Nanoparticles encapsulated in Abelmoschus esculentus polysaccharide-based pellets as colon targeting approach.

AIM(S): This article explores the application of mesalazine-loaded nanoparticles (MLZ-NPs) encapsulated in Abelmoschus esculentus plant polysaccharide-based pellets (MLZ-NPs-Pellets) for ulcerative colitis. METHODS: MLZ-NPs were prepared and evaluated for diameter, PDI, and entrapment efficiency. In-vitro efficacy study was conducted on Caco-2 cells. MLZ-NPs were encapsulated in polysaccharides to form MLZ-NPs-Pellets and characterised for efficacy in animals and targeting efficiency in human volunteers. RESULTS: Optimised batch of MLZ-NPs were characterised for diameter, PDI, zeta potential and entrapment efficiency which was found to be 145.42 ± 6.75 nm, 0.214 ± 0.049, -31.63 mV and 77.65 ± 2.33(%w/w) respectively. ROS, superoxide and NF-kß were well controlled in Caco-2 cells when treated with MLZ-NPs. In-vivo data revealed that some parameters (body weight, colon length, lipid peroxidase, and glutathione) recovered significantly in the DSS-induced mice model treated with oral MLZ-NPs-Pellets. Gamma scintigraphy revealed that the formulation can effectively target the colon within 600 min. CONCLUSION: MLZ-NPs-Pellets can be effectively used for microbial-triggered colon targeting approach in treating ulcerative colitis.

An In Vitro Study Evaluating the Safety of Mesalazine on Human Nasoepithelial Cells.

Chronic rhinosinusitis (CRS) is a disease characterised by the inflammation of the nasal and paranasal cavities. It is a widespread condition with considerable morbidity for patients. Current treatment for chronic rhinosinusitis consists of appropriate medical therapy followed by surgery in medically resistant patients. Although oral steroids are effective, they are associated with significant morbidity, and disease recurrence is common when discontinued. The development of additional steroid sparing therapies is therefore needed. Mesalazine is a commonly used therapeutic in inflammatory bowel disease, which shares a similar disease profile with chronic rhinosinusitis. This exploratory in vitro study aims to investigate whether mesalazine could be repurposed to a nasal wash, which is safe on human nasoepithelial cells, and retains its anti-inflammatory effects. CRS patients' human nasal epithelial cells (HNECs) were collected. HNECs were grown at an air-liquid interface (ALIs) and in a monolayer and challenged with mesalazine or a non-medicated control. Transepithelial electrical resistance, paracellular permeability, and toxicity were measured to assess epithelial integrity and safety. The anti-inflammatory effects of mesalazine on the release of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) were analysed using human leukemia monocytic cell line (THP-1). mesalazine did not impact the barrier function of HNEC-ALIs and was not toxic when applied to HNECs or THP-1 cells at concentrations up to 20 mM. mesalazine at 0.5 and 1 mM concentrations significantly inhibited TNF-α release by THP-1 cells. mesalazine effectively decreases TNF-α secretion from THP-1 cells, indicating the possibility of its anti-inflammatory properties. The safety profile of mesalazine at doses up to 20 mM suggests that it is safe when applied topically on HNECs.

Impact of mesalazine on the response to COVID-19 vaccination in patients with inflammatory bowel disease: Results of a prospective multicentre study of GETECCU (VACOVEII study). / Impacto de la mesalazina en la respuesta a la vacunación contra la COVID-19 en pacientes con enfermedad inflamatoria intestinal. Resultados de un estudio prospectivo multicéntrico de GETECCU (VACOVEII).

