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1.
BMJ Open ; 14(6): e083399, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951000

ABSTRACT

INTRODUCTION: Milk fat globule membrane (MFGM) is a complex lipid-protein structure in mammalian milk and human milk that is largely absent from breastmilk substitutes. The objective of this trial is to investigate whether providing infant formula enriched with MFGM versus standard infant formula improves cognitive development at 12 months of age in exclusively formula-fed full-term infants. METHODS AND ANALYSIS: This is a randomised, controlled, clinician-blinded, researcher-blinded and participant-blinded trial of two parallel formula-fed groups and a breastfed reference group that were recruited in the suburban Adelaide (Australia) community by a single study centre (a medical research institute). Healthy, exclusively formula-fed, singleton, term-born infants under 8 weeks of age were randomised to either an MFGM-supplemented formula (intervention) or standard infant formula (control) from enrolment until 12 months of age. The reference group was not provided with formula. The primary outcome is the Cognitive Scale of the Bayley Scales of Infant Development, Fourth Edition (Bayley-IV) at 12 months. Secondary outcomes are the Bayley-IV Cognitive Scale at 24 months, other Bayley-IV domains (language, motor, emotional and behavioural development) at 12 and 24 months of age, infant attention at 4 and 9 months of age, parent-rated language at 12 and 24 months of age, parent-rated development at 6 and 18 months of age as well as growth, tolerance and safety of the study formula. To ensure at least 80% power to detect a 5-point difference in the mean Bayley-IV cognitive score, >200 infants were recruited in each group. ETHICS AND DISSEMINATION: The Women's and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/19/WCHN/140). Caregivers gave written informed consent prior to enrolling in the trial. Findings of this study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12620000552987; Australian and New Zealand Clinical Trial Registry: anzctr.org.au.


Subject(s)
Child Development , Cognition , Glycolipids , Glycoproteins , Infant Formula , Lipid Droplets , Humans , Glycolipids/administration & dosage , Infant Formula/chemistry , Glycoproteins/administration & dosage , Cognition/drug effects , Infant , Female , Infant, Newborn , Male , Randomized Controlled Trials as Topic , Dietary Supplements , Breast Feeding , Milk, Human/chemistry
2.
J Nutr Sci Vitaminol (Tokyo) ; 70(3): 273-279, 2024.
Article in English | MEDLINE | ID: mdl-38945893

ABSTRACT

The purpose of this study was to examine whether 4 wk of daily ingestion of milk fat globule membrane (MFGM) combined with exercise training improves physical performance-muscle strength, agility and muscle power-in healthy young adults. The study was designed as a randomized, double-blind, and placebo-controlled trial. Twenty healthy young adults received either an MFGM powder containing 1.6 g of fat and 160 mg of sphingomyelin or an isocaloric placebo powder daily throughout 4 wk of power or agility training. Physical performance tests and body composition measurements were conducted before and after the 4-wk intervention. Ingestion of MFGM did not affect isometric or isokinetic muscle strength, but it was associated with a greater increase in vertical jump peak power compared with placebo. There were no significant changes in body weight or lean body mass during the intervention period in either group, and no significant differences between groups. We conclude that daily MFGM supplementation combined with exercise training has the potential to improve physical performance in young adults; however, further studies with larger sample sizes should be conducted to obtain more evidence supporting achievement of improved physical performance through MFGM supplementation.


Subject(s)
Body Composition , Dietary Supplements , Exercise , Glycolipids , Glycoproteins , Lipid Droplets , Muscle Strength , Humans , Double-Blind Method , Glycolipids/administration & dosage , Glycolipids/pharmacology , Glycoproteins/administration & dosage , Male , Young Adult , Female , Muscle Strength/drug effects , Exercise/physiology , Pilot Projects , Adult , Physical Functional Performance , Body Weight , Sphingomyelins/administration & dosage , Muscle, Skeletal/physiology , Muscle, Skeletal/drug effects
3.
Biochem Biophys Res Commun ; 725: 150260, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-38878760

ABSTRACT

This study introduces an innovative brain-targeted drug delivery system, RVG-Exo/CBD, utilizing rabies virus glycoprotein (RVG)-engineered exosomes for encapsulating cannabidiol (CBD). The novel delivery system was meticulously characterized, confirming the maintenance of exosomal integrity, size, and successful drug encapsulation with a high drug loading rate of 83.0 %. Evaluation of the RVG-Exo/CBD's brain-targeting capability demonstrated superior distribution and retention in brain tissue compared to unmodified exosomes, primarily validated through in vivo fluorescence imaging. The efficacy of this delivery system was assessed using a behavioral sensitization model in mice, where RVG-Exo/CBD notably suppressed methamphetamine-induced hyperactivity more effectively than CBD alone, indicating a reduction in effective dose and enhanced bioavailability. Overall, the RVG-Exo/CBD system emerges as a promising strategy for enhancing the therapeutic efficacy and safety of CBD, particularly for neurological applications, highlighting its potential for addressing the limitations associated with traditional CBD administration in clinical settings.


