Securinine inhibits carcinogenesis in gastric cancer by targeting AURKA-ß-catenin/Akt/STAT3 and the cell cycle pathway.

BACKGROUND: Gastric cancer (GC) is difficult to treat with currently available treatments. Securinine (SCR) has a lengthy history of use in the treatment of disorders of the nervous system, and its anticancer potential has been gaining attention in recent years. The aim of this study was to explore the repressive effect of SCR on GC and its fundamental mechanism. METHODS: The efficacy of SCR in GC cells was detected by MTT assays. Colony formation, flow cytometry and Transwell assays were used to assess the changes in the proliferation, apoptosis, cell cycle distribution, migration and invasion of GC cells after treatment. AGS (human gastric carcinoma cell)-derived xenografts were used to observe the effect of SCR on tumor growth in vivo. The molecular mechanism of action of SCR in GC was explored via RNA sequencing, bioinformatics analysis, Western blotting, molecular docking, and immunohistochemistry. RESULTS: SCR was first discovered to inhibit the proliferation, migration, and invasion of GC cells while initiating apoptosis and cell cycle arrest in vitro. It was also established that SCR has excellent anticancer effects in vivo. Interestingly, AURKA acts as a crucial target of SCR, and AURKA expression can be blocked by SCR. Moreover, this study revealed that SCR suppresses the cell cycle and the ß-catenin/Akt/STAT3 pathways, which were previously reported to be regulated by AURKA. CONCLUSION: SCR exerts a notable anticancer effect on GC by targeting AURKA and blocking the cell cycle and ß-catenin/Akt/STAT3 pathway. Thus, SCR is a promising pharmacological option for the treatment of GC.

CDKN2A promoter methylation enhances self-renewal of glioblastoma stem cells and confers resistance to carmustine.

BACKGROUND: Glioblastoma, a highly aggressive form of brain cancer, poses significant challenges due to its resistance to therapy and high recurrence rates. This study aimed to investigate the expression and functional implications of CDKN2A, a key tumor suppressor gene, in glioblastoma cells, building upon the existing background of knowledge in this field. METHOD: Quantitative reverse transcription PCR (qRT-PCR) analysis was performed to evaluate CDKN2A expression in U87 glioblastoma cells compared to normal human astrocytes (NHA). CDKN2A expression levels were manipulated using small interfering RNA (siRNA) and CDKN2A overexpression vector. Cell viability assays and carmustine sensitivity tests were conducted to assess the impact of CDKN2A modulation on glioblastoma cell viability and drug response. Sphere formation assays and western blot analysis were performed to investigate the role of CDKN2A in glioblastoma stem cell (GSC) self-renewal and pluripotency marker expression. Additionally, methylation-specific PCR (MSP) assays and demethylation treatment were employed to elucidate the mechanism of CDKN2A downregulation in U87 cells. RESULT: CDKN2A expression was significantly reduced in glioblastoma cells compared to NHA. CDKN2A overexpression resulted in decreased cell viability and enhanced sensitivity to carmustine treatment. CDKN2A inhibition promoted self-renewal capacity and increased pluripotency marker expression in U87 cells. CDKN2A upregulation led to elevated protein levels of p16INK4a, p14ARF, P53, and P21, which are involved in cell cycle regulation. CDKN2A downregulation in U87 cells was associated with high promoter methylation, which was reversed by treatment with a demethylating agent. CONCLUSION: Our findings demonstrate that CDKN2A downregulation in glioblastoma cells is associated with decreased cell viability, enhanced drug resistance, increased self-renewal capacity, and altered expression of pluripotency markers. The observed CDKN2A expression changes are mediated by promoter methylation. These results highlight the potential role of CDKN2A as a therapeutic target and prognostic marker in glioblastoma.

Association between Perceived Stress and Motoric Cognitive Risk Syndrome in an Elderly Population: Rugao Longevity and Aging Study.

