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World Journal of Gastroenterology Jun 2024The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent. The gut microbiota contributes to colorectal...
BACKGROUND
The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent. The gut microbiota contributes to colorectal carcinogenesis (CRC), as demonstrated with colibactin-producing (CoPEC).
AIM
To evaluate the association between CoPEC prevalence and anxiety- and depressive-like behaviors with both preclinical and clinical approaches.
METHODS
Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric interview. Results were compared according to the CoPEC colonization. In parallel C57BL6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC strain. Their behavior was assessed using the Elevated Plus Maze test, the Forced Swimming Test and the Behavior recognition system PhenoTyper.
RESULTS
In a limited cohort, all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis, whereas only one patient (17%) without CoPEC did. This result was confirmed in C57BL6/J wild-type mice and in a CRC susceptibility mouse model (adenomatous polyposis coli). Mice exhibited a significant increase in anxiety- and depressive-like behaviors after chronic infection with a CoPEC strain.
CONCLUSION
This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties.
Topics: Animals; Mice, Inbred C57BL; Humans; Male; Polyketides; Depression; Gastrointestinal Microbiome; Anxiety; Mice; Female; Aged; Middle Aged; Escherichia coli Infections; Disease Models, Animal; Peptides; Escherichia coli; Colonic Neoplasms; Prevalence; Brain-Gut Axis
PubMed: 38899326
DOI: 10.3748/wjg.v30.i21.2817 -
Otolaryngology--head and Neck Surgery :... Jun 2024To evaluate the severity and prevalence of headache and facial pain/pressurere in the chronic rhinosinusitis (CRS) population. (Review)
Review
OBJECTIVE
To evaluate the severity and prevalence of headache and facial pain/pressurere in the chronic rhinosinusitis (CRS) population.
DATA SOURCES
CINAHL, PubMed, Scopus.
REVIEW METHODS
The literature was searched from inception through June 2023 for English language articles documenting "headache" or "facial pain/pressure" and "chronic rhinosinusitis." Data collected included Lund-MacKay computed tomography score, Lund-Kennedy endoscopy score, sinonasal outcome test, and visual analog scale. Meta-analyses were performed on continuous measures (mean), proportions (%), and regression.
RESULTS
A total of 69 studies were included with 8643 CRS patients and 703 control patients. The CRS group had a mean age of 44.1 (range: 16-82; 95% confidence interval [CI]: 40.3-48) and 86.1% [95% CI: 76.4-93.5] with nasal polyposis. The control group had a mean age of 39.2 (range: 17-88; 95% CI: 28.7-49.8). All CRS subgroups had significantly more severe headache and facial pain/pressure when compared to the control (P < .0001). Patients without polyps had significantly more severe facial pain/pressure and headache when compared to patients with polyps (P < .0001). Facial pain/pressure is a moderate problem or worse in 29.8% of polypoid patients versus 56.4% of nonpolypoid patients; Δ26.6% [95% CI: 0.7-50; P = .045].
CONCLUSIONS
Across all outcome metrics, CRS patients experience significantly more severe headache and facial pain/pressure when compared to a control population. Nonpolypoid patients experience significantly more severe facial pain/pressure and headache when compared to polypoid patients. The majority of nonpolypoid patients experience facial pain/pressure that is moderate in severity or worse.
PubMed: 38895867
DOI: 10.1002/ohn.855 -
Liver Cancer Jun 2024Immunotherapy is becoming a promising approach for unresectable-hepatocellular carcinoma (HCC); the anti-tumor response is affected by the tumor microenvironment (TME)....
INTRODUCTION
Immunotherapy is becoming a promising approach for unresectable-hepatocellular carcinoma (HCC); the anti-tumor response is affected by the tumor microenvironment (TME). Although Wnt/β-catenin mutations are reported to cause non-inflamed phenotype, their role on TME remains controversial. We aimed to clarify the heterogeneity of immunophenotype in HCC with Wnt/β-catenin mutations.
METHODS
This study includes 152 resected HCCs; mutations in the , or , or genes were defined as Wnt/β-catenin mutations. With hierarchical cluster analyses, TME was classified into inflamed or non-inflamed classes based on the gene expressions associated with T-cell activation. Expression profiles of molecules related to cell differentiation and biliary-stem cell markers were compared between the TME classes to investigate whether differences in tumor traits were associated with TME.
