Long-term low-dose nanoplastic exposure induces neurotoxicity with oxidative brain damage.

Immunosenescence in elderly patients with advanced non-small cell lung cancer: Mechanisms and therapeutic implications.

A simple oral STZ/alloxan-induced diabetic zebrafish model for chronic wound healing and therapeutic assessment.

Comparison of human and canine atopic dermatitis transcriptome: A meta-analysis and review from a one health perspective.

To evaluate diagnostic utility of reticulocyte hemoglobin equivalent (Ret-He) in identifying iron deficiency anemia (IDA) in acutely ill hospitalized children in comparison to serum ferritin. After excluding chronic inflammatory and anemic conditions unrelated to iron deficiency (ID), patients were categorized as (1) IDA: low hemoglobin+ microcytosis+ red-cell-distribution-width (RDW) index >220, (2) Non-anemia-iron-deficiency (NAID): normal haemoglobin+ microcytosis+ RDW index >220 and (3) Normal-group: normal hemoglobin+ normocytosis. Diagnostic utility indices for IDA were calculated using low hemoglobin+ microcytosis + RDW index >220 as surrogate standard. Correlation coefficients and receiver-operating-characteristic (ROC) curve cut-offs for Ret-He and ferritin were calculated. Anemic (n = 180) and non-anemic (n = 66) acutely ill children, after exclusion criteria, were classified into IDA (n = 102), NAID (n = 14) and normal (n = 21). IDA group had significantly lower Ret-He levels (p <0.001). Ferritin levels showed no significant difference (p = 0.062). For IDA detection, Ret-He cut-off of 27.7 pg yielded sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 87.2%, 80.9%, 95.7%, 56.7% and 86.2% whereas ferritin at cut-off of 147.0 ng/ml showed values of 58.8%, 66.7%, 89.5%, 25.0% and 60.2% respectively. For NAID detection, Ret-He cut-off of 29.1 pg showed sensitivity, specificity, PPV, NPV and accuracy of 71.4%, 57.1%, 52.6%, 75.0% and 62.9%, while ferritin at cut-off of 153 ng/ml showed values of 57.1%, 61.9%, 50.0%, 68.4%, and 60.0% respectively. Ret-He demonstrated superior diagnostic utility compared to serum ferritin for IDA in acutely ill hospitalized children. Optimal cut-off for serum ferritin for IDA was significantly higher than WHO reference standard.

Multiomics analyses prioritize disease genes and pathways in hidradenitis suppurativa.

B cell development and longevity of IgE plasma cells.

Keratinocytes: A key player in skin immunity and their emerging roles in secondary lymphedema.

Obesity is a major risk factor for the development of metabolic disorders, including insulin resistance, hepatic steatosis and metabolic syndrome. The mechanistic link between obesity and metabolic complications largely relay on chronic inflammation and redox status disturbances driven by excess adiposity and reduced glutathione (GSH) levels. This article reviews the latest evidence on the therapeutic potential of glutathione precursors N-acetylcysteine (NAC) and glycine in mitigating metabolic complications associated with obesity. NAC demonstrates promising benefits in improving insulin resistance, reducing hepatic steatosis, and mitigating cellular senescence mainly through its antioxidant and anti-inflammatory properties. Glycine, on the other hand, may support metabolic health by enhancing detoxification pathways and improving key metabolic markers in obesity. However, research on this field is limited and predominantly based on animal models and small-scale human trials. These findings highlight the need for continued investigation on the role of glutathione precursors as part of a broader strategy for the prevention and management of metabolic diseases linked to obesity. In particular, large-scale randomized controlled studies are required to validate the efficacy, safety and optimal dosages for these supplements.

It has been known that the cytokine TNF (tumor necrosis factor alpha) influences hematopoiesis for decades. We now know that increases in TNF in the aging microenvironment favor the persistence and expansion of myeloid progenitors, especially those that contain mutations associated with clonal hematopoiesis of indeterminate potential (CHIP). Herein, we will examine both seminal and recent studies that have advanced our understanding of how TNF shapes hematopoietic development during aging and influences clonal dynamics in CHIP. Elevated levels of TNF contribute to engraftment and expansion of CHIP-mutant clones; however, there are subtle differences between the specific CHIP mutations. Sex differences in levels of TNF may contribute to differences in the frequency and types of CHIP mutations found in males and females. Anti-TNF inhibitors reduce the frequency of CHIP mutation containing clones in multiple inflammatory diseases. The elevated levels of TNF that occur with both age and chronic inflammatory conditions contribute to both myeloid skewing and CHIP. Anti-TNF drugs reduce problematic changes in myeloid hematopoiesis. Anti-TNF drugs are not an effective strategy to treat CHIP and more research is needed as to whether other anti-inflammatory strategies, including diet and exercise, are also effective.

