Hollow microsphere probes formed by hollow core optical fiber discharging for monitoring gas pressure and temperature.

A hollow core fiber (HCF) is spliced with a single-mode fiber, and then, the end face of the HCF is etched to form a microsphere interferometer for measuring gas pressure and environmental temperature. The total length of each microsphere is less than 200 µm. We fabricated two such structures and used femtosecond laser pulses to drill micro-holes on the HCF walls of both structures. One of the structures is directly used to measure air pressure, achieving a sensitivity of up to 2.857 nm/MPa while being almost insensitive to temperature. This structure is capable of assessing pressure down to 3.4 kPa within the range of 0-0.5 MPa. Another structure is filled with thermally sensitive material dimethyl silicone oil through a micro-hole, and then, it is sealed with AB adhesive to form a harmonic Vernier effect temperature sensor, with a sensitivity of up to -5.16 nm/°C. This structure is capable of assessing temperature down to 0.38 °C within the range of 30-60 °C. Additionally, the sensors have good repeatability and stability and compact structure and simple manufacturing and can be used as a sensing probe for monitoring gas pressure and temperature under extreme environments.

Compact highly sensitive Fabry-Perot temperature and gas pressure sensing probe fabricated by a femtosecond laser and PDMS.

A high sensitivity optical fiber temperature and gas pressure sensor with integrated micro-cavity is proposed. First, a single-mode optical fiber (SMF) is spliced with a section of capillary, and then the sensitive material polydimethylsiloxane (PDMS) is filled into the capillary to form a Fabry-Perot interferometer (FPI). Finally, a femtosecond laser is used to ablate the fiber core of the SMF to form the third reflecting surface, constituting two cascaded FPIs. When two FPIs have a similar free spectral range, a Vernier effect is produced. The temperature and gas pressure sensitivity of the sensor reached 14.41 nm/°C and 113.82 nm/MPa, respectively, after using the sensitive material and Vernier effect double sensitization technology. In addition, a fiber Bragg grating is cascaded with the sensor, which can realize the simultaneous measurement of temperature and gas pressure and eliminate cross-sensitivity.

MicroRNA-486-5p suppresses inflammatory response by targeting FOXO1 in MSU-treated macrophages.

Gouty arthritis (GA) is mainly caused by the precipitation of monosodium urate (MSU) crystals in the joint. Recently, different regulatory roles of microRNAs (miRNAs) in arthritis have been widely verified. Nevertheless, the specific function of microRNA-486-5p (miR-486-5p) in GA is still unclear. GA cell models in vitro were established by the treatment of 250 µg/mL MSU crystals into THP-1 cells or J774A.1 cells. Then, the accumulation of tumor necrosis factor (TNF)-α, interleukin (IL)-8, and IL-ß was estimated by ELISA. The mRNA levels of TNF-α, IL-8, and IL-ß were measured through RT-qPCR. The protein level of forkhead box protein O1 (FOXO1) was tested via western blot. Furthermore, the interplay of miR-486-5p and FOXO1 was evaluated via the luciferase reporter assay. In this study, MSU treatment successfully stimulated the inflammatory response in macrophage cells. MiR-486-5p downregulation was observed in THP-1 and J774A.1 cells treated with MSU, and its upregulation markedly decreased the concentration and mRNA levels of TNF-α, IL-8, and IL-ß. Furthermore, FOXO1 was demonstrated to be negatively modulated by miR-486-5p. The rescue assay indicated that overexpressing FOXO1 reversed the effects of overexpressing miR-486-5p on inflammatory cytokines. Overall, this study proves that miR-486-5p inhibits GA inflammatory response via modulating FOXO1.

Highly sensitive gas pressure sensor based on the enhanced Vernier effect through a cascaded Fabry-Perot and Mach-Zehnder interferometer.