OBJECTIVE: The recommendations of the Spanish Ministry of Health on vaccination in risk groups include mesalazine among the treatments with a possible negative effect on its effectiveness. However, this is not the recommendation of most experts. Our objective was to evaluate the effect of mesalazine on the humoral response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease (IBD). METHODS: VACOVEII is a Spanish, prospective, multicenter study promoted by GETECCU, which evaluates the effectiveness of the SARS-CoV-2 vaccine in patients with IBD. This study includes IBD patients who have recieved the full vaccination schedule and without previous COVID-19 infection. Seroconversion was set at 260BAU/mL (centralized determination) and was assessed 6 months after full vaccination. In this subanalysis of the study, we compare the effectiveness of the vaccine between patients treated with mesalazine and patients without treatment. RESULTS: A total of 124 patients without immunosuppressive therapy were included, of which 32 did not receive any treatment and 92 received only mesalazine. Six months after full vaccination, no significant differences are observed in the mean concentrations of IgG anti-S between both groups. In the multivariate analysis, antibody titers were independently associated with the use of mRNA vaccines and with SARS-CoV-2 infection. CONCLUSION: Mesalazine does not have a negative effect on the response to SARS-CoV-2 vaccines in IBD patients.

Ion-pair vortex assisted liquid phase micro-extraction coupled with UV-visible spectrophotometry for the determination of mesalazine in pharmaceutical formulations.

This study demonstrates an effective, simple, and selective method for monitoring mesalazine in pharmaceutical formulations using liquid phase micro-extraction (LPME) and spectrophotometry. Combining LPME with spectrophotometry is an efficient method for analysing various compounds in different matrices. This method is based on extracting the ion-pair formed between the blue indophenol produced by the oxidative reaction of mesalazine and syringic acid in an alkaline medium and a quaternary ammonium salt into a micro-volume of organic solvent. The experimental parameters influencing LPME performance, such as the type and concentration of the quaternary ammonium ion salt and the type and volume of the extractant solvent, were optimised for optimal detection. The linear range and the limit of detection for measuring red species in pharmaceutical formulations were determined to be 0.005-0.080 µg/mL-1 and 0.003 µg/mL-1, respectively, with a relative standard deviation of 4-6%. The method had a preconcentration factor of 50 at 520nm, making it highly efficient and reliable for monitoring mesalazine in pharmaceutical formulations.

Serum Bile Acid Metabolites Predict the Therapeutic Effect of Mesalazine in Patients with Ulcerative Colitis.

Ulcerative colitis (UC) is a systematic chronic disease characterized by insufficient intestinal absorption, and mesalazine is a common medical treatment. In the present study, 20 normal healthy controls (NC group), 10 unmedicated UC patients (UC group), and 20 mesalazine-responsive and 20 mesalazine-nonresponsive UC patients were recruited. A total of 42 serum BA metabolites, including 8 primary bile acids and 34 secondary bile acids (SBAs), were quantitatively measured. Compared with the NC group, serum SBAs in the UC patients were significantly lower but increased after mesalazine therapy. Differences in the serum TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S metabolites were found between the UC and NC groups, with AUC values of 0.777, 0.800, 0.815, 0.775, and 0.740, respectively. Furthermore, we identified 12-keto LCA as a specific BA marker of UC and BA biomarkers of mesalazine responsiveness. It was concluded that serum SBAs were decreased in UC patients, and TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S might aid in the diagnosis of UC. The abundance of SBAs increased after the mesalazine therapy, and serum 12-keto LCA was identified as an alternative invasive biomarker associated with UC diagnosis and therapeutic response, thereby providing a new approach for the prediction of response to mesalazine therapy in UC patients.

Treatment with gut-specific nonsteroidal anti-inflammatory drug attenuates metabolic inflammation but not body mass in fattening ground squirrels.

The active season of hibernators corresponds to rapid adiposity in preparation for the next hibernation season. We have previously shown that this dramatic increase in adipose mass is associated with metabolic inflammation similar to what is seen in obesity and metabolic disease. We next sought to determine whether curbing this inflammation at its source (i.e., the gut) would attenuate weight gain in fattening 13-lined ground squirrels (Ictidomys tridecemlineatus). We fed active yearling ground squirrels a diet containing the gut-specific nonsteroidal anti-inflammatory drug mesalazine (5-aminosalicylic acid) for 10 wk. Mesalazine treatment had slight effects on microbial community diversity in the cecum and colon. Not surprisingly, mesalazine treatment decreased inflammatory cytokine levels in the ileum and colon. Mesalazine also decreased proinflammatory and increased anti-inflammatory cytokines in omental white adipose tissue (oWAT). Despite this, body mass was unaffected, and caloric intake increased in mesalazine-treated squirrels, mainly in males. Mass of the primary WAT depot, intra-abdominal WAT (iaWAT), or the highly metabolic oWAT were unaltered by treatment, as was adiposity index. Together, these results suggest that mesalazine treatment has some effects on adiposity in fattening ground squirrels, but this treatment needs to be modified to overcome the strong drive to fatten in this species.NEW & NOTEWORTHY Adiposity and obesity are caused, at least in part, by inflammation of metabolic tissues. Hibernators, like ground squirrels, undergo this same metabolic inflammation during their summer fattening period. We attempted to curb this inflammation, and thus fattening, using mesalazine. We found that mesalazine did curb the inflammation but did not affect fattening, likely due to the strong drive to fatten in hibernators.

