Search Results (74)

Background: Ulcerative colitis (UC) is increasing in incidence, including among pediatric populations. Treatment aims primarily to induce and maintain remission. For those inadequately responding to 5-aminosalicylic acid, remission may be induced via oral steroids or, in severe instances, intravenous methylprednisolone. This retrospective case series aims to evaluate the efficacy of high-dose intravenous methylprednisolone pulses (30 mg/kg, max 1 g per day for 3–5 days) in inducing remission in moderate and severe pediatric UC cases. Methods: From a cohort of pediatric patients (<18 years) hospitalized in 2018–2021 due to an acute flare of UC, those treated with high doses of methylprednisolone to induce remission were identified. The Pediatric Ulcerative Colitis Activity Index (PUCAI) was used to determine the response to treatment, considering a 20-point reduction or a score below 10 as significant improvement and indicative of remission induction. Results: Disease activity was severe in most patients (12/15), with 3/15 having moderate but refractory disease. We observed a clinically significant response in 9/15 patients (60%) with a mean PUCAI decrease of 39.4 ± 14.7 points. The median duration to clinical remission was 4 (IQR 3–4) days. For the 6/15 non-responders to methylprednisolone pulses, treatment was escalated. Adverse effects were not observed during the treatment period. Conclusions: High-dose methylprednisolone may be a viable alternative for inducing remission in pediatric UC. However, the small sample size and retrospective design warrant further prospective studies to validate these findings. Full article

Smart packaging materials (SPMs) combine the properties of intelligent and active packaging into a single system, enabling for the monitoring of the packaged product while enhancing its desired conditions. In this study, poly(lactic acid) (PLA) was used as the base polymer and functionalized with in situ synthesized gold nanoparticles (AuNPs) and methyl red (MR) as a pH-sensitive dye. Various additives, including poly(amic) acid (PAA), bromothymol blue (BB), 5-aminosalicylic acid (5AS), glutaraldehyde (GA), and silver and gold nanoparticles (AgNPs, Au NPs), were tested to optimize the SPMs. To evaluate their performance, the synthesized SPMs were characterized using UV-Vis spectroscopy, IR spectroscopy, SEM, microbiological assays, and mechanical tests. Our results revealed that PLA films containing AuNPs and MR exhibited excellent mechanical, chemical, and antimicrobial properties, making them highly suitable for smart packaging applications. In contrast, the addition of PAA disrupted film formation, while AgNPs and blueberry extracts increased the brittleness of the films, thereby limiting their practical use. Furthermore, BB was found to inhibit the in situ synthesis of AuNPs. A real-world application study demonstrated that cheddar cheese wrapped in the optimized PLA films remained unspoiled after 12 months of refrigeration. IR spectroscopy confirmed that no film components migrated into the cheese during the storage period. GA was identified as a critical component for maintaining the structural integrity of the films over the 12-month storage period. This is the first study to report on the development of PLA-based SPMs that incorporate AuNPs, MR, and GA, offering a promising solution for sustainable and intelligent food packaging. Full article

Background: 5-Aminosalicylic acid (5-ASA), the first-line therapy for ulcerative colitis, is a poorly soluble zwitterionic drug. Unformulated 5-ASA is thought to be extensively absorbed in the small intestine. Methods: The pH-dependent solubility of 5-ASA in vitro and the intestinal membrane distribution of 5-ASA and its N-acetyl metabolite (AC-5-ASA) after the oral administration of 5-ASA were examined in fed rats. 5-ASA was administered as a suspension in water, 0.1 M HCl, or 0.1 M NaOH to untreated rats or as a solution in 5% NaHCO₃ to lansoprazole-pretreated rats. Results: 5-ASA solubility in vitro was higher at pH < 2 and pH > 7. In rats, the 5-ASA and AC-5-ASA were detected mostly in the small intestine at 3 h and in the colonic region at 8 h after administration. The dosing vehicle (suspension or solution) and lansoprazole pretreatment did not significantly affect the pH of the luminal fluid in rats or the 5-ASA distribution in membranes. Conclusions: The 5-ASA distribution in membranes in the proximal intestine was found to be restricted by the intrinsic regional luminal pH, low solubility, and saturable membrane permeability. Unabsorbed 5-ASA in the proximal intestine was delivered to the distal intestine. The higher the oral dose of 5-ASA, the more 5-ASA may be delivered to the distal intestine due to the restricted absorption in the small intestine. Full article

