Sepsis-induced acute lung injury (ALI) leads to severe hypoxemia and respiratory failure, contributing to poor prognosis in septic patients. Endotoxin dissemination triggers oxidative stress and the release of inflammatory cytokines in macrophages, initiating diffuse alveolar damage. The role of epigenetic histone modifications in organ injury is increasingly recognized. The present study aimed to investigate the use of a histone modification inhibitor to alleviate sepsis-induced ALI, revealing a new strategy for improving sepsis patient survival. In vivo models of ALI were established through the intraperitoneal injection of lipopolysaccharide and cecal ligation and puncture surgery. Furthermore, the disease process was simulated in vitro by stimulating Tamm-Horsfall protein-1 (THP-1) cells with lipopolysaccharide. Hematoxylin and eosin staining, blood gas analysis and pulmonary function tests were utilized to assess the extent of lung tissue damage. Western blot analysis, real-time polymerase chain reaction, enzyme-linked immunosorbent assay and immunofluorescence were used to measure the levels and distribution of the indicated indicators within cells and tissues. Reactive oxygen species and autophagic flux alterations were detected using specific probes. BRD3308, which is a inhibitor of histone deacetylase 3, improved lung tissue damage, inflammatory infiltration and edema in ALI by inhibiting Nod-like receptor protein3-mediated pyroptosis in macrophages. By upregulating autophagy, BRD3308 improved the disruption of redox balance in macrophages and reduced the accumulation of reactive oxygen species. Mechanistically, BRD3308 inhibited histone deacetylase 3 activity by binding to it and altering its conformation. Following histone deacetylase 3 inhibition, acetylation of H3K27 was significantly increased. Moreover, the increase in H3K27Ac led to the upregulation of autophagy-related gene 5, a key component of autophagosomes, thereby activating autophagy. BRD3308 inhibits oxidative stress and pyroptosis in macrophages by modulating histone acetylation, thereby preventing sepsis-induced ALI. The present study provides a potential strategy and theoretical basis for the clinical treatment of sepsis-induced ALI.

Rationale: In the course of endocarditis, the development of antineutrophil cytoplasmic antibody (ANCA)-mediated disease introduces the dilemma of determining the best treatment approach for immune conditions, whether immunosuppressant therapy should be added to antibiotic treatment has remained controversial. Patient concerns: A 33-year-old man presented with progressive fever lasting for 7 months, and swelling, pain, and purpura in the arms and legs. The patient showed multiple autoantibodies including cytoplasmic ANCA, antiproteinase 3, rheumatoid factor, and anti-beta 2 glycoprotein I. Blood culture was positive for viridans streptococcus, and renal biopsy revealed glomerulonephritis and interstitial nephritis. Diagnosis: Endocarditis caused by viridans streptococci, ANCA-associated vasculitis, and congenital ventricular septal defect. Interventions: In addition to effective antibiotics, he also received twice intravenous corticosteroids and intravenous immunoglobulin therapy, and a low dose of cyclophosphamide. At last, the patient received congenital ventricular septal defect repair and debridement. Outcomes: The abnormal clinical manifestations, including renal failure and loss of strength, recovered rapidly with corticosteroid therapy in addition to antibiotic treatment. After 6 months without any medications, he remained asymptomatic and was able to live normally. Lessons: In this case with endocarditis and ANCA-associated vasculitis, we highlighted the importance of biopsy and immunosuppressive therapy. Histopathologic examination is required for diagnosis and treatment in such case. Identifying patients who have endocarditis and ANCA positivity with vasculitis pathologic features will require corticosteroid/immunosuppressives in addition to the antibiotics therapy.

Accurate identification of tumor margins during cancer surgeries relies on a rapid detection technique that can perform high-throughput detection of multiple suspected tumor lesions at the same time. Unfortunately, the conventional histopathological analysis of frozen tissue sections, which is considered the gold standard, often demonstrates considerable variability, especially in many regions without adequate access to trained pathologists. Therefore, there is a clinical need for a multitumor-suitable complementary tool that can accurately and high-throughput assess tumor margins in every direction within the surgically resected tissue. We herein describe a high-throughput three-dimensional (3D) histological electrophoresis device that uses tumor-specific proteins to identify and contour tumor margins intraoperatively. Testing on seven cell-line xenograft models and human cervical cancer models (representing five types of tissues) demonstrated the high-throughput detection utility of this approach. We anticipate that the 3D histological electrophoresis device will improve the accuracy and efficiency of diagnosing a wide range of cancers.

Atypical teratoid/rhabdoid tumour (AT/RT) is a highly malignant central nervous system tumour of early childhood. According to the latest WHO classification, the diagnosis of AT/RTs needs to be con...

Solid tissue biopsy is fundamental in guiding surgeons during intraoperative and peri-operative management of cancer patients. However, conventional histopathologic methods depend heavily on the expertise of trained pathologists, facing challenges in accuracy and efficiency.

Background: Pancreatic stellate cell (PSC) activation drives fibrogenesis in alcoholic chronic pancreatitis (ACP). While cytokines and growth factors are known regulators of PSC activation. This study investigated the role of TGF-β1/Smad pathway in ethanol (EtOH)-induced human PSC activation and collagen type I alpha 1 chain ( Col1A1) synthesis, as well as the mechanism through which all‑trans retinoic acid (ATRA) antagonizes this pathway. Methods Using human activated PSC line (HP-1 cells), we quantified the mRNA and protein levels of TGF-β1, IL-6, α-SMA and Col1A1 by qRT-PCR and ELISA respectively. Phospho-Smad2/3 and RARα/RARγ levels were analyzed by Western blot, RARα/α-SMA localization by double immunofluorescence, and serum retinol by HPLC. Results EtOH significantly upregulated TGF-β1 and IL-6 mRNA and protein levels. EtOH-induced TGF-β1 upregulation was partially inhibited by si-IL-6R or IL-6 antibody, indicating that IL-6 acts as an intermediate. Crucially, both TGF-β1 siRNA and a neutralizing antibody largely abolished EtOH-induced Smad2/3 phosphorylation and the subsequent production of α-SMA and Col1A1, underscoring the central role of TGF-β1 in this pathway. ATRA suppressed α-SMA expression and prevented Col1A1 synthesis in EtOH-treated HP-1 cells without affecting RARα. Mechanistically, these effects occurred via partial inhibition of TGF-β1 and marked downregulation of Smad2/3 phosphorylation. Clinically, a high vitamin A deficiency rate (44.7%) and elevated serum TGF-β1/Col1A1 levels were observed in 38 ACP patients. Conclusion ATRA mitigates EtOH-induced fibrogenesis in PSCs through inhibition of the TGF-β1/Smad2/3 axis. This mechanistic insight, together with the observed vitamin A deficiency in ACP patients, suggests that restoring retinoid signaling may be a viable antifibrotic strategy.