Indications of Helicobacter pylori Eradication Treatment and Its Influence on Prescriptions and Effectiveness (Hp-EuReg).

BACKGROUND: The influence of indications for Helicobacter pylori investigation on prescriptions and effectiveness is unknown. The aim of the study was to assess the impact of indications for H. pylori investigation on prescriptions, effectiveness, compliance, and tolerance. METHODS: International, prospective, non-interventional registry of the management of H. pylori infection by European gastroenterologists (Hp-EuReg). Treatment-näive patients registered from 2013 to 2023 at e-CRF AEG-REDCap were analyzed. The effectiveness was assessed by modified intention-to-treat analysis. RESULTS: Overall, 53,636 treatment-naïve cases from 34 countries were included. Most frequent indications were: dyspepsia with normal endoscopy (49%), non-investigated dyspepsia (20%), duodenal ulcer (11%), gastric ulcer (7.7%), and gastroesophageal reflux disease (GERD) (2.6%). Therapy effectiveness varied by indication: duodenal ulcer (91%), gastric ulcer (90%), preneoplastic lesions (90%), dyspepsia with normal endoscopy (89%), GERD (88%), and non-investigated dyspepsia (87%). Bismuth-metronidazole-tetracycline and clarithromycin-amoxicillin-bismuth quadruple therapies achieved 90% effectiveness in all indications except GERD. Concomitant clarithromycin-amoxicillin-tinidazole/metronidazole reached 90% cure rates except in patients with non-investigated dyspepsia; whereas sequential clarithromycin-amoxicillin-tinidazole/metronidazole proved optimal (≥90%) in patients with gastric ulcer only. Adverse events were higher in patients treated for dyspepsia with normal endoscopy and duodenal ulcer compared with the remaining indications (23% and 28%, p < 0.001). Therapeutic compliance was higher in patients with duodenal ulcer and preneoplastic lesions (98% and 99%, p < 0.001). CONCLUSION: In Europe, patients with gastric or duodenal ulcers and preneoplastic lesions showed higher H. pylori treatment effectiveness. Bismuth and non-bismuth quadruple therapies achieved optimal results in almost all indications. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02328131.

Exploring the Link between Helicobacter pylori, Gastric Microbiota and Gastric Cancer.

Gastric cancer (GC) still represents one of the leading causes of cancer-related mortality and is a major public health issue worldwide. Understanding the etiopathogenetic mechanisms behind GC development holds immense potential to revolutionize patients' treatment and prognosis. Within the complex web of genetic predispositions and environmental factors, the connection between Helicobacter pylori (H. pylori) and gastric microbiota emerges as a focus of intense research investigation. According to the most recent hypotheses, H. pylori triggers inflammatory responses and molecular alterations in gastric mucosa, while non-Helicobacter microbiota modulates disease progression. In this review, we analyze the current state of the literature on the relationship between H. pylori and non-Helicobacter gastric microbiota in gastric carcinogenesis, highlighting the mechanisms by which microecological dysbiosis can contribute to the malignant transformation of the mucosa.

A System Biology Approach Reveals New Targets for Human Thyroid Gland Toxicity in Embryos and Adult Individuals.

Compounds of natural or synthetic origin present in personal care products, food additives, and packaging may interfere with hormonal regulation and are called endocrine-disrupting chemicals (EDCs). The thyroid gland is an important target of these compounds. The objective of this study was to analyze public data on the human thyroid transcriptome and investigate potential new targets of EDCs in the embryonic and adult thyroid glands. We compared the public transcriptome data of adult and embryonic human thyroid glands and selected 100 up- or downregulated genes that were subsequently subjected to functional enrichment analysis. In the embryonic thyroid, the most highly expressed gene was PRMT6, which methylates arginine-4 of histone H2A (86.21%), and the downregulated clusters included plasma lipoprotein particles (39.24%) and endopeptidase inhibitory activity (24.05%). For the adult thyroid gland, the most highly expressed genes were related to the following categories: metallothionein-binding metals (56.67%), steroid hormone biosynthetic process (16.67%), and cellular response to vascular endothelial growth factor stimulus (6.67%). Several compounds ranging from antihypertensive drugs to enzyme inhibitors were identified as potentially harmful to thyroid gland development and adult function.

