Neutrophil Activity and Extracellular Matrix Degradation: Drivers of Lung Tissue Destruction in Fatal COVID-19 Cases and Implications for Long COVID.

Pulmonary fibrosis, severe alveolitis, and the inability to restore alveolar epithelial architecture are primary causes of respiratory failure in fatal COVID-19 cases. However, the factors contributing to abnormal fibrosis in critically ill COVID-19 patients remain unclear. This study analyzed the histopathology of lung specimens from eight COVID-19 and six non-COVID-19 postmortems. We assessed the distribution and changes in extracellular matrix (ECM) proteins, including elastin and collagen, in lung alveoli through morphometric analyses. Our findings reveal the significant degradation of elastin fibers along the thin alveolar walls of the lung parenchyma, a process that precedes the onset of interstitial collagen deposition and widespread intra-alveolar fibrosis. Lungs with collapsed alveoli and organized fibrotic regions showed extensive fragmentation of elastin fibers, accompanied by alveolar epithelial cell death. Immunoblotting of lung autopsy tissue extracts confirmed elastin degradation. Importantly, we found that the loss of elastin was strongly correlated with the induction of neutrophil elastase (NE), a potent protease that degrades ECM. This study affirms the critical role of neutrophils and neutrophil enzymes in the pathogenesis of COVID-19. Consistently, we observed increased staining for peptidyl arginine deiminase, a marker for neutrophil extracellular trap release, and myeloperoxidase, an enzyme-generating reactive oxygen radical, indicating active neutrophil involvement in lung pathology. These findings place neutrophils and elastin degradation at the center of impaired alveolar function and argue that elastolysis and alveolitis trigger abnormal ECM repair and fibrosis in fatal COVID-19 cases. Importantly, this study has implications for severe COVID-19 complications, including long COVID and other chronic inflammatory and fibrotic disorders.

3D bioprinting of gastrointestinal cancer models: A comprehensive review on processing, properties, and therapeutic implications.

Gastrointestinal tract (GIT) malignancies are an important public health problem considering the increased incidence in recent years and the high morbidity and mortality associated with it. GIT malignancies constitute 26% of the global cancer incidence burden and 35% of all cancer-related deaths. Gastrointestinal cancers are complex and heterogenous diseases caused by the interplay of genetic and environmental factors. The tumor microenvironment (TME) of gastrointestinal tract carcinomas is dynamic and complex; it cannot be recapitulated in the basic two-dimensional cell culture systems. In contrast, three-dimensional (3D) in vitro models can mimic the TME more closely, enabling an improved understanding of the microenvironmental cues involved in the various stages of cancer initiation, progression, and metastasis. However, the heterogeneity of the TME is incompletely reproduced in these 3D culture models, as they fail to regulate the orientation and interaction of various cell types in a complex architecture. To emulate the TME, 3D bioprinting has emerged as a useful technique to engineer cancer tissue models. Bioprinted cancer tissue models can potentially recapitulate cancer pathology and increase drug resistance in an organ-mimicking 3D environment. In this review, we describe the 3D bioprinting methods, bioinks, characterization of 3D bioprinted constructs, and their application in developing gastrointestinal tumor models that integrate their microenvironment with different cell types and substrates, as well as bioprinting modalities and their application in therapy and drug screening. We review prominent studies on the 3D bioprinted esophageal, hepatobiliary, and colorectal cancer models. In addition, this review provides a comprehensive understanding of the cancer microenvironment in printed tumor models, highlights current challenges with respect to their clinical translation, and summarizes future perspectives.

Fine needle aspiration cytology of chondroblastoma: A report of two cases with brief review of pitfalls.

Chondroblastoma is a rare, giant cell-rich, benign neoplasm of bone. Since the past few decades fine needle aspiration cytology (FNAC) has gained momentum in preoperative diagnosis of bone lesions. At cytology, other giant cell-rich tumors and tumorlike lesions such as aneurysmal bone cyst (ABC), giant cell tumor, and chondromyxoid fibroma fall under the differential diagnosis of chondroblastoma. Due to the difference in the treatment protocol and prognosis, preoperative diagnosis is mandatory. We describe the cytomorphology in two cases of chondroblastoma diagnosed at FNAC and confirmed by histopathology. At cytology, the presence of giant cells, chondroid matrix, mononuclear cells with nuclear indentation, and grooving along with glassy, vacuolated cytoplasm are characteristic of chondroblastoma. In addition to this, the presence of chicken wire calcification is a useful clue to the accurate diagnosis of chondroblastoma at FNAC.