Inflammatory Bowel Conditions Research Articles

Oxaliplatin triggered hypersensitivity reactions in colorectal cancer patients: Case report

Colorectal cancer stands as a significant global health concern, encompassing adenocarcinoma of both the colon and rectum. Recognized risk factors include advancing age and medical history of inflammatory bowel conditions like Crohn's disease or ulcerative colitis. Oxaliplatin, a platinum-based chemotherapy agent, serves as the frontline treatment for colorectal cancer due to its cytotoxic effects on cancerous cells. However, its use is not without complications, as hypersensitivity reactions can occur, posing challenges in patient management. This case report discusses two instances where patients undergoing chemotherapy for colorectal cancer developed grade two hypersensitivity reactions following oxaliplatin administration, the Naranjo probability scale was used to analyze the causation of the adverse drug reactions (ADRs), and a score of 6 was obtained, indicating oxaliplatin as a probable cause of the hypersensitivity reactions. In both cases, treatment was promptly halted upon manifestation of symptoms, and patients were administered intravenous steroids along with anti-histamines. This intervention resulted in significant improvement in the patients' conditions. Both genders are equally susceptible to such reactions, emphasizing the need for gender-neutral awareness and precautionary measures among medical practitioners. This case report serves as a reminder of the potential adverse effects associated with oxaliplatin therapy in colorectal cancer patients. Heightened awareness among healthcare professionals regarding the risk of hypersensitivity reactions is imperative to ensure timely detection and appropriate management, thereby optimizing patient outcomes. Consequently, while giving oxaliplatin to cancer patients, healthcare professionals need to use extreme caution.

Litchi Procyanidins Ameliorate DSS-Induced Colitis through Gut Microbiota-Dependent Regulation of Treg/Th17 Balance.

Ulcerative colitis (UC) is a common chronic, relapsing inflammatory bowel condition. Procyanidins (PC) are known for their antiangiogenic, anti-inflammatory, antioxidant, and antimetastatic properties. However, there is comparatively limited information on how PC interacts with UC. In this study, 5 mg/10 mL/kg body weight of PC was administered to mice with dextran sulfate sodium (DSS)-induced colitis mice. PC treatment prolonged the survival period of mice, ameliorated UC symptoms, reduced damage to the intestinal mucosal barrier, and increased the protein expression of ZO-1 and occludin in the DSS-treated mice. Importantly, PC treatment significantly reduced gene expression related to Th17 cell differentiation, including STAT3, SMAD3, TGF-β, and JAK1. The results of the flow cytometry analysis indicated significant increase in the number of Treg cells and a concomitant decrease in the proportion of Th17 cells in the colon following PC treatment. Additionally, PC increased the abundance of gut microbiota such as Bacteroidota, Oscillospiraceae, Muribaculaceae, and Desulfovibrionaceae, as well as the concentrations of acetate acid, propionate acid, and butyrate acid in the feces. PC also activated short-chain fatty acid receptors, such as G-protein coupled receptor 43 in the colon, which promoted the proliferation of Treg cells. The depletion of gut microbiota and subsequent transplantation of fecal microbiota demonstrated that PC's effects on gut microbiota were effective in improving UC and restoring intestinal Th17/Treg homeostasis in a microbiota-dependent manner. This suggests that PC could be a promising functional food for the prevention and treatment of UC in the future.

Fuzi lizhong pills alter microbial community compositions and metabolite profiles in ulcerative colitis rat with spleen-kidney yang deficiency syndrome

