Article in Chinese | MEDLINE | ID: mdl-24160341

ABSTRACT

OBJECTIVE: To evaluate the influence of Fuzhenghuayu decoction on fibrotic liver tissue and activated hepatic stellate cells (HSCs) using a carbon tetrachloride (CCl4)-induced liver cirrhosis rat model system. METHODS: Sixty-four Sprague-Dawley rats were randomly divided into the following groups: normal (non-model, non-drug intervention), CCl4 liver fibrosis model, and CCl4 liver fibrosis model Fuzhenghuayu drug intervention at low dose (0.75 g/kg/d) and high dose (1.5 g/kg/d). The drug intervention was administered via oral-gastric irrigation once daily for 6 times per week over a 6-week period. Four rats from each group were sacrificed at the end of week 2, 4, and 6 for serum and liver tissue collection. Liver fibrosis was evaluated by histology, and expression of a-smooth muscle actin (a-SMA) was determined by immunohistochemistry. Liver function was assessed by measuring levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil). Between-group comparisons were made by completely random design and ANOVA with Bonferroni correction. RESULTS: At the end of weeks 2, 4 and 6, all four groups showed significantly different levels of ALT, AST, and TBil; in addition, the model group and drug intervention groups had significantly higher levels of ALT, AST, and TBil than the control group, the drug intervention groups showed significantly lower levels of ALT, AST, and TBil than the model group (P less than 0.01 or less than 0.05), and the differences between the low dose and high dose groups reached statistical significance (P less than 0.01 or less than 0.05). At the end of weeks 2, 4 and 6, the model group and drug intervention groups had significantly higher area ratio of liver fibrosis than the normal group (F = model: 18.68, low dose: 49.95, high dose: 82.44, P less than 0.01), but the two drug intervention groups had significantly less area ratio of liver fibrosis than the model group (P less than 0.05) and the high dose group showed the most robust decrease. In addition, the model group and drug intervention groups showed higher expression of a-SMA than the normal group (F = model: 18.68, low dose: 49.95, high dose: 82.44, P less than 0.01), but two drug intervention groups had significantly less a-SMA than the model group (F = model: 46.32, low dose: 40.30, high dose: 58.42, P less than 0.05) and the high dose group showed the most robust decrease. CONCLUSION: The Fuzhenghuayu decoction reduces the numbers of activated HSCs, thereby leading to down-regulated a-SMA expression and reduced degree of liver fibrosis; these effects may represent the mechanism by which this drug suppresses hepatic fibrosis.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Hepatic Stellate Cells/drug effects , Liver Cirrhosis, Experimental/pathology , Liver/drug effects , Actins/metabolism , Animals , Liver/pathology , Male , Rats , Rats, Sprague-Dawley
20.
Yao Xue Xue Bao ; 48(4): 560-5, 2013 Apr.
Article in Chinese | MEDLINE | ID: mdl-23833946

ABSTRACT

The aim of this paper is to compare the cytotoxicity and cellular uptake efficiency of three kinds of poly(b-benzyl-L-amino) block-poly(ethylene glycol) nanoparticles (PXA-PEG-NPs) using Calu-3 cells, and select one as a nasal drug delivery vector for curcumin (Cur). Poly(gamma-benzyl-L-glutamate) block-poly(ethylene glycol) nanoparticles (PBLG-PEG-NPs), poly(gamma-benzyl-L-lysine) block-poly(ethyleneglycol) nanoparticles (PZLL-PEG-NPs) and poly(gamma-benzyl-L-aspartate) block-poly(ethylene glycol) nanoparticles (PBLA-PEG-NPs) were prepared by emulsion-solvent evaporation method. MTT assays were used to evaluate the cytotoxicity of PXA-PEG-NPs against Calu-3 cells. The cellular uptake of nanoparticles was visualized by an inverted fluorescence microscope and quantified by a flow cytometer. The results indicated that even at high concentration of 2 mg x mL(-1) the three nanoparticles had no cytotoxicity on Calu-3 cells. Compared to the curcumin solution, the three curcumin-loaded PXA-PEG-NPs showed significantly higher cellular uptake efficiency on Calu-3 cells (at equal concentration of curcumin with 5 microg x mL(-1) Cur solution), PBLG-PEG-NPs group was the highest. The cellular uptake increased with incubation time, and has positive correlation with nanoparticle concentration. In brief, PXA-PEG-NPs are conducive to delivery Cur into cells, and PBLG-PEG-NPs might be provided as a good nasal drug delivery carrier.


Subject(s)
Curcumin/administration & dosage , Curcumin/metabolism , Drug Carriers , Polyethylene Glycols/chemistry , Polyglutamic Acid/analogs & derivatives , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Administration, Intranasal , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Aspartic Acid/chemistry , Aspartic Acid/toxicity , Cell Line, Tumor , Cell Survival/drug effects , Ethylene Glycol/chemistry , Ethylene Glycol/toxicity , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lysine/chemistry , Lysine/toxicity , Nanoparticles , Particle Size , Polyethylene Glycols/toxicity , Polyglutamic Acid/chemistry , Polyglutamic Acid/toxicity
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