Guaiac fecal occult blood test (gFOBT) is often used to evaluate evidence of food protein-induced allergic proctocolitis (FPIAP) in children in primary care and gastroenterology settings; however, it has not been validated for this diagnosis, and little is known about the positivity rates in early infancy. In this study, we used samples from healthy asymptomatic infants aged two weeks to two months to evaluate the gFOBT positivity rate compared to those diagnosed with FPIAP.

This was a nested case-control study. Frozen stool samples from infants aged two days to five months enrolled in the Gastrointestinal Microbiome and Allergic Proctocolitis study were evaluated using gFOBT (n = 123). The results were interpreted by three blinded staff members, including a trained clinical research coordinator, a pediatric gastroenterologist, and an experienced medical assistant. Additionally, the samples were analyzed using a quantitative fecal immunochemical test (FIT) for hemoglobin to compare with gFOBT results.

Eight percent of samples from the 100 healthy asymptomatic infants were gFOBT positive (11% when including positive and equivocal results). Seventy-four percent of samples from infants diagnosed with FPIAP were gFOBT positive. The interrater reliability of gFOBT interpretation was 81%. Of the healthy samples that yielded a positive gFOBT result, 50% also yielded a positive FIT result. Of the 23 FPIAP samples that yielded a positive gFOBT result, 29% yielded a positive FIT result.

Healthy asymptomatic infants in early infancy were gFOBT positive up to 11% of the time. Caution should be used when interpreting gFOBT results in young infants in a diagnostic setting.

Microsatellite-stable colorectal cancer, which accounts for roughly 80–85% of cases, remains largely refractory to immune checkpoint inhibitors compared with microsatellite instability-high tumors. This review synthesizes current evidence on tumor-intrinsic and microenvironmental mechanisms underlying immune checkpoint inhibitor resistance in microsatellite-stable colorectal cancer—including low neoantigen burden and impaired antigen presentation, activation of Wnt/β-catenin and MAPK signaling that exclude T cells, an immunosuppressive cellular milieu (regulatory T cells, myeloid-derived suppressor cells, M2-like tumor-associated macrophages, cancer-associated fibroblasts), metabolic reprogramming, and gut microbiome dysbiosis—and evaluates translational strategies aimed at overcoming these barriers. Preclinical and early-phase clinical data indicate that rational, mechanism-guided combinations (vascular normalization, myeloid reprogramming, metabolic inhibitors, antigen-priming approaches, and microbiome modulation) can enhance immune infiltration and produce benefits in biomarker-defined subgroups. Moving the field forward will require biomarker-driven, adaptive clinical trials with embedded translational endpoints to optimize patient selection and manage toxicity.

Leishmaniasis is a dangerous yet neglected tropical disease affecting a vast population of the world. Several medicinal plants and their constituents (natural products/phytochemicals) have been considered of prime importance for the management of leishmaniasis over the years. The present review sheds light on the molecular mechanisms of the constituents obtained from medicinal plants that are pre-clinically effective against leishmaniasis. Various mechanisms by which medicinal plant-derived natural products elicit their action against leishmaniasis are illustrated in the literature. The mechanisms identified include: disruption of cytoplasmic and mitochondrial membranes, induction of apoptosis and autophagy, modulation of gene expression and immunological pathways, pro-oxidant effects (disrupting redox balance) with mitochondrial dysfunction, cell cycle arrest, impaired cellular bioenergetics, i.e., adenosine triphosphate production and coagulation of cellular contents within Leishmania parasites. Future phytochemical and pharmacological (especially clinical) studies are necessary to further understand the mechanistic details of medicinal plant-derived natural compounds and to develop new phytotherapeutic entities from nature against leishmaniasis.

Chronic diabetes mellitus is marked by hyperglycemia and metabolic dysfunction, increasing the risk of complications such as nephropathy. This study aimed to evaluate key biochemical parameters among participants with diabetic nephropathy (DNp), diabetes control (DC), nephropathy control (NC), and healthy control groups.

A prospective case-control study was conducted with 200 participants categorized into four groups: DNp, NC, DC, and healthy controls. Biochemical parameters, including glucose, glycated hemoglobin, waste metabolites, proteins, enzymes, electrolytes, and lipids, were analyzed using an Advia 1800 chemical system analyzer (Siemens, Germany) with standard kits.

Among the four investigated groups, the DNp group exhibited augmented fasting glucose (178.75 ± 61 mg/dL), glycated hemoglobin (8.13 ± 1.7%), creatinine (5.67 ± 1.8 mg/dL), and blood urea nitrogen (72.02 ± 22.8 mg/dL), indicating poor glycemic control and impaired kidney function. In contrast, the DC group showed elevated random glucose levels (280 ± 3.1 mg/dL). Elevated inflammatory markers (C-reactive protein, 6.35 ± 6.3 mg/L; lactate dehydrogenase, 1,216.43 ± 634 U/L) were observed in the NC group. Compared to the other groups, the DC group demonstrated augmented lipid profiles, including elevated triglycerides (230.67 ± 59 mg/dL), very low-density lipoprotein (48.5 ± 16.5 mg/dL), low-density lipoprotein (107.41 ± 16 mg/dL), and cholesterol (169 ± 19 mg/dL). Statistical analysis was performed using one-way analysis of variance followed by a t-test to investigate differences among groups at P < 0.05.