A high sensitivity optical fiber gas pressure sensor based on the enhanced Vernier effect is proposed. The sensor is composed of a fiber Fabry-Perot interferometer (FPI) and Mach-Zehnder interferometer (MZI). Since the interference fringes of FPI and MZI drift in the opposite direction with the change of gas pressure, when their free spectral ranges are similar, the enhanced Vernier effect is formed after their cascading. Compared with the traditional Vernier effect gas pressure sensor, the enhanced Vernier effect gas pressure sensor realizes much higher sensitivity gas pressure measurement without complex manufacturing process or desensitized reference interferometer. The experimental results show that the sensitivity of the enhanced Vernier effect sensor is 241.87 nm/MPa. In the two traditional Vernier effect gas pressure sensors formed by cascading FPI and MZI, the sensitivity of sensor is 63.02 nm/MPa and 171.26 nm/MPa, respectively. Compared with the two traditional Vernier effect sensors, the sensitivity of the enhanced Vernier effect sensor is increased by 3.8 times and 1.4 times, respectively. The proposed sensor also has the advantages of good repeatability and stability, fast response, low cost and easy manufacture. Our structure also provides a new design scheme for a high sensitivity optical fiber gas pressure sensor.

High sensitivity gas pressure sensor based on different inner diameter quartz capillary cascading and Vernier effect.

In this paper, a highly sensitive optical fiber gas pressure sensor is proposed and experimentally verified. The sensor is composed of two Fabry-Pérot (F-P) cavities, and two F-P cavities are fabricated by a single-mode fiber and two quartz capillaries with different inner diameters splicing. Among them, the small inner diameter capillary is used as a gas channel connecting the large inner diameter capillary and the external environment. The manufacturing process of the sensor only involves capillary cleaver and splicing and does not involve other complex manufacturing technologies. By correctly adjusting the length of the two quartz capillaries, when the free spectral range of the two F-P cavities is very close, the optical Vernier effect will be observed and used as a sensitive probe for detecting gas pressure. The experimental results show that, in the pressure range of 0-0.8 MPa, the gas pressure sensitivity of the sensor reaches -81.73 nm/MPa with a linearity of 99.7%, and the temperature cross-sensitivity is only 1.82 kPa/°C. Due to its easy manufacture, high sensitivity, compact structure, and small volume, the sensor has become one of the preferred structures for large-scale use in the field of gas sensing.

Dihydrotriazine derivatives display high anticancer activity and inducing apoptosis, ROS, and autophagy.

A series of dihydrotriazine derivatives bearing 5-aryloxypyrazole moieties were designed, and their anticancer activities against three human cancer cell lines (SGC-7901, HepG-2 and MCF-7) and one non-cancer cell line (LO2) were explored using the MTT assay in vitro. Most of the compounds exhibited potent antiproliferative activities against the three cancer cell lines, with compound 10e (IC50 = 2.12 µM) exhibiting the most potent antiproliferative activity against HepG-2 cells. Interestingly, autophagy was observed in the 10e-treated HepG-2 cells. Compound 10e also increased reactive oxygen species (ROS) levels and resulted in marked HepG-2 cells apoptosis. Further studies revealed that compound 10e could enhance the expression of Cl-PARP, Cl-caspase-3, and Cl-caspase-9. In addition, 10e triggered the formation of autophagosomes by promoting LC3-II and Beclin-1 expression. These results might be useful for exploring and developing dihydrotriazine derivatives as novel anticancer agents.

Class I histone deacetylase inhibitor MS-275 attenuates vasoconstriction and inflammation in angiotensin II-induced hypertension.

