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Scientific Reports May 2024N-acetyl glucosamine (NAG) is a natural amino sugar found in various human tissues with previously described anti-inflammatory effects. Various chemical modifications of...
N-acetyl glucosamine (NAG) is a natural amino sugar found in various human tissues with previously described anti-inflammatory effects. Various chemical modifications of NAG have been made to promote its biomedical applications. In this study, we synthesized two bi-deoxygenated NAG, BNAG1 and BNAG2 and investigated their anti-inflammatory properties, using an in vivo and in vitro inflammation mouse model induced by lipopolysaccharide (LPS). Among the parent molecule NAG, BNAG1 and BNAG2, BNAG1 showed the highest inhibition against serum levels of IL-6 and TNF α and the leukocyte migration to lungs and peritoneal cavity in LPS challenged mice, as well as IL-6 and TNF α production in LPS-stimulated primary peritoneal macrophages. BNAG2 displayed an anti-inflammatory effect which was comparable to NAG. These findings implied potential application of these novel NAG derivatives, especially BNAG1, in treatment of certain inflammation-related diseases.
Topics: Animals; Acetylglucosamine; Mice; Anti-Inflammatory Agents; Lipopolysaccharides; Macrophages, Peritoneal; Tumor Necrosis Factor-alpha; Interleukin-6; Inflammation; Male; Disease Models, Animal
PubMed: 38745047
DOI: 10.1038/s41598-024-61780-2 -
American Journal of Physiology.... Jul 2024Acute pancreatitis (AP) is an acute inflammatory reaction of the pancreatic tissue, which involves auto-digestion, edema, hemorrhage, and necrosis. AP can be categorized...
Acute pancreatitis (AP) is an acute inflammatory reaction of the pancreatic tissue, which involves auto-digestion, edema, hemorrhage, and necrosis. AP can be categorized into mild, moderately severe, and severe AP, with severe pancreatitis also referred to as acute necrotizing pancreatitis (ANP). ANP is characterized by the accumulation of necrotic material in the peritoneal cavity. This can result in intestinal injury. However, the mechanism of ANP-associated intestinal injury remains unclear. We established an ANP-associated intestinal injury rat model (ANP-IR model) by injecting pancreatitis-associated ascites fluid (PAAF) and necrotic pancreatic tissue at various proportions into the triangular area formed by the left renal artery and ureter. The feasibility of the ANP-IR model was verified by comparing the similar changes in indicators of intestinal inflammation and barrier function between the two rat models. In addition, we detected changes in apoptosis levels and YAP protein expression in the ileal tissues of rats in each group and validated them in vitro in rat epithelial crypt cells (IEC-6) to further explore the potential injury mechanisms of ANP-associated intestinal injury. We also collected clinical data from patients with ANP to validate the effects of PAAF and pancreatic necrosis on intestinal injury. Our findings offer a theoretical basis for restricting the buildup of peritoneal necrosis in individuals with ANP, thus promoting the restoration of intestinal function and enhancing treatment efficacy. The use of the ANP-IR model in further studies can help us better understand the mechanism and treatment of ANP-associated intestinal injury. We constructed a rat model of acute necrotizing pancreatitis-associated intestinal injury and verified its feasibility. In addition, we identified the mechanism by which necrotic pancreatic tissue and pancreatitis-associated ascites fluid (PAAF) cause intestinal injury through the HIPPO signaling pathway.
Topics: Animals; Pancreatitis, Acute Necrotizing; Disease Models, Animal; Rats; Male; Rats, Sprague-Dawley; Apoptosis; YAP-Signaling Proteins; Humans; Pancreas; Ascites; Cell Line; Intestinal Mucosa
PubMed: 38742280
DOI: 10.1152/ajpgi.00262.2023 -
Saudi Pharmaceutical Journal : SPJ :... Jun 2024Post-operative peritoneal adhesions (PA) are a common and important clinical problem. In this study, we focused on the ameliorative efficacy of ginger and gingerol...
Intra-peritoneal lavage of rhizome and its active constituent gingerol impede inflammation, angiogenesis, and fibrosis following post-operative peritoneal adhesion in male rats.
