Photooxidation of Toluene Derivatives under HAT and ROS Synergy.

The valorization of toluene offers a dual solution by addressing its environmental impact while also facilitating the synthesis of a diverse array of valuable fine chemicals and pharmaceutical intermediates, thus ensuring both ecological sustainability and economic viability. We report herein a synergistic approach that harmonizes hydrogen atom transfer (HAT) process with the generation of reactive oxygen species (ROS) under mild condition and low catalyst loading, which enables the efficient synthesis of a broad spectrum of esteemed benzoic acid derivatives and aryl ketones through the photocatalytic oxidation of toluene derivatives. Mechanistic elucidation reveals that the HAT reagent anthraquinone has both the capabilities to abstract hydrogen atoms and the ability to generate singlet oxygen 1O2 during energy transfer with triplet oxygen 3O2, and the combination of these two potencies significantly improves the catalytic efficiency of the reaction. This study not only introduces the amalgamation of HAT with ROS generation but also delineates a systematic approach for the selection of HAT reagents with energy transfer proficiency for ROS generation in catalytic oxidation reactions.

Investigation of miR-490-3p Expression in Hepatocellular Carcinoma Based on Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) and a Meta-Analysis of 749 Cases.

BACKGROUND miR-490-3p could play vital roles in multiple cancers. However, the role of miR-490-3p in hepatocellular carcinoma (HCC) remains uncertain. In this study, we sought to explore the underlying role of miR-490-3p in HCC. MATERIAL AND METHODS In this study, we explored the clinical role of miR-490-3p in HCC via quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and The Cancer Genome Atlas (TCGA) database. Then, a meta-analysis was performed to evaluate the expression trend and diagnostic value of miR-490-3p in HCC. Furthermore, 12 miRNA prediction algorithms were applied to predict the potential target genes of miR-490-3p. The differentially expressed genes in HCC in the Gene Expression Profiling Interactive Analysis (GEPIA) database were also selected. Additionally, bioinformatics analyses were utilized to investigate the possible functions and pathways of the target genes. RESULTS miR-490-3p was clearly down-regulated in HCC based on RT-qPCR (P=0.002). Consistent with the results of RT-qPCR, miR-490 was more highly expressed in normal liver tissue than in HCC (P<0.001). Additionally, the meta-analysis confirmed the results from RT-qPCR and TCGA. Furthermore, based on the prediction algorithms and GEPIA, a total of 113 genes were selected. According to the bioinformatics analyses, we found that the most remarkably enriched functional terms included protein transport, poly(A) RNA binding, and intracellular organelle part. Additionally, the miR-490-3p target genes were significantly related to the pathways in cancer. CONCLUSIONS We found that miR-490-3p is down-regulated in HCC and is related to genes that have potential tumoral functions. However, the exact mechanism should be confirmed by functional experiments.

Photocatalytic selective oxidation of toluene under encapsulated air conditions.

Benzaldehydes are indispensable building blocks in chemistry. However, the selective oxidation of toluene to benzaldehyde remains an ongoing challenge due to the low oxidation potential of benzaldehyde compared to toluene. We report herein a mild protocol that combines hydrogen atom transfer (HAT) with encapsulated air conditions and suitable catalyst loading for selective oxidation of toluene with high selectivity as well as good functional-group tolerance and a broad substrate scope for the synthesis of various high-value aromatic aldehydes. Moreover, the compatibility of this reaction with toluene derivatives of bioactive molecules further demonstrated the practicality of this approach. Mechanism studies have demonstrated that the collaboration between the oxygen quantity and the HAT catalytic system has a major impact on the high selectivity of the reaction. This study not only showcases the effectiveness of HAT strategies toward selective oxidation of toluene to benzaldehyde, but also provides an approach to controlling the selectivity of HAT reactions.

Nitrogen-doped Carbon Dots as Efficient Photocatalysts for High Selectivity of Dehalogenative Oxyalkylation of Styrene.