Subject(s)
Brain , Cannabidiol , Cannabidiol/administration & dosage , Cannabidiol/chemistry , Cannabidiol/pharmacology , Animals , Brain/metabolism , Brain/drug effects , Mice , Male , Glycoproteins/chemistry , Glycoproteins/metabolism , Glycoproteins/administration & dosage , Drug Delivery Systems/methods , Peptide Fragments , Viral Proteins
4.
Nat Commun ; 15(1): 5310, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38906867

ABSTRACT

Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV, developing vaccines targeting key entry glycoproteins to elicit robust and durable adaptive immune responses may provide better protection. EBV gHgL-, gB- and gp42-specific antibodies in healthy EBV carriers contributed to sera neutralizing abilities in vitro, indicating that they are potential antigen candidates. To enhance the immunogenicity of these antigens, we formulate three nanovaccines by co-delivering molecular adjuvants (CpG and MPLA) and antigens (gHgL, gB or gp42). These nanovaccines induce robust humoral and cellular responses through efficient activation of dendritic cells and germinal center response. Importantly, these nanovaccines generate high levels of neutralizing antibodies recognizing vulnerable sites of all three antigens. IgGs induced by a cocktail vaccine containing three nanovaccines confer superior protection from lethal EBV challenge in female humanized mice compared to IgG elicited by individual NP-gHgL, NP-gB and NP-gp42. Importantly, serum antibodies elicited by cocktail nanovaccine immunization confer durable protection against EBV-associated lymphoma. Overall, the cocktail nanovaccine shows robust immunogenicity and is a promising candidate for further clinical trials.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Epstein-Barr Virus Infections , Glycoproteins , Herpesvirus 4, Human , Animals , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/prevention & control , Epstein-Barr Virus Infections/virology , Antibodies, Neutralizing/immunology , Herpesvirus 4, Human/immunology , Humans , Female , Mice , Antibodies, Viral/immunology , Antibodies, Viral/blood , Glycoproteins/immunology , Glycoproteins/administration & dosage , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Adjuvants, Immunologic/administration & dosage , Lymphoma/immunology , Lymphoma/virology , Nanovaccines
5.
BMC Pulm Med ; 24(1): 283, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886709

ABSTRACT

OBJECTIVE: This comparative analysis aimed to investigate the efficacy of Sivelestat Sodium Hydrate (SSH) combined with Ulinastatin (UTI) in the treatment of sepsis with acute respiratory distress syndrome (ARDS). METHODS: A control group and an observation group were formed with eighty-four cases of patients with sepsis with ARDS, with 42 cases in each group. The control group was intravenously injected with UTI based on conventional treatment, and the observation group was injected with SSH based on the control group. Both groups were treated continuously for 7 days, and the treatment outcomes and efficacy of both groups were observed. The Murray Lung Injury Score (MLIS), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) were compared. Changes in respiratory function, inflammatory factors, and oxidative stress indicators were assessed. The occurrence of adverse drug reactions was recorded. RESULTS: The total effective rate in the observation group (95.24%) was higher than that in the control group (80.95%) (P < 0.05). The mechanical ventilation time, intensive care unit (ICU) hospitalization time, and duration of antimicrobial medication in the observation group were shorter and multiple organ dysfunction syndrome incidence was lower than those in the control group (P < 0.05). The mortality rate of patients in the observation group (35.71%) was lower than that in the control group (52.38%), but there was no statistically significant difference between the two groups (P > 0.05). MLIS, SOFA, and APACHE II scores in the observation group were lower than the control group (P < 0.05). After treatment, respiratory function, inflammation, and oxidative stress were improved in the observation group (P < 0.05). Adverse reactions were not significantly different between the two groups (P > 0.05). CONCLUSION: The combination of SSH plus UTI improves lung injury and pulmonary ventilation function, and reduces inflammation and oxidative stress in patients with sepsis and ARDS.


Subject(s)
Drug Therapy, Combination , Glycine , Glycoproteins , Respiratory Distress Syndrome , Sepsis , Sulfonamides , Humans , Male , Sepsis/drug therapy , Sepsis/complications , Respiratory Distress Syndrome/drug therapy , Female , Middle Aged , Glycoproteins/administration & dosage , Glycoproteins/therapeutic use , Aged , Glycine/analogs & derivatives , Glycine/therapeutic use , Glycine/administration & dosage , Sulfonamides/administration & dosage , Sulfonamides/therapeutic use , Treatment Outcome , Respiration, Artificial , APACHE , Adult , Multiple Organ Failure/etiology , Multiple Organ Failure/drug therapy , Oxidative Stress/drug effects , Organ Dysfunction Scores , Intensive Care Units , Trypsin Inhibitors/administration & dosage , Trypsin Inhibitors/therapeutic use
6.
Immun Inflamm Dis ; 11(4): e822, 2023 04.
Article in English | MEDLINE | ID: mdl-37102655