Ethnopharmacological relevanceUlcerative colitis (UC) is a chronic inflammatory bowel condition that is frequently related with Spleen-Kidney Yang Deficiency Syndrome (SKYD) in Chinese medicine. Fuzi Lizhong Pill (FLZP), a traditional medicine for SKYD, has been utilized in China for generations, although the exact mechanism by which it treats UC is unknown. Aim of the studyThe goal of this study is to further understand FLZP's therapeutic mechanism in SKYD-associated UC. Materials and methodsTo investigate the impact of FLZP on SKYD-associated UC, we used a comprehensive method that included serum metabolomics and gut microbiota profiling. The chemical composition of FLZP was determined using mass spectrometry. UC rats with SKYD were induced and treated with FLZP. Serum metabolomics and 16S rRNA microbial community analysis were used to evaluate FLZP's effects on endogenous metabolites and gut microbiota, respectively. Correlation analysis investigated the association between metabolites and intestinal flora. A metabolic pathway analysis was undertaken to discover putative FLZP action mechanisms. ResultsFLZP contains 109 components, including liquiritin (584.8176 μg/g), benzoylaconine (16.3087 μg/g), benzoylhypaconine (31.9583), and hypaconitine (8.1160 μg/g). FLZP predominantly regulated seven metabolites and eight metabolic pathways involved in amino acid and nucleotide metabolism, with an emphasis on energy metabolism and gastrointestinal digestion. FLZP also influenced intestinal flora variety, increasing probiotic abundance while decreasing pathogenic bacteria prevalence. An integrated investigation identified associations between changes in certain gut flora and energy metabolism, specifically the tricarboxylic acid (TCA) cycle. ConclusionsFLZP successfully cures UC in SKYD rats by regulating amino acid and energy metabolism. Its positive effects may include altering microbiota composition and metabolite profiles in UC rats with SKYD. These findings shed light on FLZP's mode of action and its implications for UC management.

Ethanol Extract of Limonium bicolor Improves Dextran Sulfate Sodium-Induced Ulcerative Colitis by Alleviating Inflammation and Restoring Gut Microbiota Dysbiosis in Mice.

Ulcerative colitis (UC) is a kind of inflammatory bowel condition characterized by inflammation within the mucous membrane, rectal bleeding, diarrhea, and pain experienced in the abdominal region. Existing medications for UC have limited treatment efficacy and primarily focus on symptom relief. Limonium bicolor (LB), an aquatic traditional Chinese medicine (TCM), exerts multi-targeted therapeutic effects with few side effects and is used to treat anemia and hemostasis. Nevertheless, the impact of LB on UC and its mechanism of action remain unclear. Therefore, the objective of this study was to investigate the anti-inflammatory effects and mechanism of action of ethanol extract of LB (LBE) in lipopolysaccharide-induced RAW 264.7 macrophages and dextran sulfate sodium (DSS)-induced UC. The results showed that LBE suppressed the secretion of cytokines in LPS-stimulated RAW 264.7 cells in a dose-dependent manner. LBE had protective effects against DSS-induced colitis in mice, decreased the disease activity index (DAI) score, alleviated symptoms, increased colon length, and improved histological characteristics, thus having protective effects against DSS-induced colitis in mice. In addition, it reversed disturbances in the abundance of proteobacteria and probiotics such as Lactobacillus and Blautia in mice with DSS-induced UC. Based on the results of network pharmacology analysis, we identified four main compounds in LBE that are associated with five inflammatory genes (Ptgs2, Plg, Ppar-γ, F2, and Gpr35). These results improve comprehension of the biological activity and functionality of LB and may facilitate the development of LB-based compounds for the treatment of UC.

Polyphenol-Rich Extract from 'Limoncella' Apple Variety Ameliorates Dinitrobenzene Sulfonic Acid-Induced Colitis and Linked Liver Damage.

Inflammatory bowel conditions can involve nearly all organ systems and induce pathological processes through increased oxidative stress, lipid peroxidation and disruption of the immune response. Patients with inflammatory bowel disease (IBD) are at high risk of having extra-intestinal manifestations, for example, in the hepatobiliary system. In 30% of patients with IBD, the blood values of liver enzymes, such as AST and ALT, are increased. Moreover, treatments for inflammatory bowel diseases may cause liver toxicity. Apple polyphenol extracts are widely acknowledged for their potential antioxidant effects, which help prevent damage from oxidative stress, reduce inflammation, provide protection to the liver, and enhance lipid metabolism. The aim of this study was to investigate whether the polyphenol apple extract from Malus domestica cv. 'Limoncella' (LAPE) may be an effective intervention for the treatment of IBD-induced hepatotoxicity. The LAPE was administrated in vivo by oral gavage (3-300 mg/kg) once a day for 3 consecutive days, starting 24 h after the induction of dinitro-benzenesulfonic acid (DNBS) colitis in mice. The results showed that LAPE significantly attenuated histological bowel injury, myeloperoxidase activity, tumor necrosis factor and interleukin (IL-1β) expressions. Furthermore, LAPE significantly improved the serum lipid peroxidation and liver injury in DNBS-induced colitis, as well as reduced the nuclear transcription factor-kappaB activation. In conclusion, these results suggest that LAPE, through its antioxidant and anti-inflammatory properties, could prevent liver damage induced by inflammatory bowel disease.

