A New Era for Analytical Cellular PathologyRead the full article
Analytical Cellular Pathology provides a forum for pathologists and medical practitioners working in the cellular pathology field. Topics covered include cytology, carcinogenesis, cell receptors, biomarkers, diagnostic pathology, and immunopathology.
Chief Editor, Professor Karamichos, focuses on investigating corneal wound healing and dystrophies with a particular interest in the effect of transforming growth factor-β3 or TGF- β3 on corneal stromal cells and their extracellular environment.
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Comparative Analysis of Immunoactivation by Nanosecond Pulsed Electric Fields and PD-1 Blockade in Murine Hepatocellular Carcinoma
Nanosecond pulsed electric field (NsPEF) ablation effectively eliminates early-stage hepatocellular carcinoma (HCC) by local ablation and advanced HCC by inducing a remarkable and sustained host immune response. However, this approach is not sufficient to prevent cancer progression, and complementary approaches are necessary for effective immunotherapy. In this study, we evaluated the immunoactivating effects and mechanisms of action of nsPEF ablation and PD-1 blockade on an HCC orthotopic xenograft mouse model. Briefly, 24 C57BL-6J tumor-bearing mice were randomly assigned to three groups: nsPEF ablation group, anti-PD-1 administration group, and untreated control group. Tumor-infiltrating T, B, and NK cell levels and plasma concentrations of Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4, IL-5, IL-6, and IL-10), Th9 (IL-9), and Th17 (IL-17A, IL-17F, IL-21, and IL-22) cytokines were evaluated. Both nsPEF ablation and anti-PD-1 treatment induced immune cell infiltration in local tumors and modulated cytokine levels in the peripheral blood, with distinct changes in the two treatment groups. Based on these findings, both nsPEF ablation and PD-1 antibody administration can trigger a local and systemic immune response in a partially complementary manner, and nsPEF ablation should be considered along with PD-1 blockade for the treatment of HCC.
Association of JMJD2B and Hypoxia-Inducible Factor 1 Expressions with Poor Prognosis in Osteosarcoma
Background. JMJD2B has been reported to be implicated in malignant tumors. This study is aimed at exploring the expression and prognostic significance of JMJD2B in osteosarcoma and its association with hypoxia-inducible factor 1 (HIF1). Methods. The histopathological and clinical characteristics were retrospectively reviewed from 53 osteosarcoma patients. JMJD2B and HIF1 were examined by immunohistochemical staining of paraffin-embedded osteosarcoma samples, and their association with clinical characteristics was examined by Spearman’s test. Overall survival was examined by Kaplan-Meier analysis, and prognostic factors were identified by univariate and multivariate regression analyses. Results. JMJD2B and HIF1 expression levels were both significantly associated with Enneking stage, distant metastasis, and neoadjuvant chemotherapy, and the JMJD2B and HIF1 expressions were positively correlated (, ). In addition, univariate analysis showed that the expression of both JMJD2B and HIF1 was significantly associated with overall survival, but multivariate analysis showed that only JMJD2B expression was significantly associated with overall survival in osteosarcoma patients. Conclusions. JMJD2B and HIF1 expression levels show significant correlation with osteosarcoma progression, and JMJD2B could predict poor prognosis of osteosarcoma patients.
Predictive Value of Red Blood Cell Distribution Width in Chronic Obstructive Pulmonary Disease Patients with Pulmonary Embolism
Purpose. This study is aimed at investigating the relationship between red cell distribution width (RDW) and chronic obstructive pulmonary disease (COPD) patients with pulmonary embolism (PE). Methods. We conducted a retrospective study enrolling a total of 125 patients from January 2013 to December 2019. The study group consisted of 40 COPD patients with PE, and the control group had 85 COPD patients without PE. Clinical data including demographic characteristics, comorbidities, and results of imaging examinations and laboratory tests were recorded. Blood biomarkers, including red blood cell distribution width standard deviation (RDW-SD), red blood cell distribution width coefficient of variation (RDW-CV), and D-Dimer, were included. Results. RDW-SD and RDW-CV were higher in the COPD patients with the PE group (). A higher RDW-SD led to a significantly increased risk of PE than a lower RDW-SD (adjusted odds ratio (OR): 1.188; 95% confidence interval (CI): 1.048-1.348). The area under the curve (AUC) of RDW-SD used for predicting PE was 0.737. Using 44.55 as the cutoff value of RDW-SD, the sensitivity was 80% and the specificity was 64.7%. The prediction accuracy of RDW-SD combined with D-Dimer () was higher than that of RDW-SD or D-Dimer alone. The optimal cutoff value of RDW-SD+D-Dimer for predicting PE was 0.266, which generated a sensitivity of 87.5% and specificity of 83.5%. Conclusion. RDW is significantly increased in COPD patients with PE and may thus be useful in predicting the occurrence of PE in patients with COPD.
