Image quality assessment in low-dose COVID-19 chest CT examinations.

BACKGROUND: Low-dose thoracic protocols were developed massively during the COVID-19 outbreak. PURPOSE: To study the impact on image quality (IQ) and the diagnosis reliability of COVID-19 low-dose chest computed tomography (CT) protocols. MATERIAL AND METHODS: COVID-19 low-dose protocols were implemented on third- and second-generation CT scanners considering two body mass index (BMI) subgroups (<25 kg/m2 and >25 kg/m2). Contrast-to-noise ratios (CNR) were compared with a Catphan phantom. Next, two radiologists retrospectively assessed IQ for 243 CT patients using a 5-point Linkert scale for general IQ and diagnostic criteria. Kappa score and Wilcoxon rank sum tests were used to compare IQ score and CTDIvol between radiologists, protocols, and scanner models. RESULTS: In vitro analysis of Catphan inserts showed in majority significantly decreased CNR for the low dose versus standard acquisition protocols on both CT scanners. However, in vivo, there was no impact on the diagnosis: sensitivity and specificity were ≥0.8 for all protocols and CT scanners. The third-generation scanner involved a significantly lower dose compared to the second-generation scanner (CTDIvol of 1.8 vs. 2.6 mGy for BMI <25 kg/m2 and 3.3 vs. 4.6 mGy for BMI >25 kg/m2). Still, the third-generation scanner showed a significantly higher IQ with the low-dose protocol compared to the second-generation scanner (30.9 vs. 28.1 for BMI <25 kg/m2 and 29.9 vs. 27.8 for BMI >25 kg/m2). Finally, the two radiologists had good global inter-reader agreement (kappa ≥0.6) for general IQ. CONCLUSION: Low-dose protocols provided sufficient IQ independently of BMI subgroups and CT models without any impact on diagnosis reliability.

Effects of Dietary Components on Mast Cells: Possible Use as Nutraceuticals for Allergies?

Allergic diseases affect an estimated 30 percent of the world's population. Mast cells (MC) are the key effector cells of allergic reactions by releasing pro-inflammatory mediators such as histamine, lipid mediators, and cytokines/chemokines. Components of the daily diet, including certain fatty acids, amino acids, and vitamins, as well as secondary plant components, may have effects on MC and thus may be of interest as nutraceuticals for the prevention and treatment of allergies. This review summarizes the anti-inflammatory effects of dietary components on MC, including the signaling pathways involved, in in vitro and in vivo models. Butyrate, calcitriol, kaempferol, quercetin, luteolin, resveratrol, curcumin, and cinnamon extract were the most effective in suppressing the release of preformed and de novo synthesized mediators from MC or in animal models. In randomized controlled trials (RCT), vitamin D, quercetin, O-methylated epigallocatechin gallate (EGCG), resveratrol, curcumin, and cinnamon extract improved symptoms of allergic rhinitis (AR) and reduced the number of inflammatory cells in patients. However, strategies to overcome the poor bioavailability of these nutrients are an important part of current research.

Relationship between the Biological Clock and Inflammatory Bowel Disease.

The biological clock is a molecular oscillator that generates a 24-hour rhythm in accordance with the earth's rotation. Physiological functions and pathophysiological processes such as inflammatory bowel diseases (IBD) are closely linked to the molecular clock. This review summarizes 14 studies in humans and mice on the interactions between the biological clock and IBD. It provides evidence that IBD negatively affect core clock gene expression, metabolism and immune functions. On the other hand, disruption of the clock promotes inflammation. Overexpression of clock genes can lead to inhibition of inflammatory processes, while silencing of clock genes can lead to irreversible disease activity. In both human and mouse studies, IBD and circadian rhythms have been shown to influence each other. Further research is needed to understand the exact mechanisms and to develop potential rhythm-related therapies to improve IBD.

Fecal microbiota transplantation in patients with irritable bowel syndrome: an overview of current studies.