Colonoscopy Finding: Pseudomembranous Colitis in Chronic Kidney Disease Patient

Background: Gastrointestinal symptoms are common among patients with chronic kidney disease, reported in up to 70%–80% of patients with end-stage kidney disease. Several factors are involved in the pathogenesis, including the accumulation of uremic toxins and intestinal flora changes. Pseudomembranous colitis is a manifestation of severe colonic disease that is usually associated with Clostridium difficile infection but can be caused by a number of different etiologies. Pseudomembranous colitis occurs when changes in the fecal flora allow Clostridium difficile overgrowth. Gut dysbiosis, an alteration of the composition and function of gut microorganisms, is commonly seen in patients with chronic kidney disease.
 Case presentation: This scientific report presents a case study of a 31-year-old woman diagnosed with pseudomembranous colitis and end-stage chronic kidney disease on hemodialysis. The colonoscopy showed yellow-white nodules that formed pseudomembranes, which were scattered between the edematous mucosa. The patient had been treated with metronidazole for 4 days, but there were side effects. The antibiotic was switched to meropenem for 6 days based on feces culture. The evaluation of colonoscopy result was normal.
 Conclusion: Pseudomembranous colitis is an inflammatory bowel condition most commonly caused by Clostridium difficile infection. The presence of pseudomembranous visualization in colonoscopy can significantly establish the diagnosis.

ROS/pH dual-responsive quercetin-loaded guanosine borate supramolecular hydrogel enema in dextran sulfate sodium-induced colitis in mice.

Ulcerative colitis (UC) is an inflammatory bowel disease that predominantly impacts the colon, typically starting in the rectum. A significant characteristic of UC is its propensity to affect the distal colon, which is particularly beneficial for targeted treatments such as enemas. This localized approach ensures that the medication is delivered directly to the affected areas, resulting in minimal systemic absorption. In this research, we have formulated a novel stimuli-responsive quercetin-loaded guanosine borate supramolecular hydrogel (named GBQ hydrogel), designed to prolong the residence time of the drug and protect the ulcerated intestinal tissues. The GBQ hydrogel has exhibited excellent injectability, self-healing capabilities, and biocompatibility, rendering it an ideal candidate for enema administration. In vitro studies have highlighted its ROS/pH dual-responsive release profile, which mimics the microenvironment of intestinal inflammation. Furthermore, we assessed the efficacy of the GBQ hydrogel on dextran sulfate sodium (DSS)-induced colitis, a common animal model for UC. Our findings indicate that the GBQ hydrogel significantly reduces disease activity, mitigates oxidative stress, restores the intestinal mucosal barrier, and prevents colonic cell apoptosis. Collectively, this study underscores the therapeutic potential of the GBQ hydrogel in managing inflammatory bowel conditions and paves the way for a novel hydrogel enema-based treatment strategy for UC.

The Histology-Driven Differential Diagnosis in Bowel Inflammatory Conditions Is Not All That Obvious: Evidence from a Survey Based on Digital Slides.