Prostate and gut: Any relationship? A narrative review on the available evidence and putative mechanisms.

BACKGROUND: Gut microbiome is a community of microorganisms that lives in the human intestine and exerts various functions on the host, including metabolic, immunoregulatory, and control over cell proliferation. Gut microbiome alterations have been associated with various pathological conditions, such as diabetes mellitus, obesity, and cardiovascular diseases. Gut-prostate axis is explained by the association between gut microbiome quantitative and functional alterations along with increased intestinal epithelial permeability with prostatediseases. However, the pathophysiological mechanisms and clinical importance of this association are not completely clarified yet. METHODS: We conducted a narrative review of the most relevant articles in the Medline (US National Library of Medicine, Bethesda, MD, USA), Scopus (Elsevier, Amsterdam, The Netherlands) and Web of Science Core Collection (Thomson Reuters, Toronto, ON, Canada) databases. No chronological restrictions were applied, and the most related papers published until December 2023 were included. RESULTS: Gut microbiota (GM) and its metabolites are capable of modifying host androgen level, as well as prostate cancer (PCa) therapy response. Moreover, patients with inflammatory bowel disease have higher rates of prostatitis-like symptoms and a potential risk of developing PCa. CONCLUSIONS: There is evidence that interventions on the GM and its metabolites have a high potential to serve as diagnostic and therapeutic tools for prostate diseases, including PCa.

Lower urinary tract symptoms in patients with inflammatory bowel diseases: A cross-sectional observational study.

BACKGROUND: Inflammatory Bowel Diseases (IBD), Crohn's Disease (CD), and Ulcerative Colitis (UC) may have extraintestinal manifestations, including disorders of the urinary tract. The prevalence of lower urinary tract symptoms (LUTS) in IBD patients remains unclear. AIMS: Assess the prevalence of LUTS in patients with CD or UC, evaluate the variables implicated in any difference in LUTS prevalence between CD or UC, and assess any relationship between disease activity and LUTS METHODS: LUTS were evaluated in 301 IBD patients through standardised questionnaires: Bristol Female Lower Urinary Tract Symptoms (BFLUTS), NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), and International Prostate Symptom Score (IPSS). IBD activity was determined through the Crohn's Disease Activity Index (CDAI), Partial Mayo Score (PMS), and Total Mayo Score (TMS). RESULTS: BFLUTS total score for females was 6 (3-11). Patients with a higher age at diagnosis had worse filling symptoms (p = 0.049) and a worse quality of life (p = 0.005). In males, 67.1% had mild, 28.5% moderate, and 4.4% severe IPSS symptom grades. The overall NIHCPSI prevalence of chronic prostatitis-like symptoms was 26.8%. The questionnaires revealed some significant differences in the subgroups analysed. CONCLUSION: LUTS should be evaluated in IBD patients by urologic-validated questionnaires for prompt diagnosis and early treatment.

Role of proton pump inhibitors dosage and duration in Helicobacter pylori eradication treatment: Results from the European Registry on H. pylori management.

BACKGROUND: Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. AIM: To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg). METHODS: Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022. RESULTS: Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness. CONCLUSIONS: We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme.

Effectiveness and safety of an atropine/midazolam and target controlled infusion propofol-based moderate sedation protocol during percutaneous endoscopic transgastric jejunostomy procedures in Parkinson's disease: a real-life retrospective observational study.

Patients with Parkinson's disease (PD), often elderly with various comorbidities, may require a continuous intestinal infusion of carbidopa/levodopa gel by the placement of a percutaneous endoscopic gastrostomy (PEG) with a jejunal tube (PEG-J) to improve their motor outcome and quality of life. However, it is unclear what is the best procedural sedation protocol for PEG-J procedures. Fifty patients with PD and indication for PEG-J procedure (implantation, replacement, removal) underwent, from 2017 to 2022, a sedation protocol characterized by premedication with atropine (0.01 mg/Kg i.v.), midazolam (0.015-0.03 mg/Kg i.v.) and induction with bolus propofol (0.5-1 mg/Kg i.v.) as well as, finally, sedation with continuous infusion propofol (2-5 mg/Kg/h i.v.) by Target Controlled Infusion (TCI) technique. Ninety-eight per cent of patients experienced no intraprocedural or peri-procedural adverse events. All the procedures were technically successful. A good discharge time was recorded. The vital parameters recorded during the procedure did not vary significantly. A PEG-J procedure conducted within 30 min showed a significant advantage over end-tidal carbon dioxide (EtCO2). Indeed, the latter showed some predictive behavior (OR: 1.318, 95% CI 1.075-1.615, p = 0.008). In the real world, this sedation protocol showed a good safety and effectiveness profile, even with reduced doses of midazolam and a TCI propofol technique in moderate sedation.

