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Blood Advances Jun 2024Hemojuvelin (HJV) is a glycosylphosphatidylinositol-anchored protein of the repulsive guidance molecule family acting as a bone morphogenetic protein (BMP) coreceptor to...
Hemojuvelin (HJV) is a glycosylphosphatidylinositol-anchored protein of the repulsive guidance molecule family acting as a bone morphogenetic protein (BMP) coreceptor to induce the hepatic iron regulatory protein hepcidin. Hepcidin causes ubiquitination and degradation of the sole known iron exporter ferroportin, thereby limiting iron availability. The detailed signaling mechanism of HJV in vivo has yet to be investigated. In the current manuscript, we used an established model of adeno-associated virus (AAV)-mediated liver-specific overexpression of HJV in murine models of hepatocyte-specific deficiency of the BMP type I receptors Alk2 or Alk3. In control mice, HJV overexpression increased hepatic Hamp messenger RNA (mRNA) levels, soluble HJV (sHJV), splenic iron content (SIC), as well as phosphorylated small mothers against decapentaplegic protein (pSMAD1/5/8) levels. In contrast, in Alk2fl/fl;Alb-Cre and Alk3fl/fl;Alb-Cre mice, which present with moderate and severe iron overload, respectively, the administration of AAV-HJV induced HJV and sHJV. However, it did not rescue the iron overload phenotypes of those mice. Serum iron levels were induced in Alk2fl/fl;Alb-Cre mice after HJV overexpression. In phosphate-buffered saline-injected Alk3fl/fl;Alb-Cre mice, serum iron levels and the expression of duodenal ferroportin remained high, whereas Hamp mRNA levels were decreased to 1% to 5% of the levels detected in controls. This was reduced even further by AAV-HJV overexpression. SIC remained low in mice with hepatocyte-specific Alk2 or Alk3 deficiency, reflecting disturbed iron homeostasis with high serum iron levels and transferrin saturation and an inability to induce hepcidin by HJV overexpression. The data indicate that ALK2 and ALK3 are both required in vivo for the HJV-mediated induction of hepcidin.
Topics: Animals; Mice; GPI-Linked Proteins; Hepcidins; Hemochromatosis Protein; Bone Morphogenetic Protein Receptors, Type I; Liver; Iron; Iron Overload; Activin Receptors, Type I; Activin Receptors, Type II
PubMed: 38588481
DOI: 10.1182/bloodadvances.2023012322 -
The American Journal of Gastroenterology Jun 2024Gut microbiome changes are linked to obesity, but findings are based on stool data. In this article, we analyzed the duodenal microbiome and serum biomarkers in subjects...
INTRODUCTION
Gut microbiome changes are linked to obesity, but findings are based on stool data. In this article, we analyzed the duodenal microbiome and serum biomarkers in subjects with normal weight, overweight, and obesity.
METHODS
Duodenal aspirates and serum samples were obtained from subjects undergoing standard-of-care esophagogastroduodenoscopy without colon preparation. Aspirate DNAs were analyzed by 16S rRNA and shotgun sequencing. Predicted microbial metabolic functions and serum levels of metabolic and inflammatory biomarkers were also assessed.
RESULTS
Subjects with normal weight (N = 105), overweight (N = 67), and obesity (N = 42) were identified. Overweight-specific duodenal microbial features include lower relative abundance (RA) of Bifidobacterium species and Escherichia coli strain K-12 and higher Lactobacillus intestinalis , L. johnsonii , and Prevotella loescheii RA. Obesity-specific features include higher Lactobacillus gasseri RA and lower L. reuteri (subspecies rodentium ), Alloprevotella rava , and Leptotrichia spp RA. Escalation features (progressive changes from normal weight through obesity) include decreasing Bacteroides pyogenes , Staphylococcus hominis , and unknown Faecalibacterium species RA, increasing RA of unknown Lactobacillus and Mycobacterium species, and decreasing microbial potential for biogenic amines metabolism. De-escalation features (direction of change altered in normal to overweight and overweight to obesity) include Lactobacillus acidophilus , L. hominis , L. iners , and Bifidobacterium dentium . An unknown Lactobacillus species is associated with type IIa dyslipidemia and overweight, whereas Alloprevotella rava is associated with type IIb and IV dyslipidemias.
