Cancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression and are known to mediate endocrine and chemotherapy resistance through paracrine signaling. Additionally, they directly ...influence the expression and growth dependence of ER in Luminal breast cancer (LBC). This study aims to investigate stromal CAF-related factors and develop a CAF-related classifier to predict the prognosis and therapeutic outcomes in LBC.
The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to obtain mRNA expression and clinical information from 694 and 101 LBC samples, respectively. CAF infiltrations were determined by estimating the proportion of immune and cancer cells (EPIC) method, while stromal scores were calculated using the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm. Weighted gene co-expression network analysis (WGCNA) was used to identify stromal CAF-related genes. A CAF risk signature was developed through univariate and least absolute shrinkage and selection operator method (LASSO) Cox regression model. The Spearman test was used to evaluate the correlation between CAF risk score, CAF markers, and CAF infiltrations estimated through EPIC, xCell, microenvironment cell populations-counter (MCP-counter), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms. The TIDE algorithm was further utilized to assess the response to immunotherapy. Additionally, Gene set enrichment analysis (GSEA) was applied to elucidate the molecular mechanisms underlying the findings.
We constructed a 5-gene prognostic model consisting of RIN2, THBS1, IL1R1, RAB31, and COL11A1 for CAF. Using the median CAF risk score as the cutoff, we classified LBC patients into high- and low-CAF-risk groups and found that those in the high-risk group had a significantly worse prognosis. Spearman correlation analyses demonstrated a strong positive correlation between the CAF risk score and stromal and CAF infiltrations, with the five model genes showing positive correlations with CAF markers. In addition, the TIDE analysis revealed that high-CAF-risk patients were less likely to respond to immunotherapy. Gene set enrichment analysis (GSEA) identified significant enrichment of ECM receptor interaction, regulation of actin cytoskeleton, epithelial-mesenchymal transition (EMT), and TGF-β signaling pathway gene sets in the high-CAF-risk group patients.
The five-gene prognostic CAF signature presented in this study was not only reliable for predicting prognosis in LBC patients, but it was also effective in estimating clinical immunotherapy response. These findings have significant clinical implications, as the signature may guide tailored anti-CAF therapy in combination with immunotherapy for LBC patients.
Roles of exosomes-derived lncRNAs in preeclampsia Gong, Rong-quan; Nuh, Abdifatah Mohamed; Cao, Heng-shan ...
European journal of obstetrics & gynecology and reproductive biology,
August 2021, 2021-08-00, 20210801, Letnik:
263
Journal Article
Recenzirano
Preeclampsia is a pregnancy-specific hypertensive syndrome, which seriously threatens the safety of mother and infant. However, there is still no accurate biomarkers for the diagnosis of ...preeclampsia, and its etiology and pathogenesis have not been fully elucidated. Exosomes are extracellular vesicles widely existing in body fluids, which carry a variety of bioactive molecules such as proteins, lipids and nucleic acids with various biological functions. The lncRNAs carried by exosomes are characterized by specificity, plurality, anti-degradation and stable detection. Multiple differentially expressed lncRNAs were found in exosomes secreted by placental tissues of patients with preeclampsia, suggesting that they may be involved in the occurrence and development of preeclampsia. In this paper, we summarized the structures and functions of exosomes-derived lncRNAs and their relationships with preeclampsia in order to provide new ideas for the pathogenesis, early prediction, diagnosis and treatment of preeclampsia.
Hoplobatrachus rugulosus (Anura: Dicroglossidae) is distributed in China and Thailand and the former can survive substantially lower temperatures than the latter. The mitochondrial genomes of the two ...subspecies also differ: Chinese tiger frogs (CT frogs) display two identical ND5 genes whereas Thai tiger frogs (TT frogs) have two different ND5 genes. Metabolism of ectotherms is very sensitive to temperature change and different organs have different demands on energy metabolism at low temperatures. Therefore, we conducted studies to understand: (1) the differences in mitochondrial gene expression of tiger frogs from China (CT frogs) versus Thailand (TT frogs); (2) the differences in mitochondrial gene expression of tiger frogs (CT and TT frogs) under short term 24 h hypothermia exposure at 25 °C and 8 °C; (3) the differences in mitochondrial gene expression in three organs (brain, liver and kidney) of CT and TT frogs.