ABSTRACT

INTRODUCTION: This study determined the therapeutic effect of ulinastatin (UTI) on unliquefied pyogenic liver abscesses complicated by septic shock (UPLA-SS). METHODS: This was a randomized controlled trial involving patients with UPLA-SS who underwent treatment at our hospital between March 2018 and March 2022. The patients were randomly divided into control (n = 51) and study groups (n = 48). Both groups received routine treatment, but the study group received UTI (200,000 units q8h for >3 days). Differences in liver function, inflammatory indices, and effectiveness between the two groups were recorded. RESULTS: Following treatment, the white blood cell count, and lactate, C-reactive protein, procalcitonin, tumor necrosis factor-α, and interleukin-6 levels were significantly decreased in all patients compared to the admission values (p < .05). The study group had a faster decline with respect to the above indices compared to the control group (p < .05). The study group length of intensive care unit stay, fever duration, and vasoactive drug maintenance time were all significantly shorter than the control group (p < .05). The total bilirubin, alanine aminotransferase, and aspartate aminotransferase levels were significantly lower in the study and control groups after treatment compared to before treatment (p < .05); however, the study group had a faster recovery of liver function than the control group (p < .05). The overall mortality rate was 14.14% (14/99); 10.41% of the study group patients died and 17.65% of the control group patients died, but there was no statistically significant difference between the two groups (p > .05). CONCLUSION: UTI combined with conventional treatment significantly controlled the infection symptoms, improved organ function, and shortened the treatment time in patients with UPLA-SS.


Subject(s)
Glycoproteins , Liver Abscess, Pyogenic , Shock, Septic , Trypsin Inhibitors , Humans , Liver Abscess, Pyogenic/blood , Liver Abscess, Pyogenic/complications , Liver Abscess, Pyogenic/drug therapy , Glycoproteins/administration & dosage , Trypsin Inhibitors/administration & dosage , Shock, Septic/drug therapy , Shock, Septic/microbiology , Shock, Septic/parasitology , Male , Female , Middle Aged , Anti-Bacterial Agents/administration & dosage
7.
Mol Nutr Food Res ; 66(22): e2200177, 2022 11.
Article in English | MEDLINE | ID: mdl-36068654

ABSTRACT

SCOPE: Milk fat globule membrane (MFGM) is an essential component of milk. Bovine MFGM (bMFGM) has been shown to support cognitive development and increase relative concentrations of serum phospholipids. This study investigates bioavailability of bMFGM components after oral administration in two preclinical models to explore whether dietary bMFGM induces parallel changes to plasma and brain lipidomes. METHODS AND RESULTS: Transgenic APOE*3.Leiden mice (n = 18 per group) and Sprague-Dawley rats (n = 12 per group) are fed bMFGM-enriched (MFGM+) or Control diet, followed by phospholipid profile-determination in plasma, hippocampus, and prefrontal cortex tissue by targeted mass spectrometry. Multivariate analysis of lipidomic profiles demonstrates a separation between MFGM+ and Control plasma across rodents. In plasma, sphingomyelins contributed the most to the separation of lipid patterns among both models, where three sphingomyelins (d18:1/14:0, d18:1/23:0, d18:1/23:1[9Z]) are consistently higher in the circulation of MFGM+ groups. A similar trend is observed in rat prefrontal cortex, although no significant separation of the brain lipidome is demonstrated. CONCLUSION: bMFGM-enriched diet alters plasma phospholipid composition in rodents, predominantly increasing sphingomyelin levels in the systemic circulation with similar, but non-significant, trends in central brain regions. These changes may contribute to the beneficial effects of bMFGM on neurodevelopment during early life.


Subject(s)
Dietary Supplements , Glycolipids , Glycoproteins , Lipid Droplets , Lipidomics , Animals , Mice , Rats , Brain , Lipid Droplets/chemistry , Phospholipids/pharmacology , Rats, Sprague-Dawley , Sphingomyelins/pharmacology , Glycoproteins/administration & dosage , Glycolipids/administration & dosage
8.
Am J Respir Cell Mol Biol ; 67(3): 320-333, 2022 09.
Article in English | MEDLINE | ID: mdl-35696344