As dysbiosis is a key factor associated with irritable bowel syndrome (IBS), modulation of the intestinal microbiota could improve IBS symptoms and quality of life. Fecal microbiota transplantation (FMT) could be one efficient way to restore bacterial composition in IBS patients. This review comprises 12 clinical trials published from 2017 to 2021. Inclusion criteria were the assessment of IBS symptoms using the IBS symptom severity score, quality of life measured by the lBS quality of life scale, and gut microbiota analysis. Improved symptoms were reported in all 12 studies, paralleling with an increased quality of life after FMT, but also partly after placebo treatment. The use of oral capsules showed that the placebo treatment can have similar or even stronger positive effects on IBS patients than FMT. Gastroscopic FMT appears to link modulation of the gut microbiome to significant symptom reduction in patients. The patient's microbiota profile shifted toward their respective donors. Symptom worsening or decreased quality of life after FMT was not reported. The results show that FMT could be a therapeutic approach in IBS patients. Further research is needed to investigate whether FMT has a more beneficial effect on IBS patient than placebo treatment with the patient's own stool, placebo capsules, or bowel cleansing. Moreover, optimal donor selection, frequency, dosage, and route of delivery still need to be defined.

Erratum.

Erratum for: Probiotics in the Treatment of Inflammatory Bowel Diseases in Adulthood: A Systematic Review. J Gastrointest. Liv. Dis. 2022; 31: 74-84.

Molecular links between allergy and cancer.

Epidemiologic studies show both positive and negative associations between allergies and cancer. Allergic diseases may protect against tumorigenesis by promoting the immune surveillance, while carcinogenesis may be promoted through inflammatory responses from allergies. Histamine receptor antagonists are the focus of recent cancer studies because of their promising beneficial effect on tumor development. Also, cytokines, particularly IL-4 or IL-33, IgE as well as allergy-related immune cells such as eosinophils can contribute to tumor growth suppression. Depending on cancer types, cancer therapy may be more beneficial when considering combinatorial immunotherapy. In this review, we give an overview on molecular links between allergies and cancer.

Ataxin-3, The Spinocerebellar Ataxia Type 3 Neurodegenerative Disorder Protein, Affects Mast Cell Functions.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph Disease, is a progressive neurodegenerative disorder characterized by loss of neuronal matter due to the expansion of the CAG repeat in the ATXN3/MJD1 gene and subsequent ataxin-3 protein. Although the underlying pathogenic protein expansion has been known for more than 20 years, the complexity of its effects is still under exploration. The ataxin-3 protein in its expanded form is known to aggregate and disrupt cellular processes in neuronal tissue but the role of the protein on populations of immune cells is unknown. Recently, mast cells have emerged as potential key players in neuroinflammation and neurodegeneration. Here, we examined the mast cell-related effects of ataxin-3 expansion in the brain tissues of 304Q ataxin-3 knock-in mice and SCA3 patients. We also established cultures of mast cells from the 304Q knock-in mice and examined the effects of 304Q ataxin-3 knock-in on the immune responses of these cells and on markers involved in mast cell growth, development and function. Specifically, our results point to a role for expanded ataxin-3 in suppression of mast cell marker CD117/c-Kit, pro-inflammatory cytokine TNF-α and NF-κB inhibitor IκBα along with an increased expression of the granulocyte-attracting chemokine CXCL1. These results are the beginning of a more holistic understanding of ataxin-3 and could point to the development of novel therapeutic targets which act on inflammation to mitigate symptoms of SCA3.

Resveratrol Attenuates Mast Cell Mediated Allergic Reactions: Potential for Use as a Nutraceutical in Allergic Diseases?

Allergic diseases are one of the most common health disorders affecting about 30% of the world population. Mast cells (MCs) are key effector cells of allergic reactions by releasing proinflammatory mediators including histamine, lipid mediators, and cytokines/chemokines. Natural substances like secondary plant substances such as resveratrol (RESV), which can contribute to prevention and treatment of diseases, are becoming increasingly interesting for use as nutraceuticals. In this review, the anti-inflammatory effects of RESV on MC-mediated allergic reactions in vitro and in vivo models are summarized. The studies indicate that RESV inhibits MC degranulation, synthesis of arachidonic acid metabolites, expression of cytokines and chemokines as well as activation of signal molecules involved in proinflammatory mechanisms. Also, beneficial impacts by this polyphenol are reported in randomized controlled trials with allergic rhinitis patients. Although it cannot yet be concluded that RESV can be used successfully in allergy patients in general, there are many results that indicate a possible role for RESV for use as an anti-inflammatory nutraceutical. However, strategies to favorably influence the poor bioavailability of RESV would be helpful.