Dysregulated anti-oxidant signalling and compromised mitochondrial integrity negatively influence regulatory T cell function and viability in liver disease.

BACKGROUND: Dysregulated inflammatory responses and oxidative stress are key pathogenic drivers of chronic inflammatory diseases such as liver cirrhosis (LC). Regulatory T cells (Tregs) are essential to prevent excessive immune activation and maintain tissue homeostasis. While inflammatory cues are well known to modulate the function and stability of Tregs, the extent to which Tregs are influenced by oxidative stress has not been fully explored. METHODS: The phenotypic and functional properties of CD4+CD25+CD127lo/- Tregs isolated from patients with LC were compared to healthy controls (HC). Treg redox state was investigated by characterizing intracellular reactive oxygen species (ROS), NADPH oxidase-2 (Nox2) activity, mitochondrial function, morphology, and nuclear factor-erythroid 2-related factor (Nrf2) antioxidant signalling. The relevance of Nrf2 and its downstream target, Heme-oxygenase-1 (HO-1), in Treg function, stability, and survival, was further assessed using mouse models and CRISPR/Cas9-mediated HO-1 knock-out. FINDINGS: Circulating Tregs from LC patients displayed a reduced suppressive function, correlating with liver disease severity, associated with phenotypic abnormalities and increased apoptosis. Mechanistically, this was linked to a dysregulated Nrf2 signalling with resultant lower levels of HO-1, enhanced Nox2 activation, and impaired mitochondrial respiration and integrity. The functional deficit in LC Tregs could be partially recapitulated by culturing control Tregs in patient sera. INTERPRETATION: Our findings reveal that Tregs rely on functional redox homeostasis for their function, stability, and survival. Targeting Treg specific anti-oxidant pathways may have therapeutic potential to reverse the Treg impairment in conditions of oxidative damage such as advanced liver disease. FUNDING: This study was funded by the Wellcome Trust (211113/A/18/Z).

Quantitative proteomic profile analysis of thyroid dysfunction effects on seminal vesicles and repercussions on male fertility.

Hypothyroidism and thyrotoxicosis are associated with male reproductive disorders, but little is known about the influence of the thyroid hormone milieu on seminal vesicle (SV) function and metabolism. In this sense, we investigated the effects of hypothyroidism and thyrotoxicosis induced in adulthood Wistar male rats on SV function and identified new thyroid hormone targets on male reproduction regulation using novel proteomic approaches. Hypothyroidism reduces SV size and seminal fluid volume, which are directly associated with low testosterone and estradiol levels, while thyrotoxicosis increases Esr2 and Dio1 expression in the SV. We found 116 differentially expressed proteins. Hypothyroidism reduces the expression of molecular protein markers related to sperm viability, capacitation and fertilization, protection against oxidative stress and energetic metabolism in SV, while it increases the expression of proteins related to tissue damage. In conclusion, thyroid dysfunction in the adult phase impairs several morphological, molecular and functional characteristics of SV.

The effects of glyphosate-based herbicide on the hypothalamic-pituitary thyroid axis are tissue-specific and dependent on age exposure.

The significant increase in glyphosate-based herbicide (GBH) use raises concerns about residues in the environment and food, potentially jeopardizing human health. The involvement of GBHs in the increased incidence of thyroid disorders is speculated, since glyphosate has been linked to an increased risk of thyroid disease in farmers. In this sense, this study aims to investigate the potential effects of low levels of GBH exposure (0, 0.5 or 5 mg/kg) from weaning (postnatal day PND23) to adult life (PND60 and PND90) in male Wistar rats on hypothalamic-pituitary-thyroid (HPT) axis function. The serum levels of T4 were increased. The hypothalamus showed reduced expression of Dio2, Thra1, and Thra2. The pituitary showed reduced expression of Mct8 and Dio2 and increased expression of Thra1. The thyroid showed increased expression of Tshr and Thra1. The heart showed increased expression of Mct8 and Myh6. The liver showed reduced expression of Mct8 and Thra2 and increased expression of Thra1. In thyroid morphometry, a decrease in both follicular diameter and area and decreased follicular and colloid diameters and areas were observed. These results suggested that GBH may affect several steps of HPT axis regulation at the transcriptional level in an age-dependent manner and alter the morphometric parameters of the thyroid gland and TH synthesis, with potential repercussions in the TH-target organs.

