Dysfunction of the intestinal barrier is a prevalent phenomenon observed across a spectrum of diseases, encompassing conditions such as mesenteric artery dissection, inflammatory bowel disease, cirrhosis, and sepsis. In these pathological states, the integrity of the intestinal barrier, which normally serves to regulate the selective passage of substances between the gut lumen and the bloodstream, becomes compromised. This compromised barrier function can lead to a range of adverse consequences, including increased permeability to harmful substances, the translocation of bacteria and their products into systemic circulation, and heightened inflammatory responses within the gut and beyond. Understanding the mechanisms underlying intestinal barrier dysfunction in these diverse disease contexts is crucial for the development of targeted therapeutic interventions aimed at restoring barrier integrity and ameliorating disease progression. Lipocalin-2 (LCN2) expression is significantly upregulated during episodes of intestinal inflammation, making it a pivotal indicator for gauging the extent of such inflammatory processes. Notably, however, LCN2 derived from distinct cellular sources, whether intestinal epithelial cells or immune cells, exhibits notably divergent functional characteristics. Furthermore, the multifaceted nature of LCN2 is underscored by its varying roles across different diseases, sometimes even demonstrating contradictory effects.

Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients.

This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients.

RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71-22.92) versus 9.59 (6.57-13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7.

Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.

The present meta-analysis aimed to elucidate the association of Behçet's disease (BD) with the risk of metabolic syndrome (MetS) and its components. Observational cohort studies were searched from the Embase, Web of Science, Medline, and Cochrane Library databases. The primary outcome was the association of BD with the risk of MetS and its relevant components. Effect estimates with odds ratios (ORs) were pooled using either the random-effects or fixed-effects models, according to heterogeneity. Leave-one-out sensitivity analyses were used to determine the stability of the results. Twenty-three studies, comprising 42,834 patients with BD, were included. Overall, a significant association between BD and the risk of MetS was found (pooled OR 2.26; 95% confidence interval [CI] 1.61-3.17; P < 0.0001). Among the components of MetS, significant associations were found between BD and diabetes mellitus (OR 1.21; 95% CI 1.10-1.33; P < 0.0001), BD and hypertension (OR 1.39; 95% CI 1.13-1.70; P = 0.002), and BD and dyslipidemia (OR 1.21; 95% CI 1.01-1.45; P = 0.04). Our study indicated an association between BD and the risk of MetS and some of its components (diabetes mellitus, hypertension, and dyslipidemia). Physician should consider these associations so that specific treatments are available for patients with comorbidities. Moreover, patients with BD should regularly monitor their blood pressure, fasting plasma glucose, and blood lipid levels.

Psoriasis vulgaris is a chronic skin disease which is related to cardiovascular and metabolic diseases. In the pathogenesis of these diseases, adipokines, including retinol binding protein-4 (RBP-4), play crucial roles. Studies have also shown that RBP-4 might be a meaningful factor in psoriasis however, relying on the analysis of a single study have some drawbacks.

To evaluate the association between RBP-4 and psoriasis vulgaris more comprehensively.

Six databases were searched to obtain relevant publications. The selection of the included studies was based on a criteria. The standardized mean difference (SMD) was used for analysis. A value of p < 0.05 was defined as significance.

Seven studies were included, with 271 cases and 235 controls. In the comparison between patients and controls, the merged data suggested that levels of RBP-4 were significantly higher in patients (SMD = 0.61, 95%CI: 0.14, 1.07, p < 0.05). In five studies containing the data of RBP-4 levels before and after treatment, no significance was found, either for RBP-4 levels in the after-treatment group and control group in these five studies (p > 0.05). Subgroup analysis was conducted based on the therapy method. Patients with systematic treatment showed a significant decrease of BRP-4 level after the treatment (SMD = -0.64, 95%CI: -1.26, -0.03, p < 0.05).