INTRODUCTION: Previous studies have indicated a correlation between perceived stress and cognitive decline. However, it remains unknown whether high levels of perceived stress can result in motoric cognitive risk (MCR) syndrome. This study investigated the relationship between perceived stress and MCR in a community-based population. METHODS: The study cohort comprised 852 elderly individuals from the Rugao Longitudinal Aging Cohort. Perceived stress was assessed using the 10-item Perceived Stress Scale (PSS-10), while MCR was defined as the coexistence of subjective memory complaints (SMCs) and slow gait speed. RESULTS: The average age of the study participants is 79.84 ± 4.34 years. The mean score of PSS-10 among participants is 10.32 (range = 0-33; [SD] = 5.71), with a median score of 10.00 (6.00, 14.00). The prevalence of MCR is 9.3%. In the logistic regression analysis, for each 1-SD (5.71) increase in the global PSS-10 score, the risk of MCR increased by 40% (95% CI 1.09-1.80). Additionally, in the aspect of two components of MCR, with a 1-SD increase (5.71) in the global PSS-10 score, there was a 50% (95% CI 1.29-1.75) increase in the risk of SMCs and a 27% (95% CI 1.04-1.55) increase in the risk of slow gait speed. In terms of specific walking speed, there was a reverse correlation between the global PSS-10 score and walking speed (r = -0.14, p < 0.001). CONCLUSIONS: This study provided preliminary evidence that high levels of perceived stress were associated with the risk of MCR in a community-dwelling population.

Ischemic stroke prediction using machine learning in elderly Chinese population: The Rugao Longitudinal Ageing Study.

OBJECTIVE: Compared logistic regression (LR) with machine learning (ML) models, to predict the risk of ischemic stroke in an elderly population in China. METHODS: We applied 2208 records from the Rugao Longitudinal Ageing Study (RLAS) for ischemic stroke risk prediction assessment. Input variables included 103 phenotypes. For 3-year ischemic stroke risk prediction, we compared the discrimination and calibration of LR model and ML methods, where ML methods include Random Forest (RF), Gaussian kernel Support Vector Machines (SVM), Multilayer perceptron (MLP), K-Nearest Neighbors Algorithm (KNN), and Gradient Boosting Decision Tree (GBDT) to develop an ischemic stroke risk prediction model. RESULTS: Age, pulse, waist circumference, education level, ß2-microglobulin, homocysteine, cystatin C, folate, free triiodothyronine, platelet distribution width, QT interval, and QTc interval were significant induced predictors of ischemic stroke. For ischemic stroke prediction, the ML approach was able to tap more biochemical and ECG-related multidimensional phenotypic indicators compared to the LR model, which placed more importance on general demographic indicators. Compared to the LR model, SVM provided the best discrimination and calibration (C-index: 0.79 vs. 0.71, 11.27% improvement in model utility), with the best performance in both validation and test data. CONCLUSION: In a comparison of LR with five ML models, the accuracy of ischemic stroke prediction was higher by combining ML with multiple phenotypes. Combined with other studies based on elderly populations in China, ML techniques, especially SVM, have shown good long-term predictive performance, inspiring the potential value of ML use in clinical practice.

[Research progress in prevention and treatment of radiation-induced intestinal injury by traditional Chinese medicine active components].

Radiation-induced intestinal injury(RIII), a common complication of radiotherapy for pelvic malignancies, affects the quality of life and the radiotherapy efficacy for cancer. Currently, the main clinical approaches for the prevention and treatment of RIII include drug therapy, hyperbaric oxygen therapy, and surgical treatment. Among these methods, drug therapy is cost-effective. Traditional Chinese medicine(TCM) containing a variety of active components demonstrates mild side effects and good efficacy in preventing and treating RIII. Studies have proven that TCM active components, such as flavonoids, terpenoids, phenylpropanoids, and alkaloids, can protect the intestine against RIII by inhibiting oxidative stress, regulating the expression of inflammatory cytokines, modulating the mitochondrial apoptosis pathway, adjusting intestinal flora, and suppressing cell apoptosis. These mechanisms can help alleviate the symptoms of RIII. The paper aims to provide a theoretical reference for the discovery of new drugs for the prevention and treatment of RIII by reviewing the literature on TCM active components in the last 10 years.

Single-cell transcriptomics reveals cellular heterogeneity and macrophage-to-mesenchymal transition in bicuspid calcific aortic valve disease.