(1) Background: when the pathologist faces histologic slides from colonoscopies in daily practice, given the large number of entities and etiologies under inflammatory bowel conditions, in-depth definition of the histological spectrum and the recommendations of current guidelines are often not enough to conclusively define a diagnostic framework. Histological patterns should be organized hierarchically in flowcharts that consider the correlation with clinical data. We conducted an online survey asking a group of gastroenteropathologists to apply a pattern classification based on the most significant lesions in colitis differential diagnosis: crypt distortion and activity. (2) Methods: digital slides from 20 endoscopy samples were analyzed by twenty pathologists and classified according to the occurrence of crypt distortion (nondestructive-destructive colitis) and subsequently to the evidence of activity (ND1-2-3, D1-2). (3) Results: in 8 out of 20 (40%) cases, the participants reached a full agreement regarding the evaluation of crypt distortion (5 cases: nondestructive colitis; 3 cases: destructive colitis). The calculated agreement was k = 0.432. In the second-level quiz (ND1-2-3 and D1-2), full agreement between participants was achieved for 7 of the 28 (25%) possible classifications, with k = 0.229. (4) Conclusions: The findings from this survey are indicative of an unexpectedly low consensus, even among dedicated pathologists, about the recognition of histological changes that are commonly considered critical lesions in the histologic identification of bowel non-neoplastic diseases. In our opinion, these divergences imply a significant risk of misdiagnosis of bowel inflammatory conditions, hampering the usefulness of histological assessment.

Prophylactic vs. Therapeutic Effect of Probiotics on the Inflammation Mediated by the NF-κB Pathway in Inflammatory Bowel Conditions.

Probiotic supplements consumed adequately at the proper time can affect health by modulating inflammatory pathways in gastrointestinal epithelial cells and modifying the resultant inflammatory response. The current study applied in vitro models to investigate the effectiveness of probiotics in modulating inflammatory pathways and altering inflammatory gene expression in gastrointestinal epithelial cells, with the ultimate goal of promoting probiotic consumption as a therapeutic and preventive measure for chronic inflammatory bowel conditions. HT-29 cells were treated with Gram-negative bacteria to evaluate the changes in pathways related to inflammation activities before and after treatment with a Lactobacillus spp. cocktail (L. plantarum, L. rhamnosus, L. brevis, and L. ruteri) and a Bifidobacterium spp. cocktail (B. bifidum, B. langum, and B. breve) using the real-time PCR method and ELISA for IL-1β and IL-6 as pro-inflammatory cytokines. The results showed that the expression of NF-κB signaling pathway genes and IL-1β and IL-6 cytokines increased after exposure to Gram-negative components. In contrast, all probiotic combinations significantly decreased the expression of genes and the secretion of cytokines. However, this decrease was significantly smaller in cells that underwent probiotic treatment after inflammation induction. In addition, cocktails containing combined Lactobacillus and Bifidobacterium demonstrated robust anti-inflammatory activity relative to solo cocktails. Our observations confirm that probiotic consumption could positively impact inflammatory conditions and alleviate inflammatory symptoms; they can be particularly effective as a preventive measure. Our study provides preliminary evidence to support the lifetime consumption of probiotics.

A National Inpatient Sample Analysis of Racial Disparities After Segmental Colectomy for Inflammatory Colorectal Diseases.

Racial disparities and poor access to care are common among African Americans (AA), potentially adversely affecting surgical outcomes in inflammatory bowel conditions. We aimed to analyze the effect of race on outcomes in patients undergoing segmental colectomy for inflammatory bowel conditions. Retrospective review of data from the National Inpatient Sample between 2010 and 2015 identified patients who underwent segmental colectomy without ostomy for Crohn's or diverticular disease. AA patients were compared with Caucasians using a multivariable analysis model. Primary outcomes of interest were overall complications, mortality, and extended hospital stay. 38,143 admissions were analyzed; AA patients constituted 8% of the overall cohort. Diagnoses included Crohn's (11%) and diverticular disease (89%). After multivariable analysis, AA patients had significantly higher overall risk of complications (OR = 1.27; 95% CI, 1.15-1.40) and extended hospital stay (OR = 1.59; 95% CI, 1.45-1.75) than Caucasians. On bivariate analysis, there was no significant difference in mortality between AA and Caucasian patients. AA patients had significantly higher rates of Medicaid insurance (14% vs 6%, P < .001), lower rates of private insurance (35% vs 47%, P < .001), and were less likely to undergo surgery at a private hospital (31% vs 41%, P < .001). AA patients requiring segmental colectomy for inflammatory colorectal conditions experience significantly higher rates of postoperative complications, longer hospital stays, and lower rates of private insurance. Direct correlation between insurance status and postoperative outcomes could not be established, but we speculate such great disparity in outcomes may stem from these socioeconomic differences.

