Gastrointestinal motility disorders in inflammatory bowel diseases

The relationship between motility and inflammatory gastrointestinal disorders is at the same time complex and intriguing since these conditions might share some genetic, environmental, immunological and microbial predisposing factors. In addition, significant symptom overlapping may occur, muddling the waters within the clinical context. Although on one hand this represents a challenge for the clinician for a potential under- or over-treatment and diagnostic delay, on the other hand it possibly represents an opportunity for the researcher to better disclose the intimate relationship between chronic (often low-grade) inflammation, motor disorders and deranged sensory function. The best example is probably represented by Crohn’s disease and ulcerative colitis. In fact, a number of gastrointestinal motor disorders have been described in association with these diseases, disorders which span from the esophagus to the anorectum, and which will be extensively covered in this review. It is conceivable that at least part of this derangement is strictly related to inflammatory cytokine trafficking and neuromuscular changes; however, given the high prevalence of functional gastrointestinal disorders in the general population, this overlap might also be serendipitous. However, it is worth noting that literature data on this topic are relatively scarce, sometimes quite outdated, and mostly focused on the interplay between irritable bowel syndrome and inflammatory bowel disease. Nevertheless, both researchers and clinicians must be aware that symptoms related to gastrointestinal motility disorders may be highly prevalent in both active and inactive inflammatory bowel disease, correlate with greater psychological comorbidity and poorer quality of life, and may negatively influence the therapeutic approaches.

Severe inflammatory disorder in trisomy 8 without myelodysplastic syndrome and response to methylprednisolone:A case report

BACKGROUND Patients with trisomy 8 consistently present with myeloid neoplasms and/or auto-inflammatory syndrome.A possible link between myelodysplastic syndromes(MDS)with trisomy 8(+8-MDS)and inflammatory disorders is well recognized,several cases having been reported.However,inflammatory disorders in patients without MDS have been largely overlooked.Generally,Behçet's disease is the most common type in+8-MDS.However,inflammatory disorders with pulmonary involvement are less frequent,and no effective treatment has been established.CASE SUMMARY A 27-year-old man with recurrent fever,fatigue for>2 mo,and unconsciousness for 1 day was admitted to our emergency department with a provisional diagnosis of severe pneumonia.Vancomycin and imipenem were administered and sputum collected for metagenomic next-generation sequencing.Epstein–Barr virus and Mycobacterium kansasii were detected.Additionally,chromosomal analysis showed duplications on chromosome 8.Two days later,repeat metagenomic next-generation sequencing was performed with blood culture.Cordyceps portugal,M.kansasii,and Candida portugal were detected,and duplications on chromosome 8 confirmed.Suspecting hematological disease,we aspirated a bone marrow sample from the iliac spine,examination of which showed evidence of infection.We added fluconazole as further antibiotic therapy.Seven days later,the patient’s condition had not improved,prompting addition of methylprednisolone as an anti-inflammatory agent.Fortunately,this treatment was effective and the patient eventually recovered.CONCLUSION Severe inflammatory disorders with pulmonary involvement can occur in patients with trisomy 8.Methylprednisolone may be an effective treatment.

Emerging therapies for inflammatory bowel disorder

Inflammatory bowel disorder(IBD)affects over 5.2 million individuals in North America and Europe alone.IBD is a term used to describe a condition of chronic inflammation in the Gastrointestinal tract-primarily the intestines.While the exact etiology is not fully understood,it is generally accepted that the cause of the inflammation may be due to an abnormal immune response to the gut bacteria.IBD is a progressive disease and can cause various gastrointestinal-related complications.This makes it crucial to discover new treatments and to improve the treatments that are already available.The aim of the study is to answer the question,“What are the emerging therapies for IBD”?In this section,the currently available therapies for IBD are discussed,among which some have already been shown to be effective against IBD whereas some are still in various stages of clinical trials.These therapies include drugs that affect janus kinase-signal transducer and activator of transcription pathway,drugs that impact anti-adhesion molecules,drugs that inhibit anti-interleukin,drugs that modulate sphingosine-1-phosphate receptor,drugs that inhibit phosphodiesterase-4,and finally a technique known as fecal microbial transplant.Many treatments are available today,and new ones are constantly emerging.Some therapies like phosphodiesterase-4 inhibitors and fecal microbiota transplantation that may be the optimum treatment are still under clinical trials,and more research is required for them to be safe,viable,and beneficial options,whereas others are available for usage by the patient but have adverse complications and side effects such as anti-tumor necrosis factor-αor janus kinase-signal transducer and activator of transcription inhibitors.

