Search Results (79)

The anti-inflammatory scaffold 5-aminosalicylic acid, which is widely used in therapeutic applications, was chosen for the synthesis of N-[3-(hydrazinecarbonyl)-4-hydroxyphenyl]acetamide (1) to enhance its antibacterial properties. The condensation of hydrazide 1 with aromatic aldehydes provided hydrazone derivatives 2a–f, whereas cyclocondensation reactions and other related transformations afforded five-membered heterocycles, including pyrrole 3, pyrazole 4, pyrrolidinone 7, oxadiazoles 9, 10, thiadiazole 14, and triazole 15. Additional modifications yielded acetylhydrazine derivative 11, which was O-alkylated to analogue 12. Antibacterial evaluation showed stronger activity against Gram-positive bacteria such as S. aureus and MRSA than against Gram-negative strains of E. coli and S. Enteritidis, consistent with differences in cell membrane permeability. Notably, derivatives containing pyrrolidinone 7, thiosemicarbazide 13, and 1,3,4-thiadiazole 14 exhibited potent bactericidal activity against S. aureus and MRSA, while hydrazones 2b, 2c, 2f, pyrrole 3, and pyrrolidinone 7 exhibited activity against E. coli. These results provide a practical strategy for the discovery of heterocyclic compounds and emphasise the potential of functionalised 5-aminosalicylic acid derivatives as prime candidates for the development of broad-spectrum antibacterial agents. Full article

The formation of interfacial charge transfer (ICT) complexes between phenolic ligands and metal oxide surfaces enables surface functionalization strategies with potential applications in catalysis and bioconjugation. In this study, magnetite (Fe₃O₄) nanoparticles were modified with two phenolic ligands, 5-aminosalicylic acid (5ASA) and caffeic acid (CA), to generate ICT complexes capable of covalent or non-covalent enzyme immobilization, respectively. The modified nanomaterials were structurally characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FTIR). Horseradish peroxidase (HRP) was immobilized on these functionalized supports using varying nanoparticle amounts (10–30 mg) and initial enzyme concentrations (25–250 µg mL⁻¹). Catalytic activity was evaluated using pyrogallol oxidation assays. The Fe₃O₄/5ASA–HRP system exhibited a maximum activity of 2.5 U per 20 mg of support (approximately 125 U g⁻¹), whereas Fe₃O₄/CA showed minimal activity under the same conditions. Enzyme loading studies confirmed that 5ASA-enabled covalent attachment resulted in significantly higher immobilization efficiency (up to 1068 mg g⁻¹) compared to the CA system. Reusability tests demonstrated that the Fe₃O₄/5ASA system retained high absolute catalytic activity during the initial reaction cycles and consistently outperformed the non-covalently immobilized Fe₃O₄/CA system upon repeated reuse. The magnetic properties of Fe₃O₄ allowed rapid recovery of the biocatalysts using an external magnetic field. These results highlight the effectiveness of ICT-based functionalization for enzyme immobilization, positioning Fe₃O₄/5ASA as a promising platform for robust and reusable biocatalysts in environmental and industrial applications. Full article

Gallium-based liquid metals have been extensively studied in the field of biomedical engineering, including applications in tumor and inflammatory disease therapy, as well as targeted drug delivery. Among these, leveraging the photothermal effect of gallium liquid metals enables effective treatment of heat-sensitive cells in tumor regions and enhances the diffusion capability of liquid metal microdroplets. However, research on the active treatment of ulcerative colitis (UC) using photothermal therapy with liquid metals remains unexplored. This study focuses on constructing an active composite colloidal motor based on gallium indium liquid metal alloy, using liquid metal microdroplets as the core. Through layer-by-layer assembly of polyelectrolytes, a liquid metal active droplet loaded with the drug mesalazine (5-aminosalicylic acid), named as LMAD-A was developed. Under asymmetric light fields generated by NIR-II light source irradiation, LMAD-A exhibits autonomous locomotion, achieving an effective diffusion coefficient more than 800 times greater than that of Brownian motion in liquid metal microdroplets of similar size. Furthermore, LMAD-A demonstrates phototactic behavior, moving toward the NIR light source autonomously. Through in vitro and in vivo experiments in mice, it was verified that LMAD-A can aggregate, deform, and fuse in the mouse colon under photothermal effects, leading to enhanced release of the loaded drug. In simulated treatments, LMAD-A significantly alleviated DSS-induced colitis in mice, confirming the targeted therapeutic capability of active liquid metal microdroplets as an active therapeutic agent in UC-affected regions. Full article