For patients with psoriasis vulgaris, RBP-4 levels are elevated, and systematic treatment can lower these levels. RBP-4 might act as a key indicator for the diagnosis, efficacy assessment, and comorbidity monitoring of the patients. Further studies with well-designed protocols and enlarged populations are still needed.

Some studies have investigated the relationship between Behçet's disease (BD) and insulin resistance; however, since they did not exclude obese patients from their sample, it remains unclear whether BD itself causes insulin resistance independently of obesity.

The study included 60 patients with BD and 45 age-, gender-, and body mass index (BMI)-matched healthy controls. Obese patients with a BMI of ≥30 kg/m² were excluded. Insulin resistance according to the homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI), fasting plasma glucose, and one-hour and two-hour plasma glucose in the oral glucose tolerance test (OGTT 1-h and OGTT 2-h PG, respectively) were evaluated in all patients.

The mean fasting plasma glucose levels and the rate of those with impaired glucose tolerance according to OGTT 2-h PG were significantly higher in the BD patients compared to the controls. The rates of those with insulin resistance according to HOMA-IR and QUICKI were significantly higher in the BD patients than in the controls. When compared to the control group, the rates of those with impaired fasting glucose and impaired glucose tolerance were significantly higher, and the mean QUICKI value was significantly lower in the active group, in contrast to the inactive group.

Insulin resistance occurs in BD patients independently of obesity. In the follow-up of BD patients, especially in the active phase, not only fasting blood glucose but also other diagnostic tests for insulin resistance should be added to the examination panels.

Recent evidence suggests an association between allergic sensitization and metabolic markers. However, this association has rarely been examined in the elderly. Retinol-binding protein-4 (RBP-4) is a recently identified adipokine that acts on the muscle and liver affecting insulin sensitivity. We evaluated the association between metabolic parameters and allergic sensitization in the elderly.

We analysed the database of the Korean Longitudinal Study on Health and Aging cohort study conducted during 2005 to 2006. Atopy was identified by inhalant allergen skin prick test. Metabolic conditions were assessed using anthropometric indices and serum biomarkers such as fasting glucose, lipid, adiponectin, and RBP-4.

Among the 854 elderly subjects, 17.2% had atopy. Plasma RBP-4 levels were significantly higher in the atopic elderly than nonatopic elderly (p = 0.003). When RBP-4 percentiles were categorized as under three groups, the prevalence of atopy and current rhinitis increased significantly with percentiles of RBP-4 levels (p = 0.019 and p = 0.007, respectively). Log RBP-4 was associated with atopy (odds ratio [OR], 4.10; p = 0.009) and current rhinitis (OR, 2.73; p = 0.014), but not with current asthma (OR, 1.17; p = 0.824). Higher RBP-4 level in atopic elderly was also observed in current rhinitis patients. Atopy, but not current rhinitis, showed significant relationships with log RBP-4 levels in multivariate analyses adjusted for other metabolic markers including body mass index.

RBP-4 positively associated with atopy in the general elderly population irrespective of other metabolic markers.

Blood-retinal barrier cells are known to exhibit a massive phenotypic change during experimental autoimmune uveitis (EAU) development. In an attempt to investigate the mechanisms of blood-retinal barrier (BRB) breakdown at a global level, we studied the gene regulation of total retinal cells and retinal endothelial cells during non-infectious uveitis.

Retinal endothelial cells were isolated by flow cytometry either in Tie2-GFP mice (CD31+ CD45- GFP+ cells), or in wild type C57BL/6 mice (CD31+ CD45- endoglin+ cells). EAU was induced in C57BL/6 mice by adoptive transfer of IRBP1-20-specific T cells. Total retinal cells and retinal endothelial cells from naïve and EAU mice were sorted and their gene expression compared by RNA-Seq. Protein expression of selected genes was validated by immunofluorescence on retinal wholemounts and cryosections and by flow cytometry.