ABSTRACT

As shown in our previous studies, the intratracheal-administration of STC1 (stanniocalcin-1) ameliorates pulmonary fibrosis by reducing oxidative and endoplasmic reticulum stress through the uncoupling of respiration in a bleomycin-treated mouse model. However, the overall effect of STC1 on metabolism was not examined. Therefore, we first conducted a comprehensive metabolomics analysis to screen the overall metabolic changes induced by STC1 in an alveolar epithelial cell line using capillary electrophoresis time-of-flight mass spectrometry. The results were subsequently validated in multiple alveolar epithelial and fibroblast cell lines by performing precise analyses of each substance. STC1 stimulated glycolysis, acetyl-CoA synthesis, and the methionine and cysteine-glutathione pathways, which are closely related to the uncoupling of respiration, modulation of epigenetics, and reduction in oxidative stress. These results are consistent with our previous study. Subsequently, we focused on the inhibitory factor SMAD7, which exerts an antifibrotic effect and is susceptible to epigenetic regulation. STC1 upregulates SMAD7 in an uncoupling protein 2-dependent manner, induces demethylation of the SMAD7 promoter region and acetylation of the SMAD7 protein in human alveolar epithelial and fibroblast cell lines and a bleomycin-treated mouse model, and subsequently attenuates fibrosis. The antifibrotic effects of STC1 may partially depend on the regulation of SMAD7. In the evaluation using lung tissue from patients with idiopathic pulmonary fibrosis, SMAD7 expression and acetylation were high in the alveolar structure-preserving region and low in the fibrotic region. The intratracheal administration of STC1 may prevent the development of pulmonary fibrosis by regulating the metabolism-mediated epigenetic modification of SMAD7 in patients.


Subject(s)
Epigenesis, Genetic , Glycoproteins , Idiopathic Pulmonary Fibrosis , Smad7 Protein , Animals , Bleomycin , Disease Models, Animal , Glycoproteins/administration & dosage , Glycoproteins/therapeutic use , Humans , Idiopathic Pulmonary Fibrosis/genetics , Idiopathic Pulmonary Fibrosis/therapy , Mice , Smad7 Protein/genetics
9.
J Cell Mol Med ; 26(11): 3153-3168, 2022 06.
Article in English | MEDLINE | ID: mdl-35322540

ABSTRACT

Autologous adipose tissue is an ideal soft tissue filling material, and its biocompatibility is better than that of artificial tissue substitutes, foreign bodies and heterogeneous materials. Although autologous fat transplantation has many advantages, the low retention rate of adipose tissue limits its clinical application. Here, we identified a secretory glycoprotein, leucine-rich-alpha-2-glycoprotein 1 (LRG-1), that could promote fat graft survival through RAB31-mediated inhibition of hypoxia-induced apoptosis. We showed that LRG-1 injection significantly increased the maintenance of fat volume and weight compared with the control. In addition, higher fat integrity, more viable adipocytes and fewer apoptotic cells were observed in the LRG-1-treated groups. Furthermore, we discovered that LRG-1 could reduce the ADSC apoptosis induced by hypoxic conditions. The mechanism underlying the LRG-1-mediated suppression of the ADSC apoptosis induced by hypoxia was mediated by the upregulation of RAB31 expression. Using LRG-1 for fat grafts may prove to be clinically successful for increasing the retention rate of transplanted fat.


Subject(s)
Adipose Tissue , Apoptosis , Biocompatible Materials , Glycoproteins , Graft Survival , rab GTP-Binding Proteins , Adipose Tissue/transplantation , Apoptosis/drug effects , Glycoproteins/administration & dosage , Glycoproteins/pharmacology , Graft Survival/drug effects , Graft Survival/physiology , Humans , Hypoxia/pathology , Injections, Subcutaneous , Transplantation, Autologous , rab GTP-Binding Proteins/metabolism
10.
Nutrition ; 97: 111599, 2022 05.
Article in English | MEDLINE | ID: mdl-35193081

ABSTRACT

OBJECTIVE: The aim of this study was to assess the effects of an experimental formula (EF) with added whey protein-lipid concentrate (5 g/L; source of bovine milk fat globule membrane [bMFGM]) on growth, body composition, and safety through 24 mo of age in term infants. METHODS: This was a double-blinded, randomized controlled trial conducted in Santiago, Chile. Infants were enrolled before 120 d and randomized to receive standard cow's milk-based formula (SF) or EF through the first year of life. Breastfed infants were the reference (HM). Growth (weight-for-age [WAZ], length-for-age [LAZ], BMI-for-age [BAZ], headcircumference-for-age [HCZ] z-scores); body composition (fat mass [FM] and fat-free mass, percentage body fat [%BF]); and adverse events through day 730 were recorded. Outcome trajectories were analyzed using a single generalized estimating equation testing the interaction between group and visit. RESULTS: We recruited 582 infants (HM = 235; SF = 174; EF = 173); 478 (>80%) completed the study. At baseline, only WAZ was different between the formula groups (0.14 lower in EF versus SF group, P = 0.035). WAZ, LAZ, and BAZ trajectories were higher from baseline to days 365 and 730 in EF or SF compared with HM (all P < 0.05). No differences in changes in body composition were observed between the formula groups. For EF versus HM, %BF was lower at day 180; however, this difference reversed from day 365. Fat-free mass was higher in formula groups compared with HM at all time points. No group difference in adverse event incidence rate was detected. CONCLUSION: During the first 2 y of life, infant formula with added bMFGM supports typical growth and safety compared with a standard formula.