Probiotics in the Treatment of Inflammatory Bowel Disease in Adulthood: A Systematic Review.

BACKGROUND AND AIMS: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by chronic uncontrolled inflammation with an increasing prevalence in western countries. Standard medications are often associated with adverse side effects. Thus, alternative therapies such as probiotic treatment are of great interest. We aimed to review the effect of probiotics in IBD patients. METHODS: A systematic search strategy was carried out in PubMed in June 2021 and 22 studies published from 1997 to 2019 were included; they analyzed the influence of probiotics in adult IBD patients both in active and inactive stage of disease. RESULTS: Probiotic treatment in CD patients had no effect in 6 of 7 studies. Only in one study a positive effect of an adjunctive probiotic treatment next to standard treatment in CD patients was reported. In patients with active UC, a combination of standard treatment with probiotics resulted in improvement of the disease in 5 of 9 studies. Three of 7 studies among UC patients in remission demonstrated that probiotic treatment could be as effective as standard treatment. No clear evidence was found in studies comparing probiotics to placebo in inactive UC patients with ongoing standard medication. CONCLUSION: There is no clear evidence of the benefit of probiotic treatment in CD patients. In contrast, combining standard treatment with probiotics might be an option to achieve remission in active UC patients.

Resveratrol Treatment Prevents Increase of Mast Cells in Both Murine OVA Enteritis and IL-10-/- Colitis.

Mast cells are involved in allergic and other inflammatory diseases. The polyphenol resveratrol is known for its anti-inflammatory properties and may be used as nutraceutical in mast cell associated diseases. We analyzed the effect of resveratrol on mast cells in vivo in ovalbumin-induced allergic enteritis as well as experimental colitis in IL-10-/- mice which received resveratrol via drinking water. Treatment with resveratrol prevented the increase in mast cells in both allergic enteritis and chronic colitis in duodenum as well as in colon. Further, it delayed the onset of diseases symptoms and ameliorated diseases associated parameters such as tissue damage as well as inflammatory cell infiltration in affected colon sections. In addition to the findings in vivo, resveratrol inhibited IgE-dependent degranulation and expression of pro-inflammatory cytokines such as TNF-α in IgE/DNP-activated as well as in LPS-activated bone marrow-derived mast cells. These results indicate that resveratrol may be considered as an anti-allergic and anti-inflammatory plant-derived component for the prevention or treatment of mast cell-associated disorders of the gastrointestinal tract.

Resveratrol Is a Natural Inhibitor of Human Intestinal Mast Cell Activation and Phosphorylation of Mitochondrial ERK1/2 and STAT3.

Mast cells play a critical role as main effector cells in allergic and other inflammatory diseases. Usage of anti-inflammatory nutraceuticals could be of interest for affected patients. Resveratrol, a natural polyphenol found in red grapes, is known for its positive properties. Here, we analyzed the effects of resveratrol on FcεRI-mediated activation of mature human mast cells isolated from intestinal tissue (hiMC). Resveratrol inhibited degranulation and expression of cytokines and chemokines such as CXCL8, CCL2, CCL3, CCL4, and TNF-α in a dose-dependent manner. Further, resveratrol inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and signal transducer and activator of transcription (STAT) 3. ERK1/2 is known to be involved in cytokine expression of hiMC and to directly interact with STAT3. Mitochondrial STAT3 is phosphorylated by ERK1/2 and contributes to mast cell degranulation. We were able to isolate mitochondrial fractions from small hiMC numbers and could show that activation of mitochondrial STAT3 and ERK1/2 in hiMC was also inhibited by resveratrol. Our results indicate that resveratrol inhibits hiMC activation by inhibiting the phosphorylation of mitochondrial and nuclear ERK1/2 and STAT3, and it could be considered as an anti-inflammatory nutraceutical in the treatment of mast cell-associated diseases.

Probiotic Potential of Lactobacillus Species in Allergic Rhinitis.