Carbon dots (CDs) are a type of carbon-based luminescent material with a zero-dimensional structure and a size of less than 10 nm, which are composed of sp2/sp3 hybrid carbon nuclei and surface functional groups. Because CDs has strong photoluminescence and good light absorption in the ultraviolet and near visible regions, it is an excellent candidate for photocatalytic applications. However, the use of nonmetallic doped CDs as photosensitizers for direct photocatalytic organic reactions has been limited to several scattered reports. Herein, we present nitrogen-doped carbon dots (N-CDs) that has a capability for not only produce reactive oxygen species (ROS), including superoxide anion radical (O2⋅-) and singlet oxygen (1O2), but also provide an unprecedented high activity of dehalogenative oxyalkylation of styrene with a yield of 93 %. This work develops a novel opportunity to utilize cost-effective and easily accessible CDs for the advancement of photocatalysis.

Construction of an efficient artificial light-harvesting system based on hyperbranched polyethyleneimine and improvement of photocatalytic performance.

An artificial light-harvesting system (ALHS) was developed in aqueous solution by employing the electrostatic co-assembly of a tetraphenylethylene derivative modified with two sulfonate groups (TPE-BSBO) and hyperbranched polyethyleneimine (PEI) as the energy donors, and 4,7-bis(2-thienyl)-2,1,3-benzothiadiazole (DBT) as the energy acceptors. The ALHS exhibits not only high efficiency in energy transfer and conversion but also a significant enhancement in the generation of reactive oxygen species (ROS), especially superoxide anion radicals (O2˙-), facilitating its utilization in photocatalytic oxidation reactions.

Construction of aggregation-induced emission photosensitizers through host-guest interactions for photooxidation reaction and light-harvesting.

In the present work, we have designed and synthesized a triphenylamine modified cyanophenylenevinylene derivative (TPCI), which can self-assembly with cucurbit[6]uril (CB[6]) and cucurbit[8]uril (CB[8]) through host-guest interactions to form supramolecular complexes (TPCI-CB[6]) and supramolecular polymers (TPCI-CB[8]) in the aqueous solution. The supramolecular assemblies of TPCI-CB[6] and TPCI-CB[8] not only exhibited high singlet oxygen (1O2) production efficiency as photosensitizers, but also realized the application in the construction of artificial light-harvesting systems due to the excellent fluorescence properties in the aqueous solution. The production efficiency of 1O2 has been effectively improved after the addition of CB[6] and CB[8] for TPCI, which were applied as efficient photosensitizers in the photooxidation reactions of thioanisole and its derivatives with the highest yield of 98% in the aqueous solution. The excellent fluorescence properties of TPCI-CB[6] and TPCI-CB[8] can be used as energy donors in artificial light-harvesting systems with energy acceptors sulforhodamine 101 (SR101) and cyanine dye 5 (Cy5), in which one-step energy transfer processes of TPCI-CB[6]+SR101 and TPCI-CB[8]+Cy5, and a two-step sequential energy transfer process of TPCI-CB[6]+SR101+Cy5 were constructed to simulate the natural photosynthesis system.

Host-Guest Photosensitizer of a Cationic BODIPY Derivative and Cucurbit[7]uril for High-Efficiency Visible Light-Induced Photooxidation Reactions.

In recent years, there has been a notable surge of interest in the fields of organic and pharmaceutical research about photocatalysts (PCs) and photosensitizers (PSs). In this study, a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) molecule adorned with quaternary ammonium (TMB) functionality was meticulously designed and synthesized. This compound has remarkable characteristics such as exceptional water solubility, great optical qualities, and commendable photostability. It can form a 1:1 complex (TMB-CB[7]) with cucurbit[7]uril (CB[7]) through host-guest interactions in the aqueous solution and shows obvious fluorescence enhancement. The reactive oxygen species (ROS) including superoxide anion radical (O2·-) and singlet oxygen (1O2) generation ability of TMB-CB[7] were promoted compared with that of TMB in the aqueous solution. More interestingly, the ROS generated from TMB-CB[7] can be used as PCs for aerobic cross dehydrogenation coupling reactions and photooxidation reactions in water with high yields of 89 and 95%, respectively. Therefore, the utilization of a host-guest PS presents a novel and environmentally friendly approach for conducting photocatalyzed organic processes under ambient conditions using visible light.