BACKGROUND: Bicuspid aortic valve (BAV) is the most prevalent congenital valvular heart defect, and around 50% of severe isolated calcific aortic valve disease (CAVD) cases are associated with BAV. Although previous studies have demonstrated the cellular heterogeneity of aortic valves, the cellular composition of specific BAV at the single-cell level remains unclear. METHODS: Four BAV specimens from aortic valve stenosis patients were collected to conduct single-cell RNA sequencing (scRNA-seq). In vitro experiments were performed to further validate some phenotypes. RESULTS: The heterogeneity of stromal cells and immune cells were revealed based on comprehensive analysis. We identified twelve subclusters of VICs, four subclusters of ECs, six subclusters of lymphocytes, six subclusters of monocytic cells and one cluster of mast cells. Based on the detailed cell atlas, we constructed a cellular interaction network. Several novel cell types were identified, and we provided evidence for established mechanisms on valvular calcification. Furthermore, when exploring the monocytic lineage, a special population, macrophage derived stromal cells (MDSC), was revealed to be originated from MRC1+ (CD206) macrophages (Macrophage-to-Mesenchymal transition, MMT). FOXC1 and PI3K-AKT pathway were identified as potential regulators of MMT through scRNA analysis and in vitro experiments. CONCLUSIONS: With an unbiased scRNA-seq approach, we identified a full spectrum of cell populations and a cellular interaction network in stenotic BAVs, which may provide insights for further research on CAVD. Notably, the exploration on mechanism of MMT might provide potential therapeutic targets for bicuspid CAVD.

A novel method for the component identification of human blood products: Mass spectrometric analysis of human fibrinogen digested after SDS-PAGE in-gel digestion.

Human fibrinogen, as a blood product of special origin, is relatively simple to prepare and purify. Therefore, completely isolating and removing the relevant impurity proteins is difficult. Further, which impurity protein components are present is not clear. In this study, human fibrinogen products from seven enterprises were collected from the market, and the presence of impurity proteins was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Subsequently, the major 12 impurity proteins were identified and screened by in-gel enzymolysis mass spectrometry, and 7 major impurity proteins with different peptide coverage were identified by enzyme-linked immunosorbent assay, in agreement with the mass spectrometry results. The seven major impurity proteins included fibronectin, plasminogen, F-XIII, F-VIII, complement factor H, cystatin-A, and α-2-macroglobulin. The final test results were in the range of undetectable to 50.94 µg/mL, with correspondingly low levels of impurity proteins between different companies and a manageable risk. Moreover, we found that these impurity proteins existed in the form of polymers, which might also be an important cause of adverse reactions. This study established a protein identification technique applicable to fibrinogen products, which provided new ideas for studying the protein composition of blood products. In addition, it provided a new means of testing for companies to monitor the flow of proteomic fractions and improve the purification yield and product quality. It laid the foundation for reducing the risk of clinical adverse reactions.

Genomic profiling of NGS-based ctDNA from Chinese non-small cell lung cancer patients.

PURPOSE: Cell-free circulating tumor DNA (ctDNA) in plasma enables rapid and repeat testing of actionable mutations. Next-generation sequencing (NGS) is an attractive platform for multiplex sequencing capabilities compared to traditional methods such as PCR. The purpose of this study is to evaluate the value of the NGS-based ctDNA assay and to identify the genomic alteration profile of ctDNA in real-world Chinese non-small cell lung (NSCLC) patients. METHODS: In total, 294 Chinese patients with pathological diagnosis of Phase III-IV NSCLC were enrolled. 3-4 mL peripheral blood was collected and NGS-based analysis was carried out using a 20-gene panel. The analytical sensitivity and specificity of ctDNA NGS-based assay was validated using droplet digital PCR (ddPCR). RESULTS: We have tested 570 sites from 286 samples using ddPCR, which included 108 positive sites and 462 negative sites from NGS results, and the concordance rate was 99.8% (418/419) for single-nucleotide variants (SNVs) and 96.7% (146/151) for insertions and deletions (InDels). The most frequent genes were TP53 (32%), EGFR (31.97%), KRAS (6.46%), PIK3CA (4.76%), and MET (4.08%). Exon 19 deletion (19del) was the most common alteration in EGFR and G12C was the most common alteration in KRAS. Furthermore, the detection rate of TP53 was higher in the male and patients with squamous cell carcinoma. We also found the prevalence of TP53 in L858R was higher than in 19del (61.29% vs. 40%; p = 0.1115). CONCLUSION: The results indicate that the results of NGS-based ctDNA assay are highly consistent with ddPCR. In Chinese NSCLC patients, TP53 mutation was more frequently associated with male and squamous cell carcinoma. The prevalence of concomitant mutations in L858R may be different from that in 19del.

Value of Methylation Status of RPRM, SDC2, and TCF4 Genes in Plasma for Gastric Adenocarcinoma Screening.