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition of the gastrointestinal tract, characterized by dysregulated inflammatory responses throughout the gastrointestinal tract. It includes two major phenotypes, Crohn’s disease (CD) and ulcerative colitis (UC), which present with varying gastrointestinal and systemic symptoms. The pathophysiology of IBD is multifactorial including genetic predisposition, mucosal and epithelial dysfunction, environmental injury, and both innate and adaptive immune response abnormalities. Several predisposing genetic factors have been associated with IBD explaining the strong hereditary risk for both CD and UC. For example, Caspase Recruitment Domain 9 (CARD9) variant rs10781499 increases risk for IBD, while other variants are specific to either CD or UC. CD is related to loss-of-function mutations in the nucleotide oligomerization domain containing the protein 2 (NOD2) gene and Autophagy-Related 16-like 1 (ATG16L1) gene. UC risk is increased particularly in Chinese populations by the A-1661G polymorphism of the Cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene. This abnormal CTLA-4 interferes with B- and T-cell responses causing predisposition to autoimmune conditions. Previous studies suggested that IBD results from breakdown of the adaptive immune system, primarily of T-cells. However, new evidence suggests that a primary breakdown of the innate immune system in both CD and UC increases susceptibility to invasion by viruses and bacteria, with a compensatory overactivation of the adaptive immune system as a result. When this viral and microbial invasion continues, further damage is incurred, resulting in a downward cycle of further cytokine activation and epithelial damage. Released biomarkers also affect the permeability of the epithelial membrane, including lactoferrin, nitric oxide (NO), myeloperoxidase (MPO) and its activation of hypochlorous acid, matrix metalloproteinases (MMPs), especially MMP-9, omentin-1, and others. Increased macrophage and dendritic cell dysfunction, increased neutrophil activity, increased numbers of innate lymphoid cells, increased T-cells with decreased regulatory T-cells (Tregs), and changes in B-cell populations and immunoglobulin (Ig) functions are all associated with IBD. Finally, treatment of IBD has typically consisted of medical management (e.g., aminosalicylates and corticosteroids) and lifestyle modification, and surgical intervention in extreme cases. New classes of medications with more favorable side effect profiles include anti-integrin antibodies, vedolizumab, etrolizumab, and carotegrast methyl. Additionally, fecal microbiota transplant (FMT) is a newer area of research for treatment of IBD along with TNF-blockers, JAK inhibitors, and S1PR modulators. However, expense and long preparation time have limited the usefulness of FMT. Full article

Amino acids are not just monomers of proteins, but they can also carry biological functions. L-cysteine (Cys), L-proline (Pro), L-asparagine (Asn), and L-glutamic acid (Glu) were used to evaluate how different amino acid chemistries alter the morphology and size of the silver nanoparticles (AgNPs) synthesized in the presence of two carbohydrate ligands, which were lactose methoxyaniline (LMA) and galactose 5-aminosalicylic acid (G5AS). UV–vis, infrared (IR), High-Resolution Transmission Electron Microscopy (HR-TEM) and X-ray diffraction (XRD) characterizations revealed that the effect of amino acids on the characteristics of the AgNPs showed dependence on the carbohydrate ligand chemistry. In the case of LMA, AgNPs shifted from aggregates to anisotropic nanoparticles, larger aggregates, and a mixture of anisotropic and 1D nanoparticles in the presence of Cys, Glu, Asn and Pro amino acids, respectively. In contrast to this, the introduction of Cys and Asn caused the formation of cluster-like AgNPs and larger rounded nanoparticles, while G5AS-synthesized AgNPs were multigonal 0D particles. Moreover, Glu and Pro contributed the resistance of silver oxide formation on the particles. Antibacterial characterization showed that LMA_Glu_AgNPs were the most effective ones, while LMA_Cys_AgNPs and G5AS_Cys_AgNPs, which were the smallest AgNPs, did not show any significant antibacterial activity. Full article

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