Utilizing RT-qPCR and comparing control groups at 25 °C with low temperature groups at 8 °C, we came to the following results. (1) At the same temperature, mitochondrial gene expression was significantly different in two subspecies. The transcript levels of two identical ND5 of CT frogs were observed to decrease significantly at low temperatures (P < 0.05) whereas the two different copies of ND5 in TT frogs were not. (2) Under low temperature stress, most of the genes in the brain, liver and kidney were down-regulated (except for COI and ATP6 measured in brain and COI measured in liver of CT frogs). (3) For both CT and TT frogs, the changes in overall pattern of mitochondrial gene expression in different organs under low temperature and normal temperature was brain > liver > kidney.
We mainly drew the following conclusions: (1) The differences in the structure and expression of the ND5 gene between CT and TT frogs could result in the different tolerances to low temperature stress. (2) At low temperatures, the transcript levels of most of mitochondrial protein-encoding genes were down-regulated, which could have a significant effect in reducing metabolic rate and supporting long term survival at low temperatures. (3) The expression pattern of mitochondrial genes in different organs was related to mitochondrial activity and mtDNA replication in different organs.
Plasma D(-)-lactate and diamine oxidase (DAO) can reflect patients' intestinal mucosal condition. We evaluated the changes of plasma D(-)-lactate, DAO and endotoxin activities and their significance ...in patients with liver cirrhosis.
Fifty liver cirrhosis patients were enrolled into experimental group and 30 healthy people into control group. The plasma levels of D(-)-lactate, DAO and endotoxin were detected spectrophotographically.
The level of D(-)-lactate was significantly higher in the experimental group than that in the control group (P<0.01). Significant differences of D(-)-lactate levels were observed in Child-Pugh subgroups of the experimental group (P<0.01). The level of DAO was significantly higher in the experimental group than that in the control group (P<0.01), but the level of DAO in Child-Pugh subgroup C was significantly lower than that in Child-Pugh subgroup B (P<0.01). The level of endotoxin was significantly increased in the experimental group except Child-Pugh subgroup A (P<0.01). The plasma levels of D(-)-lactate, DAO and endotoxin were positively correlated with each other (P<0.01).
The data suggest that both plasma D(-)-lactate and DAO activity are sensitive markers for early diagnosis of gut failure and endotoxemia in patients with liver cirrhosis. The impairment of intestinal barrier function may be one of the critical reasons for deterioration of liver cirrhosis.
AIM：The transforming growth factor-beta (TGF-β)/Smad signaling pathway system plays a prominent role in the control of cell growth and extracellular matrix formation in the progression of liver ...fibrogenesis. Smad proteins can either positively or negatively regulate TGF-β responses. In this study, the therapeutic effects of Chinese traditional compound decoction, JinSanE, and the changes of TGF-β/Smad signaling pathway system in carbon tetrachloride (CCl4)-induced rat experimental liver fibrosis were examined.METHODS: Seventy-two healthy Wistar rats were assigned to groups including normal control group, CCl4 model group, JinSanE treatment group Ⅰ and JinSanE treatment group Ⅱ. Each group contained 18 rats. All groups, except the normal control group, received CCl4 subcutaneous injection for 8 wk. Rats in JinSanE groups Ⅰ and Ⅱ were orally treated with JinSanE daily at the 1^st and 5^th wk, respectively, after exposure to CCl4. The expression of TGF-β1 and TGF-β1 type Ⅱ receptor (TRⅡ) mRNA in the liver was determined by reverse transcription polymerase chain reaction, and the expression of TGF-β1, Smad3 and Smad7 by immunohistochemistry. The liver histopathology was also examined by HE staining and observed under electron microscope. The activities of several serum fibrosis-associated enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), the levels of serum hyaluronic acid (HA) were assayed.RESULTS: Hepatic fibrosis caused by CCl4 was significantly inhibited in the JinSanE-treated groups. The degrees of necrosis/degeneration and fibrosis scores were significantly lower in the JinSanE-treated groups than in the model control group. The expression of TGF-β1, TRⅡ and Smad3 was significantly higher in the model group than that in the 3inSanE-treated groups, and the active/total TGF-β1 ratio in the JinSanE groups was suppressed. Expression of TRⅡ mRNA and Smad3 proteins showed a distribution pattern similar to that of TGF-β1 with a direct correlation in terms of the degree of hepatic fibrosis. The amount of positive staining Smad7 cells was significantly less in the model group than in the JinSanE-treated groups and the normal group. The contents of ALT, AST and HA were significantly lower in the JinSanE-treated groups than those in the model group.CONCLUSION: Traditional Chinese medicine, JinSanE, prevents the progression of hepatic damage and fibrosis through the inhibition of TGF-β1, TRⅡ and Smad3 signal proteins, and increases expression of Smad7 signal protein in vivo.