Localised Delivery of Macromolecules to the Large Intestine: Translation to Clinical Trials.

Oral administration of macromolecules aimed at systemic delivery has been at the forefront of pharmaceutical research for over 50 years. Yet, in terms of clinical translation for systemic delivery, output is limited to five US Food and Drug Administration (FDA)-approved oral peptide products to date, such are the hurdles. Somewhat neglected by comparison but with potentially lower delivery demands, the goal of local delivery of macromolecules directed mostly to the terminal ileum and colon to treat inflammatory bowel conditions has led to a range of macromolecules including gut-restricted peptides, fusion proteins, enzymes, antibodies, and antisense oligonucleotides that have reached clinical trials. While some of these trials reached primary endpoints, others are at early clinical stages, but it is likely that at least a few approvable products will emerge to supplement the current cohort of parenterally administered macromolecules and oral small molecules. The outstanding successes to date are the FDA approvals of two gut-restricted guanylate cyclase C-activating peptides to treat irritable bowel syndrome (constipated). Over-expressed targets for macromolecules in the gut wall of inflammatory bowel disease patients include α4β7 integrin, TNF-α, CD-3, ICAM-1, and SMAD-7, while reduced responses to IL-10 and melanocortin offer opportunities for macromolecular agonists. In this Leading Article, a landscape of locally delivered macromolecules to access the gut that have recently reached clinical trials is provided.

A165 VEDOLIZUMAB IS AN OPTION TO TREAT MICROSCOPIC COLITIS IN PATIENTS DEPENDENT ON ORAL STEROIDS OR HAVE FAILED A BIOLOGIC: A MULTICENTRE CANADIAN CASE SERIES

BackgroundMicroscopic colitis (MC) is an inflammatory bowel condition demonstrating normal mucosa on endoscopy, with evidence of inflammation and lymphocytosis on pathologic analysis of biopsies. The pathophysiology for this disease is largely unknown, and evidence for its management in cases refractory to oral steroids or after failing a biologic is sparse. Vedolizumab, an integrin receptor antagonist, has been used in a handful of persons with MC with limited literature.AimsReview literature on the use of Vedolizumab in treatment of MC. Present 7 cases of MC where Vedoluzimab was used to manage patients refractory to therapy (either steroid dependent, or failing biologic therapy).MethodsPatients with MC managed with Vedolizumab were identified by soliciting practicing Gastroenterologists within Winnipeg at 3 health centres. A chart review was conducted to obtain pertinent information including patient demographics, symptoms, and medications previously trialed.ResultsReview of literature revealed 3 case reports, and 4 case series reporting on the use of Vedolizumab in MC. We identified 7 cases; 6 female, and a mean age at diagnosis of 50.7. Histologies included 3 lymphocytic, 2 collagenous, 1 developed from lymphocytic to collagenous over time, and 1 with evidence of both. 4 patients were on a biologic prior to initiating Vedolizumab with a mean duration of therapy of 24.25 months. Indications for initiating Vedolizumab included: 3 with steroid dependency, 3 Infliximab failures, and 1 with Adalimumab-associated hepatotoxicity. Mean disease duration prior to initiating Vedolizumab was 112.7 months. Number of stools pre-Vedolizumab were: 1–3 = 0, 4–6 = 2, 7–9 = 2, >/=10 = 3, compared to >6 months post-Vedolizumab: 1–3 = 5, 4–6 = 1, 7–9 = 1, >/=10 = 0. Symptoms pre-Vedolizumab compared to >6 months post-Vedolizumab included: 4 with urgency pre-Vedolizumab versus 1, 3 had incontinence versus 0, and 4 had nocturnal symptoms versus 0. Use of alternative medications included anti-diarrheals, oral 5-aminosalicylic acid, and immunomodulators. On average, patients tried 7.6 different treatments prior to starting Vedolizumab. 1 case is considered to have failed Vedolizumab due to increasing symptoms.ConclusionsThis multicentre case series is the first in Canada to assess patient characteristics and symptoms before and after Vedolizumab induction in persons with MC who are either steroid dependent or have failed a biologic. Our results demonstrate an overall improvement in symptoms when assessed >6 months after induction therapy. This review was limited in not having a symptom inventory/severity index completed at each clinic visit, resulting in a number of difficult-to-compare and incomplete data points.Funding AgenciesNone

