Quercetin, widely distributed in fruits and vegetables, is a flavonoid known for its antioxidant, antiviral, antimicrobial, and antiinflammatory properties. Several studies highlight the potential ...use of quercetin as an antiviral, due to its ability to inhibit the initial stages of virus infection, to be able to interact with proteases important for viral replication, and to reduce inflammation caused by infection. Quercetin could also be useful in combination with other drugs to potentially enhance the effects or synergistically interact with them, in order to reduce their side effects and related toxicity. Since there is no comprehensive compilation about antiviral activities of quercetin and derivates, the aim of this review is providing a summary of their antiviral activities on a set of human viral infections along with mechanisms of action. Thus, the following family of viruses are examined: Flaviviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, Hepadnaviridae, Retroviridae, Picornaviridae, Pneumoviridae, and Filoviridae.
Alterations of the gut microbiota may cause dysregulated mucosal immune responses leading to the onset of inflammatory bowel diseases (IBD) in genetically susceptible hosts. Restoring immune ...homeostasis through the normalization of the gut microbiota is now considered a valuable therapeutic approach to treat IBD patients. The customization of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics and faecal microbiota transplantation, is therefore considered to support current therapies in IBD management. In this review, we will discuss recent advancements in the understanding of host-microbe interactions in IBD and the basis to promote homeostatic immune responses through microbe-targeted therapies. By considering gut microbiota dysbiosis as a key feature for the establishment of chronic inflammatory events, in the near future it will be suitable to design new cost-effective, physiologic, and patient-oriented therapeutic strategies for the treatment of IBD that can be applied in a personalized manner.
COVID-19 has rapidly become a major health emergency worldwide. Patients with IBD are at increased risk of infection, especially when they have active disease and are taking immunosuppressive ...therapy. The characteristics and outcomes of COVID-19 in patients with IBD remain unclear.
This Italian prospective observational cohort study enrolled consecutive patients with an established IBD diagnosis and confirmed COVID-19. Data regarding age, sex, IBD (type, treatments and clinical activity), other comorbidities (Charlson Comorbidity Index (CCI)), signs and symptoms of COVID-19 and therapies were compared with COVID-19 outcomes (pneumonia, hospitalisation, respiratory therapy and death).
Between 11 and 29 March 2020, 79 patients with IBD with COVID-19 were enrolled at 24 IBD referral units. Thirty-six patients had COVID-19-related pneumonia (46%), 22 (28%) were hospitalised, 7 (9%) required non-mechanical ventilation, 9 (11%) required continuous positive airway pressure therapy, 2 (3%) had endotracheal intubation and 6 (8%) died. Four patients (6%) were diagnosed with COVID-19 while they were being hospitalised for a severe flare of IBD. Age over 65 years (p=0.03), UC diagnosis (p=0.03), IBD activity (p=0.003) and a CCI score >1 (p=0.04) were significantly associated with COVID-19 pneumonia, whereas concomitant IBD treatments were not. Age over 65 years (p=0.002), active IBD (p=0.02) and higher CCI score were significantly associated with COVID-19-related death.
Active IBD, old age and comorbidities were associated with a negative COVID-19 outcome, whereas IBD treatments were not. Preventing acute IBD flares may avoid fatal COVID-19 in patients with IBD. Further research is needed.
Colorectal cancer represents a life-threatening complication of inflammatory bowel diseases. Statistics indicate that the risk to develop colorectal cancer is higher in patients affected by ...ulcerative colitis and to a lesser extent by Crohn's disease and that such a risk is directly proportional to the number of years of active disease. These observations suggest that chronic inflammation may substantially contribute to cancer development. However the molecular mechanisms underlying this process have been only recently started to be clarified. Indeed from the initial concept that the release of free radicals during inflammation might induce the accumulation of genetic mutations thus leading to the onset of dysplastic cells, it is now becoming clear that the large amount of cytokines and growth factors released during inflammation by immune and non immune cells may influence the carcinogenesis process. IL-6 and IL-23, cytokines which play key roles in the induction and maintenance of gut inflammation during IBDs, have been recently shown to influence the development and growth of colitis associated colorectal cancer. Moreover, the activation of the nuclear factor kappa B (NF kappa B), a transcription factor activated by several cytokines released during inflammation and responsible for many of their proinflammatory effects, have been shown to promote the growth of the colon tumors in experimental models.