Background/Objectives: 5-Aminosalicylic acid (5-ASA) is a first-line therapy for ulcerative colitis (UC). This study examined the mucosa-associated microbiota (MAM) in UC patients, distinguishing between those who were 5-ASA tolerant and intolerant. Methods: Brushing samples were collected from the sigmoid and ileal end of patients with UC during endoscopic procedures. The samples were profiled by using the Illumina MiSeq platform. The V3–V4 regions of the 16S rRNA gene (460 bp) were amplified by using tailed PCR. Results: A total of 15 patients with 5-ASA intolerance, 38 patients with 5-ASA tolerance, and 19 healthy controls were recruited in this study. The α-diversity indices were remarkably different among the three groups in the ileum mucosa but not in the sigmoid colon. In the ileum mucosa, Alistipes, Ruminococcaceae, and Odoribacter were less abundant in the 5-ASA-intolerant group than in the control and 5-ASA-tolerant groups. On the contrary, Merdibacter, Brevundimonas, and Porphyromonas were more abundant in the 5-ASA-intolerant group than in other groups. Conclusions: The present study showed that the changes in MAM were characterized by a decrease in mucoprotective bacteria rather than an increase in harmful bacteria. Full article

Biliverdin IXβ reductase (BLVRB) has emerged as a promising therapeutic target for thrombocytopenia due to its involvement in reactive oxygen species (ROS) mechanisms. During the pursuit of inhibitors targeting BLVRB, olsalazine (OSA) became apparent as one of the most potent candidates. However, the direct application of OSA as a BLVRB inhibitor faces challenges, as it is prone to degradation into 5-aminosalicylic acid through cleavage of the diazenyl bond by abundant azoreductase (AzoR) enzymes in gut microbiota and eukaryotic cells. To overcome this obstacle, we devised olsalkene (OSK), an inhibitor where the diazenyl bond in OSA has been substituted with an alkene bond. OSK not only matches the efficacy of OSA but also demonstrates improved stability against degradation by AzoR, presenting a promising solution to this limitation. Furthermore, we have found that both OSK and OSA inhibit BLVRB, regardless of the presence of nicotinamide adenine dinucleotide phosphate, unlike other known inhibitors. This discovery opens new avenues for investigating the roles of BLVRB in blood disorders, including thrombocytopenia. Full article

Background: Current management of mild-to-moderate ulcerative colitis (UC) involves monitoring clinical markers of disease activity, such as stool frequency (SF) and rectal bleeding (RB), and adjusting treatment accordingly. Our aim was to assess whether targeting treatment based on faecal calprotectin (FC) levels (treat-to-target; T2T) provides greater UC disease control versus a symptom-based approach. Methods: This was a pragmatic, randomised (1:1) controlled study of patients with mild-to-moderate UC (global Mayo score 2–6) treated with ≤2.4 g/day 5-aminosalicylic acid that compared the effectiveness of two management strategies with (interventional arm) and without (reference arm) FC home monitoring over 12 months of follow-up. Treatment was optimised in the interventional arm using FC values and clinical symptoms (PRO-2), while the reference arm used only PRO-2. Results: 193 patients completed the study. No significant difference was found for the primary endpoint (Mayo Endoscopic Subscore [MES] = 0 at 12 months). A numerical advantage for the interventional arm over the reference arm for the primary endpoint (37.0% vs. 33.4%, respectively) and for MES ≤ 1, RB = 0, and SF ≤ 1 at 12 months was found following imputation for missing data. The composite endpoint of MES = 0, RB = 0, and SF ≤ 1 at 12 months was achieved at a significantly higher rate in the interventional arm than the reference arm (effect size [ES]: 0.17, 95% CI 0.02–0.32; p < 0.05). A similar result was obtained for MES ≤ 1, RB = 0 and SF ≤ 1 (ES: 0.22; 95% CI 0.07–0.37; p < 0.05). Conclusions: T2T using FC monitoring was effective in patients with mild-to-moderate UC at 12 months. Further longer-term studies are required to confirm the results. Full article

