In haploidentical hematopoietic stem cell transplantation (HSCT), the addition of post-transplantation cyclophosphamide (Cy) can help to induce immunotolerance between the donor and haploidentical immune system, preventing graft-versus-host disease between the haploidentical immune system and organs/ tissues of the recipient. We hypothesized that the situation could be reversed and replicated during the transplantation of allogenic tissue and syngeneic (autologous model) HSCT with post-HSCT Cy. We hypothesized that conditioning (pre-HSCT Cy) causes immunoablation of the recipient, and post-HSCT Cy deletes allo-reactive clones from transplanted HSC thus enabling immunotolerance to simultaneously transplanted tissue (organ). To test this hypothesis, we developed a model of autologous HSCT (syngeneic HSCT) with simultaneous transplantation of allogenic tissue in rat. The study rats received: first immunoablation, then allogenic skin graft and syngeneic HSCT, and later post-transplantation Cy. The administration of Cy before and after syngeneic HSCT with simultaneous transplantation of skin graft prolonged skin graft survival from 3 to 12 days and changed the pattern of rejection. The addition of Cy post-HSCT resulted in a statistically significant increase in TNFα secretion before rejection compared to acute rejection without Cy post-HSCT. The sole administration of Cy before and after syngeneic HSCT with simultaneous organ transplantation is not sufficient to achieve full tolerance to allogenic tissue. However, with changes to conditioning or additional immunosuppression, this goal could be achieved.
In many autoimmune and autoinflammatory diseases, the head and neck are the first sites of symptom manifestation. Recognizing these early signs is crucial to prevent diagnostic delays and fatal consequences. This review addresses: (1) specific otorhinolaryngological (ENT) manifestations indicating systemic diseases (2), evidence for differentiating these from isolated ENT disorders, and (3) the multidisciplinary role in patient management. A comprehensive narrative literature review was conducted utilizing established scientific databases, including PubMed/Medline, Scopus, Web of Science, and Embase, covering articles published from 1983 up to 2026. A structured search strategy applied keywords like “systemic disorders,” “ENT symptoms,” “granulomatosis with polyangiitis,” and “Sjögren syndrome.” Peer-reviewed clinical trials, mechanistic studies, and authoritative guidelines were included to synthesize current evidence regarding the clinical detection and management of systemic diseases through ENT manifestations. ENT symptoms typically manifest locally before systemic organ involvement. Sensorineural hearing loss (SNHL) frequently accompanies autoinflammatory diseases. Auricular chondritis strongly indicates relapsing polychondritis (RP). Granulomatosis with Polyangiitis (GPA) and RP classically present with refractory rhinosinusitis, nasal crusting, and saddle-nose deformities. Orally, Sjögren syndrome causes severe sicca syndrome, while Behçet’s disease leads to mucosal ulcerations. Furthermore, GPA (developing in 2–20
This meta-analysis explored the association of immune checkpoint–related single-nucleotide polymorphisms (SNPs) in programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) genes with susceptibility to various genitourinary (GU) cancers, including urothelial carcinoma (UC), renal cell carcinoma (RCC), and prostate cancer (PCa). PubMed, Embase, Cochrane Library, and Web of Science were searched for case–control studies from inception to April 2026. Six SNPs, including PD-1 (rs2227981), PD-L1 (rs4143815), and CTLA-4 (rs3087243, rs231775, rs5742909, and rs11571302), were examined. The relationships between the SNPs and cancer susceptibility were evaluated using pooled odds ratios (ORs) and 95
NOD-like cytosolic receptors (NLRs) are crucial in both nonspecific and specific immunity. Among them, the NLRP3 (NOD-like receptor family pyrin domain-containing 3) gains clinical attention, where its hyperactivation causes inflammatory, autoimmune, and metabolic illnesses. We investigated the effects of the flavone eupatorin (3’, 5-Dihydroxy 4’, 6, 7-trimethoxy flavone) on the NLRP3 inflammasome and associated proteins utilizing in vitro and in silico approaches. Eupatorin modulates the NLRP3 and associated molecules’ expression in lipopolysaccharide (LPS)-primed, adenosine 5’-triphosphate (ATP)-stimulated THP-1 cells through downregulation of NF-ĸB phosphorylation, with promising effects as observed with standard tranilast. Additionally, the suppression of zymosan-induced intracellular oxidative stress and LPS-induced nitric oxide (NO) revealed anti-inflammatory effects. The strong binding affinity of -8.276 kcal/mol of the compound with NLRP3 was observed at the ATP binding pocket as shown by the standard tranilast, -7.834 kcal/mol, where interaction with NF-kB also provides comparable results with binding affinities of -3.93 and − 3.17 kcal/mol, respectively. The in silico results support the in vitro findings. Eupatorin appears to be a potential medication option for NLRP3-driven inflammatory and metabolic diseases and deserves further development as an inflammasome inhibitor.
