Identification and exploration of the pyroptosis-related molecular subtypes of breast cancer by bioinformatics and machine learning.

OBJECTIVES: To classify breast cancer (BRCA) according to the expression of pyroptosis-related genes and explore their molecular characteristics. METHODS: Nonnegative matrix factorization (NMF) was used for subtype classification based on 21 pyroptosis-related genes in the TCGA database. Survival analysis and t-distributed stochastic neighbor embedding (t-SNE) analysis were conducted to assess the NMF results' performance. XGBoost, CatBoost, logistic regression, neural network, random forest, and support vector machine were utilized to perform supervised machine learning and construct prediction models. Genetic mutations, tumor mutational burden, immune infiltration, methylation, and drug sensitivity were analyzed to explore the molecular signatures of different subtypes. Lasso, RF, and Cox regression were operated to construct a prognostic model based on differentially expressed genes. RESULTS: BRCA patients were divided into two subtypes (named Cluster1 and Cluster2). Survival analysis (P = 0.02) and t-SNE analysis demonstrated that Cluster1 and Cluster2 were well classified. The XGBoost model achieved reliable predictions on both training and validation sets. Regarding molecular characteristics, Cluster1 had higher TMB, immune cell infiltration, and m6A methylation-related gene expression than Cluster2. There was also a statistically significant difference between the two subtypes concerning drug susceptibility. Finally, a 5-gene prognostic model was constructed using Lasso, RF, and Cox regression and validated in the GEO database. CONCLUSION: Our study may provide new insights from bioinformatics and machine learning for exploring pyroptosis-related subtypes and their respective molecular signatures in BRCA. In addition, our models may be helpful for the treatment and prognosis of BRCA.

Astaxanthin inhibiting oxidative stress damage of placental trophoblast cells in vitro.

Oxidative stress from the trophoblasts is one of the possible pathological mechanisms of Preeclampsia (PE). This study aimed at exploring the potential effects of astaxanthin (ATX) on oxidative stress damaged placental trophoblast cell line HTR-8/SVneo. Oxidative stress-induced damaged through H2O2 treatment was checked by MTS CellTiter 96® cell viability, 2',7'-dichlorofluorescein diacetate (DCFH-DA) induced fluorescence, the level of the intracellular malondialdehyde (MDA), and the detection of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT). Different concentrations of ATX were applied, and then the proliferation rate, apoptotic percentage, cell cycle distribution, invasion test and relative biological function of the rescued cells were followed. We provide evidence that ATX had an anti-oxidative effect against oxidative stress induced by H2O2 on the trophoblast cell line and had beneficial role in promoting cell proliferation, inhibiting cell apoptosis, and inducing cell invasion.Abbreviations: UV: ultraviolet; DCFH-DA: 2',7'-dichlorofluorescein diacetate; EVT: extravillous trophoblast; MMPs: matrix metalloproteinases; IUGR: intrauterine growth restriction.

[Effect of TGF-ß3 transfected with adipose derived stem cells and OGP-HA-chondroitin sulfate scaffold on repair of condylar cartilage in rabbits].

PURPOSE: To investigate the feasibility of repairing damaged cartilage of rabbit condylar with TGF-ß3-transfected adipose stem cells combined with OGP (osteogenesis peptide)-HA (hyaluronic acid)-ChS (chondroitin sulfate) scaffold. METHODS: Rabbit ADSCs were isolated and cultured. The expression vector carrying TGF-ß3 gene was constructed using recombinant adenovirus and transfected into rabbit ADSCs. The fluorescence expression of the cells was observed after 14 days and the efficiency of virus transfection was calculated. Western blot was used to detect the expression of TGF-ß3 protein. Fifty rabbits were randomly divided into 5 groups: group A as blank group, group B as TGF-ß3 transfected ADSCs group, group C as OGP-HA-ChS scaffold group, group D as ADSCs complex OGP-HA-ChS group, E group was TGF-ß3 transfected ADSCs with OGP-HA-ChS. After the rabbit temporomandibular joint osteoarthrosis model was established, the animals were transplanted according to the experimental design. The animals in each group were sacrificed after the 3rd and 9th weeks of transplantation. Scanning electron microscopy, histological observation and real-time fluorescent quantitative PCR were performed accordingly. SPSS17.0 software package was used for analysis of variance and t test. RESULTS: Scanning electron microscopy and histological observation showed that the repair of cartilage lesions in group D and E was better than those in group B and C. Compared with group B, the results of real-time quantitative PCR showed that the expression of MMP-3 in group E was similar to that in group A, but significantly lower than that in group C and D (P<0.05). The expression of TIMP-1 in group E was similar to that of group A, but significantly higher than group C and D (P<0.05). CONCLUSIONS: TGF-ß3 transfected ADSCs composite OGP-HA-ChS scaffold has repairing effect on rabbit condylar damaged cartilage.

