ACSL4 upregulates IFI44 and IFI44L expression and promotes the proliferation and invasiveness of head and neck squamous cell carcinoma cells.

Reprogramming of cellular energy metabolism, including deregulated lipid metabolism, is a hallmark of head and neck squamous cell carcinoma (HNSCC). However, the underlying molecular mechanisms remain unclear. Long-chain acyl-CoA synthetase 4 (ACSL4), which catalyzes fatty acids to form fatty acyl-CoAs, is critical for synthesizing phospholipids or triglycerides. Despite the differing roles of ACSL4 in cancers, our data showed that ACSL4 was highly expressed in HNSCC tissues, positively correlating with poor survival rates in patients. Knockdown of ACSL4 in HNSCC cells led to reduced cell proliferation and invasiveness. RNA sequencing analyses identified interferon-induced protein 44 (IFI44) and interferon-induced protein 44-like (IFI44L), encoded by two interferon-stimulated genes, as potential effectors of ACSL4. Silencing IFI44 or IFI44L expression in HNSCC cells decreased cell proliferation and invasiveness. Manipulating ACSL4 expression or activity modulated the expression levels of JAK1, tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 1 (STAT1), interferon α (IFNα), IFNß, and interferon regulatory factor 1 (IRF1), which regulate IFI44 and IFI44L expression. Knockdown of IRF1 reduced the expression of JAK1, TYK2, IFNα, IFNß, IFI44, or IFI44L and diminished cell proliferation and invasiveness. Our results suggest that ACSL4 upregulates interferon signaling, enhancing IFI44 and IFI44L expression and promoting HNSCC cell proliferation and invasiveness. Thus, ACSL4 could serve as a novel therapeutic target for HNSCC.

Histopathology of fluoroscopy-induced radiation ulcer: a case series study in comparison with morphea.

BACKGROUND AND OBJECTIVES: Histopathologic diagnosis of fluoroscopy-induced radiation ulcer (FIRU) can be challenging if the past history of radiation exposure is unknown. Morphea is the most important differential diagnosis. This study was intended to identify clinical and pathologic features that can be used to distinguish FIRU from morphea. PATIENTS AND METHODS: We performed a retrospective study on 25 specimens from 15 patients with FIRU and 21 specimens from 21 patients with morphea. Clinical findings and pathological features were analyzed. RESULTS: Thirteen of 15 patients (86.7 %) with FIRU underwent angioplasty for coronary artery disease, and eleven patients had lesions in the right subscapular area. Compared with morphea, FIRU patients were more likely to display non-inflammatory infiltrates (28 %), bizarre fibroblasts (100 %), sclerosis (48 %), telangiectasia (96 %), vascular damage (64 %), and loss of skin appendages (100 %). In morphea, bizarre fibroblasts were rare (14 %), while telangiectasia (62 %) and loss of skin appendages (62 %) were variable. Loss of CD34+ cells and compression of elastic fibers could not be used to distinguish between FIRU and morphea. CONCLUSIONS: Skin lesion in the right subscapular area with presence of bizarre fibroblasts, sclerosis, telangiectasia, and loss of cutaneous appendages as seen with histology are highly characteristic of the radiation damage associated with fluoroscopic angiography.

Reactivated Toxoplasmic Encephalitis-A case report with histopathology, ultrastructure and pathogenesis analysis.

We report a patient who developed reactivated toxoplasmic encephalitis due to human immunodeficiency (HIV)-associated immune compromise, resulting in a breakdown of the balance between the host immunity and toxoplasma cyst. Through detailed pathological analysis, spilling of tachyzoites from the ruptured wall of toxoplasma cyst can be identified. It was also proved that Toxoplasma gondii would infect endothelial cells of blood vessels, leading to vasculitis and brain ischemic necrosis. By transmission electron microscope (TEM), apical complex of the parasite can be identified, as well as tachyzoites in rapid reproduction through fission. Rhoptry, a club-shaped specialized organelle, which is characteristic of the motile stages of Apicomplexa protozoans, was also identified. The prevention of toxoplasma infection is still an issue to be emphasized in public health. This article is special in its pathophysiology-based description of the morphology. 'Form ever follows function' is a famous quote from the architect Louis Sullivan. In this case report, we make effort to depict a pathophysiology-based or a 'form-function correlation' interpretation of the histopathological findings by light microscope, IHC and ultrastructural examination. We believe such an approach should also be included in the daily pathology resident training program.