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Nano Convergence Feb 2024Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a family of chronic disorders along the gastrointestinal tract. Because of its...
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a family of chronic disorders along the gastrointestinal tract. Because of its idiopathic nature, IBD does not have a fundamental cure; current available therapies for IBD are limited to prolonged doses of immunomodulatory agents. While these treatments may reduce inflammation, limited therapeutic efficacy, inconsistency across patients, and adverse side effects from aggressive medications remain as major drawbacks. Recently, excessive production and accumulation of neutrophil extracellular traps (NETs) also known as NETosis have been identified to exacerbate inflammatory responses and induce further tissue damage in IBD. Such discovery invited many researchers to investigate NETs as a potential therapeutic target. DNase-I is a natural agent that can effectively destroy NETs and, therefore, potentially reduce NETs-induced inflammations even without the use of aggressive drugs. However, low stability and rapid clearance of DNase-I remain as major limitations for further therapeutic applications. In this research, polymeric nanozymes were fabricated to increase the delivery and therapeutic efficacy of DNase-I. DNase-I was immobilized on the surface of polymeric nanoparticles to maintain its enzymatic properties while extending its activity in the colon. Delivery of DNase-I using this platform allowed enhanced stability and prolonged activity of DNase-I with minimal toxicity. When administered to animal models of IBD, DNase-I nanozymes successfully alleviated various pathophysiological symptoms of IBD. More importantly, DNase-I nanozyme administration successfully attenuated neutrophil infiltration and NETosis in the colon compared to free DNase-I or mesalamine.
PubMed: 38332364
DOI: 10.1186/s40580-024-00414-9 -
World Journal of Clinical Cases Jan 2024Ischemic colitis (IC) is also known as colon ischemia and is caused by colon vascular occlusion or nonocclusion, which results in a reduced blood supply to the colon and...
BACKGROUND
Ischemic colitis (IC) is also known as colon ischemia and is caused by colon vascular occlusion or nonocclusion, which results in a reduced blood supply to the colon and is not significant enough to maintain the metabolic function of cells, leading to intestinal wall ischemia. Its main symptoms include abdominal pain, diarrhea, and bloody stool. In severe cases, intestinal gangrene, peritonitis, intestinal stenosis and even intestinal obstruction may occur. IC induced by long-term use of certain special drugs is relatively rare in clinical practice. This article describes the clinical diagnosis and treatment of a typical case and provides a new treatment idea for the treatment of IC.
CASE SUMMARY
The patient was admitted to the hospital with "abdominal pain for half a month and bloody stool with mucous and pus for 3 d" and was diagnosed with "IC". Symptomatic and supportive treatment, such as antibiotics (levofloxacin), acid inhibition and stomach protection, fluid replenishment, and intravenous nutrition, was given. The patient's colonic ulcers were considered to be related to the oral administration of platelet (PLT)-raising capsules; the patient was asked to stop PLT-raising drugs for selective review colonoscopy, and antibiotics and mesalazine enteric-coated tablets were stopped. Under the guidance of hematology consultation, 60 mg of methylprednisolone was given in combination with PLT infusion to increase the PLT. After treatment, the patient's condition stabilized, the patient's stool turned yellow, the patient's symptoms improved, and the patient was allowed to leave the hospital.
CONCLUSION
PLT-raising capsules can lead to IC, so clinicians should have a full understanding of the application of these drugs in the treatment of various causes of thrombocytopenia, weigh the advantages and disadvantages, and observe patients closely.
PubMed: 38322454
DOI: 10.12998/wjcc.v12.i3.607 -
European Journal of Medical Research Feb 2024To explore the mechanism of huankuile (HKL) in colon injury repair in rats with ulcerative colitis (UC).
OBJECTIVE
To explore the mechanism of huankuile (HKL) in colon injury repair in rats with ulcerative colitis (UC).
METHODS
Fifty SPF Wistar male rats were divided randomly into a normal group, a negative control group, an HKL intervention group ('HKL group') and a 5-aminosalicylic acid intervention group ('5-ASA group'). After 14 days of intervention with corresponding drugs, pathological scores were obtained using the results of immunohistochemical staining; morphological changes were observed by hematoxylin-eosin staining, and the mRNA expression levels of tumour necrosis factor-α (TNF-α), matrix metalloproteinase 9 (MMP9) and interleukin-13 (IL-13) were detected by real-time quantitative PCR.