Subject(s)
Glycoproteins , Infant Formula , Lipid Droplets , Whey Proteins , Animals , Body Composition , Breast Feeding , Cattle , Child Development , Child, Preschool , Female , Glycolipids , Glycoproteins/administration & dosage , Humans , Infant , Whey Proteins/administration & dosage
11.
Biomed Res Int ; 2022: 2621732, 2022.
Article in English | MEDLINE | ID: mdl-35047630

ABSTRACT

OBJECTIVE: This study is aimed at exploring the effect of ulinastatin combined with Xingnaojing injection on severe traumatic craniocerebral injury and its influence on oxidative stress response and inflammatory response in patients. METHODS: A total of 100 patients with severe traumatic craniocerebral injury admitted to our hospital from January 2018 to January 2020 were selected and equally assigned into a study group (50 cases) and a control group (50 cases) according to a random sampling method. Patients in study group received treatment of ulinastatin combined with Xingnaojing injection, while those in control group were treated with ulinastatin only. The study compared the two groups on the oxidative stress response, inflammatory response, the therapeutic effect, and the incidence rate of adverse reactions. RESULTS: It is observed that patients in study group obtained lower levels of free cortisol (FC) and norepinephrine (NE) in the serum and higher level of total thyroxine (TT4) after treatment compared with those in control group with significant difference (P < 0.05); in the meantime, they were examined to have significantly fewer oxidative stress response products, lower serum inflammatory factor level, and serum indicator levels of craniocerebral injury as opposed to those in control group, suggesting significant differences (P < 0.05); study group demonstrated higher treatment response rate and lower incidence rate of adverse reactions compared with control group with a significant difference (P < 0.05). CONCLUSION: The study found that ulinastatin combined with Xingnaojing infection has a significant effect in the treatment of severe traumatic craniocerebral injury, which can reduce the degree of craniocerebral injury and the level of inflammatory factors in the serum of patients. It is worthy of being promoted and applied clinically.


Subject(s)
Craniocerebral Trauma , Drugs, Chinese Herbal/administration & dosage , Glycoproteins/administration & dosage , Oxidative Stress/drug effects , Aged , Craniocerebral Trauma/blood , Craniocerebral Trauma/drug therapy , Craniocerebral Trauma/epidemiology , Female , Humans , Inflammation/blood , Inflammation/drug therapy , Inflammation/epidemiology , Male , Middle Aged
12.
J Extracell Vesicles ; 11(1): e12185, 2022 01.
Article in English | MEDLINE | ID: mdl-35029057

ABSTRACT

Major depressive disorder (MDD) is the most prevalent psychiatric disorder worldwide and severely limits psychosocial function and quality of life, but no effective medication is currently available. Circular RNAs (circRNAs) have been revealed to participate in the MDD pathological process. Targeted delivery of circRNAs without blood-brain barrier (BBB) restriction for remission of MDD represents a promising approach for antidepressant therapy. In this study, RVG-circDYM-extracellular vesicles (RVG-circDYM-EVs) were engineered to target and preferentially transfer circDYM to the brain, and the effect on the pathological process in a chronic unpredictable stress (CUS) mouse model of depression was investigated. The results showed that RVG-circDYM-EVs were successfully purified by ultracentrifugation from overexpressed circDYM HEK 293T cells, and the characterization of RVG-circDYM-EVs was successfully demonstrated in terms of size, morphology and specific markers. Beyond demonstrating proof-of-concept for an RNA drug delivery technology, we observed that systemic administration of RVG-circDYM-EVs efficiently delivered circDYM to the brain, and alleviated CUS-induced depressive-like behaviours, and we discovered that RVG-circDYM-EVs notably inhibited microglial activation, BBB leakiness and peripheral immune cells infiltration, and attenuated astrocyte disfunction induced by CUS. CircDYM can bind mechanistically to the transcription factor TAF1 (TATA-box binding protein associated factor 1), resulting in the decreased expression of its downstream target genes with consequently suppressed neuroinflammation. Taken together, our findings suggest that extracellular vesicle-mediated delivery of circDYM is effective for MDD treatment and promising for clinical applications.


Subject(s)
Depressive Disorder, Major/drug therapy , Extracellular Vesicles/metabolism , RNA, Circular/administration & dosage , Animals , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Brain/drug effects , Brain/metabolism , Brain/physiopathology , Depressive Disorder, Major/metabolism , Depressive Disorder, Major/physiopathology , Disease Models, Animal , Glycoproteins/administration & dosage , Glycoproteins/genetics , Glycoproteins/metabolism , HEK293 Cells , Histone Acetyltransferases/genetics , Humans , Inflammation , Mice , Microglia/drug effects , Microglia/metabolism , Peptide Fragments/administration & dosage , Peptide Fragments/genetics , Peptide Fragments/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , Recovery of Function/drug effects , TATA-Binding Protein Associated Factors/genetics , Transcription Factor TFIID/genetics , Viral Proteins/administration & dosage , Viral Proteins/genetics , Viral Proteins/metabolism
13.
Vet Comp Orthop Traumatol ; 35(2): 90-95, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34598303