Microscopic colitis and the role of the specialist inflammatory bowel disease nurse: a clinical review

Microscopic colitis (MC) is an inflammatory bowel condition similar to but distinct from classical inflammatory bowel disease (IBD). Unlike ulcerative colitis and Crohn's disease, MC is predominately a self-limiting and treatable condition. It is characterised by colonic inflammation and symptoms of watery, non-bloody diarrhoea, alongside abdominal pain and weight loss, causing anxiety, fatigue and reduced quality of life. The prevalence of MC is 119 per 100 000 population and growing. Its aetiology and pathophysiology are poorly understood, but it is likely multifactorial, and possible risk factors include smoking and certain medications and autoimmune conditions. Diagnosis relies on endoscopic biopsy to identify intraepithelial lymphocytosis. Management and treatment begin with excluding possible risk factors and can include anti-diarrhoeal medications, bile acid binders and budesonide, which is highly effective at inducing and maintaining remission. Refractory disease is rare, but it may require biological medications or even surgery. Disease activity is monitored with the Hjortswang criteria and Microscopic Colitis Disease Activity Index. This narrative clinical review draws on recent guidelines and study data to explore the uncertain role of the clinical nurse specialist in caring for these patients.

Patients With Microscopic Colitis Have Altered Levels of Inhibitory and Stimulatory Biomarkers in Colon Biopsies and Sera Compared to Non-inflamed Controls.

Introduction: Microscopic colitis (MC) is an inflammatory bowel condition with two subtypes, lymphocytic colitis (LC) and collagenous colitis (CC). Unlike patients with ulcerative colitis (UC) and non-inflamed individuals, MC patients have reduced risk of developing colorectal cancer, possibly due to increased immune surveillance in MC patients.Aim: To examine differences in levels of immunomodulatory molecules, including those involved in immune checkpoint mechanisms, in sera from patients with MC and in colonic biopsies from patients with MC and UC compared with controls.Methods: Using Luminex, 23 analytes (4-1BB, 4-1BBL, APRIL, BAFF, BTLA, CD27, CD28, CD80, CTLA-4, E-cadherin, Galectin-3, GITR, HVEM, IDO, IL-2Rα, LAG-3, MICA, MICB, PD-1, PD-L1, PD-L2, sCD40L and TIM-3) were studied in serum from patients with active MC (n = 35) and controls (n = 23), and in colonic biopsies from patients with active LC (n = 9), active CC (n = 16) and MC in histological remission (LC n = 6, CC n = 6), active UC (n = 15) and UC in remission (n = 12) and controls (n = 58).Results: In serum, IDO, PD-1, TIM-3, 4-1BB, CD27, and CD80 were decreased whereas 4-1BBL and IL-2Rα were increased in MC patients compared with controls. In contrast, in biopsies, levels of PD-L2 and 4-1BB were increased in MC and UC patients with active disease. Furthermore, in biopsies from CC and UC but not LC patients with active disease, CTLA-4, PD-1, APRIL, BAFF, and IL-2Rα were increased compared with controls. PD-L1 was increased in CC but not UC or LC patients. CD27 and TIM-3 were decreased in biopsies from MC patients in comparison to controls whereas levels of MICB were decreased in patients with active UC compared with controls.Conclusions: Compared with non-inflamed controls, levels of soluble and membrane-bound immunomodulatory molecules were systemically and locally altered in MC and UC patients, with most analytes being decreased in serum but enhanced in colonic biopsies. These findings contribute to knowledge about checkpoint molecules and their role as biomarkers in MC and may also contribute to knowledge about possible mechanisms behind the seemingly protective effects of MC against colorectal cancer.