OBJECTIVE: Non-selective histone deacetylase (HDAC) inhibitors are known to improve hypertension. Here, we investigated the therapeutic effect and regulatory mechanism of the class I HDAC selective inhibitors, MS-275 and RGFP966, in angiotensin (Ang) II-induced hypertensive mice. METHODS AND RESULTS: MS-275 inhibited the activity of HDAC1, HDAC2, and HDAC3, while RGFP966 weakly inhibited that of HDAC3 in a cell-free system. MS-275 and RGFP966 treatment reduced systolic blood pressure and thickness of the aorta wall in Ang II-induced hypertensive mice. MS-275 treatment reduced aorta collagen deposition, as determined by Masson's trichrome staining. MS-275 decreased the components of the renin angiotensin system and increased vascular relaxation of rat aortic rings via the nitric oxide (NO) pathway. NO levels reduced by Ang II were restored by MS-275 treatment in vascular smooth muscle cells (VSMCs). However, MS-275 dose (3 mg·kg-1·day-1) was not enough to induce NO production in vivo. In addition, MS-275 did not prevent endothelial nitric oxide synthase (eNOS) uncoupling in the aorta of Ang II-induced mice. Treatment with MS-275 failed to inhibit Ang II-induced expression of NADPH oxidase (Nox)1, Nox2, and p47phox. MS-275 treatment reduced proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and monocyte chemoattractant protein (MCP)-1, as well as adhesion molecules. Histological analysis showed that Ang II-induced macrophage infiltration was reduced by MS-275 and RGFP966 administration. CONCLUSIONS: Our results indicate that class I HDAC selective inhibitors may be good therapeutic agents for the treatment of hypertension through the regulation of vascular remodeling and vasoconstriction, as well as inflammation.

Dendropanax morbifera Prevents Cardiomyocyte Hypertrophy by Inhibiting the Sp1/GATA4 Pathway.

An extract of Dendropanax morbifera branch exerts antioxidant, anti-inflammatory, antithrombotic, and anticancer activities. The purpose of this study was to investigate the effect of the extract in isoproterenol-induced cardiac hypertrophy. Phalloidin staining showed that treatment with the extract dramatically prevents isoproterenol-induced H9c2 cell enlargement and the expression of cardiac hypertrophic marker genes, including atrial natriuretic peptide (ANP) and B-type brain natriuretic peptide (BNP). Further, pretreatment with the extract decreased isoproterenol-induced GATA4 and Sp1 expression in H9c2 cells. Overexpression of Sp1 induced the expression of GATA4. The forced expression of Sp1 or its downstream target GATA4, as well as the co-transfection of Sp1 and GATA4 increased the expression of ANP, which was decreased by treatment with the extract. To further elucidate the regulation of the Sp1/GATA4-mediated expression of ANP, knockdown experiments were performed. Transfection with small interfering RNAs (siRNAs) for Sp1 or GATA4 decreased ANP expression. The extract did not further inhibit the expression of ANP reduced by the transfection of GATA4 siRNA. Sp1 knockdown did not affect the expression of ANP that was induced by the overexpression of GATA4; however, GATA4 knockdown abolished the expression of ANP that had been induced by Sp1 overexpression. The extract treatment also attenuated the isoproterenol-induced activation of p38 MAPK, ERK1/2, and JNK1. Hesperidin, catechin, 2,5-dihydroxybenzoic acid, and salicylic acid are the main phenolic compounds present in the extract as observed by high performance liquid chromatography. Hesperidin and 2,5-dihydroxybenzoic acid attenuated isoproterenol-induced cardiac hypertrophy. These findings suggest that the D. morbifera branch extract prevents cardiac hypertrophy by downregulating the activation of Sp1/GATA4 and MAPK signaling pathways.

Inhibition of class IIa histone deacetylase activity by gallic acid, sulforaphane, TMP269, and panobinostat.