Bickerstaff's brainstem encephalitis: a rare case of neurologic complication in Ulcerative Colitis.

Bickerstaff's brainstem encephalitis is a rare autoimmune disorder that presents with ataxia, ophthalmoplegia, disturbance of consciousness and quadriplegia. A 45-year-old man with a history of ulcerative colitis (UC) taking mesalazine (5-aminosalicylic acid) visited the emergency room presenting with ataxia, ophthalmoplegia and a progressively worsening cognitive impairment. Cerebrospinal fluid analysis showed mild elevation in protein and white blood cell count and increased intracranial pressure. Anti-GQ1b autoantibodies were found positive in the patient's serum and contrast-enhanced brain magnetic resonance imaging showed diffuse leptomeningeal enhancement and pontine lesions. Based on these findings and the patient's clinical course and history, he was diagnosed with Bickerstaff's brainstem encephalitis. Mesalazine was discontinued and high-dose steroid pulse therapy was started, followed by intravenous immunoglobulin, which resulted in gradual improvement of the neurologic symptoms. When an ulcerative colitis patient presents with progressive cognitive impairment, quadriplegia and disturbance of consciousness and gait, Bickerstaff brainstem encephalitis should be considered in the differential diagnosis and prompt immunotherapy may lead to favorable prognosis.

The long-term effect on surgery-free survival of biological compared to conventional therapy in Crohn's disease in real world-data: a retrospective study.

BACKGROUND: The introduction of biological drugs has led to great expectations and growing optimism in the possibility that this new therapeutic strategy could favourably change the natural history of Inflammatory Bowel Disease (IBD) and, in particular, that it could lead to a significant reduction in surgery in the short and long term. This study aims to assess the impact of biological versus conventional therapy on surgery-free survival time (from the diagnosis to the first bowel resection) and on the overall risk of surgery in patients with Crohn's disease (CD) who were never with the surgical option. METHODS: This is a retrospective, double-arm study including CD patients treated with either biological or conventional therapy (mesalamine, immunomodulators, antibiotics, or steroids). All CD patients admitted at the GI Unit of the S. Salvatore Hospital (L'Aquila. Italy) and treated with biological therapy since 1998 were included in the biological arm. Data concerning the CD patients receiving a conventional therapy were retrospectively collected from our database. These patients were divided into a pre-1998 and post-1998 group. Our primary outcome was the evaluation of the surgery-free survival since CD diagnosis to the first bowel resection. Surgery-free time and event incidence rates were calculated and compared among all groups, both in the original population and in the propensity-matched population. RESULTS: Two hundred three CD patients (49 biological, 93 conventional post-1998, 61 conventional pre-1998) were included in the study. Kaplan-Meier survivorship estimate shows that patients in the biological arm had a longer surgery-free survival compared to those in the conventional arm (p = 0.03). However, after propensity matching analysis, conducted on 143 patients, no significant difference was found in surgery-free survival (p = 0.3). A sub-group analysis showed shorter surgery-free survival in patients on conventional therapy in the pre-biologic era only (p = 0.02; Hazard Ratio 2.9; CI 1.01-8.54) while no significant difference was found between the biologic and conventional post-biologic groups (p = 0.15; Hazard Ratio 2.1; CI 0.69-6.44). CONCLUSION: This study shows that the introduction of biological therapy has only a slight impact on the eventual occurrence of surgery in CD patients over a long observation period. Nevertheless, biological therapy appears to delay the first intestinal resection.