Molecular subtypes based on DNA sensors predict prognosis and tumor immunophenotype in hepatocellular carcinoma.

DNA sensors play crucial roles in inflammation and have been indicated to be involved in antitumor or tumorigenesis, while it is still unclear whether DNA sensors have potential roles in the prognosis and immunotherapy of hepatocellular carcinoma (HCC). Herein, The Cancer Genome Atlas and Gene Expression Omnibus databases were used to analyze RNA sequencing data and clinical information. A total of 14 DNA sensors were collected and performed consensus clustering to determine their molecular mechanisms in HCC. Two distinct molecular subtypes (Clusters C1 and C2) were identified and were associated with different overall survival (OS). Immune subtype analysis revealed that C1 was mainly characterized by inflammation, while C2 was characterized by lymphocyte depletion. Immune scoring and immunomodulatory function analysis confirmed the different immune microenvironment of C1 and C2. Notably, significant differences in "Hot Tumor" Immunophenotype were observed between the two subtypes. Moreover, the prognostic model based on DNA sensors is capable of effectively predicting the OS of HCC patients. Besides, the chemotherapeutic drug analysis showed the different sensitivity of two subtypes. Taken together, our study shows that the proposed DNA sensors were a reliable signature to predict the prognosis and immunotherapy response with potential application in the clinical decision and treatment of HCC.

Construction of artificial light-harvesting systems based on a variety of polyelectrolyte materials and application in photocatalysis.

In the present work, we designed and synthesized a cationic cyano-substituted p-phenylenevinylene derivative (PPTA), which can form supramolecular assemblies through electrostatic interaction with a type of polyelectrolyte material anionic guar gum (GP5A). A polyelectrolyte-based artificial light-harvesting system (LHS) was constructed by selecting a fluorescent dye sulforhodamine 101 (SR101) that matched its energy level as an energy acceptor. The energy harvested by the acceptors was used in the aqueous phase cross dehydrogenation coupling (CDC) reaction with a yield of up to 87%. In addition, the general applicability of polyelectrolyte materials to build artificial LHS was demonstrated by three other polyelectrolyte materials sodium polyphenylene sulfonate (RSS), sodium carboxymethyl cellulose (CMC), and sodium polyacrylate (PAAS), in which the CDC reaction was also carried out by these three LHSs and obtained high yields. This work not only provides a new method to construct LHSs by using polyelectrolyte materials, but also provides a beneficial exploration for further applying the energy harvested in LHSs to the field of photocatalysis in an aqueous solution.

Qi Sui Zhu Shui Plaster Inhibits AQP1 and MAPK Signaling Reduces Liver Damage Induced by Cirrhotic Ascites.

Objective: At present, there is no special treatment for cirrhotic ascites in modern medicine. Qi Sui Zhu Shui plaster (QSZSP) has been used in ascites. The purpose of this study was to investigate the mechanism of action of QSZSP in the treatment of cirrhotic ascites and its relationship with aquaporin 1 (AQP1). Methods: Twenty-four rats were divided into four groups, six rats in each group. Carbon tetrachloride-olive oil is injected into modeling. The control and model groups are treated with blank gel plaster (2 cm × 2 cm), QSZSP low-dose group is treated with Qi Sui Zhu Shui plaster (1 cm × 1 cm), and QSZSP high-dose group is treated with Qi Sui Zhu Shui plaster (2 cm × 2 cm). The changes in body weight and abdominal circumference were measured, the histopathological changes in liver, kidney, and peritoneum were observed in HE staining, the biochemical indexes related to liver function were detected, and the changes in AQP1 expression and the activation of MAPK pathway in the liver, kidney, and peritoneal tissues were evaluated in IHC staining and Western blot. Results: After one week of injection of carbon tetrachloride-olive oil, the rats in the model group increased their body weight slowly, the abdominal circumference of the model rats continued to increase with time. After 16 weeks of construction of the cirrhotic ascites model, the liver, kidney, and peritoneum were significantly damaged, and the serum levels of TBiL, AST, ALT, Cr, BUN, K, Na, and Ca in the rats were significantly higher (P < 0.001) and ALB levels were significantly lower (P < 0.001) than those in the control group. After 4 weeks of treatment, the liver, kidney, and peritoneal injury were improved. TBiL, AST, ALT, Cr, BUN, K, Na, and Ca levels were significantly lower (P < 0.001) and ALB levels were significantly higher (P < 0.001) than those in the model group. The protein expression of AQP1, p-ERK, p-JNK, and p-p38 was found to be inhibited in the liver, kidney, and peritoneum. Conclusion: QSZSP inhibits the protein expression of AQP1 and MAPK signaling pathway in the liver, peritoneum, and kidney to alleviate liver, kidney, and peritoneal injury caused by cirrhotic ascites, thus reducing the abnormal growth of abdominal circumference.