The transforming growth factor-beta (TGF-beta)/Smad signaling pathway system plays a prominent role in the control of cell growth and extracellular matrix formation in the progression of liver ...fibrogenesis. Smad proteins can either positively or negatively regulate TGF-beta responses. In this study, the therapeutic effects of Chinese traditional compound decoction, JinSanE, and the changes of TGF-beta/Smad signaling pathway system in carbon tetrachloride (CCl(4))-induced rat experimental liver fibrosis were examined.
Seventy-two healthy Wistar rats were assigned to groups including normal control group, CCl(4) model group, JinSanE treatment group I and JinSanE treatment group II. Each group contained 18 rats. All groups, except the normal control group, received CCl(4) subcutaneous injection for 8 wk. Rats in JinSanE groups I and II were orally treated with JinSanE daily at the 1(st) and 5(th) wk, respectively, after exposure to CCl(4). The expression of TGF-beta1 and TGF-beta1 type II receptor (TRII) mRNA in the liver was determined by reverse transcription polymerase chain reaction, and the expression of TGF-beta1, Smad3 and Smad7 by immunohistochemistry. The liver histopathology was also examined by HE staining and observed under electron microscope. The activities of several serum fibrosis-associated enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), the levels of serum hyaluronic acid (HA) were assayed.
Hepatic fibrosis caused by CCl(4) was significantly inhibited in the JinSanE-treated groups. The degrees of necrosis/degeneration and fibrosis scores were significantly lower in the JinSanE-treated groups than in the model control group. The expression of TGF-beta1, TRII and Smad3 was significantly higher in the model group than that in the JinSanE-treated groups, and the active/total TGF-beta1 ratio in the JinSanE groups was suppressed. Expression of TRII mRNA and Smad3 proteins showed a distribution pattern similar to that of TGF-beta1 with a direct correlation in terms of the degree of hepatic fibrosis. The amount of positive staining Smad7 cells was significantly less in the model group than in the JinSanE-treated groups and the normal group. The contents of ALT, AST and HA were significantly lower in the JinSanE-treated groups than those in the model group.
Traditional Chinese medicine, JinSanE, prevents the progression of hepatic damage and fibrosis through the inhibition of TGF-beta1, TRII and Smad3 signal proteins, and increases expression of Smad7 signal protein in vivo.