DISCUSSION
Direct analysis of the duodenal microbiome has identified key genera associated with overweight and obesity, including some previously identified in stool, e.g., Bifidobacterium and Lactobacillus . Specific species and strains exhibit differing associations with overweight and obesity, including escalation and de-escalation features that may represent targets for future study and therapeutics.
Topics: Humans; Obesity; Female; Male; Overweight; Middle Aged; Gastrointestinal Microbiome; Adult; Duodenum; RNA, Ribosomal, 16S; Biomarkers; Lactobacillus; Bifidobacterium; Aged
PubMed: 38578969
DOI: 10.14309/ajg.0000000000002790 -
World Journal of Clinical Cases Mar 2024Mycobacterium tuberculosis (TB) is the causative agent of TB, a chronic granulomatous illness. This disease is prevalent in low-income countries, posing a significant...
BACKGROUND
Mycobacterium tuberculosis (TB) is the causative agent of TB, a chronic granulomatous illness. This disease is prevalent in low-income countries, posing a significant global health challenge. Gastrointestinal TB is one of the three forms. The disease can mimic other intra-abdominal conditions, leading to delayed diagnosis owing to the absence of specific symptoms. While gastric outlet obstruction (GOO) remains a frequent complication, its incidence has declined with the advent of proton pump inhibitors and eradication therapy. Gastroduodenal TB can cause upper gastrointestinal hemorrhage, obstruction, and malignancy-like tumors.
CASE SUMMARY
A 23-year-old male presented with recurrent epigastric pain, distension, nausea, vomiting, and weight loss, prompting a referral to a gastroenterologist clinic. Endoscopic examination revealed distorted gastric mucosa and signs of chronic inflammation. However, treatment was interrupted, possibly owing to vomiting or comorbidities such as human immunodeficiency virus infection or diabetes. Subsequent surgical intervention revealed a dilated stomach and diffuse thickening of the duodenal wall. Resection revealed gastric wall effacement with TB.
CONCLUSION
Primary gastric TB is rare, frequently leading to GOO. Given its rarity, suspicions should be promptly raised when encountering relevant symptoms, often requiring surgical intervention for diagnosis and treatment.
PubMed: 38576818
DOI: 10.12998/wjcc.v12.i8.1536 -
World Journal of Clinical Cases Mar 2024The role of primary-level medical pharmacists in medical institutions in China is limited; therefore, it is necessary to explore the role of pharmacists in the process...
BACKGROUND
The role of primary-level medical pharmacists in medical institutions in China is limited; therefore, it is necessary to explore the role of pharmacists in the process of drug treatment.
CASE SUMMARY
A Chinese pharmacist participated in the complete treatment of a patient with a duodenal ulcer. The rationale for drug treatment was evaluated, and adjustments were made to the antacid and anti-infective regimen, as well as the dose and frequency of administration. Body temperature, routine blood examination, and adverse drug reactions were strictly monitored. During treatment, the pharmacist recommended anti-infective therapy with ampicillin-sulbactam, which effectively controlled the infection. Additionally, the pharmacist suggested changing famotidine to lansoprazole for acid suppression and gastroprotective treatment, combined with Chinese patent medicine such as Kangfuxin Liquid. This is the first case report of a pharmacist in primary-level medical institutions adjusting drug use for patients with duodenal ulcer and pulmonary infection.
CONCLUSION
A pharmacist participated in the treatment process, provided individualized medication adjustment, and achieved good clinical results.