Primary mucinous adenocarcinoma of the lung: A case report and review of the literature.

Mucinous adenocarcinoma is an unusual histological type of lung cancer, and its clinicopathological feature is distinctive from that of other histopathological types of lung adenocarcinoma. Mucinous adenocarcinoma has a mucus-producing function, which explains its name. The present study reports a rare case of a mucus-producing adenocarcinoma of the lung. A 60-year-old Chinese female patient was diagnosed with mucinous adenocarcinoma of the lung, which manifested as respiratory symptoms, including fever, cough and expectoration. The patient received thoracic exploratory operation and right pneumonectomy, since the above respiratory symptoms seriously affected her daily life, and other inspections could not establish the diagnosis. Histopathology revealed no mutations in epidermal growth factor receptor. The patient received adjuvant chemotherapy using taxol and cisplatin. However, metastases in the left lung were detected 7 months after the operation. Pemetrexed and cisplatin were used as the second-line treatment. The patient survived 3 years after the initial diagnosis. The present study reports a rare mucus-producing adenocarcinoma of the lung, which is of bad prognosis. Therefore, further studies on this type of cancer are urgently required.

[Application of multispectral animal living imaging technology in evaluating osteoarthritis model].

OBJECTIVE: To observe application value of multispectral animal living imaging technology in rats model of osteoarthritis. METHODS: Fifteen male SD rats weighed (180 +/- 20) g (3 months old) were received intra-articular injection of iodoacetic acid for establishing osteoarthritis. Articular cavity of left knee of rats were injected into 50 microl iodoacetic acid. The same volume of sterile saline was injected into right knee articular cavity as control. X-ray living imaging and bone mineral density were observed at 2 and 4 weeks after establishment of model. After 4 weeks,rats were sacrificed and their bilateral joints were collected and determined histologically based on Collins classification and Kellgren-Lawrence classification. RESULTS: Osteoarthritis model was successfully established, compared with control group, model group showed typical manifestation of osteoarthritis, including irregular cartilage surface,osteophyte formation,joint deformity and cartilage defect,and combined with significant decrease of bone density (P < 0.01), while the decrease was not obvious in proximal tibia (P < 0.05). After 2 weeks, knee joints in model group was classified as Collins grade 1 and Kellgren-Lawrence grade 2,then classified as Collins grade 4 and Kellgren-Lawrence grade 3 after 4 weeks,control group showed smooth articular surface,normal joint space and intact cartilage surface, knee joints was classified as Collins and Kellgren-Lawrence grade 0, and bone density of distal femur and proximal tibia were normal. CONCLUSION: Multispectral animal living imaging technology could be used in dynamic observation of living imaging and detection of bone density in the animal model of osteoarthritis, and it is significant for evaluation of osteoarthritis model, and its realted tesearch.

[Expression and clinical significance of Cox-2 and XIAP in malignant tumors of the salivary gland].

PURPOSE: To detect the expression of Cox-2 and XIAP in adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC) of salivary glands. To study the role and correlation between the expression of Cox-2 and XIAP in malignant tumors of salivary gland. METHODS: Immunohistochemical SP staining method was used to quantify the protein expression levels of Cox-2 and XIAP in 95 patients with malignant tumors of the salivary gland (50 ACCs,45 MECs),10 patients with pleomorphic adenoma and 10 persons with normal salivary gland tissues. SPSS17.0 software package was used to analyze the data. RESULTS: Cox-2 and XIAP were expressed strongly in malignant tumors of the salivary gland, while they not expressed in pleomorphic adenoma and normal salivary gland tissues. The expression of Cox-2 and XIAP in malignant tumors of salivary gland was correlated with clinical stage and lymphnode metastasis, while they not correlated with primary sites (P>0.05). CONCLUSIONS: The high expression of Cox-2 and XIAP in malignant tumors of salivary gland may play an important role in the development of malignant tumors of the salivary gland.

[The isolation and identification of bone marrow mesenchymal stem cells derived from rabbit mandible].