Since conventional allergy medication for asthma or allergic rhinitis (AR) can cause side effects which limit the patients' quality of life, it is of interest to find other forms of therapy. In particular, probiotic bacteria, such as Lactobacillus species, have shown anti-allergic effects in various mouse and human studies. For instance, administration of some Lactobacillus species resulted in nasal and ocular symptom relief and improvement of quality of life in children and adults suffering from rhinitis. Different changes in cytokine profiles, such as elevated Th1 and decreased Th2 cytokines, reduced allergy-related immunoglobulins and cell immigration have been found in both human and murine studies. Positive effects on patients like less activity limitations or fewer rhinitis episodes and longer periods free from asthma or rhinitis were also described following oral administration of Lactobacillus bacteria. However, it is still unclear how this type of lactic acid bacteria leads to changes in the immune system and thus inhibits the development of allergies or relieves their symptoms. This review gives an overview of current studies and draws conclusions concerning the usage of probiotic Lactobacillus strains in AR.

Dietary restrictions modulate the gut microbiota: Implications for health and disease.

The health benefits of carefully restricting the energy intake in a strategic manner whilst avoiding malnutrition are widely discussed. In the recent years, the great impact of the gut microbiota on its host has been clarified more and more. Since the gut microbiota produces a number of metabolites and molecules that can affect host metabolism, modulating it with dietary restriction can influence the health and the progression of disease of its host on various levels. This review comprises 15 studies investigating the effect of different variants of fasting and caloric restriction on the gastrointestinal microbiome and its metabolites. The data suggest that changing the gut microbiota composition by dietary restriction has the potential to positively influence the progression of several diseases such as obesity, diabetes, neurological diseases or inflammatory bowel disease. Finally, the relevance of the findings for clinical practice is evaluated and approaches for future research are proposed.

Role of the microbiota in circadian rhythms of the host.

Life for meta-organisms is based on a strong relationship between gut bacteria and body cells. This review summarizes to what extent the microbiota can influence host circadian rhythms via a literature review on the topic. The results show that microbiota can influence the host's circadian gene expression through direct interactions via immunoreceptors and microbiota-derived metabolites, especially in peripheral tissues. Noteworthy metabolites that are only attributable to the microbiota are short-chain fatty acids and unconjugated bile acids. The microbiota also serves as a mediator for the interplay between the host's diet and circadian rhythmicity. This work furthermore displays that the microbiota is subject to diurnal variations in terms of structure and function and that the host and the host's diet influence these fluctuations. As most of these results originate in mouse models, we hope this work stimulates further research in human derived tissue to verify these conclusions.

Mast Cells in Irritable Bowel Syndrome: A Systematic Review.

BACKGROUND AND AIMS: As mast cells (MC) serve as a link between mucosal immune activity and the nervous system, it is likely they also play a role in the pathogenesis of irritable bowel syndrome (IBS). This connection might be an important factor in the development of IBS-related symptoms. METHOD: This overview comprises 36 case-control studies published from 2000 to 2018 that investigated MC in bowel biopsies of IBS patients and controls. The studies were selected from PubMed, EMBASE, Central, SemanticScholar by an electronic search, performed using RISMed R package. RESULTS: Significantly increased mucosal MC counts/or density in IBS patients compared to controls was observed in 30 studies. Five studies reported no differences and only one of the studies found a decreased amount of MC in an IBS patient. Furthermore, 15 studies made a statement regarding the correlation between the amount of MC and IBS associated symptoms. A significant positive correlation between MC count and IBS-associated symptoms was found in six investigations. A negative correlation was not reported. CONCLUSION: The results support the idea that MC are involved in IBS pathophysiology as key players in the interplay between psychological factors and the frequency and severity of IBS symptoms.

Nobiletin acts anti-inflammatory on murine IL-10-/- colitis and human intestinal fibroblasts.