PubMed: 38576803
DOI: 10.12998/wjcc.v12.i8.1530 -
Cureus Mar 2024Cholangiocarcinoma is a malignancy that is hard to detect and resect, due mostly to its location as well as a lack of current screening tests. When found, it is often in...
Cholangiocarcinoma is a malignancy that is hard to detect and resect, due mostly to its location as well as a lack of current screening tests. When found, it is often in the advanced stage as patients are usually asymptomatic during the early course of the disease; the overall prognosis is modest in patients diagnosed at this stage. Here, we discuss the case of a 48-year-old female with no significant past medical history or family history who presented to our hospital with symptoms of acute cholecystitis with a supporting ultrasound. She proceeded to get a laparoscopic cholecystectomy for the same, but an ensuing workup and pathology revealed advanced-stage cholangiocarcinoma. The patient ultimately opted for palliative care given her poor prognosis.
PubMed: 38571825
DOI: 10.7759/cureus.55448 -
Diabetologia Jul 2024Metformin lowers postprandial glycaemic excursions in individuals with type 2 diabetes by modulating gastrointestinal function, including the stimulation of... (Randomized Controlled Trial)
Randomized Controlled Trial
Impact of the timing of metformin administration on glycaemic and glucagon-like peptide-1 responses to intraduodenal glucose infusion in type 2 diabetes: a double-blind, randomised, placebo-controlled, crossover study.
AIMS/HYPOTHESIS
Metformin lowers postprandial glycaemic excursions in individuals with type 2 diabetes by modulating gastrointestinal function, including the stimulation of glucagon-like peptide-1 (GLP-1). The impact of varying the timing of metformin administration on postprandial glucose metabolism is poorly defined. We evaluated the effects of metformin, administered at different intervals before an intraduodenal glucose infusion, on the subsequent glycaemic, insulinaemic and GLP-1 responses in metformin-treated type 2 diabetes.
METHODS
Sixteen participants with type 2 diabetes that was relatively well-controlled by metformin monotherapy were studied on four separate days in a crossover design. On each day, participants were randomised to receive a bolus infusion of metformin (1000 mg in 50 ml 0.9% saline) via a nasoduodenal catheter at t = -60, -30 or 0 min (and saline at the other timepoints) or saline at all timepoints (control), followed by an intraduodenal glucose infusion of 12.56 kJ/min (3 kcal/min) at t = 0-60 min. The treatments were blinded to both participants and investigators involved in the study procedures. Plasma glucose, insulin and total GLP-1 levels were measured every 30 min between t = -60 min and t = 120 min.
RESULTS
There was a treatment-by-time interaction for metformin in reducing plasma glucose levels and increasing plasma GLP-1 and insulin levels (p<0.05 for each). The reduction in plasma glucose levels was greater when metformin was administered at t = -60 or -30 min vs t = 0 min (p<0.05 for each), and the increases in plasma GLP-1 levels were evident only when metformin was administered at t = -60 or -30 min (p<0.05 for each). Although metformin did not influence insulin sensitivity, it enhanced glucose-induced insulin secretion (p<0.05), and the increases in plasma insulin levels were comparable on the 3 days when metformin was given.
CONCLUSIONS/INTERPRETATION
In well-controlled metformin-treated type 2 diabetes, glucose-lowering by metformin is greater when it is given before, rather than with, enteral glucose, and this is associated with a greater GLP-1 response. These observations suggest that administration of metformin before meals may optimise its effect in improving postprandial glycaemic control.
TRIAL REGISTRATION
www.anzctr.org.au ACTRN12621000878875 FUNDING: The study was not funded by a specific research grant.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Cross-Over Studies; Male; Glucagon-Like Peptide 1; Blood Glucose; Female; Middle Aged; Double-Blind Method; Hypoglycemic Agents; Glucose; Insulin; Aged; Adult; Postprandial Period; Duodenum
PubMed: 38561463
DOI: 10.1007/s00125-024-06131-6 -
Fish & Shellfish Immunology May 2024The genome evolution of Antarctic notothenioids has been modulated by their extreme environment over millennia and more recently by human-caused constraints such as...
