Colonic drug delivery offers numerous pharmaceutical opportunities, including direct access to local therapeutic targets and drug bioavailability benefits arising from the colonic epithelium\'s reduced abundance of cytochrome P450 enzymes and particular efflux transporters. Current workflows for developing colonic drug delivery systems involve time-consuming, low throughput in vitro and in vivo screening methods, which hinder the identification of suitable enabling materials. Polysaccharides are useful materials for colonic targeting, as they can be utilised as dosage form coatings that are selectively digested by the colonic microbiota. However, polysaccharides are a heterogeneous family of molecules with varying suitability for this purpose. To address the need for high-throughput material selection tools for colonic drug delivery, we leveraged machine learning (ML) and publicly accessible experimental data to predict the release of the drug 5-aminosalicylic acid from polysaccharide-based coatings in simulated human, rat, and dog colonic environments. For the first time, Raman spectra alone were used to characterise polysaccharides for input as ML features. Models were validated on 8 unseen drug release profiles from new polysaccharide coatings, demonstrating the generalisability and reliability of the method. Further, model analysis facilitated an understanding of the chemical features that influence a polysaccharide\'s suitability for colonic drug delivery. This work represents a major step in employing spectral data for forecasting drug release from pharmaceutical formulations and marks a significant advancement in the field of colonic drug delivery. It offers a powerful tool for the efficient, sustainable, and successful development and pre-ranking of colon-targeted formulation coatings, paving the way for future more effective and targeted drug delivery strategies.

BACKGROUND: Currently, traditional Chinese medicine (TCM) formulas are commonly being used as adjunctive therapy for ulcerative colitis in China. Network meta-analysis, a quantitative and comprehensive analytical method, can systematically compare the effects of different adjunctive treatment options for ulcerative colitis, providing scientific evidence for clinical decision-making.
OBJECTIVE: To evaluate the clinical efficacy and safety of commonly used TCM for the treatment of ulcerative colitis (UC) in clinical practice through a network meta-analysis.
METHODS: Clinical randomized controlled trials of these TCM formulas used for the adjuvant treatment of UC were searched from the establishment of the databases to July 1, 2022. Studies that met the inclusion criteria were screened and evaluated for literature quality and risk of bias according to the Cochrane 5.1 standard. The methodological quality of the studies was assessed using ReviewManager (RevMan) 5.4, and a funnel plot was constructed to test for publication bias. ADDIS 1.16 statistical software was used to perform statistical analysis of the treatment measures and derive the network relationship and ranking diagrams of the various intervention measures.
RESULTS: A total of 64 randomized controlled trials involving 5456 patients with UC were included in this study. The adjuvant treatment of UC using five TCM formulations was able to improve the clinical outcome of the patients. Adjuvant treatment with Baitouweng decoction (BTWT) showed a significant effect [mean difference = 36.22, 95% confidence interval (CI): 7.63 to 65.76]. For the reduction of tumor necrosis factor in patients with UC, adjunctive therapy with BTWT (mean difference = -9.55, 95%CI: -17.89 to -1.41), Shenlingbaizhu powder [SLBZS; odds ratio (OR) = 0.19, 95%CI: 0.08 to 0.39], and Shaoyao decoction (OR = -23.02, 95%CI: -33.64 to -13.14) was effective. Shaoyao decoction was more effective than BTWT (OR = 0.12, 95%CI: 0.03 to 0.39), SLBZS (OR = 0.19, 95%CI: 0.08 to 0. 39), and Xi Lei powder (OR = 0.34, 95%CI: 0.13 to 0.81) in reducing tumor necrosis factor and the recurrence rate of UC.
CONCLUSIONS: TCM combined with mesalazine is more effective than mesalazine alone in the treatment of UC.