Histone deacetylase (HDAC) inhibitors are gaining increasing attention as potential therapeutics for cardiovascular diseases as well as cancer. We recently reported that the class II HDAC inhibitor, MC1568, and the phytochemical, gallic acid, lowered high blood pressure in mouse models of hypertension. We hypothesized that class II HDACs may be involved in the regulation of hypertension. The aim of this study was to determine and compare the effects of well-known HDAC inhibitors (TMP269, panobinostat, and MC1568), phytochemicals (gallic acid, sulforaphane, and piceatannol), and anti-hypertensive drugs (losartan, carvedilol, and furosemide) on activities of class IIa HDACs (HDAC4, 5, 7, and 9). The selective class IIa HDAC inhibitor, TMP269, and the pan-HDAC inhibitor, panobinostat, but not MC1568, clearly inhibited class IIa HDAC activities. Among the three phytochemicals, gallic acid showed remarkable inhibition, whereas sulforaphane presented mild inhibition of class IIa HDACs. Piceatannol inhibited only HDAC7 activity. As expected, the anti-hypertensive drugs losartan, carvedilol, and furosemide did not affect the activity of any class IIa HDAC. In addition, we evaluated the inhibitory effect of several compounds on the activity of class l HDACs (HDAC1, 2, 3, and 8) and class IIb HDAC (HDAC6). MC1568 did not affect the activities of HDAC1, HDAC2, and HDAC3, but it reduced the activity of HDAC8 at concentrations of 1 and 10 µM. Gallic acid weakly inhibited HDAC1 and HDAC6 activities, but strongly inhibited HDAC8 activity with effectiveness comparable to that of trichostatin A. Inhibition of HDAC2 activity by sulforaphane was stronger than that by piceatnnaol. These results indicated that gallic acid is a powerful dietary inhibitor of HDAC8 and class IIa/b HDAC activities. Sulforaphane may also be used as a dietary inhibitor of HDAC2 and class IIa HDAC. Our findings suggest that the class II HDAC inhibitor, MC1568, does not inhibit class IIa HDAC, but inhibits HDAC8.

Gallic acid attenuates calcium calmodulin-dependent kinase II-induced apoptosis in spontaneously hypertensive rats.

Hypertension causes cardiac hypertrophy and leads to heart failure. Apoptotic cells are common in hypertensive hearts. Ca2+ /calmodulin-dependent protein kinase II (CaMKII) is associated with apoptosis. We recently demonstrated that gallic acid reduces nitric oxide synthase inhibition-induced hypertension. Gallic acid is a trihydroxybenzoic acid and has been shown to have beneficial effects, such as anti-cancer, anti-calcification and anti-oxidant activity. The purpose of this study was to determine whether gallic acid regulates cardiac hypertrophy and apoptosis in essential hypertension. Gallic acid significantly lowered systolic and diastolic blood pressure in spontaneously hypertensive rats (SHRs). Wheat germ agglutinin (WGA) and H&E staining revealed that gallic acid reduced cardiac enlargement in SHRs. Gallic acid treatment decreased cardiac hypertrophy marker genes, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), in SHRs. The four isoforms, α, ß, δ and γ, of CaMKII were increased in SHRs and were significantly reduced by gallic acid administration. Gallic acid reduced cleaved caspase-3 protein as well as bax, p53 and p300 mRNA levels in SHRs. CaMKII δ overexpression induced bax and p53 expression, which was attenuated by gallic acid treatment in H9c2 cells. Gallic acid treatment reduced DNA fragmentation and the TUNEL positive cells induced by angiotensin II. Taken together, gallic acid could be a novel therapeutic for the treatment of hypertension through suppression of CaMKII δ-induced apoptosis.

Gallic Acid Reduces Blood Pressure and Attenuates Oxidative Stress and Cardiac Hypertrophy in Spontaneously Hypertensive Rats.