Mild-to-moderate ulcerative colitis (UC) management is centred on 5-aminosalicylic acid (5-ASA) derivatives. Whether supplementing 5-ASA with nutraceuticals can provide real advantages in UC-relevant outcomes is unclear. This retrospective multicentre study compared clinical remission, response rates, and faecal calprotectin levels in a two-arm design, including patients treated with 5-ASA alone and those with additional H. erinaceus-based multi-compound supplementation. In the 5-ASA alone group, clinical response rates were 41% at three months (T₁) and 60.2% at six months (T₂), while corresponding clinical remission rates were 16.9% and 36.1%. In the nutraceutical supplementation group, clinical response rates were 49.6% (T₁) and 70.4% (T₂), with clinical remission rates of 30.4% (T₁) and 50.9% (T₂). No significant differences in clinical response rates between the groups at T₁ (p = 0.231) and T₂ (p = 0.143) emerged. Clinical remission rates differed significantly at both time points (p = 0.029 and p = 0.042, respectively). Faecal calprotectin levels decreased significantly in both groups during the retrospective follow-up (p < 0.05), and this was more pronounced in nutraceutical supplementation patients at both T₁ (p = 0.005) and T₂ (p = 0.01). No adverse events were reported. This multi-component nutraceutical supplementation offers real-world potential in controlling disease activity in patients with mild-to-moderate UC. Full article

Diabetic wounds (DWs) are considered chronic complications observed in patients suffering from type 2 diabetes mellitus (DM). Usually, DWs originate from the interplay of inflammation, oxidation, impaired tissue re-epithelialization, vasculopathy, nephropathy, and neuropathy, all of which are related to insulin resistance and sensitivity. The conventional approaches available for the treatment of DWs are mainly confined to the relief of wound pressure, debridement of the wound, and management of infection. In this paper, we speculate that treatment of DWs with 5-aminosalicylic acid (5-ASA) and subsequent activation of peroxisome proliferator-activated receptor gamma (PPAR-γ) and transforming growth factor beta (TGF-β) via the AhR pathway might be highly beneficial for DW patients. This estimation is based on several lines of evidence showing that 5-ASA and PPAR-γ activation are involved in the restoration of insulin sensitivity, re-epithelialization, and microcirculation. Additionally, 5-ASA and TGF-β activate inflammation and the production of pro-inflammatory mediators. Suitable stabilized formulations of 5-ASA with high absorption rates are indispensable for scrutinizing its probable pharmacological benefits since 5-ASA is known to possess lower solubility profiles because of its reduced permeability through skin tissue. In vitro and in vivo studies with stabilized formulations and a control (placebo) are mandatory to determine whether 5-ASA indeed holds promise for the curative treatment of DWs. Full article

Ulcerative colitis (UC) is characterized by continuous mucosal ulceration of the colon, starting in the rectum. 5-Aminosalicylic acid (5-ASA) is the main therapy for ulcerative colitis; however, it has side effects. Physical exercise effectively increases the number of anti-inflammatory and anti-immune cells in the body. In the current study, the effects of simultaneous treatment of treadmill exercise and 5-ASA were compared with monotherapy with physical exercise or 5-ASA in UC mice. To induce the UC animal model, the mice consumed 2% dextran sulfate sodium dissolved in drinking water for 7 days. The mice in the exercise groups exercised on a treadmill for 1 h once a day for 14 days after UC induction. The 5-ASA-treated groups received 5-ASA by enema injection using a 200 μL polyethylene catheter once a day for 14 days. Simultaneous treatment improved histological damage and increased body weight, colon weight, and colon length, whereas the disease activity index score and collagen deposition were decreased. Simultaneous treatment with treadmill exercise and 5-ASA suppressed pro-inflammatory cytokines and apoptosis following UC. The benefits of this simultaneous treatment may be due to inhibition on nuclear factor-κB/mitogen-activated protein kinase signaling activation. Based on this study, simultaneous treatment of treadmill exercise and 5-ASA can be considered as a new therapy of UC. Full article