OBJECTIVE: Colorectal cancer is an extremely aggressive form of cancer that often leads to death. Lactoferrin shows potential for targeting and treating colorectal cancer; however, oral delivery faces hurdles hampering clinical applications. We engineered dual-responsive lactoferrin nanostructured microbeads to overcome delivery hurdles and enhance drug targeting.
METHODS: The hydrophobic drug mesalazine (MSZ) was coupled to lactoferrin to form amphiphilic conjugate nanoparticles, dispersed in water. The lipid-soluble polyphenolic drug resveratrol (RSV) was then encapsulated into the hydrophobic core of LF-MSZ nanoparticles. To impart thermoresponsive properties, the dual-payload NPs were coupled with a PNIPAAm shell; finally, to further endow the nanoparticles with gastrointestinal resistance and pH responsiveness, the nanoparticles were microencapsulated into ionically cross-linked pectin-alginate beads.
RESULTS: The nanoparticles showed enhanced internalization and cytotoxicity against HCT colon cancer cells via LF-receptor-mediated endocytosis. Thermal triggering and tuned release were conferred by the temperature-sensitive polymer. The coatings protected the drugs from degradation. Orally delivered microbeads significantly reduced tumor burden in a mouse colon cancer model, lowering carcinoembryonic antigen and elevating antioxidant enzymes. Apoptotic pathways were stimulated, indicated by heightened Bax/Bcl2 ratio and caspase-3/9 expression.
CONCLUSIONS: Overall, we propose the innovative lactoferrin nanostructured microbeads as a paradigm shift in oral colorectal cancer therapeutics.

BACKGROUND: The benefits and risks of Xileisan (XLS) in the treatment of ulcerative colitis (UC) remain unclear.
OBJECTIVE: The present study aimed to evaluate the efficacy and safety of the combination of XLS and mesalazine when treating UC.
METHODS: We searched eight databases for clinical trials evaluating the combination of XLS and mesalazine in the treatment of UC, up to January 2024. Meta-analysis and trial sequential analysis (TSA) were performed using Revman 5.3 and TSA 0.9.5.10 beta, respectively.
RESULTS: The present study included 13 clinical studies involving 990 patients, of which 501 patients received XLS combined with mesalazine while 489 patients received mesalazine alone. The meta-analysis showed that, in terms of efficacy, the combination of XLS and mesalazine significantly improved the clinical efficacy rate by 22% [risk ratio (RR) = 1.22; 95%CI: 1.15-1.28; P < 0.00001] and mucosal improvement rate by 25% (RR = 1.25; 95%CI: 1.12-1.39; P = 0.0001), while significantly reducing the duration of abdominal pain by 2.25 days [mean difference (MD) = -2.25; 95%CI: -3.35 to -1.14; P < 0.0001], diarrhea by 2.06 days (MD = -2.06; 95%CI: -3.92 to -0.20; P = 0.03), hematochezia by 2.32 days (MD = -2.32; 95%CI: -4.02 to -0.62; P = 0.008), tumor necrosis factor alpha by 16.25 ng/mL (MD = -16.25; 95%CI: -20.48 to -12.01; P < 0.00001), and interleukin-6 by 14.14 ng/mL (MD = -14.14; 95%CI: -24.89 to -3.39; P = 0.01). The TSA indicated conclusiveness in the meta-analysis of the efficacy endpoints. In terms of safety, the meta-analysis revealed that the combination of XLS and mesalazine did not increase the occurrence of total and gastrointestinal adverse events, abdominal distension, and erythema (P > 0.05). The TSA showed non conclusive findings in the meta-analysis of the safety endpoints. Harbord\'s test showed no publication bias (P = 0.734).
CONCLUSIONS: Treatment with XLS alleviated the clinical symptoms, intestinal mucosal injury, and inflammatory response in patients with UC, while demonstrating good safety.

Mesalazine represents a key treatment for intestinal bowel diseases and only in rare cases produces cardiac toxicity, with a not completely known mechanism. We report a case of a 25-year-old man with a first episode of myocarditis after 2 weeks from the first mesalazine intake, documented also by a characteristic cardiac magnetic resonance pattern. Then, after less than 1 month, he suffered myocarditis recurrence and so, guided by a multidisciplinary team evaluation, in the suspicion of mesalazine-induced myocarditis, the drug was promptly stopped, with consequent recovery of cardiac damage. In our patient, the recurrence of myocarditis because of the non-interruption of the drug is very peculiar (only three cases described in literature) and definitively confirms the diagnosis.
This paper reports an exemplary case of cardiac toxicity induced by mesalazine, a key treatment for inflammatory bowel diseases such as Crohn\'s disease and ulcerative colitis. In rare cases, this drug can lead to cardiac impairment, with a mechanism not yet clarified. The young patient described experiencing a first episode of myocarditis (inflammation of the heart muscle cells) after 2 weeks of starting mesalazine. The diagnosis was possible thanks to cardiac magnetic resonance, a noninvasive exam providing high-definition images associated with tissue characterization. Mesalazine was not discontinued because drug-induced etiology was not suspected, due to its rarity. Consequently, the patient suffered a second episode of myocarditis, diagnosed by endomyocardial biopsy, an invasive technique that can accurately assess the etiology of myocardial damage, leading to prompt cessation of treatment. Since myocarditis can have various causes, diagnosis was also facilitated through a multidisciplinary team, which ruled out other possible causes for this condition. This case report is highly educational and underscores the importance of clinicians being vigilant about this side effect and considering it in patients taking mesalazine who present with myocarditis, to promptly discontinue the treatment. Mesalazine interruption is otherwise the only effective therapy for this condition, in addition to anti-inflammatory and analgesic drugs. Furthermore, this paper highlights the increasing importance of multidisciplinary teams, comprising various specialists, for accurate diagnosis and therapeutic decisions. The authors also propose an algorithm for diagnosing mesalazine-induced myocarditis, with certainty derived from recurrence after drug rechallenge, either voluntarily or accidentally, as demonstrated in this case.