Mesalazine Inhibits Amyloid Formation and Destabilizes Pre-formed Amyloid Fibrils in the Human Insulin.

Amyloid formation due to protein aggregation is associated with several amyloid diseases (amyloidosis). The use of small organic ligands as inhibitors of protein aggregation is an attractive strategy for the treatment of these diseases. In the present study, we evaluated the in vitro inhibitory and destabilizing effects of Mesalazine on human insulin fibrillation. To induce fibrillation, human insulin was incubated in 50 mM glycine buffer (pH 2.0) at 50 °C. The effect of Mesalazine on insulin amyloid aggregation was studied using spectroscopic, imaging, and computational approaches. Based on the results, the Mesalazine in a concentration-dependent manner (different ratios (1:0.1, 1:0.5, 1:1, and 1:5) of the insulin to Mesalazine) prevented the formation of amyloid fibrils and destabilized pre-formed fibrils. In addition, our molecular docking study confirmed the binding of Mesalazine to insulin through hydrogen bonds and hydrophobic interactions. Our findings suggest that Mesalazine may have therapeutic potential in the prevention of insulin amyloidosis and localized amyloidosis.

Significance of 5-Aminosalicylic Acid Intolerance in the Clinical Management of Ulcerative Colitis.

BACKGROUND: Two major types of 5-aminosalicylic acid (5-ASA)-containing preparations, namely, mesalazine/5-ASA and sulfasalazine (SASP), are currently used as first-line therapy for ulcerative colitis. Recent reports show that optimization of 5-ASA therapy is beneficial for both patient outcomes and healthcare costs. Although 5-ASA and SASP have good efficacy and safety profiles, clinicians occasionally encounter patients who develop 5-ASA intolerance. SUMMARY: The most common symptoms of acute 5-ASA intolerance syndrome are exacerbation of diarrhea, fever, and abdominal pain. Patients who discontinue 5-ASA therapy because of intolerance have a higher risk of adverse clinical outcomes, such as hospital admission, colectomy, need for advanced therapies, and loss of response to anti-tumor necrosis factor (TNF) biologics. When patients develop symptoms of 5-ASA intolerance, the clinician should consider changing the type of 5-ASA preparation. Recent genome-wide association studies and meta-analyses have shown that 5-ASA allergy is associated with certain single-nucleotide polymorphisms. Although there are no modalities or biomarkers for diagnosing 5-ASA intolerance, the drug-induced lymphocyte stimulation test can be used to assist in the diagnosis of acute 5-ASA intolerance syndrome with high specificity and low sensitivity. This review presents a general overview of 5-ASA and SASP in the treatment of inflammatory bowel disease and discusses the latest insights into 5-ASA intolerance. KEY MESSAGES: 5-ASA is used as first-line therapy for ulcerative colitis. Optimization of 5-ASA may be beneficial for patient outcomes and healthcare systems. Acute 5-ASA intolerance syndrome is characterized by diarrhea, fever, and abdominal pain. Periodic renal function monitoring is recommended for patients receiving 5-ASA.

Molecular Mechanisms of the Antitumor Effects of Mesalazine and Its Preventive Potential in Colorectal Cancer.

Chemoprevention is one of the ways to fight colorectal cancer, which is a huge challenge in oncology. Numerous pieces of evidence indicate that chronic inflammation in the course of Crohn's disease or ulcerative colitis (UC) is a significant cancer risk factor. Epidemiologic studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs), including mesalazine, has beneficial effects on colitis-associated colorectal cancer. Mesalazine is a first-line therapy for UC and is also widely used for maintaining remission in UC. Data showed that mesalazine has antiproliferative properties associated with cyclooxygenase (COX) inhibition but can also act through COX-independent pathways. This review summarizes knowledge about mesalazine's molecular mechanisms of action and chemopreventive effect by which it could interfere with colorectal cancer cell proliferation and survival.

Mesalazine dose modification based on faecal calprotectin levels in patients with ulcerative colitis in clinical remission. / Modificación de la dosis de mesalazina en función de los niveles de calprotectina fecal en pacientes con colitis ulcerosa en remisión clínica.