Altered biochemical variations were noted among groups. The DNp group showed renal dysfunction and poor glycemic control, the DC group had dyslipidemia and hyperglycemia, and the NC group showed elevated inflammatory markers. Early testing is indispensable for the timely diagnosis and management of diabetic complications.

Drug-induced liver injury (DILI) represents a prevalent adverse event associated with medication use. However, the exact mechanisms underlying DILI remain incompletely understood, and the lack of specific diagnostic and prognostic biomarkers poses significant challenges to the clinical diagnosis and treatment of this condition. Consequently, our study aimed to endeavor to identify serum and fecal metabolic biomarkers, enabling more accurate DILI diagnosis and improved prediction of chronic progression.

Untargeted metabolomics analysis was performed on serum and fecal samples obtained from a cohort of 32 DILI patients (causality confirmed via the updated Roussel Uclaf Causality Assessment Method) and 36 healthy controls. Utilizing techniques such as partial least squares-discriminant analysis modeling and t-tests, we identified significantly differentially expressed metabolites and metabolite sets. Causality assessment was performed using the updated Roussel Uclaf Causality Assessment Method.

The findings from the analysis of serum and fecal metabolomics association pathways suggested that perturbations in bile acid metabolism might serve as potential mechanisms underlying the progression of DILI. Our study revealed 22 overlapping differential metabolites between serum and feces, displaying significant concentration differences between the DILI and healthy control groups. Notably, we identified chenodeoxycholic acid and deoxycholic acid as promising markers that not only distinguished DILI patients from healthy individuals but also exhibited predictive potential for DILI chronicity.

The integrated analysis of serum and fecal metabolites uncovers the significant disruption of bile acid metabolites as a key contributing factor in the pathogenesis of DILI. Our study offers promising potential biomarkers for the diagnosis and prognosis of DILI, paving the way for a novel perspective in the realm of DILI diagnosis and treatment.

Emerging evidence implicates immune dysregulation and neuroinflammation in the pathogenesis of epilepsy, yet the causal mechanisms remain unclear. This study aimed to investigate the causal effects of immune cells and inflammatory proteins on epilepsy and evaluate the mediating role of inflammatory proteins.

This study utilized the largest available genome-wide association study data on immune cell phenotypes and inflammatory proteins as exposures, and epilepsy genome-wide association study data from the FinnGen dataset as outcomes. Five Mendelian randomization (MR) methods were applied within a two-sample MR framework to assess causal effects. Furthermore, a two-step MR analysis was conducted to quantify the proportion of epilepsy and its subtypes influenced by immune cells through inflammatory proteins.

The two-sample MR analysis identified 32 immune cell phenotypes associated with epilepsy risk (19 risk-increasing, e.g., CD19+ B cells; 13 protective, e.g., regulatory T cell subsets). Subtype analyses revealed 30 immune phenotypes associated with generalized epilepsy and 26 with focal epilepsy. Eight inflammatory proteins showed suggestive causal effects on epilepsy: C-C chemokine ligand 23, C-X-C motif chemokine ligand 6, C-X-C motif chemokine ligand 11, and vascular endothelial growth factor A increased epilepsy risk, while interleukin-13 (IL-13), leukemia inhibitory factor receptor, tumor necrosis factor, and osteoprotegerin conferred protection. Mediation analysis indicated that inflammatory proteins mediated 6.3–13.5% of the immune effects on epilepsy. Specifically, CD14+CD16+ monocytes increased epilepsy risk through elevated C-C chemokine ligand 23 levels (8.5% mediation), while effector memory double-negative (CD4−CD8−) T cells reduced epilepsy risk via upregulation of IL-13 (6.3%). Sensitivity analyses confirmed the robustness of these findings (P heterogeneity/pleiotropy > 0.05). Although no associations reached Bonferroni-corrected significance, the findings implicate B cells, monocytes, regulatory T cells, and cytokines (e.g., IL-13, leukemia inhibitory factor receptor) in the pathogenesis of epilepsy, with inflammatory proteins acting as partial mediators.

These results enhance our understanding of immune-inflammatory pathways in epilepsy and highlight potential therapeutic targets. Future studies should validate these findings across diverse populations and further elucidate the molecular mechanisms underlying the identified associations.

Liver failure syndromes are characterised by a dysregulated immune response leading to immune paralysis. Adrenomedullin (ADM) is a potent vasodilator and immunoregulator. This study aimed to explore the role of ADM in liver failure, hypothesising that there is a detrimental imbalance between ADM and adrenomedullin binding protein (AMBP)1 that promotes a switch of monocytes/macrophages towards a pro-restorative phenotype and function.