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by recurrent inflammation of the gastrointestinal tract and has been linked to an imbalance in gut bacteria. Synbiotics, which combine probiotics and prebiotics, are emerging as potential IBD treatments.
OBJECTIVE: To examine the effects of four synbiotic formulations on intestinal inflammation and peripheral biomarkers in a rodent IBD model of both sexes.
METHODS: Colitis was induced in male and female C57BL/6 mice using 1% dextran sulfate sodium (DSS). Concurrently, a non-exposed control group was maintained. Starting on day 4 post-induction, DSS-exposed mice received one of four synbiotic preparations (Synbio1-4 composed of lactic acid bacteria, Bifidobacterium and dietary fibres), an anti-inflammatory drug used to treat IBD (mesalazine), or placebo (water) until day 14. Clinical symptoms and body weight were monitored daily. Blood samples (taken on days -3, 4, and 14, relative to DSS introduction), were used to analyze plasma biomarkers. At the end of the study, intestinal tissues underwent histological and morphological evaluation.
RESULTS: Compared to placebo, the Synbio1-, 2- and 3-treated groups had improved clinical scores by day 14. Synbio1 was the only preparation that led to clinical improvements to scores comparable to those of controls. The Synbio1-and 3-treated groups also demonstrated histological improvements in the colon. Plasma biomarker analyses revealed significant Synbio1-induced changes in plasma IL17A, VEGFD, and TNFRSF11B levels that correlated with improved clinical or histological scores. Sex-stratified analyses revealed that most therapeutic-like effects were more pronounced in females.
CONCLUSIONS: Our findings underscore the potential therapeutic benefits of specific synbiotics for IBD management. However, further research is needed to validate these outcomes in human subjects.

BACKGROUND: The efficacy data on treatment in older adults are scarce, while the greatest increase in ulcerative colitis (UC) prevalence is observed in age groups of individuals 40 to 65 years of age and ≥65 years of age.
OBJECTIVE: We assessed the difference in rates of clinical and endoscopic response and remission in UC adults (≤60 years) and older adults (>60 years) treated with mesalazine.
METHODS: We performed a post hoc analysis of data from a phase 3 noninferiority trial of 817 UC patients treated with mesalazine for 8 and additional 26 weeks in a double-blind and open-label study, respectively. We used Wilcoxon rank sum or chi-square test to analyze differences between groups and multivariable logistic regression to determine the associations between endoscopic remission as outcome (Mayo endoscopic subscore [MES] = 0 or ≤1) and independent variables including disease duration, baseline MES, age, sex, comedications, and comorbidities.
RESULTS: Older adults had a longer disease duration, a higher number of comorbidities, concomitant medications, and higher baseline MES (2.38 ± 0.486 in older adults vs 2.26 ± 0.439 in adults; P = .008) compared with adults. We observed no difference in rates of combined clinical and endoscopic remission, clinical remission and response, and endoscopic remission and response at week 8 and 38 post-treatment. In addition to other well-known predictors of worse outcome, patients with ≥3 comedications were less likely to achieve an MES = 0 at week 8 and 38 and an MES ≤1 at week 38.
CONCLUSIONS: We observed similar efficacy of mesalazine in adult and older adult UC patients. The increased comedication number rather than age may decrease effectiveness of UC medications, highlighting the importance of healthy aging.
We investigated the rates of clinical and endoscopic response in adult (≤60 years) and older adult (>60 years) ulcerative colitis patients treated with oral mesalazine; our results demonstrated that age did not influence the efficacy and safety.

