Abstract Relevant studies have confirmed that the stimulation of spleen function caused by low-dose splenic irradiation can have positive effects on tumors and other diseases. This study aimed to determine radiation-induced changes in spleen index, lymphocyte subsets, spleen cell apoptosis, and pathological features of the spleen in mice. The mouse model was established by irradiating the spleen at different doses. The mice were divided into the following groups: blank control, low-dose, low-dose fractionated irradiation, and challenge dose irradiation. The mice were sacrificed under humanitarian conditions, and spleen tissue and peripheral blood were collected. The spleen index was calculated, and flow cytometry was used to analyze spleen T lymphocyte subsets and spleen apoptosis. The pathological changes in the spleen were determined by hematoxylin and eosin (H&E) staining. The spleen index of mice in the low-dose fractionated irradiation group was significantly increased compared with that in the blank control group. The spleen indexes of the low-dose irradiation and low-dose fractionated irradiation groups were much higher than that of the challenge dose irradiation group. Compared with the blank control group, the percentage of CD3+ and CD4+ T lymphocytes in the peripheral blood and spleen tissues in the low-dose irradiation and low-dose fractionated irradiation groups was significantly increased, whereas that from the challenge dose irradiation group was obviously decreased. CD8+ T lymphocytes in the peripheral blood and spleen tissues in the low-dose irradiation, low-dose fractionated irradiation, and challenge dose irradiation groups were significantly lower than those in the blank control group. The apoptosis rate of the spleen in the challenge dose irradiation group was significantly higher than that in the blank control, low-dose irradiation, and low-dose fractionated irradiation groups. H&E staining analysis of the spleen showed pathological changes in the different irradiation groups compared with the blank control group. Low-dose irradiation and low-dose fractionated irradiation can change the T lymphocyte subsets in the peripheral blood and spleen of mice, which can promote immune excitation and improve immune effects.
BACKGROUND:Chemotherapy is widely used in gastric cancer treatment, but multidrug resistance remains a leading cause of chemotherapy failure. Trop2 is highly expressed in gastric tumor tissues and greatly influences cancer progression. However, little is known about the relationship between Trop2 and drug resistance in gastric cancer. MATERIAL AND METHODS:In the present study, Trop2 was knocked down in BGC823 cells and overexpressed in HGC27. CCK-8 assay was performed to explore the relationship of Trop2 expression and cell proliferation treated with anticancer drugs. Flow cytometry was performed to assess the relationship between Trop2 and cell apoptosis after chemotherapy. Subcutaneous xenograft models were generated to explore the curative effect of DDP to GC in vivo. MRP1 and Notch1 expressions were assessed by Western blot. RESULTS:Trop2 decreased cell proliferation inhibition and apoptosis after chemotherapeutic treatments. DDP showed stronger therapeutic effects on Trop2-knockdown tumor than control in vivo. MRP1 and Notch1 signaling pathway were confirmed to participate in Trop2-induced drug resistance. CONCLUSIONS:Our findings suggest that Trop2 promotes the resistance of gastric cancer to chemotherapy by activating the Notch1 pathway.
Gastric cancer (GC) is a common cancer in humans. Although overexpression of eukaryotic translation elongation factor eEF1Bα is associated with cancer onset and progression, little is known about its expression in GC and its prognostic significance. Here we used immunohistochemistry to analyze eEF1Bα expression in the following tissue types: GC, normal gastric, chronic gastritis, intestinal metaplasia, and intraepithelial neoplasia. These data were correlated with patients' clinical information. eEF1Bα was expressed at levels approximately three times higher in GC tissues compared with normal gastric tissues. High expression of eEF1Bα was significantly associated with histological type, TNM stage, tumor size, and distant metastases. GC patients with high eEF1Bα expression experienced significantly shorter overall survival. Bioinformatics analysis indicated that eEF1Bα may be associated with protein synthesis, energy metabolism, cell cycle, and the p53 signaling pathway. We identified the products of RPL10A and RPS13 as critical components of a network comprising eEF1Bα. We concluded that high eEF1Bα expression is associated with poor overall survival and may serve as an independent prognostic factor of GC. Further, we proposed that eEF1Bα likely mediates the development of GC through the cell cycle and p53 signaling pathway. Together, our findings suggest that eEF1Bα could be an effective prognostic biomarker for GC.