The genome evolution of Antarctic notothenioids has been modulated by their extreme environment over millennia and more recently by human-caused constraints such as overfishing and climate change. Here we investigated the characteristics of the immune system in Notothenia rossii and how it responds to 8 h immersion in viral (Poly I:C, polyinosinic: polycytidylic acid) and bacterial (LPS, lipopolysaccharide) proxies. Blood plasma antiprotease activity and haematocrit were reduced in Poly I:C-treated fish only, while plasma protein, lysozyme activity and cortisol were unchanged with both treatments. The skin and duodenum transcriptomes responded strongly to the treatments, unlike the liver and spleen which had a mild response. Furthermore, the skin transcriptome responded most to the bacterial proxy (cell adhesion, metabolism and immune response processes) and the duodenum (metabolism, response to stress, regulation of intracellular signal transduction, and immune system responses) to the viral proxy. The differential tissue response to the two proxy challenges is indicative of immune specialisation of the duodenum and the skin towards pathogens. NOD-like and C-type lectin receptors may be central in recognising LPS and Poly I:C. Other antimicrobial compounds such as iron and selenium-related genes are essential defence mechanisms to protect the host from sepsis. In conclusion, our study revealed a specific response of two immune barrier tissue, the skin and duodenum, in Notothenia rossii when exposed to pathogen proxies by immersion, and this may represent an adaptation to pathogen infective strategies.
Topics: Humans; Animals; Conservation of Natural Resources; Immersion; Lipopolysaccharides; Fisheries; Perciformes; Poly I; Antarctic Regions
PubMed: 38548189
DOI: 10.1016/j.fsi.2024.109516 -
Frontiers in Endocrinology 2024Motilin is a hormone secreted by specialised enteroendocrine cells in the small intestine, and is known to modulate gastrointestinal motility in humans, regulating the...
INTRODUCTION
Motilin is a hormone secreted by specialised enteroendocrine cells in the small intestine, and is known to modulate gastrointestinal motility in humans, regulating the migratory motor complex. It is understudied at least in part due to the lack of commercially available immunoassays.
METHOD
A multiplexed liquid chromatography mass spectrometry (LC-MS/MS) method was optimised to measure motilin, insulin, C-peptide, GIP (1-42) and GIP (3-42). Corresponding active ghrelin concentrations were determined by immunoassay. Ten healthy volunteers with no prior history of gastroenterological or endocrine condition attended after overnight fast and had blood samples taken every 15 minutes for 4 hours whilst continuing to fast, and then further sampling for 2 hours following a liquid mixed meal. Hunger scores were taken at each time point using a visual analogue scale. Normal bowel habit was confirmed by 1 week stool diary.
RESULTS
Motilin levels fluctuated in the fasting state with an average period between peaks of 109.5 mins (SD:30.0), but with no evidence of a relationship with either ghrelin levels or hunger scores. The mixed meal interrupted cyclical motilin fluctuations, increased concentrations of motilin, insulin, C-peptide, GIP(1-42) and GIP(3-42), and suppressed ghrelin levels.
DISCUSSION
This study highlights the utility of LC-MS/MS for parallel measurement of motilin alongside other peptide hormones, and supports previous reports of the cyclical nature of motilin levels in the fasting state and interruption with feeding. This analytical method has utility for further clinical studies into motilin and gut hormone physiology in human volunteers.
Topics: Humans; Motilin; Ghrelin; Healthy Volunteers; C-Peptide; Chromatography, Liquid; Liquid Chromatography-Mass Spectrometry; Duodenum; Tandem Mass Spectrometry
PubMed: 38544692
DOI: 10.3389/fendo.2024.1348146 -
Viruses Mar 2024Pathogenic lagoviruses (Rabbit hemorrhagic disease virus, RHDV) are widely spread across the world and are used in Australia and New Zealand to control populations of...