New contributions to Goodyerinae and Dendrobiinae (Orchidaceae) in the flora of China.

Eight new species from China, Cheirostylis chuxiongensis, C. yei, Myrmechis lingulata, M. longii, Bulbophyllum ximaense, B. xizangense, B. retusum and B. pulcherissimum, are described and illustrated. Cheirostylis chuxiongensis differs from C. thailandica by having 5-9 irregular and papillae-like calli on each side in the sac of the lip, epichile with entire lobes, petals narrowly obliquely obovate and an apex that is not recurved. Cheirostylis yei is easily distinguished from its relatives similar by having a long stem, pubescent ovary and sepals, epichile lobes with irregular and undulate margins, a subquadrate callus without teeth in the saccate hypochile. Myrmechis lingulata differs from M. chinensis by having a simple and lanceolate to ligulate lip, glabrous bracts and ovary, oblique and narrowly ovate petals. Myrmechis longii differs from M. pumila by having white-veined leaves, oblong-lanceolate epichile lobes, and viscidium attached to the middle of the caudicle. Bulbophyllum ximaense is easily distinguished from its relatives similar by having distant pseudobulbs, shorter scape, an inflorescence with 9-16 orange-red flowers, shorter lateral sepals with a long acuminate apex, incurved and tubular apical margins, a papillate lip disk and triangular-subulate stelidia. Bulbophyllum xizangense is easily distinguished from its relatives similar by having narrow lanceolate leaves, shorter inflorescence with 1-3 greenish-yellow flowers, falcate-ovoid lateral sepals, a lip with small lateral lobes and 3 keels at the base. Bulbophyllum retusum differs from B. spathulatum by having shorter inflorescence, peduncles with 2 tubular sheaths, dorsal sepals with a retuse apex, lateral sepals with lower edges that are connate to each other and free and divergent toward the apex, obovate petals with an acute or slightly retuse apex. Bulbophyllum pulcherissimum differs from B. lopalanthum by its 5-veined dorsal sepal, ovate-lanceolate lateral sepals, obliquely ovate-oblong petal, erose-toothed margins and obovate lip with a large, oblong basal callus, and an obtuse base. In addition, three species (Bulbophyllum frostii, B. raskotii and B. nematocaulon) are reported for the first time in China.

Role of NO and EDHF-mediated endothelial function in the porcine pulmonary circulation: comparison between pulmonary artery and vein.

