It has been long recognized that NOD1 and NOD2 are critical players in the host immune response, primarily by their sensing bacterial peptidoglycan‐conserved motifs. Significant advances have been ...made from efforts that characterize their upstream activators, assembly of signaling complexes, and activation of downstream signaling pathways. Disruption in NOD1 and NOD2 signaling has also been associated with impaired host defense and resistance to the development of inflammatory diseases. In this review, we will describe how NOD1 and NOD2 sense microbes and cellular stress to regulate host responses that can affect disease pathogenesis and outcomes.
To evaluate the effect on visual acuity of the implantation of a new intraocular pinhole device (Xtrafocus) in cases of irregular corneal astigmatism with significant visual impairment.
University of ...São Paulo, São Paulo, Brazil.
Prospective case series.
Pseudophakic eyes of patients with irregular corneal astigmatism were treated with the pinhole device. The causes of irregular corneal astigmatism were keratoconus, post radial keratotomy (RK), post-penetrating keratoplasty (PKP), and traumatic corneal laceration. The device was implanted in the ciliary sulcus in a piggyback configuration to minimize the effect of corneal aberrations. Preoperative and postoperative visual parameters were compared. The main outcome variables were manifest refraction, uncorrected and corrected distance and near visual acuities, subjective patient satisfaction, and intraoperative and postoperative adverse events and complications.
Twenty-one patients (ages 35 to 85 years) were included. There was statistically significant improvement in uncorrected and corrected (CDVA) distance visual acuities. The median CDVA improved from 20/200 (range 20/800 to 20/60) preoperatively to 20/50 (range 20/200 to 20/20) in the first month postoperatively and remained stable over the following months. Manifest refraction remained unchanged, while a subjective visual performance questionnaire revealed perception of improvement in all the tested working distances. No major complication was observed. One case presented with decentration of the device, which required an additional surgical intervention.
The intraocular pinhole device performed well in patients with irregular astigmatism caused by keratoconus, RK, PKP, and traumatic corneal laceration. There was marked improvement in visual function, with high patient satisfaction.
Diets high in cholesterol alter intestinal immunity. Here, we examined how the cholesterol metabolite 25-hydroxycholesterol (25-HC) impacts the intestinal B cell response. Mice lacking cholesterol ...25-hydroxylase (CH25H), the enzyme generating 25-HC, had higher frequencies of immunoglobulin A (IgA)-secreting antigen-specific B cells upon immunization or infection. 25-HC did not affect class-switch recombination but rather restrained plasma cell (PC) differentiation. 25-HC was produced by follicular dendritic cells and increased in response to dietary cholesterol. Mechanistically, 25-HC restricted activation of the sterol-sensing transcription factor SREBP2, thereby regulating B cell cholesterol biosynthesis. Ectopic expression of SREBP2 in germinal center B cells induced rapid PC differentiation, whereas SREBP2 deficiency reduced PC output in vitro and in vivo. High-cholesterol diet impaired, whereas Ch25h deficiency enhanced, the IgA response against Salmonella and the resulting protection from systemic bacterial dissemination. Thus, a 25-HC-SREBP2 axis shapes the humoral response at the intestinal barrier, providing insight into the effect of high dietary cholesterol in intestinal immunity.
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•CH25H deficiency enhances Ag-specific IgA plasma cell differentiation in Peyer’s patches•25-HC suppresses SREBP2 transcriptional activity in activated B cells•Srebf2−/− germinal center B cells fail to differentiate into IgA plasma cells•Dietary cholesterol increases 25-HC level and reduces IgA against enteric pathogen
25-hydroxycholesterol (25-HC) is a metabolite of cholesterol generated by the enzyme CH25H. Trindade et al. demonstrate that 25-HC, produced by follicular dendritic cells in response to dietary cholesterol, inhibits the activity of the transcription factor SREBP2 in intestinal germinal center B cells, thereby reducing antigen-specific IgA responses during enteric infection.
Sulforaphane is a bioactive metabolite with anti-inflammatory activity and is derived from the glucosinolate glucoraphanin, which is highly abundant in broccoli sprouts. However, due to its inherent ...instability its use as a therapeutic against inflammatory diseases has been limited. There are few studies to investigate a whole food approach to increase sulforaphane levels with therapeutic effect and reduce inflammation. In the current study, using a mouse model of inflammatory bowel disease, we investigated the ability of steamed broccoli sprouts to ameliorate colitis and the role of the gut microbiota in mediating any effects. We observed that despite inactivation of the plant myrosinase enzyme responsible for the generation of sulforaphane via steaming, measurable levels of sulforaphane were detectable in the colon tissue and feces of mice after ingestion of steamed broccoli sprouts. In addition, this preparation of broccoli sprouts was also capable of reducing chemically-induced colitis. This protective effect was dependent on the presence of an intact microbiota, highlighting an important role for the gut microbiota in the metabolism of cruciferous vegetables to generate bioactive metabolites and promote their anti-inflammatory effects.
Clostridium difficile infection (CDI) is one of the most common nosocomial infections worldwide and an urgent public health threat. Epidemiological and experimental studies have demonstrated an ...association between nonsteroidal anti-inflammatory drug (NSAID) exposure and enhanced susceptibility to, and severity of, CDI. NSAIDs target cyclooxygenase enzymes and inhibit the production of prostaglandins (PGs), but the therapeutic potential of exogenous introduction of PGs for the treatment of CDI has not been explored. In this study, we report that treatment with the FDA-approved stable PGE1 analogue, misoprostol, protects mice against C. difficile-associated mortality, intestinal pathology, and CDI-mediated intestinal permeability. Furthermore, we report that the effect of misoprostol on the gastrointestinal tract contributes to increased recovery of the gut microbiota following antibiotic perturbation. Together, these data implicate PGs as an important host-factor associated with recovery to C. difficile-associated disease and demonstrate the potential for misoprostol in the treatment of CDI. Further studies to explore the safety and efficacy of misoprostol treatment of CDI in humans is needed.