RESULTS
Forty of 152 (26.3%) HCCs carried the Wnt/β-catenin mutations. Of these, 33 were classified as non-inflamed (33/40, 82.5%) and 7 as inflamed (7/40, 17.5%). Non-inflamed class was characterized by low number of CD3+, CD4+, and CD8+ cells on immunostaining, and high mRNA expressions of which are involved in the canonical Wnt/β-catenin signaling and hepatocyte differentiation, respectively. Non-inflamed tumors showed higher enhancement on the hepatobiliary-phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) compared to inflamed tumors. HCCs classified as inflamed class are revealed to have high numbers of CD3+, CD4+, and CD8+ tumor infiltrating lymphocytes on immunostaining. This class is associated with increased expression of anti-epithelial cell adhesion molecule and FOXM1 accompanied by upregulation of genes related to interferon-gamma signaling, dendritic cell migration, regulatory T cells, and myeloid-derived suppressor cell activation and recognized as low enhancement nodule on Gd-EOB-DTPA-enhanced MRI.
CONCLUSION
Heterogeneity of tumor traits and TME was observed in HCC with Wnt/β-catenin mutation. The potential was indicated that tumor traits and TME are determined not only by the activation of the but also by , both of which are downstream transcription factor of the Wnt/β-catenin signaling pathway.
PubMed: 38894812
DOI: 10.1159/000533818 -
International Journal of Molecular... May 2024Thymic stromal lymphopoietin (TSLP), is a protein belonging to a class of epithelial cytokines commonly called alarmins, which also includes IL-25 and IL-33.... (Review)
Review
Thymic stromal lymphopoietin (TSLP), is a protein belonging to a class of epithelial cytokines commonly called alarmins, which also includes IL-25 and IL-33. Functionally, TSLP is a key player in the immune response to environmental insults, initiating a number of downstream inflammatory pathways. TSLP performs its role by binding to a high-affinity heteromeric complex composed of the thymic stromal lymphopoietin receptor (TSLPR) chain and IL-7Rα. In recent years, the important role of proinflammatory cytokines in the etiopathogenesis of various chronic diseases such as asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), chronic obstructive pulmonary diseases (COPDs), and chronic spontaneous urticaria has been studied. Although alarmins have been found to be mainly implicated in the mechanisms of type 2 inflammation, studies on monoclonal antibodies against TSLP demonstrate partial efficacy even in patients whose inflammation is not definable as T2 and the so-called low T2. Tezepelumab is a human anti-TSLP antibody that prevents TSLP-TSLPR interactions. Several clinical trials are evaluating the safety and efficacy of Tezepelumab in various inflammatory disorders. In this review, we will highlight major recent advances in understanding the functional role of TSLP, its involvement in Th2-related diseases, and its suitability as a target for biological therapies.
Topics: Humans; Cytokines; Thymic Stromal Lymphopoietin; Antibodies, Monoclonal, Humanized; Animals; Receptors, Cytokine; Molecular Targeted Therapy; Respiratory Tract Diseases; Asthma
PubMed: 38892164
DOI: 10.3390/ijms25115972 -
International Journal of Molecular... May 2024Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by multiple juvenile polyps in the gastrointestinal tract, often associated with...
Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by multiple juvenile polyps in the gastrointestinal tract, often associated with mutations in genes such as and 1. This study explores the impact of knock-out on the development of intestinal polyps using collaborative cross (CC) mice, a genetically diverse model. Our results reveal a significant increase in intestinal polyps in knock-out mice across the entire population, emphasizing the broad influence of on polyposis. Sex-specific analyses demonstrate higher polyp counts in knock-out males and females compared to their WT counterparts, with distinct correlation patterns. Line-specific effects highlight the nuanced response to knock-out, underscoring the importance of genetic variability. Multimorbidity heat maps offer insights into complex relationships between polyp counts, locations, and sizes. Heritability analysis reveals a significant genetic basis for polyp counts and sizes, while machine learning models, including k-nearest neighbors and linear regression, identify key predictors, enhancing our understanding of juvenile polyposis genetics. Overall, this study provides new information on understanding the intricate genetic interplay in the context of knock-out, offering valuable insights that could inform the identification of potential therapeutic targets for juvenile polyposis and related diseases.
Topics: Animals; Female; Male; Mice; Collaborative Cross Mice; Disease Models, Animal; Genetic Background; Intestinal Polyposis; Intestinal Polyps; Mice, Knockout; Neoplastic Syndromes, Hereditary; Smad4 Protein
PubMed: 38891999
DOI: 10.3390/ijms25115812 -
International Journal of Molecular... May 2024DNA methylation is an epigenetic process that commonly occurs in genes' promoters and results in the transcriptional silencing of genes. DNA methylation is a frequent...