Adult eosinophilic esophagitis and advances in its treatment

Eosinophilic esophagitis(EoE)is a chronic eosinophil inflammation that seems to be T helper type 2 antigen-driven.The disease is one of several eosinophilic gastrointestinal disorders in which there appears to be inflammation of the gastrointestinal tract without any apparent underlying causes.Differential diagnosis needs to be made with gastroesophageal reflux,which is characterized by chronic inflammation due to gastric refluxate from disorders related to motility.EoE,however,is considered a chronic allergic inflammatory disorder related to destructive tissue remodeling.There seems to be a higher prevalence of EoE in Western countries.It is typically found in atopic male individuals.Physiopathological risk factors include atopy,environmental factors,esophageal epithelial barrier dysfunctions,etc.EoE can cause several symptoms that include retrosternal burning sensation,dysphagia,food impaction,chronic reflux symptoms,nausea,and vomiting.Early diagnosis,which requires a biopsy to assess for esophageal inflammation,is essential for proper treatment.The aim of our brief overview is to summarize the current literature regarding the characteristics,diagnosis,complications,mechanisms of pathology,clinical features,influence of comorbidities,and treatment in patients with EoE.

Koena, a Novel Compound That Dampens Inflammation in the Skin

Inflammatory skin diseases are characterized by the activation of the innate and adaptive immune system via the production of pro-inflammatory cytokines. The main proinflammatory cytokines responsible for this development include TNF-alpha, Interleukin 1, 6 and 17, also the transcription factor NF-kappa B. Small molecule anti-inflammatory compounds such as those detailed in the paper, show much promise in dealing with these skin disorders. Four nutraceutical molecules that are well characterized by their capacity to interact with many of the pro-inflammatory cytokines, importantly IL-17, are found in an Australian product, Koena. Koena has been shown to not only decrease these cytokines but also help increase the production of Interleukin 10 and important anti-inflammatory cytokines. This paper reports clinical benefits of Koena in a variety of circumstances;eczema and psoriasis;insect bites and sting;solar damaged skin and keratosis. An analysis of patient/purchaser reviews via the website Koena.com.au to ascertain what condition they purchased the product for, if any, and the satisfaction rating after use. More than 35% of reviewers reported purchasing Koena to help with inflamed skin. Those reporting being satisfied with the result was 95% for this use. This paper reports on the benefit of small molecule anti-inflammatories in modulating and not blocking an immune response. It also illustrates the benefits of multitherapy when dealing with complex inflammatory responses as opposed to monotherapy.

Tissue-resident memory T cells and their biological characteristics in the recurrence of inflammatory skin disorders

The skin is the largest organ of the body.The establishment of immunological memory in the skin is a crucial component of the adaptive immune response.Once naive T cells are activated by antigen-presenting cells,a small fraction of them differentiate into precursor memory T cells.These precursor cells ultimately develop into several subsets of memory T cells,including central memory T(TCM)cells,effector memory T(TEM)cells,and tissue resident memory T(TRM)cells.TRM cells have a unique transcriptional profile,and their most striking characteristics are their long-term survival(longevity)and low migration in peripheral tissues,including the skin.Under physiological conditions,TRM cells that reside in the skin can respond rapidly to pathogenic challenges.However,there is emerging evidence to support the vital role of TRM cells in the recurrence of chronic inflammatory skin disorders,including psoriasis,vitiligo,and fixed drug eruption,under pathological or uncontrolled conditions.Clarifying and characterizing the mechanisms that are involved in skin TRM cells will help provide promising strategies for reducing the frequency and magnitude of skin inflammation recurrence.Here,we discuss recent insights into the generation,homing,retention,and survival of TRM cells and share our perspectives on the biological characteristics of TRM cells in the recurrence of inflammatory skin disorders.

Post-infectious irritable bowel syndrome:Mechanistic insights into chronic disturbances following enteric infection

Irritable bowel syndrome(IBS)is a commonly encountered chronic functional gastrointestinal(GI)disorder.Approximately 10%of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysentery.The appearance of new IBS symptoms following an infectious event is defined as post-infectiousIBS.Indeed,with the World Health Organization estimating between 2 and 4 billion cases annually,infectious diarrheal disease represents an incredible international healthcare burden.Additionally,compounding evidence suggests many commonly encountered enteropathogens as unique triggers behind IBS symptom generation and underlying pathophysiological features.A growing body of work provides evidence supporting a role for pathogen-mediated modifications in the resident intestinal microbiota,epithelial barrier integrity,effector cell functions,and innate and adaptive immune features,all proposed physiological manifestations that can underlie GI abnormalities in IBS.Enteric pathogens must employ a vast array of machinery to evade host protective immune mechanisms,and illicit successful infections.Consequently,the impact of infectious events on host physiology can be multidimensional in terms of anatomical location,functional scope,and duration.This review offers a unique discussion of the mechanisms employed by many commonly encountered enteric pathogens that cause acute disease,but may also lead to the establishment of chronic GI dysfunction compatible with IBS.

