Quercetin ameliorates acute lung injury in a rat model of hepatopulmonary syndrome.

BACKGROUND: Common bile duct ligation (BDL) is a rat experimental model to induce biliary cirrhosis. Lung fibrosis and pulmonary vascular angiogenesis and congestion are the most common complications of biliary cirrhosis that is known as hepatopulmonary syndrome. The aim of the present work is to investigate the acute lung injury in a BDL model and to investigate the possible protective effect of quercetin on this injury. METHODS: Twenty-four adult male albino rats of the Wister strain (weighing 150-250 g). Animals were divided into 3 groups, with 8 rats each: Group I: Sham-operated group (control). Group II: Bile duct ligation group (BDL) sacrificed after 28 days from the surgery. Group III: Quercetin-treated bile duct ligation group (Q-BDL) was given orally by gastric gavage in a dose of 50 mg/kg/day, starting from the 4th day of the operation until the 28th day. At the end of the experiment, at day 28, all rats were sacrificed. Lung specimens were processed to measure Endothelin B receptor gene expression by PCR, lung surfactant by ELISA, "eNO" s by immunohistochemistry. Histological assessment was done using; H&E, Masson's trichrome, PAS, toluidine blue-stained semi-thin sections, transmission electron microscope. Histomorphometric and statistical studies were done. RESULTS: BDL group showed significant increase in lung index together with mononuclear cellular infiltration denoting lung inflammatory state. Also, the significant increase in pulmonary endothelial nitric oxide synthase ("eNO" s) area percent and endothelin B receptor (ETB) gene expression indicates enhanced angiogenesis. Pulmonary surfactant concentration was significantly decreased together with thickening of interalveolar septa denoting lung injury and fibrosis. Quercetin led to significant decrease in lung index, pulmonary "eNO" s area percent, ETB gene expression and significant increase in pulmonary surfactant concentration. Quercetin treatment improved histological changes and morphometric measurements, limited mononuclear cellular infiltration and decreased perivascular and perialveolar collagen deposition. CONCLUSION: Quercetin ameliorates the hepatopulmonary syndrome-induced lung injury through its anti-inflammatory, antioxidative and antifibrotic effects.

Accuracy of Classifying Lung Carcinoma Using Immunohistochemical Markers on Limited Biopsy Material: A Two-Center Study.

Introduction Accurate classification of lung cancer into primary and metastatic carcinomas is critical for treatment approaches. Immunohistochemistry (IHC) has always been pivotal in unveiling the diverse cell differentiation lineages present in lung cancer by using specific biomarkers such as TTF1 and p63/p40, which closely reflect the relationship between genotype and phenotype.. Methods A retrospective cross-sectional study was conducted to evaluate 57 Tru-Cut biopsies over two years, from 2020-2022. Tumour morphology was evaluated, and IHC for TTF-1, Napsin A, CK-7, P-63, P-40, and CD-56 was performed in two steps. Results Of the lung cancer cases, 58.5% were adenocarcinoma (ADC), 24.5% were squamous cell carcinoma (SCC), 9.4% were small cell carcinoma, and 7.5% were poorly differentiated carcinoma. TTF1 stain had sensitivity and specificity of 78.9% and 50% in 33 cases of ADC, respectively, while CK7 and Napsin A had 100% sensitivity. P63 stain had 77% sensitivity and 50% specificity in 15 cases of SCC, while P-40 had 100% sensitivity. The CD56 stain was 100% sensitive in five cases of small cell carcinoma. Conclusion IHC staining on small lung biopsies allows accurate sub-classification of poorly differentiated lung cancers; however, there is still significant variability. Surgical resection specimens can be further classified due to architectural features that biopsies lack. Morphological findings would be beneficial in the development of an algorithm for sub-classifying lung carcinoma using a variety of markers.

Impact of TCF3 rearrangement on CNS relapse in egyptian pediatric acute lymphoblastic leukemia.

BACKGROUND: TCF3 rearrangement mostly t(1;19) (q23;p13)/ TCF3-PBX1 gene is associated with favorable outcome in acute lymphoblastic leukemia (ALL) upon treatment with intensification protocols; however, it is associated with higher incidence of central nervous system (CNS) relapse which may affect outcome of patients. OBJECTIVES: We aimed to assess TCF3 rearrangement in newly diagnosed pediatric ALL patients in relation to clinical and laboratory parameters, CNS relapse, and clinical outcome. PATIENTS AND METHODS: Eighty newly diagnosed pediatric ALL patients following at Pediatric Hematology Oncology Clinic, Ain Shams University Hospitals were included in this study. Their ages ranged from 0.75 to 16 years. Seventy six (95%) patients had B-lineage ALL and four (5%) had T-lineage ALL. Data recorded included; age, sex, extramedullary manifestations, CNS, and testes infiltrations, risk stratification, response to treatment, and CBC and BM findings. TCF3 rearrangement was assessed by FISH technique using dual color break-apart probe. RESULTS: TCF3 rearrangement [t(1;19) (q23;p13)] was detected in 16 (20%) out of the 80 studied patients, and it was significantly associated with splenomegaly, lymphadenopathy, CNS infiltration at presentation, high total leucocytic count, low platelet count, high-risk group, and isolated CNS relapse. These results identify a group of high-risk ALL patients with high incidence of CNS relapse and poor response to standard therapeutic regimen. CONCLUSION: Analysis of TCF3 rearrangement [t(1;19) (q23;p13)] at diagnosis may provide a valuable target for modified and intensified CNS-directed chemotherapeutic protocol aiming to improve the patients' outcome.