•The prostaglandin E1 analogue misoprostol protects mice against C. difficile-associated mortality and intestinal pathology.•The effect of misoprostol contributes to increased recovery of the gut microbiota following antibiotic perturbation.•Prostaglandins may be important host factors associated with recovery from C. difficile infection.
To evaluate the effect on the nonsteroidal anti-inflammatory drug indomethacin on Clostridium difficile infection (CDI) severity.
Indomethacin was administered in two different mouse models of ...antibiotic-associated CDI in two different facilities, using a low and high dose of indomethacin.
Indomethacin administration caused weight loss, increased the signs of severe infection and worsened histopathological damage, leading to 100% mortality during CDI. Indomethacin-treated, antibiotic-exposed mice infected with C. difficile had enhanced intestinal inflammation with increased expression of KC, IL-1β and IL-22 compared with infected mice unexposed to indomethacin.
These results demonstrate a negative impact of nonsteroidal anti-inflammatory drugs on antibiotic-associated CDI in mice and suggest that targeting the synthesis or signaling of prostaglandins might be an approach to ameliorating the severity of CDI.
The Role of Radiomics in Rectal Cancer Miranda, Joao; Horvat, Natally; Araujo-Filho, Jose A. B. ...
Journal of gastrointestinal cancer,
12/2023, Volume:
54, Issue:
4
Journal Article
Peer reviewed
Purpose
Radiomics is a promising method for advancing imaging assessment in rectal cancer. This review aims to describe the emerging role of radiomics in the imaging assessment of rectal cancer, ...including various applications of radiomics based on CT, MRI, or PET/CT.
Methods
We conducted a literature review to highlight the progress of radiomic research to date and the challenges that need to be addressed before radiomics can be implemented clinically.
Results
The results suggest that radiomics has the potential to provide valuable information for clinical decision-making in rectal cancer. However, there are still challenges in terms of standardization of imaging protocols, feature extraction, and validation of radiomic models. Despite these challenges, radiomics holds great promise for personalized medicine in rectal cancer, with the potential to improve diagnosis, prognosis, and treatment planning. Further research is needed to validate the clinical utility of radiomics and to establish its role in routine clinical practice.
Conclusion
Overall, radiomics has emerged as a powerful tool for improving the imaging assessment of rectal cancer, and its potential benefits should not be underestimated.
Diets high in cholesterol alter intestinal immunity. Here, we examined how the cholesterol metabolite 25-hydroxycholesterol (25-HC) impacts the intestinal B cell response. Mice lacking cholesterol ...25-hydroxylase (CH25H), the enzyme generating 25-HC, had higher frequencies of IgA-secreting antigen-specific B cells upon immunization or infection. 25-HC did not affect class switch recombination, but rather restrained plasma cell (PC) differentiation. 25-HC was produced by follicular dendritic cells and increased in response to dietary cholesterol. Mechanistically, 25-HC restricted activation of the sterol sensing transcription factor SREBP2, thereby regulating B cell cholesterol biosynthesis. Ectopic expression of SREBP2 in germinal center B cells induced rapid PC differentiation, whereas SREBP2 deficiency reduced PC output in vitro and in vivo. High cholesterol diet impaired, whereas Ch25h deficiency enhanced, the IgA response against Salmonella and the resulting protection from systemic bacterial dissemination. Thus, a 25-HC-SREBP2 axis shapes the humoral response at the intestinal barrier, providing insight into the impact of high dietary cholesterol in intestinal immunity.
25-hydroxycholesterol (25-HC) is a metabolite of dietary cholesterol generated by the enzyme CH25H. Trindade et al. demonstrate that 25-HC produced by follicular dendritic cells inhibits the activity of the transcription factor SREBP2 in intestinal germinal center B cells and thereby reduces antigen-specific IgA response during enteric infection.
In the present work we examine the contribution of 5-lipoxygenase- (5-LO-) derived lipid mediators to immune responses during the acute phase of Trypanosoma cruzi infection in 5-LO gene knockout ...(5-LO−/−) mice and wild-type (WT) mice. Compared with WT mice, the 5-LO−/− mice developed less parasitemia/tissue parasitism, less inflammatory cell infiltrates, and a lower mortality. This resistance of 5-LO−/− mice correlated with several differences in the immune response to infection, including reduced PGE2 synthesis; sustained capacity of splenocytes to produce high levels of interleukin (IL)-12 early in the infection; enhanced splenocyte production of IL-1β, IL-6, and IFN-γ; rapid T-cell polarization to secrete high quantities of IFN-γ and low quantities of IL-10; and greater numbers of CD8+ C D 4 4 h i g h C D 62 L l o w memory effector T cells at the end of the acute phase of infection. The high mortality in WT mice was associated with increased production of LTB4/LTC4, T cell bias to produce IFN-γ, high levels of serum nitrite, and marked protein extravasation into the peritoneal cavity, although survival was improved by treatment with a cys-LT receptor 1 antagonist. These data also provide evidence that 5-LO-derived mediators negatively affect host survival during the acute phase of T. cruzi infection.
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