Surgical management of pilonidal sinus disease in pediatric population: An updated systematic review and meta-analysis.

Epidermal barrier (EB) function is too often reduced to the role of a passive, inanimate upper strata of dead corneocytes surrounded by extruded lipids. However, this summary fails to appreciate the lower strata keratinocytes (KCs) which serve as both sensors and effectors of immune signaling and thus contribute a dynamic, responsive nature to EB and maintenance and possible decline. In this context, underpinnings of chronic inflammatory skin diseases, e.g. psoriasis and atopic dermatitis, can be better recognized as a feed forward loop in which barrier dysfunction and runaway inflammatory signaling reinforce one another. Traditional therapies addressing these diseases focus on quelling effects and activities of pro-inflammatory extracellular cytokines and their cognate receptors. This paradigm overlooks the promising alternative of augmenting endogenous negative regulators of inflammatory signaling, e.g. the proteins A20 (TNFAIP3) and TNIP1 (ABIN-1) which we propose act as "guardians" restricting NF-κB-dependent inflammatory pathways. Here, we explore the rationale and possible means for targeting these regulators to protect or restore EB integrity. Bolstering these intrinsic quenchers of inflammatory signal progression may offer a path to restore tissue homeostasis and repair the EB in chronic inflammatory disease states.

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition affecting the sinuses, resulting in the appearance of nasal polyps and is often associated with comorbidities. Many cases do not respond to corticosteroid treatment or surgery.ObjectiveThis study aimed to explore the role of tezepelumab in the treatment of CRSwNP.MethodsPubmed, Embase, Scopus, Web of Science, and Cochrane Library were searched. Three randomized controlled trials (RCTs) comparing tezepelumab and placebo in 655 patients with CRSwNP were included. The main outcomes were nasal polyp size (nasal polyp score, NPS), nasal congestion or obstruction (nasal congestion score, NCS), and quality of life using the sino-nasal outcome test (SNOT-22).ResultsThree RCTS were included, in which tezepelumab was used to treat CRSwNP. The mean age was 50.9 years, with 56.9% male patients and 75.6% of patients with coexisting asthma. The mean difference (MD) for NPS ranged from -0.9 to -2.0 compared to placebo. Consistent benefits were observed for NCS with MD between -0.8 and -1.0 compared to placebo and SNOT-22 with MD ranging from -10 to -28 points compared to placebo.ConclusionIn conclusion, evidence suggests that tezepelumab may improve NPS and NCS, SNOT-22, loss of sense of smell, and clinically relevant endpoints (reduced need for surgery and corticosteroid use), as demonstrated in all included trials. However, the certainty and clinical applicability remain limited due to small trial size, industry sponsorship, and the lack of direct comparison with standard management and endoscopic sinus surgery. Large-scale, independent clinical trials are needed to confirm the position of tezepelumab in clinical practice for patients with moderate to severe CRSwNP.

Anorectal fistulas (AFs) are chronic inflammatory conditions featured by abdominal tracts linking the anal canal to the perineal skin, and precise delineation of such tracts is essential for effective surgical management. Magnetic resonance (MR) fistulogram clearly visualizes fistulous pathways and associated abscesses. However, literature remains limited on its association with intraoperative findings. Thus, the present study explored the role of MR fistulogram in the preoperative assessment of AFs. This prospective observational study was conducted over 2 years (January 2024-December 2025) in the Department of Radiodiagnosis. The study included 125 adult patients of AF confirmed via clinical examination as well as radiological investigations, and scheduled for surgical intervention. MR fistulogram characteristics were noted, and the findings were confirmed with intraoperative observations. Patients were predominantly female (87.2%), with a mean age of 42.6 ± 13.2 years. Most patients presented within 1-6 months of symptom onset (40.8%), while perianal tenderness and external opening at the left perineum were common clinical findings (each 18.4%). According to the St. James University Hospital classification, Grade 1 (34.4%) and Grade 4 (26.4%) fistulas were most common. In all patients (100%), magnetic resonance imaging findings were confirmed intraoperatively. Fistula grades were significantly associated with male sex (P = 0.020), but not with age groups (P = 0.421) and duration of symptoms (P = 0.767). MR fistulogram had strong concordance with intraoperative findings, with male sex being significantly associated with fistula grades, thereby highlighting demographic dependency in preoperative AF assessment.