Background/Objectives: The treatment of patients with mild-to-moderate ulcerative colitis (UC) is challenging. Although there are commonly used guidelines, therapy optimization is not standardized. We conducted a survey to investigate the management and treatment of patients with mild-to-moderate UC. Methods: Physicians with experience in treating inflammatory bowel diseases (IBD) were invited to participate in an anonymous, multiple-choice survey between June and July 2023. The survey addressed various issues of patient care such as patient monitoring, treatment optimization, follow-up, treatment decision making, and therapy de-escalation. Results: The survey included 222 physicians (59.9% men; mean age = 50.4 years) from 66 countries worldwide. Gastroenterologists were the most represented specialists (89.6%), followed by surgeons (3.2%), and internal medicine doctors (2.7%). Two-thirds of the participants (66.7%) had >10 years of experience in the field of IBD. The combination of oral (≥4 g/day) and rectal 5-aminosalicylic acid (5-ASA) was the preferred choice when optimizing therapy. Budesonide MMX (41.8%) and systemic steroids (39.9%) were preferred in patients who failed 5-ASA. Treatment decisions were predominantly based on endoscopic (99.0%) or clinical (59.8%) activity. A significant percentage of clinicians did not optimize therapy in the case of increased fecal calprotectin alone (45.1%) or radiological/ultrasound activity (39.8%) alone. Conclusions: The guidelines for the management of mild-to-moderate UC are well accepted in clinical practice. Endoscopic remission remains the main therapeutic target, followed by clinical remission. Fecal calprotectin and intestinal ultrasound still elicit complaints from physicians. Full article

Introduction: Hepatitis B virus (HBV) infection has been associated with chronic hepatitis and cirrhosis. Patients with inflammatory bowel disease (IBD) may be at a higher risk of HBV infection reactivation, especially those on biologic therapies. This study intends to compare the effectiveness of the HBV vaccine in patients with ulcerative colitis (UC) on infliximab (IFX) compared to those on 5-aminosalicylic acid (5-ASA). Methods: Patients with UC aged >18 years old were prospectively enrolled in the study. The patients were divided into two groups: patients treated with 5-ASA (control group) and patients treated with IFX (study group). HBV vaccination was administered (20 mcg) following the standard regimen, and Hepatitis B serum antibody (HbsAb) titers were assessed three months after the final dose. The response to HBV vaccines was categorized as an ‘adequate’ immune response (≥10 IU/L) and ‘effective’ immune response (≥100 IU/L). Results: In our final analysis of 118 patients with UC, 54.2% were male and 52.5% had extensive colitis. HBsAb titer levels were significantly higher in the 5-ASA group (126.7 ± 37.5) compared to the IFX group (55.5 ± 29.4). Stratifying HBsAb levels into two categories (≥10–99 IU/L and ≥100 IU/L) revealed a significantly greater proportion of subjects in the 5-ASA group with levels ≥100 IU/L compared to the IFX group (76.7% vs. 12.1%, p < 0.001). Logistic regression analysis demonstrated that patients with UC receiving 5-ASA were 23.94 times more likely to exhibit HBsAb levels ≥ 100 compared to those treated with IFX (OR = 23.94, 95% CI 8.89–64.49). Conclusion: The immune response to hepatitis B vaccination in patients with ulcerative colitis treated with IFX is attenuated compared to those treated with 5-ASA. Therefore, emphasizing the importance of HBV vaccination for patients with IBD before starting anti-TNF therapy, especially IFX, and advocating for screening is imperative in high-risk countries. Determining what levels of HBsAb provide protection and what happens to the levels over time after a booster dose are important clinical questions to be answered by follow-up studies. Full article

Biocatalysis processes based on oxidoreductases, such as fungal laccase, are important for discovering new organic compounds with broad structures and potential applications. They include bioactive compounds, which can be obtained through laccase-mediated oxidation of organic substrates having hydroxyl and/or amino groups especially, e.g., 5-aminosalicylic acid (5-ASA) is characterised for its potential for oxidation by a fungal laccase obtained from a Cerrena unicolor strain. The biotransformation process was optimised in terms of the buffer and co-solvent concentration, buffer pH value, and laccase activity. Selected crude dyes were analysed for their bioactive properties, toxicity, and suitability for the dyeing of wool fibres. The data obtained clearly indicated that a low concentration of the reaction buffer in the pH range from 5 to 6 and in the presence of 10% acetonitrile increased the rate of substrate oxidation and the amount of the product formed. The red-brown compound obtained via laccase-mediated oxidation of 5-aminosalicylic acid showed antioxidant properties and unique antimicrobial activity against Staphylococcus aureus and Staphylococcus epidermidis strains with the MIC value of 0.125 mg/mL detected for the purest dye. In addition, it was reported to have good wool fibre dyeing properties and no irritant effect after patch tests on a selected group with increased skin sensitivity. Full article