OBJECTIVE: To compare electrophysiological measurement of nitric oxide (NO) release and endothelium-derived hyperpolarizing factor (EDHF)-mediated endothelial function in porcine pulmonary arteries and veins. METHODS: Isolated pulmonary interlobular arteries (PA) and veins (PV) were obtained from a local slaughterhouse. By using a NO-specific electrode and a conventional intracellular microelectrode, the amount of NO released from endothelial cells and hyperpolarization of smooth muscle cells were investigated. The bradykinin (BK)-induced relaxation in the precontraction by U(46619) was examined in the absence or presence of N(G)-nitro-l-arginine (l-NNA), indomethacin (INDO) plus oxyhemoglobin (HbO). RESULTS: The basal release of NO was 7.0+/-1.2 nmol/L in PA (n=8) and 5.5+/-1.6 nmol/L in PV (n=8, p<0.01). BK-induced release of NO was 160.4+/-10.3 nmol/L in PA (n=8) and 103.0+/-14.7 nmol/L in PV (n=8, p<0.001) with longer releasing duration in PA than in PV (14.3+/-1.3 vs. 12.1+/-0.8 min, p<0.01). BK evoked an endothelium-dependent hyperpolarization and relaxation that were reduced by l-NNA, INDO, and HbO (hyperpolarization: 12.8+/-1.3 vs. 8.0+/-1.4 mV in PA, n=6, p<0.001 and 8.3+/-1.4 vs. 3.0+/-0.8 mV in PV, n=6, p<0.001; relaxation: 92.8+/-3.1% vs. 19.6+/-11.1% in PA n=8, p<0.001 and 70.3+/-7.9% vs. 6.0+/-6.8% in PV, n=8, p<0.001). Both hyperpolarization (8.0+/-1.4 vs. 3.0+/-0.8 mV, p<0.001) and relaxation (19.6+/-11.1% vs. 6.0+/-6.8%, p<0.01) were greater in PA than in PV. CONCLUSIONS: Both NO and EDHF play an important role in regulation of porcine pulmonary arterial and venous tones. The more significant role of NO and EDHF is revealed in pulmonary arteries than in veins.

Effect of Rheum palmatum L. on NF-κB signaling pathway of mice with acute liver failure.

OBJECTIVE: To explore the regulation effect of Rheum palmatum (R. palmatum) L. on NF-κB signaling pathway of ALF mice. METHODS: The intraperitoneal injection of d-GalN/LPS was employed for the model building. Mice in the treatment group and positive control group were given the R. palmatum L. and bifendate before the model building. Mice in the normal group were given the intraperitoneal injection of equivalent normal saline for continuously 3 d. After 16 h of model building, the blood was collected from eyeballs of mice and then mice were executed. The measurement was performed on the content of ALT, AST, NO and Il-1ß in the serum of mice in each group, as well as the activity of Caspase 3 and Caspase 8 in the liver tissue. HE staining was employed to detect the pathological morphology of liver; and the western blot was used to detect the expression of iNOS, COX-2, Bax, Bcl-2, PCNA, NF-κB p65 and IκBα. RESULTS: The content of ALT, AST, NO and Il-1ß in the serum and the activity of Caspase 3 and Caspase 8 in the liver tissue were increased in the mice of ALF model group. Besides, the expression of iNOS, COX-2 and Bax was increased, the expression of Bcl-2 and PCNA was decreased, the phosphorylation of NF-κB p65 and IκBα was significant and the treatment group of R. palmatum L. could inhibit such change. CONCLUSIONS: Through NF-κB signaling pathway, the R. palmatum L. could reduce the content of enzyme of liver function and inflammation factor in the serum of ALF mice, regulate the expression of cell apoptosis-related protein and improve the symptoms of ALF mice.

Adjunctive aripiprazole in the treatment of risperidone-induced hyperprolactinemia: A randomized, double-blind, placebo-controlled, dose-response study.

Hyperprolactinemia is an unwanted adverse effect associated with several antipsychotics. The addition of partial dopamine receptor agonist aripiprazole may attenuate antipsychotic-induced hyperprolactinemia effectively. However, the ideal dosing regimen for this purpose is unknown. We aimed to evaluate the dose effects of adjunctive treatment with aripiprazole on prolactin levels and hyperprolactinemia in schizophrenia patients. Stable subjects 18-45 years old with schizophrenia and hyperprolactinemia (i.e., >24 ng/ml for females and >20 ng/ml for males) were randomly assigned to receive 8 weeks of placebo (n=30) or oral aripiprazole 5mg/day (n=30), 10mg/day (n=29), or 20mg/day (n=30) added on to fixed dose risperidone treatment. Serum prolactin levels were measured at baseline and after 2, 4 and 8 weeks; clinical symptoms and side effects were assessed at baseline and week 8 using the Positive and Negative Syndrome Scale, Clinical Global Impressions Severity scale, Barnes Akathisia Scale, Simpson-Angus Scale and UKU Side Effects Rating Scale. Of 119 randomized patients, 107 (89.9%) completed the 8-week study. At study end, all three aripiprazole doses resulted in significantly lower prolactin levels (beginning at week 2), higher response rates (≥30% prolactin reduction) and higher prolactin normalization rates than placebo. Effects were significantly greater in the 10 and 20mg/day groups than the 5mg/day group. No significant changes were observed in any treatment groups regarding psychopathology and adverse effect ratings. Adjunctive aripiprazole treatment was effective and safe for resolving risperidone-induced hyperprolactinemia, producing significant and almost maximal improvements by week 2 without significant effects on psychopathology and side effects.