BACKGROUND: Faecal calprotectin (FC) shows an excellent correlation with endoscopic and histological activity of ulcerative colitis (UC) and it is the best predictor of clinical relapse. Our aim was to evaluate the usefulness of modifying the dose of mesalazine based on FC levels, in clinical practice. METHODS: Retrospective, single-centre study in UC patients in clinical remission while treated with mesalazine which dosage was decreased (DOWN) or increased (UP) according to FC levels. The main endpoint was the long-term maintenance of clinical remission. RESULTS: A total of 56 patients were included (39 DOWN, 17 UP). In the DOWN group, the median baseline dose of mesalazine was 3.6g/day and the median baseline FC was 36µg/g. After a median follow-up of 22 months, 28% required rescue therapy. The cumulative relapse-free survival after tapering was 91% and 82% at 12 and 24 months, respectively. In the UP group, the median baseline dose of mesalazine was 2.4g/day, with a median baseline FC of 524µg/g. After a median follow-up of 12 months, 29% required rescue therapy. The cumulative relapse-free survival after dose increase was 86% and 72% at 12 and 24 months, respectively. CONCLUSIONS: Mesalazine dose modification based on FC monitoring seems to be a safe strategy in patients with UC in clinical remission, with a probability of clinical relapse around 20% at two years.

Clinical and endoscopic outcomes of patients with colonic Crohn's disease treated with 5-aminosalicylates as monotherapy.

BACKGROUND: In spite of the lack of evidence regarding the clinical benefits of oral 5-aminosalicylic acid (5-ASA) compounds in Crohn's disease (CD), these drugs are frequently used in daily clinical practice, particularly for colonic CD. Our aim is to assess the use and clinical outcomes of 5-ASA of those patients with colonic CD treated with 5-ASA as monotherapy. METHODS: Patients diagnosed with isolated colonic CD and treated with 5-ASA but never exposed to immunosuppressants or biologicals were identified from the local databases of five referral centres. A retrospective review of clinical and endoscopic outcomes was performed. RESULTS: Out of 545 patients with isolated colonic CD, 106 (19%) were treated with oral 5-ASA in monotherapy as maintenance therapy. The median follow-up was 144 months (interquartile range [IQR], 48-234). Almost all of the patients (92%) presented an inflammatory pattern and 11% developed perianal disease. Half of the patients had already received 5-ASA at diagnosis, and the median duration of 5-ASA treatment was 107 months (IQR 22.5-187). Endoscopic remission, as defined by the absence of ulcers at the last complete colonoscopy, was observed in 65% of those patients undergoing at least one colonoscopy during follow-up. Male gender and extraintestinal manifestations were associated with a lower likelihood of achieving endoscopic remission. Nine patients required colectomy, but mostly soon after CD diagnosis. CONCLUSIONS: 5-ASA seems to be of benefit in the long-term in one fifth of patients with colonic CD as the only maintenance therapy and should be considered in fragile patients with Crohn's colitis.

Multinational evaluation of clinical decision-making in the treatment and management of mild-to-moderate ulcerative colitis.

OBJECTIVES: To understand current thinking and clinical decision-making in the treatment and management of patients with mild-to-moderate ulcerative colitis (UC). METHODS: This multinational, survey-based study was conducted in 2021. Two meetings were held, involving 11 IBD specialists, that used a series of questions and discussion to identify all factors possibly related to the management of UC. The importance of identified factors was assessed using an online questionnaire covering three scenarios - active disease, remission and patient empowerment. Each factor was scored on a scale of 0 (very-unimportant) to 100 (very-important) within each scenario, by a separate group of healthcare professionals working in IBD. RESULTS: A total of 157 individual factors were identified by the 11 IBD specialists and scored in the three scenarios by 56 respondents (52; 93% specialist gastroenterologists) from Europe and North America (25; 45%), South America (19; 34%) and the Middle East, Asia and Australia (12; 21%). For all scenarios, factors related to educating patients regarding UC and its treatment and understanding of patient goals ranked highest, ahead of clinical considerations regarding disease activity and treatment history. Setting realistic short-term treatment targets was a key consideration. 5-ASA optimisation and use of faecal calprotectin monitoring were core strategies across the three scenarios tested. Support for patients during longer-term management of their disease, starting from initial flare, was an important recurring theme. CONCLUSION: The current management approach for mild-to-moderate UC was found to be guided primarily by the patient's perspectives and goals, alongside assessment of their medical and disease history.