Cardiovascular risk and metabolomic profile in adolescents: A comparative study between anorexia nervosa, normal weight, and obesity.

Cajaninstilbene Acid in Macrophage Immunometabolism and Angiogenesis: Mechanisms and Therapeutic Potential.

The interplay between gut microbiota and mitochondria represents a dynamic relationship that profoundly impacts host physiology, ranging from maintaining intestinal homeostasis to regulating systemic metabolic and neurological functions. Microbial metabolites such as short-chain-fatty-acids, bile acids, and amino acid derivatives serve as pivotal modulators of mitochondrial bioenergetics, oxidative stress management, and fission-fusion processes. These interactions are vital for preserving epithelial integrity, supporting energy metabolism, shaping immune responses, and managing inflammatory signaling pathways. Disruptions within this microbiota-mitochondria axis are associated with various pathologies, including non-alcoholic fatty liver disease, obesity, type 2 diabetes, and chronic inflammatory conditions like inflammatory bowel disease. Additionally, growing evidence connects gut dysbiosis and mitochondrial dysfunction to neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease, highlighting the importance of this bidirectional relationship in maintaining neuronal health. On a mechanistic level, pathways involving AMPK, sirtuins, and PGC-1α govern mitochondrial biogenesis and adaptive responses to microbial signals. Dysregulation of these pathways can heighten oxidative stress, hinder mitophagy, and contribute to systemic inflammation. Emerging therapeutic strategies aim to target this axis through dietary modifications, probiotics and engineered microbes, FMT, and mitochondria-specific pharmacological treatments. These interventions focus on restoring metabolic stability, enhance resilience against oxidative damage, and slowing disease progression. By integrating insights from fields such as metabolism, immunology, and neuroscience, this review positions the microbiota-mitochondria axis as a critical area of focus in biomedical research. A deeper understanding of this communication network offers promising opportunities for precision therapies aimed at addressing metabolic, inflammatory, and neurodegenerative diseases.

Systemic lupus erythematosus (SLE) is an established, independent risk factor for cardiovascular disease (CVD), most notably premature atherosclerotic cardiovascular disease (ASCVD). This association is thought to relate to chronic immune mediated inflammation. Clonal expansion of haematopoietic stem and progenitor cells (HSPCs) with acquired mutations, but no evidence of a blood disorder, is known as clonal haematopoiesis of indeterminate potential (CHIP). CHIP is associated with a pro-inflammatory immune phenotype, driven predominantly by mutant myeloid cells, and is similarly strongly associated with ASCVD. When SLE and CHIP co-occur, there may be synergy of their canonical cellular and molecular inflammatory pathways or even convergence of pathways through shared mechanisms of immune dysregulation, which accelerate CVD. Furthermore, enrichment of HSPC clones carrying CHIP driver mutations has been observed in chronic inflammatory conditions, including SLE. In this review, we explore the emerging role of CHIP in the relationship between SLE and ASCVD, proposing it as a pathogenic nexus in a triangular inflammatory network. Defining these relationships will help early identification of high-risk individuals and facilitate therapeutic targeting of CHIP to mitigate ASCVD complications in SLE patients.

Atherosclerosis is now widely recognized as a chronic inflammatory condition driven by the recruitment of leukocytes, with CXCR4 playing a critical role in plaque inflammation and disease progression. In this study, we report the development and initial assessment of five novel 68Ga-labeled small-molecule CXCR4 radiotracers ([68Ga]Ga-SDNUM08-12), engineered on an aniline-benzylamine scaffold with varying PEG linker lengths (PEG1 vs PEG2) and bridging amino acids (glutamic vs aspartic acid). Notably, [68Ga]Ga-SDNUM11, incorporating dual PEG2 units and glutamic acid, exhibited optimal hydrophilicity, rapid blood clearance, excellent stability and high binding affinity. In a turpentine-induced sterile muscle inflammation mouse model, [68Ga]Ga-SDNUM11 emerged as the lead radiotracer with optimal imaging efficacy. Subsequently, in a rat common carotid artery (CCA) atherosclerosis model, it exhibited focal uptake colocalizing with CXCR4-positive plaques. These findings establish [68Ga]Ga-SDNUM11 as a promising CXCR4-targeted radiotracer for PET imaging of atherosclerotic plaque inflammation and cardiovascular risk stratification.

Prenatal glucocorticoids and long-term brain vulnerability: GR signaling, epigenetic programming, and crosstalk with peripheral tissues.