Post-operative peritoneal adhesions (PA) are a common and important clinical problem. In this study, we focused on the ameliorative efficacy of ginger and gingerol compounds on surgical-induced peritoneal adhesion, and their strategies that disrupted the PA formation pathways to suppress their incidence. First, liquid chromatography-mass spectrometry (LC-MS) was established to separate and identify several chemical groups of ginger rhizome extract. In the next steps, male Wistar albino rats were randomly selected and divided into various groups, namely sham, control, ginger extract (0.6, 1.8, 5 %w/v), and gingerol (0.05, 0.1, 0.3, and 1 %w/v). Finally, we investigated the macroscopic parameters such as wound healing, body weight as well as spleen height and weight. In addition, visual peritoneal adhesion assessment was performed via Nair et al and Adhesion Scoring Scheme. Moreover, the microscopic parameters and biological assessment was performed via and immunoassays. The present findings revealed significant improvement in wound healing and reduction of the adhesion range, as Nair et al. and Adhesion Scoring Scheme scoring, in both the ginger and gingerol groups compared to the PA group (). Whereas, gingerol (0.3 % w/v) was able to increase the body weight in rats () at end stage of experiment. Also, inflammation, angiogenesis, and fibrosis were significantly decreased due to the downregulation of interleukin (IL)-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF), respectively, in the ginger and gingerol groups compared to the PA group (). In contrast, the levels of IL-10 were increased in the ginger and gingerol groups compared to the control group (). Our results proved that ginger rhizome and gingerol, as novel therapeutic compounds, could be used to prevent PA for their beneficial anti-inflammatory as well as anti-fibrosis properties in clinical trials. However, further clinical studies are required to approve the effectiveness of ginger and gingerol.
PubMed: 38737808
DOI: 10.1016/j.jsps.2024.102092 -
Nutrients Apr 2024Polyunsaturated fatty acids (PUFAs) can alter adipose tissue function; however, the relative effects of plant and marine n3-PUFAs are less clear. Our objective was to...
Differential Modulation by Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) of Mesenteric Fat and Macrophages and T Cells in Adipose Tissue of Obese / Zucker Rats.
Polyunsaturated fatty acids (PUFAs) can alter adipose tissue function; however, the relative effects of plant and marine n3-PUFAs are less clear. Our objective was to directly compare the n3-PUFAs, plant-based α-linolenic acid (ALA) in flaxseed oil, and marine-based eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in high-purity oils versus n6-PUFA containing linoleic acid (LA) for their effects on the adipose tissue and oral glucose tolerance of obese rats. Male / Zucker rats were assigned to faALA, faEPA, faDHA, and faLA groups and compared to baseline / rats (faBASE) and lean Zucker rats (lnLA). After 8 weeks, faEPA and faDHA had 11-14% lower body weight than faLA. The oral glucose tolerance and total body fat were unchanged, but faEPA had less mesenteric fat. faEPA and faDHA had fewer large adipocytes compared to faLA and faALA. EPA reduced macrophages in the adipose tissue of / rats compared to ALA and DHA, while faLA had the greatest macrophage infiltration. DHA decreased (~10-fold) T-cell infiltration compared to faBASE and faEPA, whereas faALA and faLA had an ~40% increase. The n3-PUFA diets attenuated tumour necrosis factor-α in adipose tissue compared to faBASE, while it was increased by LA in both genotypes. In conclusion, EPA and DHA target different aspects of inflammation in adipose tissue.
Topics: Animals; Rats, Zucker; Eicosapentaenoic Acid; Docosahexaenoic Acids; Obesity; Male; Macrophages; Adipose Tissue; Rats; T-Lymphocytes; alpha-Linolenic Acid; Mesentery
PubMed: 38732558
DOI: 10.3390/nu16091311 -
Cureus Apr 2024Chronic mesenteric ischemia (CMI) is a vascular disorder primarily caused by atherosclerosis, resulting in intestinal ischemia. While endovascular treatment has become...