R5; AIM: The transforming growth factor-beta (TGF-β)/Smad signaling pathway system plays a prominent role in the control of cell growth and extracellular matrix formation in the progression of liver ...fibrogenesis. Smad proteins can either positively or negatively regulate TGF-β responses.In this study, the therapeutic effects of Chinese traditional compound decoction, JinSanE, and the changes of TGF-β/Smad signaling pathway system in carbon tetrachloride (CCl4)-induced rat experimental liver fibrosis were examined.METHODS: Seventy-two healthy Wistar rats were assigned to groups including normal control group, CCl4model group, JinSanE treatment group Ⅰ and JinSanE treatment group Ⅱ. Each group contained 18 rats. All groups, except the normal control group, received CCl4subcutaneous injection for 8 wk. Rats in JinSanE groups Ⅰand Ⅱ were orally treated with JinSanE daily at the 1st and 5th wk, respectively, after exposure to CCl4. The expression of TGF-β1 and TGF-β1 type Ⅱ receptor (TRⅡ) mRNA in the liver was determined by reverse transcription polymerase chain reaction, and the expression of TGF-β1,Smad3 and Smad7 by immunohistochemistry. The liver histopathology was also examined by HE staining and observed under electron microscope. The activities of several serum fibrosis-associated enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), the levels of serum hyaluronic acid (HA) were assayed.RESULTS: Hepatic fibrosis caused by CCl4 was significantly inhibited in the JinSanE-treated groups. The degrees of necrosis/degeneration and fibrosis scores were significantly lower in the JinSanE-treated groups than in the model control group. The expression of TGF-β1, TRⅡ and Smad3was significantly higher in the model group than that in the JinSanE-treated groups, and the active/total TGF-β1ratio in the JinSanE groups was suppressed. Expression of TRⅡ mRNA and Smad3 proteins showed a distribution pattern similar to that of TGF-β1 with a direct correlation in terms of the degree of hepatic fibrosis. The amount of positive staining Smad7 cells was significantly less in the model group than in the JinSanE-treated groups and the normal group. The contents of ALT, AST and HA were significantly lower in the JinSanE-treated groups than those in the model group.CONCLUSION: Traditional Chinese medicine, JinSanE,prevents the progression of hepatic damage and fibrosis through the inhibition of TGF-β1, TRⅡ and Smad3 signal proteins,and increases wxpression of Smad7 signal protein in vivo.
A Mythen detector has been equipped at the beamline 4B9A of Beijing Synchrotron Radiation Facility （BSRF）, which is expected to enable BSRF to perform time-resolved measurement of X-ray diffraction ...（XRD） full-profiles. In this paper, the thermal expansion behavior of metal indium has been studied by using the in-situ XRD technique with the Mythen detector. The indium was heated from 303 to 433 K with a heating rate of 2 K/rain. The in-situ XRD full-profiles were collected with a rate of one profile per 10 seconds. Rietveld refinement was used to extract the structural parameters. The results demonstrate that these collected quasi-real-time XRD profiles can be well used for structural analysis. The metal indium was found to have a nonlinear thermal expansion behavior from room temperature to the melting point （429.65 K）. The a-axis of the tetragonal unit cell expands with a biquadratic dependency on temperature, while the c-axis contracts with a cubic dependency on temperature. By the time-resolved XRD measurements, it was observed that the 200 preferred orientation can maintain to about 403.15 K. While （110） is the last and detectable crystal plane just before melting of the polycrystalline indium foil. This study is not only beneficial to the application of metal indium, but also exhibits the capacity of in-situ time-resolved XRD measurements at the X-ray diffraction station of BSRF.
The study is to investigate the effects of a Chinese herbal medicine, JinSanE decoction, on the TGF-beta1/Smads signal transduction pathway in a carbon tetrachloride (CCl(4))-induced hepatic fibrosis ...model in rats. Rats were randomly divided into 4 study groups: namely, a normal control group, a hepatic fibrosis model group, and 2 treatment groups with different doses of JinSanE (6 and 12 g/kg). Ten rats in each group were sacrificed at 4 and 8 weeks after exposure to CCl(4) respectively. The levels of TGF-beta1 and TRII mRNA in liver tissue were analyzed by RT-PCR. The expressions of TGF-beta1, Smad3 and Smad7 in liver tissues were evaluated by immunohistochemistry. The liver histopathology was examined by hematoxylin and eosin (HE) staining and electron microscopy respectively. The liver hydroxyproline (HYP), liver function and hyaluronic acid (HA) were examined by biochemistry and radioimmunoassay (RIA) respectively. Compared with the hepatic fibrosis model group, the levels of TGF-beta1, TRII mRNA and Smad3 expression significantly decreased in the 2 treatment groups. The expression of Smad7 was significantly increased in the liver of the rats treated with JinSanE (p < 0.05 or p < 0.01). The histological changes of fibrotic liver were obviously improved in the treatment rats. The levels of liver HYP, serum liver function and HA were also remarkably improved in the treatment rats. Moreover, the effects of JinSanE occurred in a dose- and time-dependent manner in the process of the protection of liver injury and fibrosis. JinSanE decoction had a protective effect on liver injury and could ameliorate hepatic fibrosis in rats. The mechanisms might be associated with their effects of down-regulating TGF-beta1, TRII mRNA and Smad3, and up-regulating Smad7.
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