Transcription and Secretion of Interleukin-1β and HMGB1 in Keratinocytes Exposed to Stimulations Mimicking Common Inflammatory Damages

Objective:Interleukin-1β(IL-1β)and high-mobility group box 1(HMGB1)are widely known damage-associated molecular patterns(DAMPs).However,their expression and secretion in different skin diseases,especially in inflammatory skin disorders,remain to be further elucidated.This study was performed to explore and compare the transcriptional and secretory levels of IL-1β and HMGB1 in keratinocytes under 3 types of stimulation:ultraviolet B(UVB)irradiation;co-stimulation by tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)(simulation of T helper 1 cell inflammatory challenge);and psoriasis-like stimulation by M5,a mixture of 5 proinflammatory cytokines.Methods:We used quantitative reverse-transcription polymerase chain reaction to determine the transcription levels of IL-1β and HMGB1.Western blotting and enzyme-linked immunosorbent assay were used to detect the secretion levels of IL-1β and HMGB1.The results were statistically analyzed by t test.Results:A rapid transcriptional and secretory response of IL-1β from keratinocytes occurred in all 3 types of stimulation mimicking common inflammatory environments(P<0.05).Transcription of HMGB1 was inhibited in all 3 types of stimulation(P<0.05),but secretion was increased after exposure to UVB irradiation and co-stimulation by TNF-α and IFN-γ(P<0.05).We observed no change in the secretion level of HMGB1 after treatment with M5(P=0.196).Conclusion:IL-1β is a critical cytokine for the immunomodulatory functions of keratinocytes in inflammatory responses.In this study,keratinocytes restrained transcription of HMGB1 when the secretion of HMGB1 was induced in certain stimulations(eg,by UVB exposure or stimulation by TNF-α and IFN-γ).

Recent Progress in Capturing and Neutralizing Inflammatory Cytokines

Inflammatory cytokines are key players in modulating immune responses to mount effective host defense.However,excessive production of inflammatory cytokines contributes to the destructive components responsible for various inflammatory disorders.As a result,treatment strategies have been developed to lower the cytokine levels or block their bioactivity.In particular,therapeutic agents that directly capture and neutralize cytokines have gained significant attention as they bypass the interactions with the host cells,and therefore,are less likely to induce immunogenic response and clearance.Among them,“monoplex”platforms such as cytokine-neutralizing antibodies(CNAs)are commonly designed to target a specific cytokine for neutralization.Meanwhile,to address the multiplexity of the cytokine targets in diseases,multiplex platforms such as glycosaminoglycan-containing biomaterials and cell-membrane-coated nanoparticles are emerging.Herein,we have reviewed the recent progress of these cytokine-neutralizing platforms(CNPs)and discussed their applications in treating inflammatory disorders.Overall,understanding the structure–function relationships underlying these CNPs would lead to the design of novel therapeutics toward effective management of inflammatory diseases.

Effect of soothing-liver and nourishing-heart acupuncture on early selective serotonin reuptake inhibitor treatment onset for depressive disorder and related indicators of neuroimmunology:a randomized controlled clinical trial

OBJECTIVE:To observe the effect of soothing-liver and nourishing-heart acupuncture on selective serotonin reuptake inhibitor(SSRIs) treatment effect onset in patients with depressive disorder and related indicators of neuroimmunology.METHODS:Overall,126 patients with depressive disorder were randomly divided into a medicine and acupuncture-medicine group using a random number table.Patients were treated for 6 consecutive weeks.The two groups were evaluated by the Montgomery-Asberg Depression Rating Scale(MADRS) and Side Effects Rating Scale(SERS) to assess the effect of the soothing-liver and nourishing-heart acupuncture method on early onset of SSRI treatment effect.Changes in serum 5-hydroxytryptamine(5-HT) and inflammatory cytokines before and after treatment were recorded and compared between the medicine group and the acupuncture-medicine group.RESULTS:The acupuncture-medicine group had significantly lower MADRS scores at weeks 1,2,4,and 6 after treatment compared with the medicine group(P < 0.01).The acupuncture group had significantly lower SERS scores at weeks 1,2,4,and 6 after treatment compared with the medicine group(P < 0.01).At 6 weeks after treatment,serum 5-HT in the acupuncture-medicine group was significantly higher compared with the medicine group(P <0.01).lnterleukin-6(IL-6) in the acupuncture-medicine group was significantly lower than that in the medicine group(P < 0.01),whereas there was no significant difference in IL-1(3 between the groups(P > 0.05).Anti-inflammatory cytokines IL-4 and IL-10 were significantly higher in the acupuncture-medicine group compared with the medicine group(P < 0.01,P < 0.05,respectively).CONCLUSION:The soothing-liver and nourishing-heart acupuncture method can effectively accelerate the onset of SSRI effects when treating depressive disorder and can significantly reduce the adverse reactions of SSRIs.Moreover,acupuncture can enhance serum 5-HT and regulate the balance of pro-inflammatory cytokines and anti-inflammatory cytokines.