Acute transverse myelitis in an adult-patient with underlying ulcerative colitis: a case report.

BACKGROUND: Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease that limits to colon mucosa, which characterised by relapsing and remitting abdominal pain and diarrhea. Neurological complications in UC patients are usually underestimated. The most frequently reported neurological disorders associated with UC are peripheral neuropathy, cerebrovascular disease and demyelinating disease. However, acute transverse myelitis (TM) is rarely reported in UC patients. CASE PRESENTATION: We report a case of a 39-year-old man presented with fatigue, muscle weakness, numbness in the lower limbs and fingers with underlying UC. Laboratory results revealed elevated neutrophil count, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. Strip-shaped high signal intensity was identified in the cervical and thoracic spinal cord on T2-weighted magnetic resonance imaging. Acute TM was diagnosed. Significant improvements after intravenous high-dose methylprednisolone were observed. CONCLUSION: We speculate that acute TM may be the extraintestinal manifestation of UC, which may be related to the abnormalities of cell-mediated and humoral immunity rather than the side effect of mesalazine.

The insoluble excretion of multi-matrix system mesalazine preparations in patients with ulcerative colitis.

BACKGROUND: Multi-matrix mesalazine (MMX) is an important treatment for ulcerative colitis (UC); however, it is often excreted intact, which increases the risk of relapse. This study aimed to clarify the risk factors for insoluble MMX excretion. METHODS: The subjects were 102 UC patients who were newly prescribed MMX alone to induce remission. Their stools were evaluated on the Bristol Stool Form Scale (BSFS), the presence/absence of insoluble MMX excretion was investigated in interviews, and defecation frequency at the start of treatment and disease type were retrospectively investigated by examining their medical records. RESULTS: The insoluble excretion rate (IER) was 14.7%. It tended to be higher in the patients with left-sided colitis or extensive colitis, although the differences among the disease types were not significant (p = 0.053). The mean defecation frequency of the patients that reported insoluble MMX excretion was significantly higher than that of the patients that did not report it (6.27 ± 5.28 vs. 3.69 ± 3.17, p < 0.05). The IER tended to be higher among the patients with soft stools (4.5%, 21.9%, and 23.1% in those with BSFS scores of ≤ 4, 5, and ≥ 6, respectively). In ROC analysis of defecation frequency, ≥ 3.5 defecations was found to exhibit sensitivity and specificity of 66.7% and 65.5%, respectively, for predicting insoluble MMX excretion. CONCLUSIONS: The likelihood of insoluble MMX excretion is influenced by defecation frequency and the extent of inflammation. It is important to keep the possibility of insoluble excretion in mind when prescribing MMX.

Development of An HPLC Method for the Determination of Mesalazine in Human Plasma by Fluorimetric Derivatization and Application to A Prototype Pharmacokinetic Study.

In this study, a new, fast and sensitive HPLC method with fluorometric detection was developed for the determination of mesalazine in human plasma and applied to a pharmacokinetic study. Mesalazine was precolumn derivatized with NBD-Cl and the fluorescent derivative was separated on a C18 (150 × 4.6 mm × 2.6 µm) analytical column at 30 ºC using a mobile phase composed of acetonitrile-0.1% o-phosphoric acid in water (70:30, v/v) by isocratic elution with flow rate of 1.0 mL min-1. The method was based on the measurement of the derivative using fluorescence detection (λex = 280 nm, λem = 325 nm). The retention time of mesalazine is 3.08 ± 0.06 min. Nortriptiline was used as internal standard. This currently developed method was validated according to ICH criteria by evaluating the specificity, linearity, precision, accuracy and robustness. The method was determined to be linear in a concentration range of 0.25-1.5 µg mL-1 with the correlation coefficient of 0.9997. LOD and LOQ were found to be 0.075 and 0.25 µg mL-1, respectively. Intraday and interday RSD values were less than 5.92%. The plasma concentration-time profile and pharmacokinetic parameters such as AUC0-t, AUC0-∞, Cmax, tmax, t1/2, were calculated according to the assays. The presented method can certainly be used for bioequivalence and bioavailability investigations and routine analysis of the drug in plasma.