PURPOSE: To investigate the methods of isolation, culture and identification of BMMSCs derived from rabbit mandible. METHODS: BMMSCs were collected from rabbit mandible and isolated by density gradient centrifugation. Cells were adherently cultured in vitro, and P2 or P3 BMMSCs populations were collected and examined. Cell growth was observed by inverted microscopy; the propagation of BMMSCs were tested by MTT and a growth curve was drawn after statistical analysis; colony-forming unit-fibroblast(CFU-F) was detected by examination of colony formation; the potential of multi-directional differentiation into osteoblasts, adipocytes and skeletal muscle cells was estimated by pertinent methods; the surface marks of BMMSCs were detected by flow cytometry, the data was analysed using SPSS16.0 software package. RESULTS: The majority of adherent cells were long fusiform, and few were small triangle; the growth curve of BMMSCs showed that every passage experienced incubation period, log phase and platform period; the rate of colony formation was 37%. Growth of BMMSCs represented the appearance of CFU-F; BMMSCs after inducted differentiation showed osteogenic and adipogenic potential. The staining of mineralized nodules was positive by alizarin red S and the positive staining of oil red O appeared in lipid drops around cell nucleus. The staining of skeletal muscle cells was positive by desmin immunofluorescence; the cell surface marks assessed with flow cytometry indicated that these BMMSCs expressed CD90 and CD146 in high percentage (about 98.7% and 98.1%, respectively). CONCLUSIONS: The highly uniformed BMMSCs derived from rabbit mandible can be collected. These BMMSCs have the ability of self-replication and propagation, as well as potential of multi-directional differentiation in vitro.

Digestive tract hemorrhage due to complications with gastrointestinal stromal tumor treated with sunitinib: A case report.

Gastrointestinal stromal tumors (GISTs) are rare, and account for 1% of all gastrointestinal neoplasms. GISTs are the most frequent mesenchymal tumors of the gastrointestinal tract. However, the clinical and pathological characteristics of these neoplasms are not adequately understood. The best treatment approach for GISTs remains unclear. In the present study, we report a case of a GIST originating from the stomach. A digestive tract hemorrhage occurred as a complication of sunitinib treatment. This is the first report of a digestive tract hemorrhage due to sunitinib treatment.

[Effects of Xinjierkang on two kidney one clip-induced hypertension and target organ injury in rats].

OBJECTIVE: To investigate the effects of Xinjierkang on two kidney one clip -induced hypertension and target organ injury in rats. METHODS: Two kidney one clip-induced hypertension rats model was established. Rats were divided into control group, model group, Xinjierkang group, and fosinopril group. At the end of 8th w, the hemodynamics indexes were recorded. The cardiac hypertrophy index was expressed as heart weight/body weight (HW/BW), the histological changes of heart, aorta and kidney were investigated by HE and/or Van Gieson stain. RESULTS: Compared with control group, the heart systolic and diastolic function were impaired, the heart weight index, cardiomyocytes cross section area (CSA), cardiac collagen deposition, vascular remodeling index and glomerulus area were increased markedly in model group rats. Administration of Xinjierkang and fosinopril markedly ameliorated hemodynamic indexes, inhibited the elevation of HW/BW ratio, CSA of cardiomyocytes, vascular remodeling index and glomerulus hypertrophy, decreased collagen deposition in heart. CONCLUSION: Xinjierkang has protective effects against two kidney one clip-induced hemodynamic impairment, cardiovascular remodeling and glomerulus hypertrophy in rats.

[Effects of a compound Chinese medicine Xinji' erkang on isoproterenol-induced ventricular remodeling in mice].