Hericium erinaceus, in combination with natural flavonoid/alkaloid and B3/B8 vitamins, can improve inflammatory burden in Inflammatory bowel diseases tissue: an ex vivo study.

Hericium erinaceus, berberine, and quercetin are effective in experimental colitis. It is unknown whether they can ameliorate inflammatory bowel diseases in humans. This ex vivo study aimed to evaluate the anti-inflammatory potential of a nutraceutical compound of HBQ-Complex® (H. erinaceus, berberine, and quercetin), biotin, and niacin in inflammatory bowel disease patients. Tissue specimens were obtained either from Normal-Appearing Mucosa (NAM) or from Inflamed Mucosa (IM) in 20 patients with inflammatory bowel disease. mRNA and protein expression of COX-2, IL-10, and TNF-α were determined in NAM and IM biopsy samples (T0). IM samples were then incubated in HBQ-Complex® (with the addition of niacin and biotin), and COX-2, IL-10, and TNF-α tissue levels were evaluated at 120 minutes (T1) and 180 minutes (T2). Incubation with this compound resulted in a progressive decrease in gene and protein COX-2 and TNF-α expression at T1/T2 in the IM. IL-10 showed an opposite trend, with a progressive increase of mRNA and protein expression over the same time window. HBQ-Complex® (with the addition of niacin and biotin) decreased the expression of proinflammatory cytokines at the mRNA and protein levels in IBD tissue. On the contrary, mRNA and protein expression of the anti-inflammatory cytokine IL-10 showed a progressive increase.

Soluble Collectin 11 (CL-11) Acts as an Immunosuppressive Molecule Potentially Used by Stem Cell-Derived Retinal Epithelial Cells to Modulate T Cell Response.

Retinal pigment epithelium (RPE) cell allotransplantation is seen as a possible solution to retinal diseases. However, the RPE-complement system triggered by the binding of collectin-11 (CL-11) is a potential barrier for RPE transplantation as the complement-mediated inflammatory response may promote T cell recognition. To address this, we investigated the role of CL-11 on T cell immuno-response. We confirmed that RPE cells up-regulated MHC class I and expressed MHC class II molecules in an inflammatory setting. Co-cultures of RPE cells with T cells led to the inhibition of T cell proliferation. We found that CL-11 was partially responsible for this effect as T cell binding of CL-11 inhibited T cell proliferation in association with the downregulation of CD28. We also found that the suppressive action of CL-11 was abrogated in the presence of the RGD peptide given to block the T cell binding of CL-11 by its collagen-like domain. Because RPE cells can bind and secrete CL-11 under stress conditions, we postulate that soluble CL-11 contributes to the immunosuppressive properties of RPE cells. The investigation of this dual biological activity of CL-11, namely as a trigger of the complement cascade and a modulator of T cell responses, may provide additional clues about the mechanisms that orchestrate the immunogenic properties of RPE cells.

Prepubertal oral exposure to relevant doses of acrylamide impairs the testicular antioxidant system in adulthood, increasing protein carbonylation and lipid peroxidation.