Objective: To explore the clinical value of the combined screening of the methylation statuses of the RPRM, SDC2, and TCF4 genes in plasma of gastric cancer patients. Methods: Differential expressed genes (DEGs) were selected from the Gene Expression Omnibus database, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using DAVID, and a protein-protein interaction network was constructed. Hub genes were obtained using Cytoscape. Screening results combined with literature reports identified three genes (RPRM, SDC2, and TCF4). Further analysis was done using biopsies collected through gastroscopy at Shanxi Cancer Hospital from January 8, 2020 to February 22, 2021. The patients were divided into two groups: gastric adenocarcinoma group, and control group which are not gastric adenocarcinoma according to pathological or gastroscopic results. The methylation statuses of the three genes in peripheral blood plasma were detected by fluorescence polymerase chain reaction, and the relationships between the positive rates of the three combined genes with pathology and/or gastroscopy results were analyzed. The clinical value of the combined detection of the three genes was evaluated according to these indicators. The diagnostic specificity and sensitivity of this detective method were analyzed. Results: A total of 197 DEGs were identified and 12 hub genes were obtained. The enriched functions and pathways of DEGs include regulation of cell proliferation, extracellular space, cytokine activity, and pathways in cancer. The combination of RPRM, SDC2, and TCF4 gene methylation had a specificity of 93.39% and sensitivity of 80.33%. The combined positive rate of RPRM, SDC2, and TCF4 gene methylation in patients with gastric adenocarcinoma was significantly higher compared with those without gastric adenocarcinoma (χ2=151.179, P<0.05). Conclusion: Combined detection of RPRM, SDC2, and TCF4 gene methylation in peripheral blood plasma maybe helpful in screening for gastric adenocarcinoma, and maybe a complementary method to gastroscopy and serum tumor markers.

Protective effect of total flavonoids of Engelhardia roxburghiana Wall. leaves against radiation-induced intestinal injury in mice and its mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Irradiation-induced intestinal injury (RIII) often occurs during radiotherapy in patients, which would result in abdominal pain, diarrhea, nausea, vomiting, and even death. Engelhardia roxburghiana Wall. leaves, a traditional Chinese herb, has unique anti-inflammatory, anti-tumor, antioxidant, and analgesic effects, is used to treat damp-heat diarrhea, hernia, and abdominal pain, and has the potential to protect against RIII. AIM OF THE STUDY: To explore the protective effects of the total flavonoids of Engelhardia roxburghiana Wall. leaves (TFERL) on RIII and provide some reference for the application of Engelhardia roxburghiana Wall. leaves in the field of radiation protection. MATERIALS AND METHODS: The effect of TFERL on the survival rate of mice was observed after a lethal radiation dose (7.2 Gy) by ionizing radiation (IR). To better observe the protective effects of the TFERL on RIII, a mice model of RIII induced by IR (13 Gy) was established. Small intestinal crypts, villi, intestinal stem cells (ISC) and the proliferation of ISC were observed by haematoxylin and eosin (H&E) and immunohistochemistry (IHC). Quantitative real-time PCR (qRT-PCR) was used to detect the expression of genes related to intestinal integrity. Superoxide dismutase (SOD), reduced glutathione (GSH), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the serum of mice were assessed. In vitro, cell models of RIII induced by IR (2, 4, 6, 8 Gy) were established. Normal human intestinal epithelial cells HIEC-6 cells were treated with TFERL/Vehicle, and the radiation protective effect of TFERL on HIEC-6 cells was detected by clone formation assay. DNA damage was detected by comet assay and immunofluorescence assay. Reactive oxygen species (ROS), cell cycle and apoptosis rate were detected by flow cytometry. Oxidative stress, apoptosis and ferroptosis-related proteins were detected by western blot. Finally, the colony formation assay was used to detect the effect of TFERL on the radiosensitivity of colorectal cancer cells. RESULTS: TFERL treatment can increase the survival rate and time of the mice after a lethal radiation dose. In the mice model of RIII induced by IR, TFERL alleviated RIII by reducing intestinal crypt/villi structural damage, increasing the number and proliferation of ISC, and maintaining the integrity of the intestinal epithelium after total abdominal irradiation. Moreover, TFERL promoted the proliferation of irradiated HIEC-6 cells, and reduced radiation-induced apoptosis and DNA damage. Mechanism studies have found that TFERL promotes the expression of NRF2 and its downstream antioxidant proteins, and silencing NRF2 resulted in the loss of radioprotection by TFERL, suggesting that TFERL exerts radiation protection by activating the NRF2 pathway. Surprisingly, TFERL reduced the number of clones of colon cancer cells after irradiation, suggesting that TFERL can increase the radiosensitivity of colon cancer cells. CONCLUSION: Our data showed that TFERL inhibited oxidative stress, reduced DNA damage, reduced apoptosis and ferroptosis, and improved IR-induced RIII. This study may offer a fresh approach to using Chinese herbs for radioprotection.

Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma model.

Chemoprevention of hepatocellular carcinoma (HCC) is highly desirable in clinic. Berberine (BBR) is reported to play potential roles in cancer treatment and prevention. We studied the chemopreventive effect of BBR on hepatocellular carcinogenesis in an inflammation-driven mouse model, as it was enriched in liver after oral administration. Oral BBR significantly decreased the number and volume of visible nodular tumors, and prolonged the median overall survival by 9 and 8 weeks in the diethylnitrosamine (DEN)-injected male and female mice respectively. The nodular tumors were induced through activation of the lysophosphatidic acid (LPA) pathway in liver. LPA stimulated the abnormal leptin transcription through interacting with LPA receptor-2 (LPAR2) followed by p38 activation, and BBR inhibited carcinogenesis by suppressing the bioactivity of LPA. Specifically, BBR significantly reduced the expression of the LPA synthetase autotaxin (ATX) and LPAR2 in the nodular tumors of DEN-injected mice. Subsequently, BBR repressed the abnormal transcription of leptin stimulated by LPA-induced phosphorylation of p38 in hepatoma cells. In fact, BBR reduced the abnormal expression of leptin in livers of DEN-injected male mice throughout the course of an 8-month experiment. BBR might be a preventive agent for HCC, working at least partially through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in liver.

Molecular mechanisms of isoflavone puerarin against cardiovascular diseases: What we know and where we go.

Puerarin (Pue), known as a phytoestrogen, has salient bioactivities and is promising against cardiovascular diseases. This article summarizes the underlying molecular mechanisms of Pue in treating cardiovascular diseases, especially regulating the intracellular signal transduction, influencing ion channels, modulating the expression of microRNA, and impacting on the autophagy, which are mainly involved in the inflammatory signaling pathways, fatty acid/lipid metabolism, oxidative stress, apoptosis, and the like. The protective effect of Pue against cardiovascular diseases mainly involves attenuating the myocardial injury and decreasing the myocardial fibrosis, improving the myocardial ischemia/reperfusion injury, as well as inhibiting the myocardial hypertrophy and atherosclerosis. The molecular mechanisms of Pue's cardiovascular protective effects for the first time and comment on the state-of-the-art research methods and principles of Pue's regulation of small molecules were reviewed, so as to provide the rationale for its basic research and clinical applications.

Discovery of Natural Ursane-type SENP1 Inhibitors and the Platinum Resistance Reversal Activity Against Human Ovarian Cancer Cells: A Structure-Activity Relationship Study.

Platinum-resistant ovarian cancer is one of the most common and refractory gynecologic cancers around the world. The SENP1/JAK2 (small ubiquitin-like modifier-specific protease 1/Janus activating kinase 2) axis activation has been proposed as a critical mechanism in platinum-resistant ovarian cancer, and as such, SENP1 inhibitors become a feasible alternative to reverse platinum resistance. In this work, 29 commercially available natural ursane-type aglycones were tested for their SENP1 inhibitory activities, among which 12 aglycones showed IC50 activity at the concentration below 5 µM. Pomolic acid and tormentic acid were identified as potent SENP1 inhibitors with the IC50 values of 5.1 and 4.3 µM, respectively. The structure-activity relationship (SAR) of ursane-type SENP1 inhibitors was evaluated. A molecular docking model of the SENP1-tormentic acid complex was obtained and applied to describe the SAR. Moreover, the combinations of cisplatin with pomolic acid (IC50 = 3.69 µM, combination index (CI) = 0.23) and tormentic acid (IC50 = 2.40 µM, CI = 0.30) exhibited potent platinum-resistant reversal activities to cisplatin only (IC50 = 28.23 µM) against the human ovarian cancer SKOV3 cells. The data suggested a potential for pomolic acid and tormentic acid to be promising compounds for in vivo studies of platinum-resistant ovarian cancer with SENP1 activation.

