Analytical Cellular Pathology最新文献

Platelet-rich plasma (PRP) and its byproduct platelet-poor plasma (PPP) are rich sources of cytokines in tissue damage repair. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have received more and more attention for their ability to treat multiple diseases. The purpose of our study was to investigate the biologic action of PPP and PRP on BM-MSCs. The adipogenic potential of BM-MSCs revealed no obvious change, but the osteogenic ability of BM-MSCs was enhanced after treated with PRP. CCK8 assays and cell colony formation assays showed that PRP promoted cell proliferation, while this effect of PPP was not obvious. No obvious difference was found in cell cycle and apoptosis of BM-MSCs between PRP and PPP treatment. Expression of β-galactosidase, a biological marker of senescence, was decreased upon PRP treatment which indicated that PRP provided significant protection against cellular senescence. The migratory capacity of BM-MSCs was detected by scratch and transwell assays. The results indicated that PRP could affect the migration ability of BM-MSCs. From immunofluorescence detection and western blot, we demonstrated that the level of epithelial-mesenchymal transition-related proteins was changed and several pluripotency marker genes, including Sox2, Sall4, Oct4, and Nanog, were increased. Finally, the expression of the key signal pathway such as PI3K/AKT was examined. Our findings suggested that PRP promoted cell migration of BM-MSCs via stimulating the signaling pathway of PI3K/AKT.

Background: Tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) contribute significantly to the development of immunosuppressive properties of a tumor. In this study, we performed immunohistochemical analysis of immune cells of esophageal tumors stroma.

Methods: Paraffin-embedded tissue specimens from 48 esophageal squamous cell carcinoma (ESCC) patients were retrospectively collected for immunohistochemical analysis of stromal cells. For staining of macrophages, CD68, CD163, CD206, PU.1, and iNOS were used. For T cell detection, CD8, CD3, and FOXP3 were used. Also, we performed staining for PD-L1 that can be expressed on TAMs and tumor cells. Clinicopathological and survival data were collected and analyzed using the χ ² and Fisher exact tests, Kaplan-Meier curves, and the log-rank test. The correlation analysis was performed with Spearman's rank correlation coefficient.

Results: We found that FOXP3 expression was associated with age (p = 0.042) and iNOS expression was associated with the disease stage (p = 0.044). In addition, FOXP3 and CD163 appeared to be markers of good prognosis (HR = 0.4420, p = 0.0325, and HR = 0.4447, p = 0.0456, respectively). Significant association between PU.1+ and CD68+ macrophages (r = 0.833; p ≤ 0.001) and between PU.1+ and CD163+ macrophages (r = 0.500; p ≤ 0.001) was established; positive association between PU.1 and CD206 expression was also observed (r = 0.250; p = 0.043).

Conclusions: Large amounts of CD163+ macrophages and FOXP3+ Т cells appear to be markers of good prognosis of ESCC. The number of PU.1+ macrophages strongly correlates with the number of CD68+ macrophages; therefore, usage of PU.1 as a potential macrophage marker can be recommended for esophageal tumors.

Long noncoding RNA (lncRNA) plays a critical role in the development of tumors. The aim of our study was construction of a lncRNA signature model to predict breast cancer (BRCA) patient survival. We downloaded RNA-seq data and relevant clinical information from the Cancer Genome Atlas (TCGA) database. Differentially expressed lncRNA were computed using the "edgeR" package and subjected to the univariate and multivariate Cox regression analysis. Corresponding protein-coding genes were used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis. Finally, 521 differentially expression lncRNA were obtained. We constructed a ten-lncRNA signature model (LINC01208, RP5-1011O1.3, LINC01234, LINC00989, RP11-696F12.1, RP11-909N17.2, CTC-297N7.9, CTA-384D8.34, CTC-276P9.4, and MAPT-IT1) to predict BRCA patient survival using the multivariate Cox proportional hazard regression model. The C-index was 0.712, and AUC scores of training, test, and entire sets were 0.746, 0.717, and 0.732, respectively. Univariate Cox regression analysis indicated that age, tumor status, N status, M status, and risk score were significantly related to overall survival in patients with BRCA. Further, the multivariate analysis showed that risk score and M status had outstanding independent prognostic values, both with p < 0.001. The Gene Ontology (GO) function and KEEG pathway analysis was primarily enriched in immune response, receptor binding, external surface of plasma membrane, signal transduction, cytokine-cytokine receptor interaction, and cell adhesion molecules (CAMs). Finally, we constructed a ten-lncRNA signature model that can serve as an independent prognostic model to predict BRCA patient survival.

Aims: To evaluate the expression of DSG1 and DSG2 and investigate their clinicopathological significance in EHCC.

Method: The protein expression of DSG1 and DSG2 was measured by EnVision immunohistochemistry in 15 normal biliary tract tissues, 10 biliary tract adenoma tissues, 30 peritumoral tissues, and 100 EHCC tumour tissues.

Result: The expression of the DSG1 and DSG2 proteins was significantly lower in EHCC tumour tissues than in normal biliary tract tissues, biliary tract adenoma, and peritumoral tissues (P < 0.05). Adenoma and peritumoral tissues with negative DSG1 and/or DSG2 protein expression exhibited atypical hyperplasia. DSG1 expression was positively correlated with DSG2 expression in EHCC (P < 0.01). In patients with good differentiation, no invasion, no lymph metastasis, TNM I + II stage, and radical surgery, the positive expression of DSG1 and DSG2 proteins was higher (P < 0.05). In comparison to patients with negative DSG1 and/or DSG2 expression, the average overall survival time of those with positive expression was significantly longer (P = 0.000). Cox multivariate analysis revealed that negative DSG1 and DSG2 expressions were independent of poor prognosis factors in EHCC patients. The AUC calculated for DSG1 was 0.681 (95% confidence interval: 0.594-0.768) and that for DSG2 was 0.645 (95% confidence interval: 0.555-0.734), while that for DSG1 and DSG2 was 0.772 (95% confidence interval: 0.609-0.936).

Conclusions: Negative protein expression of DSG1 and DSG2 is closely related to the pathogenesis, severe clinicopathological characteristics, aggressive biological behaviours, and dismal prognosis in EHCC.

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.

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 (p < 0.001, R = 0.752). 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.

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 (p < 0.001). 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 (AUC = 0.897) 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.

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 (p < 0.001).

Conclusion: Diabetes may induce adverse health effects on the male reproduction through upregulation of HSP90 and iNOS in the testicular tissue of diabetic rats.

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 (P = 0.798, 95% confidence interval (CI) 0.686 to 1.336) or more than 6-month treatment (P = 0.534, 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 (P = 0.001). 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.