Adults with Crohn\u2019s disease exhibit elevated gynoid fat and reduced android fat irrespective of disease relapse or remission

Crohn’s disease (CD) is a debilitating inflammatory bowel condition of unknown aetiology that is growing in prevalence globally. Large-scale studies have determined associations between female obesity or low body mass index (BMI) with risk of CD at all ages or 8– < 40 years, respectively. For males, low BMI entering adult life is associated with increased incidence of CD or ulcerative colitis up to 40 years later. Body composition analysis has shown that combinations of lean tissue loss and high visceral fat predict poor CD outcomes. Here, we assessed dietary intake, physical activity and whole or regional body composition of patients with CD relapse or remission. This anthropometric approach found people with CD, irrespective of relapse or remission, differed from a large representative healthy population sample in exhibiting elevated gynoid fat and reduced android fat. CD is associated with mesenteric adipose tissue, or “creeping fat”, that envelops affected intestine exclusive of other tissue; that fat is localised to the android region of the body. In this context, CD mesenteric adiposity represents a stark juxtaposition of organ-specific and regional adiposity. Although our study population was relatively small, we suggest tentatively that there is a rationale to refer to Crohn’s disease as a fatty intestine condition, akin to fatty liver conditions. We suggest that our data provide early insight into a subject that potentially warrants further investigation across a larger patient cohort.

Protective effect of sarsasapogenin in TNBS induced ulcerative colitis in rats associated with downregulation of pro-inflammatory mediators and oxidative stress

Background Ulcerative colitis (UC) is a chronic inflammatory bowel condition considered by oxido-nitrosative stress and the release of pro-inflammatory cytokines that affects the mucosal lining of the colon. Sarsasapogenin (SG), as an active component, has been found in many plants, and it exhibits potential protective effects, such as anti-inflammatory, antioxidant, anti-psoriasis, anti-arthritis, anti-asthma, anti-depressant and anti-cancer. However, the effects of SG on UC remain unknown. Objective The purpose of this study was to investigate the effects of SG on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced UC in rats. Method Thirty Wistar rats were randomized into five groups: (i) Normal control, (ii) Disease control (TNBS), (iii) Sarsasapogenin (SG) (50 µg/rat), (iv) Fluticasone (FC) (50 µg/rat), (v) Sarsasapogenin + Fluticasone (SG + FC) (25 µg/rat). UC was induced in rats by trans-rectal instillation of TNBS (10 mg/kg). SG, FC and SG + FC were administered for 11 days and on the 8th day colitis was induced. Several molecular, biochemical and histological alterations were evaluated in the colon tissue. All treatment group results were compared to the TNBS group results. Result The study results revealed that treatment of rats with SG and SG + FC combination significantly decreased the colon weight/length ratio, macroscopic inflammation score, lesions score, diarrhea score and adhesion score. Combination treatment in rats significantly reduced the production of biochemical parameters, proinflammatory cytokines, haematological parameters, serum IgE levels and restored the oxidative stress markers. SG and SG + FC treatment also considerably restored the histopathological changes induced by TNBS. Conclusion Thus, SG and SG + FC combination could alter the disease progression and could be a hopeful therapeutic target for the management of UC by reducing its dose in combination with FC to elude the long term adverse effects of FC.

The Microbiome as a Potential Target for Therapeutic Manipulation in Pancreatic Cancer.