Sodium salicylate and 5-aminosalicylic acid synergistically inhibit the growth of human colon cancer cells and mouse intestinal polyp-derived cells.

As colon cancer is one of the most common cancers in the world, practical prevention strategies for colon cancer are needed. Recently, treatment with aspirin and/or 5-aminosalicylic acid-related agents was reported to reduce the number of intestinal polyps in patients with familial adenomatous polyposis. To evaluate the mechanism of aspirin and 5-aminosalicylic acid for suppressing the colon polyp growth, single and combined effects of 5-aminosalicylic acid and sodium salicylate (metabolite of aspirin) were tested in the two human colon cancer cells with different cyclooxygenase-2 expression levels and intestinal polyp-derived cells from familial adenomatous polyposis model mouse. The combination induced cell-cycle arrest at the G1 phase along with inhibition of cell growth and colony-forming ability in these cells. The combination reduced cyclin D1 via proteasomal degradation and activated retinoblastoma protein. The combination inhibited the colony-forming ability of mouse colonic mucosa cells by about 50% and the colony-forming ability of mouse intestinal polyp-derived cells by about 90%. The expression level of cyclin D1 in colon mucosa cells was lower than that in intestinal polyp-derived cells. These results suggest that this combination may be more effective in inhibiting cell growth of intestinal polyps through cyclin D1 down-regulation.

[Features of the intestine conditions at patients with a new coronavirus infection].

COVID-19 infection may present with gastrointestinal lesions in up to 25% of patients. One of the target organs of the SARS-CoV-2 virus is the intestine. The pathogenesis of intestinal damage in a new coronavirus infection remains unclear and requires further in-depth study. Possible mechanisms include a direct cytotoxic effect of the virus, a persistent reduction in butyrate-producing bacteria, side effects of drugs, Clostridioides difficile infection, microvascular thrombosis, and the immune-mediated inflammatory reactions in the intestine. The most common symptom of intestinal damage during coronavirus infection, both in the acute phase and in the post-COVID period, is diarrhea. The impact of many aggressive factors on the intestines can form both long-term functional disorders and be the cause of the onset of organic diseases. Treatment should be aimed at possible causes of intestinal damage (Clostridioides difficile), as well as reducing inflammation, restoring intestinal permeability, cytoprotection of mucosal cells, replenishing butyric acid deficiency. When choosing a therapy for intestinal disorders, preference should be given to drugs with a pleiotropic effect in order to influence various possible pathogenetic mechanisms.

Ultraperformance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry-Based Metabolomics and Lipidomics Identify Biomarkers for Efficacy Evaluation of Mesalazine in a Dextran Sulfate Sodium-Induced Ulcerative Colitis Mouse Model.

This study aims to identify biomarkers for evaluating the therapeutic efficacy of mesalazine on ulcerative colitis by metabolomics and lipidomics. A dextran sulfate sodium-induced mouse model was used. The disease status was assessed by a disease activity index, the TNF-α level of colon was measured by an enzyme-linked immunosorbent assay, and the pathological changes of colon tissue was examined by hematoxylin-eosin staining. Serum metabolomics and lipidomics analysis based on ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry were applied to decipher the metabolic profile changes. Multivariate analysis was applied to differentiate the metabolites of controls, models, and mesalazine-treated mice. By the receiver operating characteristic (ROC) analysis, 40 differential metabolites with an area under curve (AUC) >0.80 were screened out between control and model groups. Among them, four potential biomarkers (palmitoyl glucuronide, isobutyrylglycine, PC (20:3 (5Z, 8Z, 11Z)/15:0) and L-arginine) had a signficantly reversed level of peak areas in the mesalazine group, and three of them were closely correlated with mesalazine efficacy by linear regression analysis. Furthermore, metabolic pathway analysis revealed several dysregulated pathways in colitis mice, including glycerophospholipid metabolism, pyrimidine metabolism, linoleic acid metabolism, arginine biosynthesis, etc. This study indicates that serum metabolomics is a useful approach that can noninvasively evaluate the therapeutic effect and provide unique insights into the underlying mechanism of mesalazine.