Antegrade Aorto-Mesenteric Bypass Using a Prefabricated Bovine Pericardium Tube Graft for the Treatment of Chronic Mesenteric Ischemia Complicated With Intestinal Necrosis and Biliary Peritonitis.
Chronic mesenteric ischemia (CMI) is a vascular disorder primarily caused by atherosclerosis, resulting in intestinal ischemia. While endovascular treatment has become the primary modality for most patients, open mesenteric revascularization remains crucial for complex cases. We present a case of CMI in a patient with critical ischemia, leading to small bowel necrosis, where the endovascular recanalization failed and a surgical approach was needed. A supraceliac antegrade aortomesenteric bypass was performed, and successful revascularization of intestinal circulation was achieved. A novel prefabricated bovine pericardium tube was used as a graft, and the bypass was placed behind the pancreas to ensure maximal isolation from the contaminated abdominal cavity. Despite the intestinal revascularization, in the early postoperative period, the overall condition of the patient worsened with obvious signs of peritonitis. The second look operation revealed a ruptured gallbladder with severe biliary peritonitis, likely caused by the preceding splanchnic ischemia. A cholecystectomy, lavage, and drainage were performed. No further intestinal necrosis was observed, and the bowel passage was restored with latero-lateral jejuno-lejunostomy. The follow-up of the patient showed no signs of graft infection. Despite the complications, the patient's postoperative period was stable, and he was discharged on day sixteen. Regular follow-ups confirmed an excellent patency of the bypass.
PubMed: 38707110
DOI: 10.7759/cureus.57530 -
World Journal of Gastrointestinal... Apr 2024With less than 90 reported cases to date, stercoral perforation of the colon is a rare occurrence. Stercoral ulceration is thought to occur due to ischemic pressure...
BACKGROUND
With less than 90 reported cases to date, stercoral perforation of the colon is a rare occurrence. Stercoral ulceration is thought to occur due to ischemic pressure necrosis of the bowel wall, which is caused by the presence of a stercoraceous mass. To underscore this urgent surgical situation concerning clinical presentation, surgical treatment, and results, we present the case of a 66-year-old man with a stercoral perforation.
CASE SUMMARY
A 66-year-old man with a history of hypertension, hyperlipidemia, and gout presented at the emergency department with lower abdominal pain and a low-grade fever lasting for a few hours. Abdominal computed tomography indicated a suspected bezoar (approximately 7.6 cm) in the dilated cecum, accompanied by pericolic fat stranding, mild proximal dilatation of the ileum, pneumoperitoneum, and minimal ascites. Intraoperatively, feculent peritonitis with isolated cecal perforation were observed. Consequently, a right hemicolectomy with peritoneal lavage was performed. A histopathological examination supported the intraoperative findings.
CONCLUSION
In stercoral perforations, a diagnosis should be diligently pursued, especially in older adults, and prompt surgical intervention should be implemented.
PubMed: 38690055
DOI: 10.4240/wjgs.v16.i4.1189 -
Journal of Clinical Medicine Apr 2024: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor family involved in processes in many inflammatory states. OPG concentration is enhanced in the...