Histidine-tryptophan-ketoglutarate solution maximally preserves endothelium-derived hyperpolarizing factor-mediated function during heart preservation: comparison with University of Wisconsin solution.

BACKGROUND: The University of Wisconsin (UW) solution is used widely in heart preservation but has been demonstrated to be detrimental to the endothelial function. The present study compares the effect of histidine-tryptophan-ketoglutarate (HTK) and UW solutions on endothelium-derived hyperpolarizing factor (EDHF)-mediated function in porcine small coronary arteries. METHODS: An isometric force study was performed in a myograph and the membrane potential of a single smooth muscle cell was measured electrophysiologically. Small coronary arteries (diameter 457 +/- 15 microm) were incubated with UW (n = 8), HTK (n = 7) or Krebs solution (n = 15) at 4 degrees C for 4 hours. After washout, in the presence of indomethacin (Indo; 7 micromol/liter), N(G)-nitro-l-arginine (l-NNA; 300 micromol/liter) and oxyhemoglobin (HbO; 20 micromol/liter), bradykinin (BK; -10 to -6.5 log M)-induced relaxation was compared in U46619 (-8 log M) pre-contraction. EDHF-mediated hyperpolarization was elicited by BK (-6.5 log M) in the presence of Indo, l-NNA and HbO. RESULTS: BK-induced, EDHF-mediated relaxation was reduced from 93.6 +/- 2.8% to 79.7 +/- 4.6% after UW preservation (p = 0.01 by unpaired t-test and p = 0.005 by 2-way analysis of variance [ANOVA]), whereas HTK incubation did not decrease EDHF-mediated relaxation (87.0 +/- 6.5%, p = 0.3 by unpaired t-test and p = 0.6 by 2-way ANOVA, compared with control, and p = 0.001 by 2-way ANOVA, compared with UW). EDHF-mediated hyperpolarization (10.3 +/- 1.6 mV) was attenuated by UW exposure (3.4 +/- 0.6 mV, [p = 0.002] vs control), but not by HTK exposure (8.3 +/- 1.1 mV, [p = 0.3] vs control). CONCLUSIONS: HTK is superior to UW solution in protecting EDHF-mediated endothelial function in porcine small coronary arteries. The present findings supports the use of HTK solution in heart preservation.

Effect of 11,12-epoxyeicosatrienoic acid as an additive to St. Thomas' cardioplegia and University of Wisconsin solutions on endothelium-derived hyperpolarizing factor-mediated function in coronary microarteries: influence of temperature and time.

BACKGROUND: We examined the effect of 11,12-epoxyeicosatrienoic acid (EET(11,12)) added to St. Thomas' Hospital (ST) solution or University of Wisconsin (UW) solution on endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation under clinically relevant temperature and exposure time. METHODS: Porcine coronary microarteries (200 to 450 microm) were incubated with Krebs' solution (control), ST with or without EET(11,12) (300 nmol/L) at 22 degrees C for 1 hour as well as at 4 degrees C for 1 or 4 hours, and UW with or without EET(11,12) at 4 degrees C for 4 hours. The EDHF-mediated relaxation was induced by bradykinin (-10 to approximately -6.5 log M) in the precontraction evoked by U(46619) (10 nmol/L) or U(46619) (1 nmol/L) plus endothelin-1 (6 nmol/L). RESULTS: The EDHF-mediated relaxation was reduced after exposure to UW (79.7% +/- 4.6% versus 93.6% +/- 2.8%, p = 0.01) at 4 degrees C for 4 hours. One-hour exposure to ST under 22 degrees C or 4 degrees C decreased the relaxation (75.2% +/- 7.6% versus 96.7% +/- 1.6%, p < 0.05) or the sensitivity to bradykinin (-8.04 +/- 0.15 versus -8.50 +/- 0.20 log M, p < 0.05). The relaxation increased to 86.8% +/- 5.3% by addition of EET(11,12) to ST (1 hour at 22 degrees C, p < 0.05) but was unchanged when added to either ST or UW at 4 degrees C for 1 or 4 hours. CONCLUSIONS: As an additive to ST solution, EET(11,12) may partially restore EDHF-mediated endothelial function under moderate hypothermia but had no significant effect under profound hypothermia when added to either ST or UW solution. Further investigation is necessary to improve the effect.