The increased prevalence of human infertility due to male reproductive disorders has been linked to extensive exposure to chemical endocrine disruptors. Acrylamide (AA) is a compound formed spontaneously during the thermal processing of some foods that are mainly consumed by children and adolescents. We previously found that prepubertal exposure to AA causes reduced sperm production and functionality. Oxidative stress is recognized as the main cause of reduced sperm quality and quantity. In this sense, our objective was to evaluate the expression and activity of genes related to enzymatic antioxidant defense, nonprotein thiols, lipid peroxidation (LPO), protein carbonylation (PC) and DNA damage in the testes of rats exposed to acrylamide (2.5 or 5 mg/kg) from weaning to adult life by gavage. For the AA2.5 and AA5 groups, there were no alterations in the transcript expression of genes related to enzymatic antioxidant defense. The enzymatic activities and metabolic parameters were also not affected in the AA2.5 group. For the AA5 group, the enzymatic activities of G6PDH and GPX were reduced, SOD was increased, and protein carbonylation (PC) was increased. Data were also evaluated by Integrate Biomarker Response (IBRv2), a method to analyze and summarize the effects on biomarkers between doses. The IBRv2 index was calculated as 8.9 and 18.71 for AA2.5 and AA5, respectively. The following biomarkers were affected by AA2.5: decreased enzymatic activities of G6PDH, SOD, and GPX, increased GST and GSH, increased LPO and PC, and decreased DNA damage. For AA5, decreased enzymatic activities of G6PDH, GST, CAT and GPX, increased SOD and GSH, increased PC, and decreased LPO and DNA damage were observed. In conclusion, AA exposure during the prepubertal period causes imbalances in the testicular enzymatic antioxidant defense, contributing to the altered spermatic scenario in the testes of these rats.

Hericium erinaceus, a medicinal fungus with a centuries-old history: Evidence in gastrointestinal diseases.

Hericium erinaceus is an edible and medicinal mushroom commonly used in traditional Chinese medicine for centuries. Several studies have highlighted its therapeutic potential for gastrointestinal disorders such as gastritis and inflammatory bowel diseases. In addition, some components of this mushroom appear to possess strong antineoplastic capabilities against gastric and colorectal cancer. This review aims to analyse all available evidence on the digestive therapeutic potential of this fungus as well as the possible underlying molecular mechanisms.

Sexual dysfunctions of rheumatological patients are a neglected issue: Results from a national survey of Italian Society of Rheumatology.

INTRODUCTION: Sexual dysfunctions (SD) are frequently encountered in patients with rheumatologic diseases. In this scenario, a multidisciplinary approach to rheumatologic diseases is often mandatory. The aim of this survey was to assess whether Italian rheumatologists routinely explore sexual health of their patients, their knowledge on the topic, and the barriers to discussing SD in clinical practice. METHODS: A 32-items anonymous questionnaire was mailed to members of the Italian Society of Rheumatology (rheumatologists and residents in rheumatology training) in February 2023. The questionnaire aimed to determine attitudes, knowledge, and practice patterns regarding the discussion of SD with rheumatologic patients. A descriptive analysis of responses was performed. RESULTS: A total of 162 responses were received. Overall, 50.0% of respondents occasionally asked patients about SD related to their rheumatologic pathologies, while 37.1% never did so. Respondents declared that patients occasionally (82.3%) or never (16.1%) reported SD related to rheumatologic diseases. The main barriers to discussing sexual health were lack of time during medical examination (46.6%), patients' discomfort (44.8%), and lack of knowledge/experience (39.7%). Overall, 41.9% and 33.9% of respondents respectively totally and partially agreed that rheumatologists should routinely investigate patients' sexual health. Most of the respondents (79.0%) thought that discussing sexual health problems could help patients cope with their rheumatologic diseases. Of all respondents, 74.2% felt the need to broaden their personal knowledge about SD. Finally, 45.9% and 34.4% of respondents respectively partially and totally agreed that training courses for rheumatologists could be helpful in the management of sexual health in rheumatological patients. CONCLUSIONS: SD was not routinely discussed in rheumatology practice, still remaining a neglected issue. The most frequent explanations for the lack of attention toward SD were lack of time, patients' discomfort, and lack of knowledge/experience. Most of the respondents expressed the possible usefulness of attending SD courses to improve knowledge about these conditions.

