It is largely recognized that fibroblast activation protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) of many human carcinomas. Furthermore, FAP was recently also reported to be expressed in carcinoma cells of the breast, stomach, pancreatic ductal adenocarcinoma, colorectum, and uterine cervix. The carcinoma cell expression pattern of FAP has been described in several types of cancers, but the role of FAP in oral squamous cell carcinoma (OSCC) is unknown. The role of endogenous FAP in epithelium-derived tumors and molecular mechanisms has also not been reported. In this study, FAP was found to be expressed in carcinoma cells of OSCC and was upregulated in OSCC tissue samples compared with benign tissue samples using immunohistochemistry. In addition, its expression level was closely correlated with overall survival of patients with OSCC. Silencing FAP inhibited the growth and metastasis of OSCC cells in vitro and in vivo. Mechanistically, knockdown of FAP inactivated PTEN/PI3K/AKT and Ras-ERK and its downstream signaling regulating proliferation, migration, and invasion in OSCC cells, as the inhibitory effects of FAP on the proliferation and metastasis could be rescued by PTEN silencing. Our study suggests that FAP acts as an oncogene and may be a potential therapeutic target for patients with OSCC.
Combination therapy with milrinone and esmolol could improve cardiac function and the 28-day survival rate in patients with severe sepsis.
Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has spread rapidly across the world and become an international public health emergency. Both SARS-CoV-2 and SARS-CoV belong to subfamily Coronavirinae in the family Coronaviridae of the order Nidovirales and they are classified as the SARS-like species while belong to different cluster. Besides, viral structure, epidemiology characteristics and pathological characteristics are also different. We present a comprehensive survey of the latest coronavirus—SARS-CoV-2—from investigating its origin and evolution alongside SARS-CoV. Meanwhile, pathogenesis, cardiovascular disease in COVID-19 patients, myocardial injury and venous thromboembolism induced by SARS-CoV-2 as well as the treatment methods are summarized in this review.
Ischemia/reperfusion (I/R)-induced inflammatory reaction is one of the most important elements in myocardial I/R injury. In addition, autophagy serves an important role in normal cardiac homeostasis, and obstructions to the autophagy process lead to severe consequences for the heart. Hydrogen exerts an effective therapeutic role in numerous diseases associated with I/R injury via its anti-inflammation, anti-apoptosis and anti-oxidative properties. Therefore, the present study investigated the effect of hydrogen on the myocardial inflammation response and apoptosis in myocardial ischemic/reperfusion (MI/R) injury, and further explored the mechanism of PTEN-induced kinase 1 (PINK1)/Parkin-induced mitophagy in the protection of hydrogen on MI/R injury. MI/R injury was performed by surgical ligation of the left coronary artery in vivo and H9C2 cell injury was performed by hypoxia/reoxygenation (H/R) in vitro . Hydrogen-rich saline was administered twice through intraperitoneal injection at a daily dose of 10 ml/kg following the operation in the in vivo model, and hydrogen-rich medium culture was used for cells instead of normal medium in vitro . The infarction size of hearts, the levels of creati-nine kinase-muscle/brain (CK-MB) and cardiac troponin I (cTnI), cardiac function, cell viability and lactate dehydrogenase (LDH) release, levels of cytokines, apoptosis and the expression of autophagy-associated proteins were detected in the different treatment groups in vivo and in vitro . The results demonstrated that treatment with hydrogen improved the myocardial infarction size of hearts, cardiac function, apoptosis and cytokine release following MI/R in rats. In vitro , hydrogen improved cell viability and LDH release following hypoxia/reoxygenation in myocardial cells. In addition, it was demonstrated that hydrogen exerted an anti-inflammatory and anti-apoptotic effect in myocardial cells induced by H/R via PINK1/Parkin mediated autophagy. These results suggested that hydrogen-rich saline alleviated the inflammation response and apoptosis induced by MI/R or H/R in vivo or in vitro , and that hydrogen-rich saline contributed to the increased expression of proteins associated with autophagy. In summary, the present study indicated that treatment with hydrogen-rich saline improved the inflammatory response and apoptosis in MI/R via PINK1/Parkin-mediated mitophagy.
Arterial stiffness plays a key role in the pathogenesis of cardiovascular disease. However, the relationship between lipid levels and arterial stiffness is controversial. We aimed to investigate the association between lipid parameters and brachial-ankle pulse-wave velocity (baPWV) in Chinese patients with hypertension. A total of 14 071 participants with hypertension in the China Stroke Primary Prevention Trial (CSPPT) were enrolled in the present study. Patients were assigned to 4 equal groups according to their baPWV. Participants in the highest baPWV group were older with a higher prevalence of stroke and diabetes mellitus as well as higher body mass index (BMI), blood pressure, fasting plasma glucose, uric acid, total cholesterol (TC), triglycerides (TG), homocysteine (Hcy), and vitamin B12 levels (P < .001). After adjusting for age, sex, BMI, and other cardiovascular risks, highdensity lipoprotein cholesterol (HDL-C) was negatively related to baPWV (b ¼ À0.22, P ¼ .012), TC (b ¼ 0.08, P ¼ 0.001), TG (b ¼ 0.14, P ¼ .001); non-HDL-C (b ¼ 0.12, P ¼ .001) and positively related to baPWV. The effect was not observed for lowdensity lipoprotein cholesterol (LDL-C; b ¼ 0.12, P ¼ .335).These results suggested that non-HDL-C, TG, and TC were associated with arterial stiffness in a Chinese population with hypertension. HDL-C was inversely associated with arterial stiffness.