DNA methylation is an epigenetic process that commonly occurs in genes' promoters and results in the transcriptional silencing of genes. DNA methylation is a frequent event in bladder cancer, participating in tumor initiation and progression. Bladder cancer is a major health issue in patients suffering from neurogenic lower urinary tract dysfunction (NLUTD), although the pathogenetic mechanisms of the disease remain unclear. In this population, bladder cancer is characterized by aggressive histopathology, advanced stage during diagnosis, and high mortality rates. To assess the DNA methylation profiles of five genes' promoters previously known to be associated with bladder cancer in bladder tissue of NLUTD patients, we conducted a prospective study recruiting NLUTD patients from the neuro-urology unit of a public teaching hospital. Cystoscopy combined with biopsy for bladder cancer screening was performed in all patients following written informed consent being obtained. Quantitative methylation-specific PCR was used to determine the methylation status of RASSF1, RARβ, DAPK, hTERT, and APC genes' promoters in bladder tissue samples. Twenty-four patients suffering from mixed NLUTD etiology for a median duration of 10 (IQR: 12) years were recruited in this study. DNA hypermethylation was detected in at least one gene of the panel in all tissue samples. RAR-β was hypermethylated in 91.7% samples, RASSF and DAPK were hypermethylated in 83.3% samples, APC 37.5% samples, and TERT in none of the tissue samples. In 45.8% of the samples, three genes of the panel were hypermethylated, in 29.2% four genes were hypermethylated, and in 16.7% and in 8.3% of the samples, two and one gene were hypermethylated, respectively. The number of hypermethylated genes of the panel was significantly associated with recurrent UTIs ( = 0.0048). No other significant association was found between DNA hypermethylation or the number of hypermethylated genes and the clinical characteristics of the patients. Histopathological findings were normal in 8.3% of patients, while chronic inflammation was found in 83.3% of patients and squamous cell metaplasia in 16.7% of patients. In this study, we observed high rates of DNA hypermethylation of genes associated with bladder cancer in NLUTD patients, suggesting an epigenetic field effect and possible risk of bladder cancer development. Recurrent UTIs seem to be associated with increased DNA hypermethylation. Further research is needed to evaluate the impact of recurrent UTIs and chronic inflammation in DNA hypermethylation and bladder cancer etiopathogenesis in NLUTD patients.
Topics: Humans; DNA Methylation; Urinary Bladder Neoplasms; Male; Female; Promoter Regions, Genetic; Middle Aged; Aged; Urinary Bladder; Prospective Studies; Tumor Suppressor Proteins; Urinary Bladder, Neurogenic; Epigenesis, Genetic; Telomerase; Death-Associated Protein Kinases; Adenomatous Polyposis Coli Protein; Receptors, Retinoic Acid
PubMed: 38891848
DOI: 10.3390/ijms25115660 -
ACG Case Reports Journal Jun 2024Therapy-associated polyposis (TAP), an acquired gastrointestinal polyposis in childhood cancer survivors, poses diagnostic challenges resembling hereditary syndromes....
Therapy-associated polyposis (TAP), an acquired gastrointestinal polyposis in childhood cancer survivors, poses diagnostic challenges resembling hereditary syndromes. Four TAP patients were studied, revealing upper gastrointestinal lesions after radiotherapy in 2 patients, managed by endoscopic resection. Two underwent total colectomy; 1 had adenocarcinoma from a polyp. Next-generation sequencing on diseased tissue revealed no alteration in mismatch repair genes with stable microsatellite status; however, there was somatic mutation in APC gene altering Wnt signaling pathway in all 3 precancerous lesions. Integrating endoscopic and surgical interventions is crucial, although ongoing studies aim to elucidate pathophysiology for potential targeted therapies in TAP management.
PubMed: 38883581
DOI: 10.14309/crj.0000000000001379 -
Indian Journal of Otolaryngology and... Jun 2024Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the mucosa of the nasal cavity and nasal sinuses. Many patients with CRS complain of gustatory...
Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the mucosa of the nasal cavity and nasal sinuses. Many patients with CRS complain of gustatory dysfunction which affects their quality of life. To assess the gustatory function and acuity in patients with chronic rhinosinusitis using taste strips. This is a case control study carried out at our institute from May 2021 to June 2022 on 63 Patients with chronic rhinosinusitis with nasal polyposis and 63 normal controls. All patients of the study and control group will be subjected to full medical history taking including SNOT-22-Questionnaire, sinuscopic examination, computed tomography scan nose and paranasal sinuses using Lund-Mackay score. Taste strips representing five tastes (sweet, sour, salty, bitter and umami) were used to assess gustatory function in CRS patients and controls. 63 patients with CRS and 63 healthy controls were involved in our study, age 42.05 ± 14 years old for cases and 40.9 ± 13.6 years old for controls. There was a highly significant difference between cases and controls as regard SNOT-22-Questionnaire scores and Meltzer-scores with higher mean scores among cases. There was a highly significant difference between cases and controls as regard Sweet, Salt Sour, Bitter, Umami and Total Taste score, with lower mean scores among cases. This is most evident in bitter taste. There was a significant negative Correlation between each of SNOT-22-Questionnaire score, Meltzer-score and Lund-Mackay score and total taste score. Patients with chronic rhinosinusitis exhibited decreased gustatory function compared to healthy controls. The effect was most pronounced for bitter taste.
PubMed: 38883474
DOI: 10.1007/s12070-024-04512-2 -
Indian Journal of Otolaryngology and... Jun 2024The presence of osteoid bone in chronic rhinosinusitis especially the eosinophilic subtype is commonly associated with recalcitrant illness. In practice, the...
BACKGROUND
The presence of osteoid bone in chronic rhinosinusitis especially the eosinophilic subtype is commonly associated with recalcitrant illness. In practice, the radiological features of osteitis sinus alterations are frequently described, but the clinical and histopathologic implications are not well understood.
OBJECTIVE
This study was done to correlate the radiological and the clinico-histopathological aspects in patients of eosinophilic chronic rhinosinusitis.
METHODS
A cross-sectional study was done on sixty patients of chronic rhinosinusitis with nasal polyposis (CRSwNP) patients especially the eosinophilic subtype undergoing sinus surgery. Radiologically, osteitis was graded using standards that had already been published in the literature. Analysis was done on the relationships between CT documented osteitis, histopathological, and peripheral eosinophilic counts in patients of eosinophilic chronic rhinosinusitis.
RESULTS
The patients with higher tissue eosinophilia and higher peripheral eosinophils had higher osteitis score. Pearson's correlation coefficient between Tissue Eosinophils and KOS was highly significant with -value <0.001 (0.891). R2 value for KOS versus Tissue Eosinophils was 79.44%,implying that 79.44% variations were explained by Tissue Eosinophils in KOS. And R2 value for KOS versus Peripheral Eosinophils was 74.26%, implying that 74.26% variations were explained by Peripheral Eosinophils in KOS. Thereby, showing a positive relationship between the variables that were studied.
CONCLUSION
Kennedy Osteitis Score, histopathological and peripheral eosinophilia can be used as a marker to predict the disease severity in eosinophilic chronic rhinosinusitis.
PubMed: 38883472
DOI: 10.1007/s12070-024-04554-6 -
European Journal of Internal Medicine Jun 2024Eosinophilic granulomatosis with polyangiitis (EGPA), is a rare ANCA-associated systemic vasculitis. Its overlapping features with other vasculitic or eosinophilic...
BACKGROUND
Eosinophilic granulomatosis with polyangiitis (EGPA), is a rare ANCA-associated systemic vasculitis. Its overlapping features with other vasculitic or eosinophilic diseases, and the wide and heterogeneous range of clinical manifestations, often result in a delay to diagnosis.
OBJECTIVE
To identify red flags that raise a suspicion of EGPA to prompt diagnostic testing and to present an evidence-based clinical checklist tool for use in routine clinical practice.
METHODS
Systematic literature review and expert consensus to identify a list of red flags based on clinical judgement. GRADE applied to generate a strength of recommendation for each red flag and to develop a checklist tool.
RESULTS
86 studies were included. 40 red flags were identified as relevant to raise a suspicion of EGPA and assessed by the experts as being clinically significant. Experts agreed that a diagnosis of EGPA should be considered in a patient aged ≥6 years with a blood eosinophil level >1000 cells/µL if untreated and >500 cells/µL if previously treated with any medication likely to have altered the blood eosinophil count. The presence of asthma and/or nasal polyposis should reinforce a suspicion of EGPA. Red flags of asthma, lung infiltrates, pericarditis, cardiomyopathy, polyneuropathy, biopsy with inflammatory eosinophilic infiltrates, palpable purpura, digital ischaemia and ANCA positivity, usually anti-myeloperoxidase, among others, were identified.
CONCLUSION
The identification of a comprehensive set of red flags could be used to raise a suspicion of EGPA in patients with eosinophilia, providing clinicians with an evidence-based checklist tool that can be integrated into their practice.
PubMed: 38880725
DOI: 10.1016/j.ejim.2024.06.008