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the functional, systemic, synovial and articular changes after intra-articular administration of a synthetic lubricin within healthy canine stifles. STUDY DESIGN: A prospective randomized blinded placebo-controlled study composed of 10 dogs equally divided into either a treatment group (intra-articular synthetic lubricin injection, n = 5) or control group (saline, n = 5). Clinical (orthopaedic examination, gait observation, gait analysis), biochemical (complete blood count and biochemistry profile) and local tissue outcomes (joint fluid analysis, joint capsule and articular cartilage histopathology) were evaluated over a time period of 3 months. RESULTS: No significant differences between the treatment group and control group were identified with regard to baseline patient parameters. No clinically significant orthopaedic examination abnormalities, gait abnormalities, biochemical alterations, joint fluid alterations or histopathological alterations were identified over the course of the study. CONCLUSION: The synthetic lubricin studied herein is both biocompatible and safe for a single administration within the canine stifle joint. Further research is necessary to evaluate the clinical efficacy of the synthetic lubricin in canine osteoarthritic joints.


Subject(s)
Glycoproteins , Stifle , Animals , Dogs , Glycoproteins/administration & dosage , Injections, Intra-Articular/veterinary , Prospective Studies
14.
Nutrients ; 13(12)2021 Dec 18.
Article in English | MEDLINE | ID: mdl-34960093

ABSTRACT

Inclusion of bovine-derived milk fat globule membrane (bMFGM) or bMFGM components in infant formulas (IFs) may support healthy brain development. This double-blind, prospective trial evaluated growth, tolerance, and iron status in infants receiving added bMFGM and modified protein, iron, and arachidonic acid (ARA) concentrations in IF. Healthy term infants were randomized to: control (marketed, routine cow's milk-based IF/100 kcal: 2.1 g protein, 1.8 mg iron, 34 mg ARA) or INV-MFGM (investigational cow's milk-based IF/100 kcal: 1.9 g protein, 1.2 mg iron, 25 mg ARA and whey protein-lipid concentrate, 5 g/L (source of bMFGM)). Anthropometrics, stool characteristics, fussiness, and gassiness through day 365 and blood markers of iron status at day 365 were evaluated. The primary outcome was rate of weight gain from 14-120 days of age. Of 373 infants enrolled (control: 191, INV-MFGM: 182), 275 completed the study (control: 141; INV-MFGM: 134). No group differences in growth rate (g/day) from day 14-120 or study discontinuation were detected. Few group differences in growth or parent-reported fussiness, gassiness, or stool characteristics were detected. No group differences were detected in hemoglobin, hematocrit, or incidence of anemia. In healthy term infants, bMFGM and modified protein, iron, and ARA concentrations in a cow's milk-based IF were well-tolerated, associated with adequate growth throughout the first year of life, and supported normal iron status at one year of age.


Subject(s)
Child Development/physiology , Food, Fortified , Glycolipids/administration & dosage , Glycoproteins/administration & dosage , Infant Formula , Infant Nutritional Physiological Phenomena , Iron, Dietary/administration & dosage , Iron/metabolism , Age Factors , Female , Humans , Infant , Infant, Newborn , Lipid Droplets , Male
15.
Nutrients ; 13(12)2021 Nov 26.
Article in English | MEDLINE | ID: mdl-34959820

ABSTRACT

Brown adipose tissue (BAT) activation is associated with increased energy expenditure by inducing non-shivering thermogenesis. The ingestion of a milk fat globule membrane (MFGM) supplement and a high calorie diet are reported gateways into BAT activation. However, little is known about the effect of the MFGM and high calorie diets on BAT volume. To gain insight into this, mice were maintained on a high-fat (HF) or low-fat (LF) diet in conjunction with either full-cream (FC) or skim bovine dairy milk (BDM). After being maintained on their respective diets for 13 weeks, their body composition, including BAT volume, was measured using X-ray microtomography. A high calorie diet resulted in an increase in the BAT volume and mice consuming an HF diet in conjunction with FC BDM had a significantly greater BAT volume than all the other groups. Conversely, mice consuming an HF diet in addition to skim milk had a lower BAT volume compared to the HF control. The data presented suggest that the consumption of a high calorie diet in conjunction with FC BDM increases the BAT volume in wild-type mice. This study may provide valuable insight into future studies investigating BAT volume and BAT activity in relation to environmental factors, including diet.