RESULTS
After the successful construction of the rat model, it was compared with the rats in the normal group. In the negative group, it was found that the expression of TNF-α and MMP9 was significantly increased in the colonic mucosal epithelia of the rats, the pathological score was significantly increased (P < 0.05), and the mRNA expression levels of TNF-α, MMP9 and IL-13 were increased (P < 0.05). After treatment with HKL, the colonic morphology of the rats returned to normal, the expression of TNF-α and MMP9 in the colonic mucosal epithelium of the rats returned to normal, the pathological score grade was significantly reduced (P < 0.05), and the mRNA expression levels of TNF-α, MMP9 and IL-13 were reduced; these results were largely consistent with those of the normal group, with no statistically significant difference.
CONCLUSION
HKL effectively improved the general symptoms and tissue injury in UC rats, and the therapeutic effect was better than that of 5-ASA group. Ulcerative colitis in rats increased the expression of TNF-α, MMP9 and IL-13. HKL repaired UC-induced colonic injury in rats by decreasing the expression of TNF-α, MMP9 and IL-13.
Topics: Animals; Male; Rats; Colitis, Ulcerative; Colon; Interleukin-13; Matrix Metalloproteinase 9; Mesalamine; Rats, Wistar; RNA, Messenger; Thoracic Injuries; Tumor Necrosis Factor-alpha
PubMed: 38321559
DOI: 10.1186/s40001-024-01695-w -
Journal of the Canadian Association of... Feb 2024Those managing ulcerative colitis (UC) must be aware of new treatments. Mesalamine (5-ASA) is the first treatment for mild UC. Steroids have been the first therapy for...
Those managing ulcerative colitis (UC) must be aware of new treatments. Mesalamine (5-ASA) is the first treatment for mild UC. Steroids have been the first therapy for patients with more severe UC but these are not effective or safe long term. This means that other medicines are needed. Newer advanced therapies are now frequently used. There are several types of advanced therapies. These are the anti-TNF, anti-integrin and anti-IL12/23 agents as well as the JAK inhibitors and sphingosine1-phosphate receptor modulators. All of these are effective in treating UC. Choosing among treatments is complicated. There are multiple factors to think about when choosing a treatment for UC. Without research studies that directly compare the different treatments, the use of any one treatment should be based on effectiveness and safety. Other considerations include specific disease features, patient factors and the preference of patients.
PubMed: 38314181
DOI: 10.1093/jcag/gwad025 -
Nature Communications Feb 2024Osteoarthritis (OA) is a progressive and irreversible degenerative joint disease that is characterized by cartilage destruction, osteophyte formation, subchondral bone...
Osteoarthritis (OA) is a progressive and irreversible degenerative joint disease that is characterized by cartilage destruction, osteophyte formation, subchondral bone remodeling, and synovitis. Despite affecting millions of patients, effective and safe disease-modifying osteoarthritis drugs are lacking. Here we reveal an unexpected role for the small molecule 5-aminosalicylic acid (5-ASA), which is used as an anti-inflammatory drug in ulcerative colitis. We show that 5-ASA competes with extracellular-matrix collagen-II to bind to osteoclast-associated receptor (OSCAR) on chondrocytes. Intra-articular 5-ASA injections ameliorate OA generated by surgery-induced medial-meniscus destabilization in male mice. Significantly, this effect is also observed when 5-ASA was administered well after OA onset. Moreover, mice with DMM-induced OA that are treated with 5-ASA at weeks 8-11 and sacrificed at week 12 have thicker cartilage than untreated mice that were sacrificed at week 8. Mechanistically, 5-ASA reverses OSCAR-mediated transcriptional repression of PPARγ in articular chondrocytes, thereby suppressing COX-2-related inflammation. It also improves chondrogenesis, strongly downregulates ECM catabolism, and promotes ECM anabolism. Our results suggest that 5-ASA could serve as a DMOAD.