Alteration of cellular electrophysiologic properties in porcine pulmonary microcirculation after preservation with University of Wisconsin and Euro-Collins solutions.

BACKGROUND: The effect of cold storage of porcine pulmonary microvessels in University of Wisconsin (UW) and Euro-Collins (EC) solutions on the cellular electrophysiologic properties remains unknown. METHODS: The pulmonary microarteries (PA, 381.6 +/- 62.8 microm; n = 60) and microveins (PV, 360.8 +/- 54.5 microm; n = 60) were incubated with Krebs (control), UW, or EC solution at 4 degrees C for 4 hours in a myograph. The resting membrane potential and the endothelium-derived hyperpolarizing factor-mediated hyperpolarization to bradykinin (0.1 micromol/L) in the presence of inhibitors of nitric oxide and prostacyclin, N(omega)-nitro-l-arginine, hemoglobin, and indomethacin, in a single smooth muscle cell were directly measured. RESULTS: The resting membrane potential (-60.8 +/- 1.3 mV in PA and -48.1 +/- 0.7 mV in PV, n = 6) was depolarized after exposure to UW solution (to -18.4 +/- 0.7 mV in PA and -13.6 +/- 0.8 mV in PV; n = 8; p < 0.001). The amplitude of endothelium-derived hyperpolarizing factor-mediated hyperpolarization to bradykinin was also decreased (from 7.4 +/- 0.7 mV to 2.6 +/- 0.7 mV in PA and from 4.6 +/- 0.5 mV to 0.9 +/- 0.4 mV in PV; p < 0.001). In comparison, EC depolarized the membrane potential to a lesser extent (to -28.3 +/- 0.9 mV in PA and to -21.3 +/- 0.8 mV in PV; n = 8; p < 0.001) and almost abolished the hyperpolarization to bradykinin. After washout, hyperpolarization was partially restored (UW, 4.9 +/- 0.7 mV in PA and 2.0 +/- 0.3 mV in PV. p < 0.01; EC, 2.3 +/- 0.5 mV in PA and 1.0 +/- 0.3 mV in PV. p < 0.01). CONCLUSIONS: Cold storage of porcine PA and PV with UW or EC solution impairs the electrophysiologic properties (hyperpolarization) related to endothelium-smooth muscle interaction. The alteration is more profound with EC than UW solution and in veins than in arteries. The findings urge further studies on lung preservation solutions.

Mechanisms responsible for the in vitro relaxation of ligustrazine on porcine left anterior descending coronary artery.