Nanoparticles (NPs), a distinct class of particles ranging in size from 1 to 100 nm, are one of the most promising technologies of the 21st century, and titanium dioxide NPs (TiO₂ NPs) are among the most widely produced and used NPs globally. The increased application of TiO₂ NPs raises concerns regarding their global safety and risks of exposure. Many animal studies have reported the accumulation of TiO₂ NPs in female reproductive organs; however, evidence of the resultant toxicity remains ambiguous. Since the surface area and chemical modifications of NPs can significantly change their cytotoxicity, we aimed to compare the toxic effects of pristine TiO₂ powder with surface-modified TiO₂ powders with salicylic acid (TiO₂/SA) and 5-aminosalicylic acid (TiO₂/5-ASA) on the ovaries, oviducts, and uterus on the 14th day following acute oral treatment. The results, based on alterations in food and water intake, body mass, organ-to-body mass ratio, hormonal status, histological features of tissues of interest, and antioxidant parameters, suggest that the modification with 5-ASA can mitigate some of the observed toxic effects of TiO₂ powder and encourage future investigations to create NPs that can potentially reduce the harmful effects of TiO₂ NPs while preserving their positive impacts. Full article

Inflammatory bowel disease (IBD) is a group of intestinal inflammatory diseases characterized by chronic, recurrent, remitting, or progressive inflammation, which causes the disturbance of the homeostasis between immune cells, such as macrophages, epithelial cells, and microorganisms. Intestinal macrophages (IMs) are the largest population of macrophages in the body, and the abnormal function of IMs is an important cause of IBD. Most IMs come from the replenishment of blood monocytes, while a small part come from embryos and can self-renew. Stimulated by the intestinal inflammatory microenvironment, monocyte-derived IMs can interact with intestinal epithelial cells, intestinal fibroblasts, and intestinal flora, resulting in the increased differentiation of proinflammatory phenotypes and the decreased differentiation of anti-inflammatory phenotypes, releasing a large number of proinflammatory factors and aggravating intestinal inflammation. Based on this mechanism, inhibiting the secretion of IMs’ proinflammatory factors and enhancing the differentiation of anti-inflammatory phenotypes can help alleviate intestinal inflammation and promote tissue repair. At present, the clinical medication of IBD mainly includes 5-aminosalicylic acids (5-ASAs), glucocorticoid, immunosuppressants, and TNF-α inhibitors. The general principle of treatment is to control acute attacks, alleviate the condition, reduce recurrence, and prevent complications. Most classical IBD therapies affecting IMs function in a variety of ways, such as inhibiting the inflammatory signaling pathways and inducing IM2-type macrophage differentiation. This review explores the current understanding of the involvement of IMs in the pathogenesis of IBD and their prospects as therapeutic targets. Full article

Tuberculosis remains a serious challenge to human health worldwide. para-Aminosalicylic acid (PAS) is an important anti-tuberculosis drug, which requires sequential activation by Mycobacterium tuberculosis (M. tuberculosis) dihydropteroate synthase and dihydrofolate synthase (DHFS, FolC). Previous studies showed that loss of function mutations of a thymidylate synthase coding gene thyA caused PAS resistance in M. tuberculosis, but the mechanism is unclear. Here we showed that deleting thyA in M. tuberculosis resulted in increased content of tetrahydrofolate (H₄PteGlu) in bacterial cells as they rely on the other thymidylate synthase ThyX to synthesize thymidylate, which produces H₄PteGlu during the process. Subsequently, data of in vitro enzymatic activity experiments showed that H₄PteGlu hinders PAS activation by competing with hydroxy dihydropteroate (H₂PtePAS) for FolC catalysis. Meanwhile, over-expressing folC in ΔthyA strain and a PAS resistant clinical isolate with known thyA mutation partially restored PAS sensitivity, which relieved the competition between H₄PteGlu and H₂PtePAS. Thus, loss of function mutations in thyA led to increased H₄PteGlu content in bacterial cells, which competed with H₂PtePAS for catalysis by FolC and hence hindered the activation of PAS, leading to decreased production of hydroxyl dihydrofolate (H₂PtePAS-Glu) and finally caused PAS resistance. On the other hand, functional deficiency of thyA in M. tuberculosis pushes the bacterium switch to an unidentified dihydrofolate reductase for H₄PteGlu biosynthesis, which might also contribute to the PAS resistance phenotype. Our study revealed how thyA mutations confer PAS resistance in M. tuberculosis and provided new insights into studies on the folate metabolism of the bacterium. Full article