PURPOSE: Inflammatory bowel disease (IBD) shows increasing prevalence over the last years. We propose that anti-inflammatory plant substances could be used as additional or alternative agents with good compliance in prevention and/or therapy of IBD and its complication intestinal fibrosis. We could recently show that the citrus flavonoid nobiletin acts anti-inflammatory on activation of intestinal mast cells. Here, we analysed the effects of nobiletin on inflammation and fibrosis in IL-10-/- colitis. METHODS: IL-10-/- and wild-type (WT) mice were orally treated with/without vehicle or nobiletin. Clinical symptoms of colitis and disease activity index (DAI) were assessed, and colon tissue was analysed for tissue damage, cellular infiltration, bowel wall thickness, mast cell number and degranulation, as well as collagen deposition as marker for fibrosis. Human intestinal fibroblasts (hiFB) were treated with nobiletin and the expression of collagen and pro-inflammatory cytokines was measured. RESULTS: Nobiletin treatment of IL-10-/- mice resulted in a reduction of clinical colitis symptoms and a longer survival time. In addition, histological scores of colitis were reduced compared to control groups. Mast cell number and degranulation was lower in nobiletin treated IL-10-/- mice, and correlated positively with DAI. As well, fibrotic marker of collagen deposition was reduced by nobiletin. In hiFB, the expression of collagen as well as of pro-inflammatory cytokines IL-6, TNF and CCL2 was down-regulated by nobiletin treatment. CONCLUSIONS: Nobiletin decreases inflammatory symptoms and markers in murine colitis as well as fibrotic collagen deposition and expression. Thus, nobiletin could be a potential new agent in therapy of chronic colitis.

The Circadian Clock Drives Mast Cell Functions in Allergic Reactions.

Allergic diseases are known to vary in the severity of their symptoms throughout the day/night cycle. This rhythmicity is also observed in mast cell function and responsiveness. Mast cells are key effector cells of allergic reactions and release cytokines, chemokines, and important inflammatory mediators such as histamine, which have been shown to display diurnal variation. Recent research clarified that mast cells are controlled by their internal clock-which is regulated by a specific set of clock genes-as well as external factors such as light sensed by the suprachiasmatic nuclei, hormonal status, or diet. Here, we give an overview of the connections between circadian clock, mast cells, and allergic disease. Further work aimed at studying the role of chronotherapy/chronomedicine should take into account this rhythmic nature of not only mast cells but also the immune responses generated by mast cell signaling.

Increased IL-17RA and IL-17RC in End-Stage COPD and the Contribution to Mast Cell Secretion of FGF-2 and VEGF.

Mast cells are accumulated in advanced chronic obstructive pulmonary disease (COPD), and interleukin (IL)-17 signaling plays a role in disease progression. The expression, localization and functional relevance of IL-17 receptor (R)A and IL-17RC was explored in COPD by immunodetection, and functional assays.IL-17RA and IL-17RC was increased in very severe COPD, and expressed by mast cells. Increased secretion of the pro-angiogenic basic fibroblast growth factor and vascular endothelial growth factor was observed in vitro-maintained mast cells stimulated with IL-17A. Expression of these mediators was confirmed in end-stage COPD. Thus, accumulation of mast cells in COPD may contribute to vascular remodeling.

Cinnamon reduces inflammatory response in intestinal fibroblasts in vitro and in colitis in vivo leading to decreased fibrosis.

SCOPE: Intestinal fibrosis, a complication of inflammatory bowel disease, is currently being addressed by surgery alone, with no adequate alternative therapy available for patients. We propose that anti-inflammatory plant substances like cinnamon extract (CE) or its main compound cinnamaldeyde (CA) could aid in therapy. We recently found CE reducing inflammation in murine colitis. Here, we analyzed effects of CE on fibrosis in IL-10-/- colitis. METHODS AND RESULTS: IL-10-/- and wild-type (WT) mice were orally treated with/without vehicle or CE. Colonic tissue was analyzed for collagen deposition and expression of matrix metalloproteinases (MMPs). Influence of CE or CA on expression and release of cytokines, and phosphorylation of IκB in LPS-activated fibroblasts was assessed. Fibrosis score and mRNA expression of MMPs were down-regulated in colonic tissue of CE-treated IL-10-/- mice. Fibroblasts treated with CE or CA showed reduced expression and release of IL-6, KC/C-X-C motif ligand (CXCL) 8, and C-C motif ligand (CCL) 2 in response to LPS-treatment. CE and CA appear to act via reducing phosphorylation of IκB. CONCLUSIONS: Cinnamon decreases fibrotic symptoms and markers in murine colitis, and expression of inflammatory and fibrotic markers in hiFB. Thus, CE and CA could be potential anti-fibrotic agents in chronic colitis.