: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor family involved in processes in many inflammatory states. OPG concentration is enhanced in the majority of chronic kidney disease (CKD) patients and those undergoing renal replacement therapy. The aim of the study was to assess the relation of OPG and chronic inflammation in peritoneal dialysis (PD) patients and to evaluate whether OPG concentrations in plasma and dialysate were related to plasma and dialysate levels of proinflammatory mediators (interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), interleukin 33 (IL-33) and interleukin 1 receptor-like 1IL-1RL1 (IL-1RL1, sST2)). : The study included 37 patients of the Peritoneal Dialysis Center, Department of Nephrology, Transplantology and Internal Medicine, Szczecin, Poland, 4-6 weeks after the onset of peritoneal dialysis therapy. During a peritoneal equilibration test, plasma (at 2 h) and dialysate (at 4 h) OPG, IL-33, 1IL-1RL1 (sST2), IL-6 and hsCRP concentrations were determined. : Plasma concentration of OPG did not correlate with dialysate OPG level ( = 0.04, = 0.8). There was a strong positive correlation between plasma OPG concentrations and plasma IL-1RL1 (sST2) ( = 0.41; = 0.01), plasma IL-6 ( = 0.38; = 0.01) and plasma hsCRP ( = 0.35; = 0.02). Dialysate OPG concentrations were positively associated with dialysate IL-1RL1 (sST2) ( = 0.37; = 0.02) and dialysate IL-6 levels ( = 0.44; = 0.005). Multivariate analysis showed that higher IL-1RL1 (sST2) ( = +0.38, = 0.006), higher plasma hsCRP ( = +0.32, = 0.02) and older age ( = +0.35, = 0.01) were independent determinants of higher plasma OPG concentration and that higher concentrations of dialysate IL-6 ( = +0.37, = 0.02) were independent determinants of higher dialysate OPG concentration. : Both plasma and dialysate OPG levels are associated with the severity of systemic and local inflammation illustrated by the plasma and dialysate concentrations of IL-1RL1 (sST2), hsCRP and IL-6, suggesting that OPG might have a pivotal role in explaining the milieu of systemic and intraperitoneal inflammation.
PubMed: 38673616
DOI: 10.3390/jcm13082345 -
Cellular & Molecular Biology Letters Apr 2024Macrophage proinflammatory activation contributes to the pathology of severe acute pancreatitis (SAP) and, simultaneously, macrophage functional changes, and increased...
Mitochondrial (mt)DNA-cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling promotes pyroptosis of macrophages via interferon regulatory factor (IRF)7/IRF3 activation to aggravate lung injury during severe acute pancreatitis.
BACKGROUND
Macrophage proinflammatory activation contributes to the pathology of severe acute pancreatitis (SAP) and, simultaneously, macrophage functional changes, and increased pyroptosis/necrosis can further exacerbate the cellular immune suppression during the process of SAP, where cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) plays an important role. However, the function and mechanism of cGAS-STING in SAP-induced lung injury (LI) remains unknown.
METHODS
Lipopolysaccharide (LPS) was combined with caerulein-induced SAP in wild type, cGAS and sting mice. Primary macrophages were extracted via bronchoalveolar lavage and peritoneal lavage. Ana-1 cells were pretreated with LPS and stimulated with nigericin sodium salt to induce pyroptosis in vitro.
RESULTS
SAP triggered NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation-mediated pyroptosis of alveolar and peritoneal macrophages in mouse model. Knockout of cGAS/STING could ameliorate NLRP3 activation and macrophage pyroptosis. In addition, mitochondrial (mt)DNA released from damaged mitochondria further induced macrophage STING activation in a cGAS- and dose-dependent manner. Upregulated STING signal can promote NLRP3 inflammasome-mediated macrophage pyroptosis and increase serum interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α levels and, thus, exacerbate SAP-associated LI (SAP-ALI). Downstream molecules of STING, IRF7, and IRF3 connect the mtDNA-cGAS-STING axis and the NLRP3-pyroptosis axis.
CONCLUSIONS
Negative regulation of any molecule in the mtDNA-cGAS-STING-IRF7/IRF3 pathway can affect the activation of NLRP3 inflammasomes, thereby reducing macrophage pyroptosis and improving SAP-ALI in mouse model.
Topics: Animals; Pyroptosis; Interferon Regulatory Factor-3; Mice; Signal Transduction; DNA, Mitochondrial; Membrane Proteins; Nucleotidyltransferases; Pancreatitis; Macrophages; Lung Injury; Interferon Regulatory Factor-7; Mice, Inbred C57BL; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; Lipopolysaccharides; Male; Disease Models, Animal
PubMed: 38671352
DOI: 10.1186/s11658-024-00575-9 -
Cureus Mar 2024Cerebral palsy (CP) is a neurodevelopmental disorder that affects motor function and is often accompanied by secondary musculoskeletal issues. Severe scoliosis, a...