Ursolic Acid Derivative UA232 Promotes Tumor Cell Apoptosis by Inducing Endoplasmic Reticulum Stress and Lysosomal Dysfunction.

Due to increased drug and radiation tolerance, there is an urgent need to develop novel anticancer agents. In our previous study, we performed a series of structural modifications of ursolic acid (UA), a natural product of pentacyclic triterpenes, and found UA232, a derivative with stronger anti-tumor activity. In vitro experiments showed that UA232 inhibited proliferation, induced G0/G1 arrest, and promoted apoptosis in human breast cancer and cervical cancer cells. Mechanistic studies revealed that UA232 promoted apoptosis and induced protective autophagy via the protein kinase R-like endoplasmic reticulum kinase/activating transcription factor 4/C/EBP homologous protein-mediated endoplasmic reticulum stress. In addition, we also found that UA232 induced lysosomal biogenesis, increased lysosomal membrane permeability, promoted lysosomal protease release, and led to lysosome-dependent cell death. Furthermore, UA232 suppressed tumor growth in a mouse xenograft model. In conclusion, our study revealed that UA232 exerts multiple pharmacological effects against breast and cervical cancers by simultaneously triggering endoplasmic reticulum stress and lysosomal dysfunction. Thus, UA232 may be a promising drug candidate for cancer treatment.

Iron promotes Slc7a11-deficient valvular interstitial cell osteogenic differentiation: A possible mechanism by which ferroptosis participates in intraleaflet hemorrhage-induced calcification.

Calcific aortic valve disease (CAVD) is the most frequent pathogeny of aortic valve replacement in developed countries. Iron deposits are found in the intraleaflet hemorrhage (IH) areas of calcific aortic valves. Ferroptosis is a form of regulated cell death that involves metabolic dysfunction resulting from iron overload-dependent excessive lipid peroxidation. In this study, histological analysis showed that ferroptosis occurs in the IH areas of calcific aortic valves. We also demonstrated that Slc7a11 is expressed at low levels in OM-treated valvular interstitial cells (VICs) and IH areas and that low Slc7a11 expression is associated with calcification in CAVD. However, iron overload treatment did not promote VIC calcification under osteogenic conditions in vitro. Using lentiviral transfection to knockdown Slc7a11 in VICs, we found that the degree of iron overload-induced ferroptosis was positively increased in vitro. Finally, we also found that Slc7a11 knockdown promoted the osteogenic differentiation of VICs in vitro. In summary, this study reports a novel mechanism linking ferroptosis and CAVD development in which iron may promote Slc7a11-deficient VIC osteogenic differentiation by aggravating ferroptosis in vitro, thereby accelerating the progression of aortic valve calcification.

Discovery and radiosensitization research of ursolic acid derivatives as SENP1 inhibitors.

SUMOylation and deSUMOylation plays an important role in DNA damage response and the formation of radiotherapy resistance. SENP1 is the main specific isopeptidase to catalyze deSUMOylation modification. Inhibiting SENP1 upregulates cancer cell radiosensitivity and it becomes a promising target for radiosensitization. Herein, based on the structure of ursolic acid (UA), a total of 53 pentacyclic triterpene derivatives were designed and synthesized as SENP1 inhibitors. Ten derivatives exhibited better SENP1 inhibitory activities than UA and the preliminary structure-activity relationship was discussed. Most of the UA derivatives were low-cytotoxic, among which compound 36 showed the best radiosensitizing activity with the SER value of 1.45. It was the first study to develop small molecular SENP1 inhibitors as radiosensitizers.

Two cases report of secretory carcinoma of the salivary gland in the lung: one primary and one metastatic after many years.