Simple SummaryPancreatic cancer is one of the most lethal cancers. It is a difficult cancer to treat, and the complexity surrounding the pancreatic tumour is one of the contributing factors. The microbiome is the collection of microorganisms within an environment and its genetic material. They reside on body surfaces and most abundantly within the human gut in symbiotic balance with their human host. Disturbance in the balance can lead to many diseases, including cancers. Significant advances have been made in cancer treatment since the introduction of immunotherapy, and the microbiome may play a part in the outcome and survival of patients with cancer, especially those treated with immunotherapy. Immunotherapy use in pancreatic cancer remains challenging. This review will focus on the potential interaction of the microbiome with pancreas cancer and how this could be manipulated.Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and is projected to be the second most common cause of cancer-related death by 2030, with an overall 5-year survival rate between 7% and 9%. Despite recent advances in surgical, chemotherapy, and radiotherapy techniques, the outcome for patients with PDAC remains poor. Poor prognosis is multifactorial, including the likelihood of sub-clinical metastatic disease at presentation, late-stage at presentation, absence of early and reliable diagnostic biomarkers, and complex biology surrounding the extensive desmoplastic PDAC tumour micro-environment. Microbiota refers to all the microorganisms found in an environment, whereas microbiome is the collection of microbiota and their genome within an environment. These organisms reside on body surfaces and within mucosal layers, but are most abundantly found within the gut. The commensal microbiome resides in symbiosis in healthy individuals and contributes to nutritive, metabolic and immune-modulation to maintain normal health. Dysbiosis is the perturbation of the microbiome that can lead to a diseased state, including inflammatory bowel conditions and aetiology of cancer, such as colorectal and PDAC. Microbes have been linked to approximately 10% to 20% of human cancers, and they can induce carcinogenesis by affecting a number of the cancer hallmarks, such as promoting inflammation, avoiding immune destruction, and microbial metabolites can deregulate host genome stability preceding cancer development. Significant advances have been made in cancer treatment since the advent of immunotherapy. The microbiome signature has been linked to response to immunotherapy and survival in many solid tumours. However, progress with immunotherapy in PDAC has been challenging. Therefore, this review will focus on the available published evidence of the microbiome association with PDAC and explore its potential as a target for therapeutic manipulation.

Luteolin, inflammation and cancer: Special emphasis on gut microbiota.

Luteolin belongs to the family of flavonoids, which have anti-inflammatory functions, potentially useful in a clinical context, particularly for patients suffering from cancer, neuropsychiatric disorders, inflammatory bowel conditions. This peculiarity has been used for centuries in traditional Chinese medicine, for many different diseases. Its anti-inflammatory effects might be particularly relevant in cancer, with some studies reporting anti-angiogenesis, anti-metastatic, and apoptotic effects on cancer cells by luteolin and other flavonoids. In this article, we analyze the anti-inflammatory role of luteolin, discussing the pathways it may act on. We will then discuss the possible role of microbiota in inflammatory modulation by luteolin. Finally, the possible therapeutic applications of luteolin's anti-inflammatory properties will be analyzed, with a particular focus on cancer.

Low-Dose Naltrexone for Chronic Pain: Update and Systemic Review.

The purpose of this review is to evaluate and explain our current understanding of the clinical use of low-dose naltrexone in the treatment of chronic pain. Recent pre-clinical uses and clinical studies further elucidate the use of low-dose naltrexone in the treatment of chronic pain. Low-dose naltrexone (LDN) has shown promise to reduce symptoms related to chronic pain conditions such as fibromyalgia, inflammatory bowel conditions, and multiple sclerosis. The mechanism of LDN appears to be modulation of neuro-inflammation, specifically, the modulation of the glial cells and release of inflammatory chemicals in the central nervous system. These effects appear to unique at low dosage compared to dosage for food and drug administration approved use for alcohol and opioid dependence. We review the evidence that LDN has shown more than promise and should be further investigated in clinical practice.

A Microbial Relationship Between Irritable Bowel Syndrome and Depressive Symptoms.

Irritable bowel syndrome (IBS) is associated with depressive symptoms, but this relationship is poorly understood. Emerging research suggests that gut microbes are associated with symptoms in persons with IBS. The purpose of this integrative review is to describe the state of the science of the microbial relationship between IBS and depressive symptoms. PubMed, CINAHL, PsychINFO, and Web of Science were searched using "irritable bowel syndrome," "microbiome," "depression," and related terms. Included articles were published in peer reviewed journals in English from 2009 to 2018. Studies on inflammatory bowel conditions, extra-intestinal microbiomes, or animal models were excluded. Fourteen quantitative studies met inclusion criteria, were critically appraised, and were analyzed using the Whittemore and Knafl method. Analysis revealed a consistently lower microbial biodiversity and lower proportions of Bifidobacterium and Lactobacillus in persons with IBS and co-occurring depressive symptoms. Inclusion of participants with moderate or greater depressive symptoms scores distinguished the studies which reported microbe differences in depressive symptoms. The results of this integrative review underscore the need for studies with larger samples and inclusion of a larger range of depressive symptoms guided by an overarching conceptual framework, such as the biopsychosocial ecology framework. This effort needs to be combined with longitudinal designs in order to identify related microbial markers.