Subject(s)
Adipose Tissue, Brown/drug effects , Body Composition/drug effects , Eating/drug effects , Glycolipids/administration & dosage , Glycoproteins/administration & dosage , Milk/chemistry , Animals , Cattle , Diet, Fat-Restricted/methods , Diet, High-Fat/methods , Lipid Droplets , Lipids/administration & dosage , Mice , Thermogenesis/drug effects
16.
Oxid Med Cell Longev ; 2021: 2801263, 2021.
Article in English | MEDLINE | ID: mdl-34925690

ABSTRACT

BACKGROUND: The disruption of the blood brain barrier (BBB) is the key factor leading to neurological impairment after intracerebral hemorrhage (ICH) injury. Adiponectin receptor 1 (AdipoR1) has an important effect contributing to the integrity of BBB. As a homologue of adiponectin, recombinant C1q/TNF-related protein 9 (rCTRP9) has neuroprotective effect in cerebrovascular diseases. The aim of this study was to investigate the protective effect of AdipoR1 activation with rCTRP9 on BBB integrity after ICH injury and the potential mechanisms. METHODS: 177 male mice were subjected in this study. ICH was induced by injecting collagenase into the right basal ganglia. rCTRP9 was treated intranasally at 1 hour after ICH. Selective siRNA was administered prior to ICH. Western blot, immunofluorescence staining, neurobehavioral tests, and BBB permeability were evaluated. RESULTS: ICH increased the expression of endogenous AdipoR1 and CTRP9. Administration of rCTRP9 ameliorated neurological deficits and reduced the BBB permeability at 24 hours in ICH mice. Furthermore, rCTRP9 promoted the expression of AdipoR1, APPL1, p-AMPK, Nrf2, and tight junctional proteins. The intervention of specific siRNA of AdipoR1, APPL1, and p-AMPK reversed the protective effects of rCTRP9. CONCLUSIONS: Activation of AdipoR1 with rCTRP9 improved neurological functions and preserved BBB integrity through the APPL1/AMPK/Nrf2 signaling pathway in ICH mice. Therefore, CTRP9 could serve as a promising therapeutic method to alleviate BBB injury following ICH in patients.


Subject(s)
Adiponectin/administration & dosage , Blood-Brain Barrier/drug effects , Cerebral Hemorrhage/prevention & control , Gene Expression Regulation/drug effects , Glycoproteins/administration & dosage , Neuroprotective Agents/administration & dosage , Receptors, Adiponectin/agonists , Recombinant Proteins/administration & dosage , AMP-Activated Protein Kinase Kinases/genetics , AMP-Activated Protein Kinase Kinases/metabolism , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Animals , Blood-Brain Barrier/metabolism , Cell Membrane Permeability , Cerebral Hemorrhage/etiology , Cerebral Hemorrhage/pathology , Male , Mice , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Signal Transduction
17.
Nutrients ; 13(10)2021 Sep 28.
Article in English | MEDLINE | ID: mdl-34684428

ABSTRACT

The nutritional requirements of preterm infants are challenging to meet in neonatal care, yet crucial for their growth, development and health. Aberrant maturation of the gastrointestinal tract and the microbiota could affect the digestion of human milk and its nutritional value considerably. Therefore, the main objective of the proposed research is to investigate how the intestinal microbiota of preterm and full-term infants differ in their ability to extract energy and nutrients from oligosaccharides and glycoproteins in human milk. This pilot study will be an observational, single-center study performed at the Neonatal Intensive Care Unit at Isala Women and Children's Hospital (Zwolle, The Netherlands). A cohort of thirty mother-infant pairs (preterm ≤30 weeks of gestation, n = 15; full-term 37-42 weeks of gestation, n = 15) will be followed during the first six postnatal weeks with follow-up at three- and six-months postnatal age. We will collect human milk of all mothers, gastric aspirates of preterm infants and fecal samples of all infants. A combination of 16S rRNA amplicon sequencing, proteomics, peptidomics, carbohydrate analysis and calorimetric measurements will be performed. The role of the microbiota in infant growth and development is often overlooked yet offers opportunities to advance neonatal care. The 'From Mum to Bum' study is the first study in which the effect of a preterm gut microbiota composition on its metabolic capacity and subsequent infant growth and development is investigated. By collecting human milk of all mothers, gastric aspirates of preterm infants and fecal samples of all infants at each timepoint, we can follow digestion of human milk from the breast of the mother throughout the gastrointestinal tract of the infant, or 'From Mum to Bum'.


Subject(s)
Clinical Protocols , Digestion , Glycoproteins , Infant, Premature , Milk Proteins , Milk, Human , Oligosaccharides , Female , Gastrointestinal Microbiome , Glycoproteins/administration & dosage , Humans , Infant , Infant Formula , Infant Nutritional Physiological Phenomena , Infant, Newborn , Milk Proteins/administration & dosage , Milk, Human/chemistry , Oligosaccharides/chemistry , Proteome , Proteomics/methods , Research Design
18.
Clin Neurol Neurosurg ; 210: 106981, 2021 11.
Article in English | MEDLINE | ID: mdl-34700272