BackgroundThe flower of the safflower (Carthamus tinctorius L.) has been widely used in traditional Chinese medicine for the ability to improve cerebral blood flow. Flavonoids are the primary bioactive components in safflower, and their biosynthesis has attracted widespread interest. Previous studies mostly used second-generation sequencing platforms to survey the putative flavonoid biosynthesis genes. For a better understanding of transcription data and the putative genes involved in flavonoid biosynthesis in safflower, we carry our study.ResultsHigh-quality RNA was extracted from six types of safflower tissue. The RNAs of different tissues were mixed equally and used for multiple size-fractionated libraries (1–2, 2–3 and 3-6 k) library construction. Five cells were carried (2 cells for 1–2 and for 2-3 k libraries and 1 cell for 3-6 k libraries). 10.43Gb clean data and 38,302 de-redundant sequences were captured. 44 unique isoforms were annotated as encoding enzymes involved in flavonoid biosynthesis. The full length flavonoid genes were characterized and their evolutional relationship and expressional pattern were analyzed. They can be divided into eight families, with a large differences in the tissue expression. The temporal expressions under MeJA treatment were also measured, 9 genes are significantly up-regulated and 2 genes are significantly down-regulated. The genes involved in flavonoid synthesis in safflower were predicted in our study. Besides, the SSR and lncRNA are also analyzed in our study.ConclusionsFull-length transcriptome sequences were used in our study. The genes involved in flavonoid synthesis in safflower were predicted in our study. Combined the determination of flavonoids, CtC4H2, CtCHS3, CtCHI3, CtF3H3, CtF3H1 are mainly participated in MeJA promoting the synthesis of flavonoids. Our results also provide a valuable resource for further study on safflower.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4946-9) contains supplementary material, which is available to authorized users.
Homocysteine-Methionine (HM) cycle produces universal methyl group donor S-adenosylmethione (SAM), methyltransferase inhibitor S-adenosylhomocysteine (SAH) and homocysteine (Hcy). Hyperhomocysteinemia (HHcy) is established as an independent risk factor for cardiovascular disease (CVD) and other degenerative disease.We selected 115 genes in the extended HM cycle (31 metabolic enzymes and 84 methyltransferases), examined their protein subcellular location/partner protein, investigated their mRNA levels and mapped their corresponding histone methylation status in 35 disease conditions via mining a set of public databases and intensive literature research. We have 6 major findings. 1) All HM metabolic enzymes are located only in the cytosol except for cystathionine-β-synthase (CBS), which was identified in both cytosol and nucleus. 2) Eight disease conditions encountered only histone hypomethylation on 8 histone residues (H3R2/K4/R8/K9/K27/K36/K79 and H4R3). Nine disease conditions had only histone hypermethylation on 8 histone residues (H3R2/K4/K9/K27/K36/K79 and H4R3/K20). 3) We classified 9 disease types with differential HM cycle expression pattern. Eleven disease conditions presented most 4 HM cycle pathway suppression. 4) Three disease conditions had all 4 HM cycle pathway suppression and only histone hypomethylation on H3R2/K4/R8/K9/K36 and H4R3. 5) Eleven HM cycle metabolic enzymes interact with 955 proteins. 6) Five paired HM cycle proteins interact with each other.We conclude that HM cycle is a key metabolic sensor system which mediates receptor-independent metabolism-associated danger signal recognition and modulates SAM/SAH-dependent methylation in disease conditions and that hypomethylation on frequently modified histone residues is a key mechanism for metabolic disorders, autoimmune disease and CVD. We propose that HM metabolism takes place in the cytosol, that nuclear methylation equilibration requires a nuclear-cytosol transfer of SAM/SAH/Hcy, and that Hcy clearance is essential for genetic protection.
Background Safflower ( Carthamus tinctorius L.) is an important cash crop, of which the dried tube flower is not only an important raw material for dyes and cosmetics but also an important herb widely used in traditional Chinese medicine. The pigment and bioactive compounds are composed of flavonoids (mainly quinone chalcones), and studies have reported that MeJA can promote the biosynthesis of quinone chalcones, but the mechanism underlying the effect of MeJA in safflower remains unclear. Here, we attempt to use metabolomics and transcriptome technologies to analyse the molecular mechanism of flavonoid biosynthesis under MeJA treatment in safflower. Results Based on a UHPLC-ESI-MS/MS detection platform and a self-built database (including hydroxysafflor yellow A, HSYA), a total of 209 flavonoid metabolites were detected, and 35 metabolites were significantly different after treatment with MeJA. Among them, 24 metabolites were upregulated upon MeJA treatment, especially HSYA. Eleven metabolites were downregulated after MeJA treatment. Integrated metabolomics and transcriptome analysis showed that MeJA might upregulate the expression of upstream genes in the flavonoid biosynthesis pathway (such as CHSs , CHIs and HCTs ) and downregulate the expression of downstream genes (such as F3Ms , ANRs and ANSs ), thus promoting the biosynthesis of quinone chalcones, such as HSYA. The transcription expressions of these genes were validated by real-time PCR. In addition, the promoters of two genes ( CtCHI and CtHCT ) that were significantly upregulated under MeJA treatment were cloned and analysed. 7 and 3 MeJA response elements were found in the promoters, respectively. Conclusions MeJA might upregulate the expression of the upstream genes in the flavonoid biosynthesis pathway and downregulate the expression of the downstream genes, thus promoting the biosynthesis of quinone chalcones. Our results provide insights and basic data for the molecular mechanism analysis of flavonoid synthesis in safflower under MeJA treatment.
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