Retinal endothelial cell sorting in wild type C57BL/6 mice was validated by comparative transcriptome analysis with retinal endothelial cells sorted from Tie2-GFP mice, which express GFP under the control of the endothelial-specific receptor tyrosine kinase promoter Tie2. RNA-Seq analysis of total retinal cells mainly brought to light upregulation of genes involved in antigen presentation and T cell activation during EAU. Specific transcriptome analysis of retinal endothelial cells allowed us to identify 82 genes modulated in retinal endothelial cells during EAU development. Protein expression of 5 of those genes (serpina3n, lcn2, ackr1, lrg1 and lamc3) was validated at the level of inner BRB cells.

Those data not only confirm the involvement of known pathogenic molecules but further provide a list of new candidate genes and pathways possibly implicated in inner BRB breakdown during non-infectious posterior uveitis.

Psoriasis is a chronic, systemic, hyper-proliferative immune-mediated inflammatory skin disease. The results of epidemiological investigations have shown that psoriasis affects around 2% of the general population worldwide, and the total number of psoriasis patients is more than 6 million in China. Apart from the skin manifestations, psoriasis has been verified to associate with several metabolic comorbidities, such as insulin resistance, diabetes and obesity. However, the underlying mechanism is still not elucidated. Adipocytes, considered as the active endocrine cells, are dysfunctional in obesity which displays increased synthesis and secretion of adipokines with other modified metabolic properties. Currently, growing evidence has pointed to the central role of adipokines in adipose tissue and the immune system, providing new insights into the effect of adipokines in linking the pathophysiology of obesity and psoriasis. In this review, we summarize the current understanding of the pathological role of adipokines and the potential mechanisms whereby different adipokines link obesity and psoriasis. Furthermore, we also provide evidence which identifies a potential therapeutic target aiming at adipokines for the management of these two diseases.

The purpose of this study was to explore the association of serum lipocalin-2 concentrations with psoriasis and psoriatic arthritis (PsA).

A systematic search of studies on the association of serum lipocalin-2 concentrations with psoriasis/PsA was conducted in PubMed, Web of Science, Elsevier ScienceDirect, and Cochrane Library. Eventually, 8 eligible studies were included. The strength of association between serum lipocalin-2 concentrations and psoriasis/PsA was assessed by pooled standard mean difference (SMD) with its 95% confidence intervals (CIs).

A total of 8 case-control studies, consisting of 349 psoriasis/PsA patients and 258 controls, were included in the meta-analysis. This meta-analysis showed significant association between serum lipocalin-2 concentrations and psoriasis/PsA in overall population (SMD: 0.757, 95%CI = 0.588-0.926, and P _H = 0.114; P _H is the P value for the heterogeneity test). Similar results were found in subgroup analysis by ethnicity.

Serum lipocalin-2 concentrations are higher in psoriasis/PsA patients than controls. However, more large-scale studies are warranted to explore the association between serum lipocalin-2 and the pathogenetic mechanisms of psoriasis/PsA.

Psoriasis has been considered as chronic systemic disease. Retinol-binding protein-4 (RBP-4) might play a role in psoriasis and its comorbidities. The aim of this study was to investigate the associations between serum RBP-4 levels and disease severity, indicators of inflammation or metabolic syndrome and changes after topical treatment in psoriatic patients.

Thirty-seven patients with relapse of plaque-type psoriasis and 16 healthy volunteers were examined. Blood samples were collected before and after 14 days of therapy. Serum RBP-4 concentrations were examined by enzyme-linked immunosorbent assay for correlation with psoriasis area and severity index (PASI), body mass index (BMI), inflammatory and biochemical markers and with efficacy of topical treatment.

RBP-4 serum levels were increased in psoriatics compared to the controls, but without statistical significance (p = 0.2). No significant correlations between investigated adipokine and several indicators of metabolic disorders, nor BMI or PASI were found. A significant negative correlation with CRP was noted. After topical treatment serum RBP-4 level did not significantly change (p = 0.3), despite clinical improvement.

RBP-4 might have a protective role in terms of chronic inflammation and comorbidities of psoriasis. The adipokine is presumably not useful in determining severity and the effectiveness of antipsoriatic treatment.