Topics: Humans; Male; Animals; Mice; Mesalamine; PPAR gamma; Osteoarthritis; Cartilage, Articular; Chondrocytes; Disease Models, Animal
PubMed: 38310093
DOI: 10.1038/s41467-024-45174-6 -
PloS One 2024Mesalazine is a well-established treatment for ulcerative colitis by oral or topical administration. However, the pharmacokinetic (PK) and safety profiles of mesalazine... (Clinical Trial)
Clinical Trial
Mesalazine is a well-established treatment for ulcerative colitis by oral or topical administration. However, the pharmacokinetic (PK) and safety profiles of mesalazine administered by an enema has not been clarified in Chinese population. We conducted an open-label study to assess the PK and safety profiles of mesalazine in 11 healthy Chinese subjects after receiving mesalazine enema (1 g/100 mL) once daily for 7 consecutive days. Blood and urine samples were collected for assay of mesalazine and N-acetyl mesalazine by liquid chromatography-tandem mass spectrometry. The PK and safety data were summarized using descriptive statistics. The mean (standard deviation) maximum plasma concentration (Cmax), area under plasma drug concentration-time curve from time 0 to the last measurable plasma concentration time point (AUC0-t) and elimination half-life (t1/2) of mesalazine were 1007.64 (369.00) ng/mL, 9608.59 (3533.08) h·ng/mL and 3.33 (1.99) h, respectively after the first dose administration. In multiple-dose study, the estimated accumulation factor of mesalazine was 1.09. The cumulative urinary excretion rate of parent and major metabolite of mesalazine was 27.77%. After the last doe administration, 2.21% of the administered dose was excreted as mesalazine and 24.47% as N-acetyl mesalazine in urine within 24 h. Overall, 9 adverse events (AEs) were reported in 4 of the 11 subjects (36.4%), including oral ulcer, toothache, upper respiratory tract infection (1 each) and laboratory abnormalities (6 cases). All AEs were mild and recovered spontaneously without treatment, and were not considered as related to mesalazine. Mesalazine enema (1 g/100 mL) was safe and well tolerated in healthy Chinese subjects. These findings support further clinical trials in Chinese patients. Trial registration: This trial was registered to Chinese Clinical Trial Registry (ChiCTR) at https://www.chictr.org.cn (registration number: ChiCTR2300073148).
Topics: Humans; Administration, Oral; Area Under Curve; China; Chromatography, Liquid; Dose-Response Relationship, Drug; Healthy Volunteers; Mesalamine; Tandem Mass Spectrometry
PubMed: 38306390
DOI: 10.1371/journal.pone.0296940 -
Journal For Immunotherapy of Cancer Jan 2024Immune checkpoint inhibitor (ICI) gastrointestinal toxicity (gastritis, enteritis, colitis) is a major cause of morbidity and treatment-related death. Guidelines agree...
BACKGROUND
Immune checkpoint inhibitor (ICI) gastrointestinal toxicity (gastritis, enteritis, colitis) is a major cause of morbidity and treatment-related death. Guidelines agree steroid-refractory cases warrant infliximab, however best management of infliximab-refractory ICI gastrointestinal toxicity (IRIGItox) is unknown.
METHODS
We conducted an international multicenter retrospective case series. IRIGItox was defined as failure of symptom resolution ≤grade 1 (Common Terminology Criteria for Adverse Events V.5.0) following ≥2 infliximab doses failure of symptom resolution ≤grade 2 after one dose. Data were extracted regarding demographics, steroid use, response to treatment, and survival outcomes. Toxicity was graded at symptom onset and time of infliximab failure. Efficacy of infliximab refractory therapy was assessed by symptom resolution, time to resolution and steroid wean duration. Survival outcomes were examined based on immunosuppressive therapy received.
RESULTS
78 patients were identified: median age 60 years; 56% men; majority melanoma (N=70, 90%); 60 (77%) received anti-cytotoxic T-lymphocyte-associated protein 4 alone or in combination with anti-programmed cell death protein-1 and most had colitis (N=74, 95%). 106 post-infliximab treatments were given: 31 calcineurin inhibitors (CNIs); 27 antimetabolites (mycophenolate, azathioprine); 16 non-systemic immunomodulatory agents (eg, mesalazine or budesonide); 15 vedolizumab; 5 other biologics (anti-interleukin-12/23, 16, Janus kinase inhibitors) and 7 interventional procedures (including colectomy); 5 did not receive post-infliximab therapy. Symptom resolution was achieved in most (N=23/31, 74%) patients treated with CNIs; 12/27 (44%) with antimetabolites; 7/16 (44%) with non-systemic immunomodulation, 8/15 (53%) with vedolizumab and 5/7 (71%) with interventional procedures. No non-vedolizumab biologics resulted in toxicity resolution. CNIs had the shortest time to symptom resolution (12 days) and steroid wean (43 days); however, were associated with poorer event-free survival (6.3 months) and overall survival (26.8 months) than other agents. Conversely, vedolizumab had the longest time to toxicity resolution and steroid wean, 66 and 124 days, but most favorable survival data: EFS 24.5 months; median OS not reached. Six death occurred (three due to IRIGItox or management of toxicity; three with persisting IRIGItox progressive disease).
CONCLUSIONS
IRIGItox causes major morbidity and mortality. Management is heterogeneous. CNIs appear most likely to result in toxicity resolution in the shortest time period, however, are associated with poorer oncological outcomes in contrast to vedolizumab.
Topics: Male; Humans; Middle Aged; Female; Infliximab; Immune Checkpoint Inhibitors; Retrospective Studies; Colitis; Steroids; Antimetabolites; Biological Products
PubMed: 38296594
DOI: 10.1136/jitc-2023-008232 -
Yakugaku Zasshi : Journal of the... 2024We experienced a case in which long-term use of nivolumab in a patient with a history of ulcerative colitis led to disease control of gastric cancer. The case is a...