MicroRNA-19a Targets Fibroblast Growth Factor-Inducible Molecule 14 and Prevents Tubular Damage in Septic AKI
Fibroblast growth factor-inducible molecule 14 (Fn14) plays a principal role in triggering tubular damage during septic acute kidney injury (AKI). Here, we explore the mechanism underlying Fn14 deregulation in septic AKI. We identify Fn14 as a bona fide target of miR-19a, which directly binds to 3 UTR of Fn14 for repression independent of cylindromatosis (CYLD), the deubiquitinase (DUB) downstream of miR-19a, and thereby antagonizes the LPS-induced tubular cell apoptosis. Genetic ablation of Fn14, but not of CYLD, abolishes the ability of miR-19a to antagonize the tubular apoptosis by lipopolysaccharide (LPS). In mice, systemic delivery of miR-19a confers protection against septic AKI. Our findings implicate that miR-19a may serve as a promising therapeutic candidate in the prevention of septic AKI.
The Compound Expression of HSP90 and INOS in the Testis of Diabetic Rats as Cellular and Pathologic Adverse Effects of Diabetes
Introduction. Diabetes is increasingly prevalent at global level and associated with various impacts including the male reproductive system. Aims. This research is aimed at investigating the influence of diabetes on the localization and expression of HSP90 and iNOS in the testicular tissue of diabetic rats. Methods. A diabetic model was developed through a single injection of alloxan monohydrate intraperitoneally (purchased from Sigma-Aldrich) 120 mg/kg body weight following fasting for 12 hrs. The experiment involved two groups, the control and diabetic groups with 10 albino rats in each group. Diabetes was considered if glucose concentration was ≥200 mg/dl. The experiment duration was for one month. After the experiment had finished, all rats were terminated and prepared for routine histological and immunohistochemical examination. Results. The results revealed that diabetes caused morphological changes at histological level in testicular tissue. Immunohistochemical examination showed that diabetes significantly upregulated the expression of both HSP90 and iNOS in the testicular tissue of diabetic rats as compared with that of the control group (). Conclusion. Diabetes may induce adverse health effects on the male reproduction through upregulation of HSP90 and iNOS in the testicular tissue of diabetic rats.
Efficacy and Safety of Rivaroxaban versus Warfarin for the Treatment of Acute Pulmonary Embolism: A Real-World Study
Background. Pulmonary embolism (PE) is a life-threatening disease. Target-specific anticoagulant rivaroxaban is a direct factor Xa inhibitor that can be safely used without laboratory monitoring. Objective. To investigate the efficacy and safety of rivaroxaban versus warfarin for the treatment of acute pulmonary thromboembolism in real-world clinical practice. Method. This was a semiretrospective, semiprospective, and real-world trial involving 128 patients with acute symptomatic pulmonary embolism with or without active tumor or frailty. We compared rivaroxaban to the standard therapy consisting of low-molecular-weight heparin combined with warfarin. The primary efficacy outcome was absorption of thrombus. The principal safety outcome was bleeding episode. Results. There was no significant difference in thrombus absorption between rivaroxaban and standard therapy after 3-month treatment (, 95% confidence interval (CI) 0.686 to 1.336) or more than 6-month treatment (, 95% confidence interval (CI) 0.795 to 1.556). There was no decline in efficacy (including computed tomographic pulmonary angiography and recurrence) when the rivaroxaban dose was reduced to 10 mg once daily after 3 months of administration. The ratio of patients without bleeding was 48.84% for rivaroxaban and 19.05% for standard therapy (). There was no significant difference in rivaroxaban monotherapy subgroups (including frail patients, tumor patients, and thrombolysis or nonthrombolysis at intermediate-high-risk patients). Conclusion. In this real-world study, the efficacy and safety of rivaroxaban alone was not different to standard therapy for pulmonary emboli absorption. With an extension in treatment duration, the rivaroxaban regimen had a higher efficacy and safety than standard therapy and there was no decline in treatment efficacy when the rivaroxaban dose was reduced to 10 mg once daily.