Abstract Nanodiamonds (NDs) are advantageous for targeted cancer treatment with payload medications due to their good biocompatibility. Herein, a nanodrug delivery system, ND‐fucoxanthin (ND‐FX), was generated by combining FX and acyl chloride‐functionalized NDs, which were created by dispersing and surface‐modifying NDs. The structure and characteristics of NDs were examined via X‐ray diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy. Subsequently, the drug‐loading and ‐release rates of ND‐FX under different pH conditions were calculated using ultraviolet‐visible spectrophotometeric analysis. The drug‐loading rate of the ND‐FX system was 13.17 %; release rate of FX at pH 7.4 and 6.5 was 27.79 % and 54.65 %, respectively; and cumulative release rate of ND‐FX reached 79.98 % over a release duration of 72 h at pH 5.0. Meanwhile, in vitro cytotoxicology experiments demonstrated that ND‐FX effectively inhibited the activity of HeLa and HepG2 cells. These results demonstrate the potential value of NDs in the field of nanodrug delivery applications.
The occurrence and development of gastric adenocarcinoma (gADC) is closely related to the interaction between tumor cells and immune cells in the tumor microenvironment (TME). Our objective was to characterize the repertoire of immune cells in the TME of gADC. To analyze the transcriptomic, immune, and spatial information of TME in gADC, we constructed single-cell RNA sequencing, 10 × Genomics V(D)J analysis, multiple immunofluorescence techniques, and OSCmap analysis of 49,765 single cells in seven samples from four gADC patients. Our integrative analysis of B cells demonstrated that a large number of mucosal associated lymphoid tissue (MALT)-B cells were detected in the gADC tissues, which have mature tertiary lymphatic structures (mTLSs), and almost no MALT-B cells in peripheral blood sample. Moreover, MALT-B cells are a class of IgA+ plasma cells, which are characterized with high expression of complement pathway activation-related genes. Next, natural killer T (NKT) cells mainly exist in gADC tissues accompanied by mTLSs. This study also classified monocytes/macrophages and epithelial cells into benign and malignant types. Interestingly, CSOmap (q < .05) and multiple immunofluorescence (p < .05) results indicated more types of immune cells can be enriched in tissues with mTLSs than normal TLSs, and the density of mTLSs were higher than normal TLSs. Our findings provide novel insights for the signature of immune cells and tumor cells in the TME of gADC with TLSs and highlight the potential importance of IgA-mediated humoral immunity in gADC patients with TLSs.
Objective To review the clinical and pathological features of pulmonary sarcomatoid carcinoma(PSC).Methods Clinical and pathologic data of 17 patients with PSC,which defined diagnosis with pathology,were reviewed.Results It showed that PSC mostly involved the upper lobe of right lung.The clinical manifestations and chest imaging of PSC were similar to that of other types of non small cell lung carcinomas(NSCLC).Multiphasic PSC was mixed with epithelial component of carcinomas(including adenocarcinoma,giant cell carcinoma,squamous cell carcinoma and bronchioalveolar carcinoma) and sarcomatoid carcinoma(SC) in 10 patients.Monophasic PSC was entirely SC in other 7 patients.The immunohistochemical results showed that Vimentin was detected in 11 cases,CK was positive in 8 cases,AE3 was positive in 4 cases and AE1 was positive in 3 cases,EMA was positive in 2 cases.Conclusion It showed that the final diagnosis of PSC was based on histopathology.The immunohistochemical staining of Vimentin,CK,AE1/AE3 and EMA may be helpful for diagnosis.
Observational studies have established an association between serum uric acid and cardiovascular disease (CVD). However, these studies are susceptible to uncontrolled confounders and reverse causality bias. To overcome these challenges, we employed a two-sample Mendelian randomization (MR) approach to investigate the causal link between serum uric acid and CVD.
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