Consecutive patients with acute liver failure (ALF), acute-on-chronic liver failure (ACLF), and decompensated cirrhosis, as well as healthy controls (HC) were included between April 2020 and June 2024. Peripheral blood mononuclear cells/monocytes were isolated and used for RNA sequencing and cell culture. ADM and AMBP1 were measured by enzyme-linked immunosorbent assay.

Fifty-four patients with ALF, 25 with ACLF, 9 with decompensated cirrhosis, and 16 with HC were included. ADM expression in isolated monocytes was increased in ALF (log fold change = 5.88, p = 0.000216413) and ACLF (log fold change = 4.62, p = 0.00057122) compared to HC. Plasma ADM concentration was higher in ALF (1,684 ± 1,156 pg/mL) vs. ACLF (836.1 ± 765.2 pg/mL) and HC (164.8 ± 62.73 pg/mL). AMBP1 was significantly reduced in ALF (59.27 ± 44 µg/mL) vs. ACLF (126.3 ± 72.23 µg/mL) and HC (252.8 ± 159.7 µg/mL) (p < 0.0001, ALF vs. HC). Treatment with LPS increased ADM concentration in peripheral blood mononuclear cell supernatant (ALF n = 6; 561.4 ± 1,038 pg/mL vs. 259.2 ± 213.7 pg/mL, ACLF n = 4; 3,202 ± 491.2 vs. 1,757 ± 1,689 pg/mL). The percentage of CD14+ cells expressing Mer tyrosine kinase was reduced after culture with LPS (2.077 ± 0.87%); however, co-culture with ADM 100 nM restored the phenotype (3.852 ± 1.063%).

ADM is increased in liver failure, whereas AMBP1 is reduced. ADM affects monocyte function, increasing Mer Tyrosine Kinase and promoting a pro-restorative, anti-inflammatory phenotype.

Micro- and nanoplastics (MNPs) are plastic particles smaller than 5 mm and 1 µm, respectively, and are emerging environmental pollutants with growing implications for human health. These particles stem from either ‘primary sources’, such as intentionally manufactured microbeads and industrial abrasives, or ‘secondary sources’, where larger plastic items break down into smaller fragments over time. Human exposure primarily occurs through ingestion and inhalation, with contaminated seafood and plastic-laden food packaging representing key routes of entry. Once ingested, MNPs can cross the intestinal barrier, accumulate in gastrointestinal (GI) tissues, and trigger biological responses. Mechanistic studies reveal that MNPs induce oxidative stress, DNA damage, chronic inflammation, and endocrine disruption, all of which are hallmarks of carcinogenic pathways. They also alter gut microbiota, potentially promoting dysbiosis and immune dysregulation. The GI tract is particularly vulnerable to these effects due to direct luminal mucosal contact and high epithelial turnover. Epidemiological data remain limited, but early evidence supports a plausible link between MNPs exposure and GI malignancies. Such findings are particularly concerning given the increasing global incidence and early age presentation of colorectal and esophageal cancers. Given that MNPs may represent a modifiable environmental risk factor in GI cancer prevention, public health strategies must prioritize reducing plastic exposure, promoting antioxidant-rich diets, and improving environmental monitoring. This review explores the potential carcinogenic effects of microplastics while also examining their emerging roles in cancer therapeutics. It highlights critical avenues for future investigation and underscores the importance of cross-disciplinary efforts to tackle this growing global health concern.

Further decompensation in cirrhosis is associated with increased mortality. However, reliable tools to predict further decompensation after transjugular intrahepatic portosystemic shunt (TIPS) are currently limited. This study aimed to investigate the incidence and risk factors of further decompensation within one year post-TIPS in patients with cirrhosis and to develop a predictive model for identifying high-risk individuals.

This retrospective cohort study enrolled 152 patients with cirrhosis undergoing TIPS for variceal bleeding and/or refractory ascites (January 2018–January 2024). Patients were stratified according to one-year decompensation outcomes. LASSO regression and multivariable logistic analysis were used to identify predictors, and a nomogram was constructed and internally validated using bootstrapping (1,000 replicates).

Among the 152 patients (median age 57.5 years [IQR 50.0–66.0]; 58.6% male; 58.6% viral/alcohol-associated etiology), 65.8% (100/152) achieved clinical stability at one year post-TIPS, while 34.2% (52/152) developed further decompensation. LASSO regression identified right hepatic lobe volume, spleen volume, and portal pressure gradient (PPG) reduction as key predictors, all independently associated with further decompensation risk in multivariable analysis (OR [95% CI]: 0.683 [0.535–0.873], 1.435 [1.240–1.661], and 0.961 [0.927–0.996], respectively). The nomogram demonstrated superior discrimination compared with PPG reduction alone and benchmark prognostic scores (AUC 0.854 [0.792–0.915] vs. 0.619–0.652; ΔAUC +0.201–+0.235, p < 0.001) with 92.3% sensitivity. High-risk patients (score > 86) had a 10.7-fold higher risk of further decompensation than low-risk patients (60.0% vs. 5.6%; p < 0.0001).

This validated model, combining hepatosplenic volumetry and PPG reduction, accurately stratifies further decompensation risk post-TIPS and may guide targeted surveillance and preventive interventions.