We experienced a case in which long-term use of nivolumab in a patient with a history of ulcerative colitis led to disease control of gastric cancer. The case is a 77-year-old man. The patient had a history of ulcerative colitis and remained in remission on mesalazine 1500 mg/d. With continuous monitoring, nivolumab could be continued up to 16 courses, but was withdrawn due to the appearance of diarrhea (grade 1) and bloody stools, which was relieved with prednisolone (PSL) 40 mg/d. After two more courses, diarrhea (grade 3) appeared again, which improved with PSL 60 mg/d and increased dose of mesalazine. It is difficult to distinguish whether colitis that occurs after nivolumab administration is due to relapse exacerbation or irAE. The onset of irAE colitis is often reported within 3 months, and the fact that this patient developed irAE colitis after 8 months, despite having ulcerative colitis, is considered novel. In the future, we hope to accumulate cases so that immune checkpoint inhibitors can be used safely in patients with ulcerative colitis, and to establish appropriate methods for their use.
Topics: Male; Humans; Aged; Nivolumab; Colitis, Ulcerative; Stomach Neoplasms; Mesalamine; Colitis; Prednisolone; Diarrhea
PubMed: 38296500
DOI: 10.1248/yakushi.23-00167 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2023The patient suffered from a mild form of COVID-19 and was treated on an outpatient basis. According to the family doctor's prescription, she took Azithromycin 500 mg a...
The patient suffered from a mild form of COVID-19 and was treated on an outpatient basis. According to the family doctor's prescription, she took Azithromycin 500 mg a day per os for 6 days, and then Ceftriaxone 1.0 g twice a day i.m. for another 6 days. Diarrhea appeared on the 10th day of treatment up to 10-15 times a day, a month later - blood admixtures in the stool appeared. The result was negative. Data from colonoscopy and histological examination of the intestinal mucosa and the clinical picture showed nonspecific ulcerative colitis, moderately severe. The patient started treatment with Salofalk first at a dose of 2 mg and then 4 mg per day. Due to the insufficient clinical effect, the patient was additionally prescribed Budenofalk in a daily dose of 9 mg with a positive clinical effect.
Topics: Female; Humans; Colitis, Ulcerative; COVID-19; Mesalamine; Azithromycin; Diarrhea
PubMed: 38290040
DOI: 10.36740/WLek202312125 -
Immunity, Inflammation and Disease Jan 2024Nexrutine is an herbal extract derived from Phellodendron amurense, known for its anti-inflammatory, antidiarrheal, and hemostatic properties. However, its effect on...
BACKGROUND
Nexrutine is an herbal extract derived from Phellodendron amurense, known for its anti-inflammatory, antidiarrheal, and hemostatic properties. However, its effect on ulcerative colitis (UC) remains unclear.
METHODS
A mouse model of UC was induced by 3% dextran sulfate sodium, while human colonic epithelial cells NCM-460 were exposed to lipopolysaccharide. Both models were treated with Nexrutine at 300 or 600 mg/kg, with Mesalazine applied as a positive control regimen. The disease activity index (DAI) of mice was calculated, and the pathological injury scores were assessed through hematoxylin and eosin staining. The viability of NCM-460 cells was determined using the CCK-8 method. Inflammatory cytokines were detected using ELISA kits. Expression of mucin 3 (MUC3), Claudin-1, and tight junction protein (ZO-1) was detected to analyze mucosal barrier integrity. Target genes of Nexrutine were predicted using bioinformatics tools. Expression of RELA proto-oncogene (RELA) was analyzed using qPCR and western blot assays.
RESULTS
The Nexrutine treatments significantly alleviated DAI of mice, mitigated pathological changes in their colon tissues, decreased the production of pro-inflammatory cytokines, enhanced the barrier integrity-related proteins, and increased NCM-460 cell viability in vitro. RELA, identified as a target gene of Nexrutine, showed elevated levels in UC models but was substantially suppressed by Nexrutine treatment. Adenovirus-mediated RELA upregulation in mice or the overexpression plasmid of RELA in cells counteracted the effects of Nexrutine treatments, exacerbating UC-related symptoms.
CONCLUSION
This study demonstrates that Nexrutine alleviates inflammatory mucosal barrier damage in UC by suppressing RELA transcription.
Topics: Humans; Animals; Mice; Colitis, Ulcerative; Mesalamine; Cytokines; Inflammation; Transcription Factor RelA; Plant Extracts
PubMed: 38270298
DOI: 10.1002/iid3.1147