Purpose: Current pharmacological treatments for Ulcerative Colitis (UC) have limitations. Therefore, it is important to elucidate any available alternative or complementary treatment, and Chinese herbal medicine shows the potential for such treatment. As a traditional Chinese herbal medicine, Danshen-related preparations have been reported to be beneficial for UC by improving coagulation function and inhibiting inflammatory responses. In spite of this, the credibility and safety of this practice are incomplete. Therefore, in order to investigate whether Danshen preparation (DSP) is effective and safe in the treatment of UC, we conducted a systematic review and meta-analysis. Methods: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database and CQVIP Database were searched for this review.The main observation indexes were the effect of DSP combined with mesalazine or DSP on the effective rate, platelet count (PLT), mean platelet volume (MPV) and C-reactive protein (CRP) of UC. The Cochrane risk of bias tool was used to assess the risk of bias. The selected studies were evaluated for quality and data processing using RevMan5.4 and Stata17.0 software. Results: A total of 37 studies were included. Among them, 26 clinical trials with 2426 patients were included and 11 animal experimental studies involving 208 animals were included. Meta-analysis results showed that compared with mesalazine alone, combined use of DSP can clearly improve the clinical effective rate (RR 0.86%, 95% CI:0.83-0.88, p < 0.00001) of UC. Furthermore it improved blood coagulation function by decreasing serum PLT and increasing MPV levels, and controlled inflammatory responses by reducing serum CRP, TNF-α, IL-6, and IL-8 levels in patients. Conclusion: Combining DSP with mesalazine for UC can enhance clinical efficacy. However, caution should be exercised in interpreting the results of this review due to its flaws, such as allocation concealment and uncertainty resulting from the blinding of the study. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/myprospero.php, identifier PROSPERO: CRD42022293287.

UNASSIGNED: Diverticular disease (DD) represents a common gastrointestinal condition that poses a heavy burden on healthcare systems worldwide. A high degree of uncertainty surrounds the therapeutic approaches for the control of symptoms in patients with symptomatic uncomplicated diverticular disease (SUDD) and primary and secondary prevention of diverticulitis and its consequences.
UNASSIGNED: To review the current knowledge and discuss the unmet needs regarding the management of SUDD and the prevention of acute diverticulitis.
UNASSIGNED: Randomized trials, observational studies, and systematic reviews on lifestyle/dietary interventions and medical treatment (rifaximin, mesalazine, and probiotics) of SUDD or prevention of acute diverticulitis.
UNASSIGNED: The literature search was performed from inception to April 2023, without language restriction, following the modified Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) reporting guidelines. References of the papers selected were checked to identify additional papers of potential interest. The final list of references was evaluated by a panel of experts, who were asked to check for any lack of relevant studies.
UNASSIGNED: Information on patient population, study design, intervention, control group, duration of the observation, and outcomes assessed was collected by two authors independently.
UNASSIGNED: The review shows a high degree of uncertainty about therapeutic interventions, both dietary/lifestyle and pharmacological, in patients with SUDD, because of the scarcity and weakness of existing evidence. Available studies are generally of low quality, heterogeneous, and outdated, precluding the possibility to draw robust conclusions. Similarly, acute diverticulitis prevention has been seldom investigated, and there is a substantial lack of evidence supporting the role of dietary/lifestyle or pharmacological approaches to reduce the risk of diverticulitis.
UNASSIGNED: The lack of robust evidence regarding therapeutic options for gastrointestinal symptoms in SUDD patients and for primary and secondary prevention of acute diverticulitis remains an important unmet need in the management of DD.

BACKGROUND: Cronkhite-Canada syndrome (CCS) is a rare disease of unknown etiology. The optimal treatment for CCS remains unknown. Treatment with corticosteroids is considered the mainstay treatment because of its high efficacy, but the therapeutic strategy for steroid-resistant CCS is not yet established.
METHODS: This is the case of an 81-year-old woman who was diagnosed with CCS. Given her severe diarrhea, nausea, vomiting, and hypoproteinemia, hormone therapy (40 mg/d) was administered, and the symptoms improved within 1 wk. After 3 mo, the patient had no obvious symptoms. The polyps were significantly reduced on review gastroscopy and colonoscopy, thus hormone reduction gradually began. The hormone level was maintained at 10 mg/d after 6 mo. Despite the age of the patient and the side effects of hormones, the patient had no obvious discomfort. However, hormone drugs were discontinued, and mesalazine was administered orally at 3 g/d. The patient\'s symptoms continued to improve after a follow-up of 5 years.
CONCLUSIONS: Corticosteroids and mesalazine are potential treatment options for CCS.