OBJECTIVE: To investigate the effects of Xinji' erkang (XJEK), a compound Chinese herbal medicine, on isoproterenol-induced ventricular remodeling in mice. METHODS: Isoproterenol was given subcutaneously (1 mg/kg, twice per day for 7 d) to induce ventricular remodeling in mice. Mice were divided into normal control group, model group, XJEK low-, medium- and high- dose groups, XJEK water layer group, XJEK n-butanol layer group and metoprolol group. All drugs were given by intragastric administration. At the end of the 7th day, the hearts of the rats were weighted, and myocardial hypertrophy index was expressed as heart weight/body weight (HW/BW). The histological changes were observed by hemotoxylin-eosin and Van Gieson staining. Colorimetric method was used to determine the content of hydroxyproline in heart, and the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in serum. RESULTS: Compared with the isoproterenol injection only, XJEK potently inhibited cardiomyocyte hypertrophy and the increase of hydroxyproline content in heart (P<0.01), improved cardiac pathology change, inhibited the decrease of SOD activity and the increase of MDA content in serum (P<0.01). XJEK water layer also inhibited the increase of cardiomyocyte hypertrophy (P<0.01) while XJEK n-butanol layer inhibited cardiomyocyte hypertrophy and fibrosis (P<0.01). CONCLUSION: XJEK possesses protective effects against isoproterenol-induced ventricular remodeling in mice, which may be related to its actions in reducing the oxidative stress and improving the antioxidant activity of the body. XJEK water layer and XJEK n-butanol layer attenuated ventricular remodeling without significant oxidative stress state changing, which indicates that a non-antioxidative stress mechanism may exist.

Proteomic analysis of dimethoate-responsive proteins in the oyster (Saccostrea cucullata) gonad.

INTRODUCTION: The organophosphorus pesticide dimethoate (DM) has been widely used in agriculture, and its extensive use could still have left many environmental problems. METHODS: In the present study, the oyster (Saccostrea cucullata) was subjected to acute DM toxicity (2 mg/L), and gas chromatographic analysis revealed and quantified residues of DM in the oyster gonad. RESULTS: Two-dimensional gel electrophoresis showed 12 differentially expressed proteins in the DM-exposed oyster gonad in comparison to the control. Among these 12 protein spots, nine were down-regulated, and three were up-regulated. Both matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry and database searching were utilized to identify these differential proteins, and revealed five proteins previously described as being related to DM toxicity. In addition, the levels of mRNA expression corresponding to these differential proteins were further proved in part by real-time PCR. The functions of these proteins were summarized as: carrying out energy metabolism, DNA repair, DNA transcriptional regulation, and oxidative protection. The remaining seven protein spots were of particular interest in terms of their responses to DM, which have seldom been reported. CONCLUSION: These data might point to a number of novel and significant biomarkers for evaluating the contamination levels of DM and provide useful insight into the mechanisms of DM toxicity in vivo.

Estimation of respiration rate from three-dimensional acceleration data based on body sensor network.

Respiratory monitoring is widely used in clinical and healthcare practice to detect abnormal cardiopulmonary function during ordinary and routine activities. There are several approaches to estimate respiratory rate, including accelerometer(s) worn on the torso that are capable of sensing the inclination changes due to breathing. In this article, we present an adaptive band-pass filtering method combined with principal component analysis to derive the respiratory rate from three-dimensional acceleration data, using a body sensor network platform previously developed by us. In situ experiments with 12 subjects indicated that our method was capable of offering dynamic respiration rate estimation during various body activities such as sitting, walking, running, and sleeping. The experimental studies also suggested that our frequency spectrum-based method was more robust, resilient to motion artifact, and therefore outperformed those algorithms primarily based on spatial acceleration information.

Differential protein expression of kidney tissue in the scallop Patinopecten yessoensis under acute cadmium stress.

Morphological and proteomic changes in the kidney of scallops exposed to acute cadmium chloride (CdCl2) were observed, analyzed and compared with those in the non-exposed control group. Under microscopy the paraffin-embedded sections of the kidney revealed that the microstructure of the tissue had been severely deformed after Cd exposure. Two dimensional electrophoresis, MALDI-TOF mass spectrometry and database searches showed 13 differentially expressed protein spots, of which 11 were up-regulated, while two were down-regulated. Among these proteins, guanylate kinase (GK) and C2H2-type zinc finger protein are considered to be tightly connected with Cd toxicity. Further studies using quantitative PCR method validated that the GK mRNA was induced under Cd stress. Other proteins identified which had some relevance to Cd toxicity are also discussed. We suggested that differential proteins such as GK could play a potential role as novel biomarkers for monitoring the level of Cd contamination in seawater.

A wearable respiratory biofeedback system based on body sensor networks.

Technology advantages of body sensor networks (BSN) have shown great deal of promises in medical applications. In this paper we introduced a wearable device for biofeedback application based on the BSN platform we had developed. The biofeedback device we have developed includes the heart rate monitoring belt with conductive fabric and the biofeedback device with respiration belt. A wearable respiratory biofeedback system was preliminarily explored based on the BSN platform. In-situ experiments showed that the BSN platform and the biofeedback device worked as intended.