Gallic acid (GA) has been reported to have beneficial effects on cancer, vascular calcification, and diabetes-induced myocardial dysfunction. We hypothesized that GA controls hypertension via oxidative stress response regulation in an animal model for essential hypertension. Spontaneously hypertensive rats (SHRs) were administered GA for 16 weeks. GA treatment lowered elevated systolic blood pressure in SHRs through the inhibition of vascular contractility and components of the renin-angiotensin II system. In addition, GA administration reduced aortic wall thickness and body weight in SHRs. In SHRs, GA attenuated left ventricular hypertrophy and reduced the expression of cardiac-specific transcription factors. NADPH oxidase 2 (Nox2) and GATA4 mRNA expression was induced in SHR hearts and angiotensin II-treated H9c2 cells; this expression was downregulated by GA treatment. Nox2 promoter activity was increased by the synergistic action of GATA4 and Nkx2-5. GA seems to regulate oxidative stress by inhibiting the DNA binding activity of GATA4 in the rat Nox2 promoter. GA reduced the GATA4-induced Nox activity in SHRs and angiotensin II-treated H9c2 cells. GA administration reduced the elevation of malondialdehyde levels in heart tissue obtained from SHRs. These findings suggest that GA is a potential therapeutic agent for treating cardiac hypertrophy and oxidative stress in SHRs.

Gallic acid attenuates pulmonary fibrosis in a mouse model of transverse aortic contraction-induced heart failure.

Gallic acid, a trihydroxybenzoic acid found in tea and other plants, attenuates cardiac hypertrophy, fibrosis, and hypertension in animal models. However, the role of gallic acid in heart failure remains unknown. In this study, we show that gallic acid administration prevents heart failure-induced pulmonary fibrosis. Heart failure induced in mice, 8weeks after transverse aortic constriction (TAC) surgery, was confirmed by echocardiography. Treatment for 2weeks with gallic acid but not furosemide prevented cardiac dysfunction in mice. Gallic acid significantly inhibited TAC-induced pathological changes in the lungs, such as increased lung mass, pulmonary fibrosis, and damaged alveolar morphology. It also decreased the expression of fibrosis-related genes, including collagen types I and III, fibronectin, connective tissue growth factor (CTGF), and phosphorylated Smad3. Further, it inhibited the expression of epithelial-mesenchymal transition (EMT)-related genes, such as N-cadherin, vimentin, E-cadherin, SNAI1, and TWIST1. We suggest that gallic acid has therapeutic potential for the treatment of heart failure-induced pulmonary fibrosis.

Gallic acid attenuates hypertension, cardiac remodeling, and fibrosis in mice with NG-nitro-L-arginine methyl ester-induced hypertension via regulation of histone deacetylase 1 or histone deacetylase 2.

OBJECTIVE: Gallic acid, a natural chemical found in plants, has been reported to show antioxidant, anticancer, and anti-inflammatory effects. We investigated the efficacy of a short-term or long-term treatment with gallic acid in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive mice and the underlying regulatory mechanism. METHODS: Hypertension was sufficiently induced after 2 weeks of L-NAME administration. Cardiac remodeling was assessed by echocardiography. Hypertrophic markers, transcription factors, and fibrosis-related gene expression were evaluated by quantitative real-time polymerase chain reaction and western blotting. RESULTS: Gallic acid effectively lowered SBP, regardless of the administration route (intraperitoneal or oral). L-NAME increased the left ventricular (LV) thickness without an increase in the total heart weight. Weekly echocardiography demonstrated that gallic acid significantly reduced LV posterior wall and septum thickness in chronic L-NAME mice from 3 to 7 weeks. The administration of gallic acid to mice showed a dual preventive and therapeutic effect on the L-NAME-induced LV remodeling. The effect was associated with the suppression of the gene expression of hypertrophy markers and the GATA-binding factor 6 (GATA6) transcription factor. Short-term or long-term treatment with gallic acid attenuated cardiac fibrosis and reduced the expression of histone deacetylase 1 and 2 in H9c2 cells and in rat primary cardiac fibroblasts, as well as in vivo. Small interfering RNA knockdown confirmed the association of these enzymes with L-NAME-induced cardiac remodeling and fibrosis. CONCLUSION: These results suggested that gallic acid may be a potential therapeutic agent for the treatment of cardiovascular diseases with hypertension and cardiac fibrosis.