Cerebral palsy (CP) is a neurodevelopmental disorder that affects motor function and is often accompanied by secondary musculoskeletal issues. Severe scoliosis, a lateral curvature of the spine over 40 degrees, poses a significant challenge for individuals with CP, impacting their mobility and overall well-being. While the association between scoliosis and gastrointestinal complications is acknowledged, the occurrence of colonic volvulus with necrosis in the context of CP and severe scoliosis is rare and complex. This case report emphasizes the importance of clinical awareness in managing gastrointestinal complications in patients with CP and severe scoliosis. An 11-year-old female presented with gastroenteritis and a concurrent viral upper respiratory tract infection. She experienced complications such as greenish vomiting, hematemesis, abdominal distention, and constipation. The patient has a medical history of epilepsy and was diagnosed with quadriplegic CP at four months old due to viral meningitis. She is currently on anti-epileptic medications and receives regular follow-ups with neurology. Severe lumbar scoliosis of more than 50 degrees Cobb angle is also noted. Physical examination revealed dehydration, bilious content in nasogastric tube (NGT) aspiration, tender abdomen, and an empty digital rectal examination. Some laboratory findings showed elevated levels of erythrocyte sedimentation rate (ESR), prothrombin time (PT), blood urea nitrogen (BUN), and sodium, while albumin levels were decreased, and white blood cell (WBC) count was mildly elevated. Abdominal computed tomography (CT) with contrast showed a distended ascending colon with air and swirling of the mesentery. The distal half of the large bowel was not dilated, and fecal matter was present. The small bowel appeared to be collapsed, and there was moderate free fluid in the peritoneal cavity, indicating colonic volvulus involving the proximal large bowel. The patient underwent surgery, which involved deflating and removing the distended colon, resecting the gangrenous colon, and performing an ilio-sigmoid anastomosis to restore gastrointestinal continuity. Postoperatively, the patient received close monitoring in the pediatric intensive care unit (PICU), received total parenteral nutrition (TPN) for five days, gradually progressed feeding, and showed overall improvement in her condition. In conclusion, this case report highlights a rare occurrence of colonic volvulus in a patient with CP and severe scoliosis. It emphasizes the complex relationship between neurological and musculoskeletal disorders in gastrointestinal complications. A multidisciplinary approach is important for optimal management. It shows the importance of musculoskeletal factors in patients with neurological conditions. Overall, it contributes to the medical literature and emphasizes tailored management strategies for gastrointestinal issues in such patients.
PubMed: 38650790
DOI: 10.7759/cureus.56743 -
Cureus Mar 2024This case report describes necrotizing enterocolitis (NEC) in an infant with a history of twin-twin transfusion syndrome (TTTS). TTTS is a volume imbalance where the...
This case report describes necrotizing enterocolitis (NEC) in an infant with a history of twin-twin transfusion syndrome (TTTS). TTTS is a volume imbalance where the anastomosis at the vascular equator between the two placentae shifts from the donor to the recipient twin. This causes a higher risk for NEC, a marked inflammation caused by bacterial infection into the intestinal wall, from prematurity and intestinal hypoperfusion. Complications include sepsis, bowel necrosis, perforation, peritonitis, and death. NEC is a leading cause of morbidity in preterm infants. A 3-month-old female with a history of TTTS and prematurity presented with her mother to the pediatric emergency department (ED) for bloody diarrhea, emesis, lack of appetite, and lethargy for 4 days. The pediatrician changed the formula due to a possible milk allergy, however, she continued to have bloody diarrhea. Over the 2 days, the patient had nonbilious and non-bloody emesis and couldn't tolerate oral intake. In the ED, labs showed neutropenia and sepsis. She had a positive fecal occult blood test (FOBT) and an abdominal x-ray that revealed dilated loops of bowel and pneumatosis intestinalis. She was started on intravenous (IV) fluids for maintenance of hydration. She was started on broad-spectrum antibiotics including intravenous (IV) vancomycin and meropenem, and had her feedings temporarily stopped. The patient was transferred to the pediatric intensive care unit (PICU) at a tertiary care/children's hospital that evening where she had a laparotomy performed to resect the diseased intestine. She was discharged 10 days after the surgery for home recovery with clinical follow-up.
PubMed: 38646314
DOI: 10.7759/cureus.56720