Standard Bismuth Quadruple Therapy versus Concomitant Therapy for the First-Line Treatment of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

(1) Background: Whether standard bismuth quadruple therapy (BQT) is superior to concomitant therapy for the first-line treatment of Helicobacter (H.) pylori infection is unclear. The aim of this systematic review and meta-analysis was to compare the efficacy of standard BQT versus concomitant therapy for H. pylori eradication in subjects naïve to treatment. (2) Methods: Online databases were searched for randomized controlled trials. We pooled risk ratio (RR) of individual studies for dichotomous outcomes using a random-effect model. (3) Results: Six studies with 1810 adults were included. Overall intention-to-treat (ITT) eradication rate was 87.4% with BQT and 85.2% with concomitant therapy (RR 1.01, 95%CI:0.94-1.07). Subgroup analysis of five Asian studies showed a small but significant superiority of BQT over concomitant therapy (87.5% vs. 84.5%; RR 1.04, 95%CI:1.01-1.08). Pooling four studies at low risk of bias yielded a similar result (88.2% vs. 84.5%; RR 1.05, 95%CI:1.01-1.09). There was no difference between the regimens in the frequency of adverse events (RR = 0.97, 95%CI:0.79-1.2). (4) Conclusions: The efficacy of BQT seems to be similar to concomitant therapy, with similar side effect profile. However, BQT showed a small but significant benefit over concomitant therapy in Asian populations and in studies at low risk of bias.

Quality of bowel preparation in patients with inflammatory bowel disease undergoing colonoscopy: What factors to consider?

An adequate bowel preparation in patients with inflammatory bowel disease (IBD) is a prerequisite for successful colonoscopy for screening, diagnosis, and surveillance. Several bowel preparation formulations are available, both high- and low-volume based on polyethylene glycol. Generally, low-volume formulations are also based on several compounds such as magnesium citrate preparations with sodium picosulphate, oral sulphate solution, and oral sodium phosphate-based solutions. Targeted studies on the quality of bowel preparation prior to colonoscopy in the IBD population are still required, with current evidence from existing studies being inconclusive. New frontiers are also moving towards the use of alternatives to anterograde ones, using preparations based on retrograde colonic lavage.

Prostaglandin E2/EP4 axis is upregulated in Spondyloarthritis and contributes to radiographic progression.

Ankylosing spondylitis (AS) is an inflammatory disease leading to spine ankylosis; however, the mechanisms behind new bone formation are still not fully understood. Single Nucleotide Polymorphisms (SNPs) in PTGER4, encoding for the receptor EP4 of prostaglandin E2 (PGE2), are associated with AS. Since the PGE2-EP4 axis participates in inflammation and bone metabolism, this work aims at investigating the influence of the prostaglandin-E2 axis on radiographic progression in AS. In 185 AS (97 progressors), baseline serum PGE2 predicted progression, and PTGER4 SNP rs6896969 was more frequent in progressors. Increased EP4/PTGER4 expression was observed in AS circulating immune cells, synovial tissue, and bone marrow. CD14highEP4 + cells frequency correlated with disease activity, and when monocytes were cocultured with mesenchymal stem cells, the PGE2/EP4 axis induced bone formation. In conclusion, the Prostaglandin E2 axis is involved in bone remodelling and may contribute to the radiographic progression in AS due to genetic and environmental upregulation.

Prepubertal to adulthood exposure to low doses of glyphosate-based herbicide increases the expression of the Havcr1 (Kim1) biomarker and causes mild kidney alterations.

Glyphosate is a nonselective and postemergent herbicide used to combat weeds in several crops, which raises concerns about risks to human health since residues are detected in urine, human milk, surface water and several types of food. Feces and urine are the major routes of elimination of glyphosate, making the kidney a sensitive target for the development of toxicity. In fact, farmers are at high risk of developing chronic kidney disease. In this sense, this study aims to investigate kidney function by measuring the serum levels of urea and creatinine, examining the histological morphology, and analyzing the mRNA expression of genes related to tubular transport of ions, urea and urates and the biomarker of kidney disease Kim1, and the levels of lead in the kidney in male Wistar rats orally exposed to low levels of glyphosate-based herbicide (GBH: 0, 0.5 or 5 mg/kg) from weaning to adult life by gavage. GBH0.5 showed reduced serum urea concentration, presence of tubulointerstitial swelling and mononuclear cell infiltration into the interstitium, increased gene expression of Kim1 and reduced gene expression of Slc14a1. GBH5 showed reduced serum urea and increased serum creatinine concentrations, tubulointerstitial swelling, interstitial fibrosis, and reduced expression of Trpm6 and Trpv5. Exposure to GBH did not affect the levels of Pb in the kidneys of animals. In conclusion, glyphosate at low doses may cause mild kidney damage. It is necessary to evaluate whether the long-term effects of this constant injury may contribute to the development of chronic kidney disease of uncertain etiology.