Pathogenic lagoviruses (Rabbit hemorrhagic disease virus, RHDV) are widely spread across the world and are used in Australia and New Zealand to control populations of feral European rabbits. The spread of the non-pathogenic lagoviruses, e.g., rabbit calicivirus (RCV), is less well studied as the infection results in no clinical signs. Nonetheless, RCV has important implications for the spread of RHDV and rabbit biocontrol as it can provide varying levels of cross-protection against fatal infection with pathogenic lagoviruses. In Chile, where European rabbits are also an introduced species, myxoma virus was used for localised biocontrol of rabbits in the 1950s. To date, there have been no studies investigating the presence of lagoviruses in the Chilean feral rabbit population. In this study, liver and duodenum rabbit samples from central Chile were tested for the presence of lagoviruses and positive samples were subject to whole RNA sequencing and subsequent data analysis. Phylogenetic analysis revealed a novel RCV variant in duodenal samples that likely originated from European RCVs. Sequencing analysis also detected the presence of a rabbit astrovirus in one of the lagovirus-positive samples.
Topics: Animals; Rabbits; Phylogeny; Chile; Caliciviridae Infections; Hemorrhagic Disease Virus, Rabbit; Lagovirus
PubMed: 38543804
DOI: 10.3390/v16030439 -
Life (Basel, Switzerland) Mar 2024The aim of this study was to investigate the effects of dietary l-glutamine (Gln) supplementation on the morphology and function of the intestine and the growth of...
The aim of this study was to investigate the effects of dietary l-glutamine (Gln) supplementation on the morphology and function of the intestine and the growth of muscle in piglets. In this study, sixteen 21-day-old piglets were randomly divided into two groups: the Control group (fed a basal diet) and the Gln group (fed a basal diet supplemented with 0.81% Gln). Blood, gut, and muscle samples were collected from all piglets on Day 20 of the trial. Compared with the Control group, the supplementation of Gln increased ( < 0.05) the villus height, villus width, villus surface area, and villus height/crypt depth ratio of the small intestine. Furthermore, the supplementation of Gln increased ( < 0.05) total protein, total protein/DNA, and RNA/DNA in both the jejunum and ileum. It also increased ( < 0.05) the concentrations of carnosine and citrulline in the jejunal mucosa, as well as citrulline and cysteine concentrations in the ileum. Conversely, Gln supplementation decreased ( < 0.05) Gln concentrations in both the jejunum and ileum, along with β-aminoisobutyric acid and 1-Methylhistidine concentrations, specifically in the ileum. Subsequent research revealed that Gln supplementation increased ( < 0.05) the mRNA levels for glutathione-S-transferase omega 2 and interferon- in the duodenum. In addition, Gln supplementation led to an increase ( < 0.05) in the number of genus in the colon, but a decrease ( < 0.05) in the level of HSP70 in the jejunum and the activity of diamine oxidase in plasma. Also, Gln supplementation reduced ( < 0.05) the mRNA levels of glutathione-S-transferase omega 2 and interferon stimulated genes, such as , , , , , and in both the jejunum and ileum, and the numbers of , genus, and family in the colon. Moreover, Gln supplementation enhanced ( < 0.05) the concentrations of total protein, RNA/DNA, and total protein/DNA ratio in the longissimus dorsi muscle, the concentrations of citrulline, ornithine, arginine, and hydroxyproline, and the mRNA level of peptide transporter 1, while reducing the contents of hydrogen peroxide and malondialdehyde and the mRNA level of glutathione-S-transferase omega 2 in the longissimus dorsi muscle. In conclusion, dietary Gln supplementation can improve the intestinal function of piglets and promote the growth of the longissimus dorsi muscle.
PubMed: 38541729
DOI: 10.3390/life14030405