Background: Secretory carcinoma of the salivary gland (SCSG) is a recently discovered salivary gland tumor that occurs mostly in the major salivary glands and occasionally in the skin, cervix, trachea, etc. Secretory carcinoma of the lung is extremely rare. To our knowledge, this is the third report of SCSG arising as a primary pulmonary tumor. The two SCSG cases reported in this paper are unique in that one was primary and the other was metastasized to the lung. Case Description: Case 1 is a primary endobronchial tumor in a 66-year-old man. He went to the doctor complaining of fever, cough and yellow phlegm, and his body weight was significantly reduced by 3 kg. The bronchoscope showed the growth of new organisms in the right upper lobe of the lung. Immunohistochemistry of his biopsy specimen was positive for AE1/AE3, Keratin7 (CK7), S-100, mammaglobin, and pan-TRK, but negative for thyroid transcription factor-1 (TTF-1), napsin-A, synaptophysin (SYN), chromogranin A (CGA), and discovered on GIST-1 (Dog-1), and the MKI-67 (Ki-67) proliferation index was 2%. This case lacked the typical ETV-6 gene rearrangement. After one cycle of chemotherapy, the tumor was significantly reduced, and surgical excision was planned. Case 2 was a metastatic secretory carcinoma with a history of parotid pleomorphic adenoma resection 30 years ago and malignant pleomorphic adenoma resection 16 years ago before the study, respectively. He presented with a complaint of a parotid gland mass. Chest CT examination revealed a mass in the upper lobe of the left lung. The biopsy tissue of him exhibited a typical histological appearance under the microscope. Immunohistochemistry was positive for AE1/AE3, CK7, S-100, and mammaglobin; partially positive for estrogen receptor (ER) and pan-TRK; and negative for TTF-1, Napsin-A, SYN, CGA, P63, P40, and Dog-1. The Ki-67 proliferation index was approximately 3%. Fluorescence in situ hybridization (FISH) revealed ETV-6 gene rearrangement. After the diagnosis of SCSG, the patient underwent resection of the lung mass, and there was no recurrence of the lung after 1 month's follow-up. Conclusions: By examining these two cases, we have a better understanding of the clinicopathological features of secretory carcinoma, which will help to improve the accuracy of pathological diagnosis.

Blastic plasmacytoid dendritic cell neoplasm with skin and bone marrow involvement: Report of three cases.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematopoietic malignancy. BPDCN is difficult to diagnose because of the overlap in morphologic and immunophenotypic features with various cutaneous lymphatic hematopoietic tumors. CASE SUMMARY: We report on three BPDCN cases, all characterized by skin nodules and examined by histology, immunohistochemical detection, in situ hybridization for Epstein-Barr virus, and follow-up. We also review the relevant literature. All patients were positive for CD56 and negative for Epstein-Barr encoded small RNA. Two patients had bone marrow involvement. Chemotherapy is the main treatment for BPDCN, but case 1 showed bone marrow suppression and case 2 developed recurrence after chemotherapy. Case 1 survived for 7 mo, case 2 for 17 mo, and case 3 for 9 mo. CONCLUSION: An accurate pathological diagnosis is a precondition for treatment, and the diagnosis of BPDCN should be based on a combination of clinical symptoms, pathological characteristics, immunophenotype, and other auxiliary examinations. It is necessary to clarify the clinicopathological features and biological behavior of BPDCN to improve its understanding by both clinicians and pathologists. Case 2 survived significantly longer than the other two cases, suggesting that the treatment received by case 2 was more effective.

Phosphate group functionalized magnetic metal-organic framework nanocomposite for highly efficient removal of U(VI) from aqueous solution.

The phosphate group functionalized metal-organic frameworks (MOFs) as the adsorbent for removal of U(VI) from aqueous solution still suffer from low adsorption efficiency, due to the low grafting rate of groups into the skeleton structure. Herein, a novel phosphate group functionalized metal-organic framework nanoparticles (denoted as Fe3O4@SiO2@UiO-66-TPP NPs) designed and prepared by the chelation between Zr and phytic acid, showing fast adsorption rate and outstanding selectivity in aqueous media including 10 coexisting ions. The Fe3O4@SiO2@UiO-66-TPP was properly characterized by TEM, FT-IR, BET, VSM and Zeta potential measurement. The removal performance of Fe3O4@SiO2@UiO-66-TPP for U(VI) was investigated systematically using batch experiments under different conditions, including solution pH, incubation time, temperature and initial U(VI) concentration. The adsorption kinetics, isotherm, selectivity studies revealed that Fe3O4@SiO2@UiO-66-TPP NPs possess fast adsorption rates (approximately 15 min to reach equilibrium), high adsorption capacities (307.8 mg/g) and outstanding selectivity (Su = 94.4%) towards U(VI), which in terms of performance are much better than most of the other magnetic adsorbents. Furthermore, the adsorbent could be reused for U(VI) removal without obvious loss of adsorption capacity after five consecutive cycles. The research work provides a novel strategy to assemble phosphate group-functionalized MOFs.