Crohn's disease and ulcerative colitis, the 2 major forms of inflammatory bowel disease (IBD) in humans, arise in genetically predisposed individuals because of an abnormal immune response direct ...against constituents of the gut flora. Defects in counter-regulatory mechanisms are supposed to amplify and maintain the IBD-associated mucosal inflammation. Therefore, restoring the balance between inflammatory and anti-inflammatory pathways in the gut could contribute to halt the IBD-associated tissue-damaging immune response. Various suppressive T cell (Tregs) subsets have been characterized phenotypically and functionally and over the last decade, there has been enormous effort for optimizing the procedures for the in vitro expansion/generation of these cells for therapeutic purposes. Here we review the mechanisms of action and functional relevance of Tregs in the maintenance of gut inflammation and analyze the available data about the use of these cells in the treatment of IBD patients.
Several anti-PD-1/PD-L1 monoclonal antibodies (mAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these mAbs is to inhibit PD-1 on immune ...cells interacting with PD-L1 on tumor cells. These mAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective mAb-mediated cancer therapies. A fully human anti-PD-L1 mAb would potentially be able to block PD-1/PD-L1 interactions and also mediate the ADCC lysis of tumor cells. MSB0010718C (designated avelumab) is a fully human IgG1 anti-PD-L1 mAb. The studies reported here demonstrate (i) the ability of avelumab to lyse a range of human tumor cells in the presence of PBMC or NK effectors; (ii) IFNγ can enhance tumor cell PD-L1 expression and, in some cases, enhance ADCC tumor cell lysis; (iii) purified NK cells are potent effectors for avelumab; (iv) similar levels of avelumab-mediated ADCC lysis of tumor cells are seen using purified NK as effectors from either healthy donors or cancer patients; (v) very low levels of avelumab-mediated lysis are seen using whole PBMCs as targets; this finding complements results seen in analyses of PBMC subsets of patients receiving avelumab; and (vi) the addition of IL12 to NK cells greatly enhances avelumab-mediated ADCC. These studies thus provide an additional mode of action for an anti-PD-L1 mAb and support the rationale for further studies to enhance avelumab-mediated ADCC activity.
➤ Bone and muscle tissues are in close relationship, and the aging process is a factor involved in the loss of the functionality of both bones and muscles.➤ Sarcopenia and osteoporosis are linked ...from a biological and functional perspective and are related to an increased fracture risk in the elderly.➤ The increased fracture risk in sarcopenic and osteoporotic subjects is due to the decline of muscle mass and strength, the decrease in bone mineral density, and limited mobility.
Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 ...signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7.
In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28.
The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P<0.001). There was no significant difference in the percentage of participants reaching clinical remission between the 10-mg group (12%) and the placebo group. The rate of clinical response was significantly greater among patients receiving 10 mg (37%), 40 mg (58%), or 160 mg (72%) of mongersen than among those receiving placebo (17%) (P=0.04, P<0.001, and P<0.001, respectively). Most adverse events were related to complications and symptoms of Crohn's disease.
We found that study participants with Crohn's disease who received mongersen had significantly higher rates of remission and clinical response than those who received placebo. (Funded by Giuliani; EudraCT number, 2011-002640-27.).
Nonalcoholic fatty liver disease (NAFLD) is a frequently reported condition in patients with inflammatory bowel disease (IBD). Both intestinal inflammation and metabolic factors are believed to ...contribute to the pathogenesis of IBD-associated NAFLD.
To evaluate the prevalence of steatosis and liver fibrosis (LF) in a cohort of IBD patients and the identification of metabolic- and IBD-related risk factors for NAFLD and LF.
IBD patients were consecutively enrolled from December 2016 to January 2018. Demographic, anthropometric and biochemical data were collected so as eating habits. Abdominal ultrasound and transient elastography were performed to evaluate the presence of NAFLD and LF respectively.
A total of 178 consecutive patients were enrolled and included in the analysis (95 Ulcerative colitis, 83 Crohn's disease). NAFLD was detected by imaging in 72 (40.4%) patients. Comparison between patients with and without NAFLD showed no significant differences in terms of IBD severity, disease duration, location/extension, use of IBD-related medications (
., steroids, anti-TNFs, and immunomodulators) and surgery. NAFLD was significantly associated with the presence of metabolic syndrome MetS; odds ratio (OR): 4.13,
= 0.001 and obesity defined by body mass index (OR: 9.21,
= 0.0002). IBD patients with NAFLD showed higher caloric intake and lipid consumption than those without NAFLD, regardless disease activity. At the multivariate analysis, male sex, advanced age and high lipid consumption were independent risk factors for the development of NAFLD. An increased liver stiffness was detected in 21 patients (16%) and the presence of MetS was the only relevant factor associated to LF (OR: 3.40,
= 0.01).
In this study, we demonstrate that risk factors for NAFLD and LF in the IBD population do not differ from those in the general population.
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