ABSTRACT

OBJECTIVE: This study aimed to discuss the influence of nimodipine+ulinastatin on the neurological function and inflammatory reaction in patients with cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). METHODS: Overall, 90 patients with CVS after SAH who were admitted to our hospital were enrolled in this study and randomly divided into research and control groups (n = 45 for both groups). On the basis of conventional therapy, patients in the control group were injected with ulinastatin and those in the research group were injected with ulinastatin+nimodipine through an intravenous drip for 7 days with the others the same as those of the control group. RESULTS: Blood flow velocity in all cerebral arteries was lower in the research group than in the control group after treatment (P < 0.05). Calcitonin gene-related peptide and nitric oxide levels were higher in the research group than in the control group after treatment (P < 0.05). Endothelin levels were lower in the research group than in the control group (P < 0.05). The total effective rate was higher in the research group than in the control group (P < 0.05). Glasgow Coma Scale scores were higher in the research group than in the control group (P < 0.05). CONCLUSION: The drug combination of nimodipine and ulinastatin improved blood flow and neurological function in patients with CVS after SAH and enhanced the therapeutic efficacy; the underlying mechanism may be associated with the regulation of vascular endothelial dilatation function and the inhibition of relevant inflammatory factors' expression.


Subject(s)
Glycoproteins/therapeutic use , Nimodipine/therapeutic use , Subarachnoid Hemorrhage/complications , Trypsin Inhibitors/therapeutic use , Vasodilator Agents/therapeutic use , Vasospasm, Intracranial/drug therapy , Adult , Blood Flow Velocity/drug effects , Cerebral Arteries/drug effects , Cerebral Arteries/physiopathology , Drug Therapy, Combination , Female , Glycoproteins/administration & dosage , Humans , Male , Middle Aged , Nimodipine/administration & dosage , Subarachnoid Hemorrhage/physiopathology , Treatment Outcome , Trypsin Inhibitors/administration & dosage , Vasodilator Agents/administration & dosage , Vasospasm, Intracranial/etiology , Vasospasm, Intracranial/physiopathology
19.
Medicine (Baltimore) ; 100(38): e27151, 2021 Sep 24.
Article in English | MEDLINE | ID: mdl-34559104

ABSTRACT

PURPOSE: This study aimed to assess the efficacy of traditional Chinese medicine (TCM) in septic patients treated with ulinastatin. METHODS: PubMed, EmBase, and the Cochrane library were searched up to January 2021 to identify randomized controlled trials. The weight mean difference (WMD) and relative risk (RR) with 95% confidence intervals were used with the random-effects model. RESULTS: Twenty-three randomized controlled trials with 1903 septic patients were included. TCM significantly reduced the APACHE II score (WMD: -5.18; P < .001), interleukin-6 (WMD: -63.00; P < .001), tumor necrosis factor-α (WMD: -8.86; P < .001), c-reactive protein (WMD: -9.47; P < .001), mechanical ventilation duration (WMD: -3.98; P < .001), intensive care unit stay (WMD: -4.18; P < .001), procalcitonin (WMD: -0.53; P < .001), lipopolysaccharide (WMD: -9.69; P < .001), B-type natriuretic peptide (WMD: -159.87; P < .001), creatine kinase isoenzyme MB (WMD: -45.67; P < .001), cardiac troponin I (WMD: -0.66; P < .001), and all-cause mortality risk (RR: 0.55; P < .001). CONCLUSIONS: TCM lowers inflammation levels and reduces the risk of all-cause mortality for septic patients.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Glycoproteins/therapeutic use , Sepsis/drug therapy , Trypsin Inhibitors/therapeutic use , Drugs, Chinese Herbal/administration & dosage , Glycoproteins/administration & dosage , Humans , Randomized Controlled Trials as Topic , Treatment Outcome , Trypsin Inhibitors/administration & dosage
20.
Nutrients ; 13(9)2021 Aug 25.
Article in English | MEDLINE | ID: mdl-34578827

ABSTRACT

The human milk fat globule membrane (MFGM) contains important lipids for growing infants. Anthropometric measurements, milk samples, and infant milk intake were collected in a cohort of eleven healthy mother-infant dyads during exclusive breastfeeding from birth to six months. One hundred and sixty-six MFGM lipids were analysed using liquid chromatography-mass spectrometry, and the infant intake was calculated. The concentrations and intake were compared and associations between infant intake and growth characteristics explored. The lipid concentrations and infant intake varied widely between mother-infant dyads and between months one and three. The infant intake for many species displayed positive correlations with infant growth, particularly phospholipid species. The high variation in lipid intake is likely an important factor in infant growth, with strong correlations identified between the intake of many MFGM lipids and infant head circumference and weight. This study highlights the need for intake measurements and inclusion in cohort studies to elucidate the role of the human milk lipidome in infant growth and development.


Subject(s)
Breast Feeding/statistics & numerical data , Glycolipids/administration & dosage , Glycolipids/analysis , Glycoproteins/administration & dosage , Glycoproteins/analysis , Milk, Human/chemistry , Adult , Chromatography, Liquid , Female , Humans , Infant , Lipid Droplets , Longitudinal Studies , Male , Mass Spectrometry , Reference Values , Western Australia
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