In this study, we have evaluated the underlying mechanisms responsible for the relaxation response of ligustrazine (2,3,5,6-tetra-methyl-pyrazine; 2,3,5,6-MP) and its structural analogues (2-methyl-pyrazine (2-MP); ethyl-pyrazine (EP); 2,3-di-methyl-pyrazine (2,3-MP); 2,5-di-methyl-pyrazine (2,5-MP); 2,6-di-methyl-pyrazine (2,6-MP) and 2,3,5-tri-methyl-pyrazine (2,3,5-MP)) in porcine left anterior descending coronary artery (tertiary branch, O.D. 2,3,5-MP>EP>2,5-MP>/=2,6-MP>/=2,3-MP>2-MP. Besides, salbutamol and forskolin caused an endothelium-independent relaxation. The relaxation response of ligustrazine, salbutamol and forskolin was blunted in the presence of cis-N-(2-phenylcyclopentyl) azacyclotridec-1-en-2-amine (MDL 12330A) (10 microM, an adenylate cyclase inhibitor) and N-[2-((bromocinnamyl)amino)ethyl]-5-isoquinoline-sulphonamide (H-89, a protein kinase A inhibitor, 3 microM). Patch-clamp, whole-cell electrophysiological studies using single smooth muscle cells of the left anterior descending coronary artery revealed that ligustrazine (300 microM), salbutamol (30 microM) and forskolin (1 microM) inhibited the nifedipine-sensitive L-type Ca(2+) channels, and the inhibitory effect was eradicated by MDL 12330A (10 microM) and H-89 (1 microM). However, neither the Ca(2+)-dependent K(+) channel nor the ATP-dependent K(+) channel was modified by ligustrazine (300 microM). In conclusion, our results indicate that ligustrazine-mediated left anterior descending coronary artery relaxation is due to the activation of adenylate cyclase/protein kinase A cascade and the subsequent inhibition of nifedipine-sensitive, voltage-dependent L-type Ca(2+) channels. However, opening of K(+) channels seems to play no role in mediating the relaxation effect of ligustrazine.

Activation of iberiotoxin-sensitive, Ca2+-activated K+ channels of porcine isolated left anterior descending coronary artery by diosgenin.

The objective of this study was to determine the vasodilating effect of 3beta-hydroxy-5-spirostene (diosgenin), a phytoestrogen found in wild yams, using porcine resistance left anterior descending coronary artery. In 5-hydroxytryptamine (3 microM) pre-contracted preparation, diosgenin caused a concentration-dependent (0.01 to 1 microM), endothelium-independent relaxation, with a maximum relaxation of approximately 72% at 1 microM. No apparent effect was observed with 17beta-oestradiol and progesterone with concentrations < or =0.3 microM, and a relaxation of approximately 15% and approximately 23% caused by 17beta-oestradiol (1 microM) and progesterone (1 microM), respectively. Diosgenin-elicited relaxation was not altered by 7alpha,17beta-[9[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol (ICI 182,780), mifepristone, (+)-bicuculline, cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL 12330A), glibenclamide and scavengers of reactive oxygen species. The iberiotoxin-sensitive, Ca2+-activated K+ (BK(Ca)) current of single vascular myocytes recorded, using patch-clamp techniques, was markedly enhanced by diosgenin, 17beta-oestradiol and progesterone. Application of (9S, 10R, 12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester (KT 5823, 300 nM) eradicated the enhancement of BK(Ca) amplitude. Diosgenin, 17beta-oestradiol and progesterone did not affect whereas phloretin, biochanin A and zearalanone (1 microM each) significantly suppressed [Ca2+]o-induced contraction. In oestrogen competition essay using human breast cancer cell (MCF-7 cells), diosgenin (0.001 nM to 10 microM) did not interact with oestrogen receptor-alpha, and no displacement of [3H]17beta-oestradiol was observed. In oestrogen receptor alpha- and beta-fluorescence polarization competitor assay, diosgenin (100 microM) demonstrated a greater competition with the beta-isoform of oestrogen receptor. These results suggest that diosgenin caused an acute, endothelium-independent coronary artery relaxation via protein kinase G signalling cascade and an activation of BK(Ca) channel of arterial smooth muscle cells. The oestrogen receptor (alpha and beta-isoforms) and progesterone receptor are probably not involved.

Regional heterogeneity of length-tension relationships in rat lymph vessels.

BACKGROUND: Heterogeneity of the length-tension relationships in lymph vessels has never been evaluated systematically. METHODS AND RESULTS: In this study we measured the length-tension relationships in lymph vessels from three different regions of the rat: thoracic duct, cervical, and femoral lymph vessels, and compared the results to our previous measurements of rat mesenteric lymph vessels. We performed isometric force measurements on activated and passive lymph vessel segments using a small-vessel wire myograph. We found that all groups of vessels had relatively broad plateaus in their active tension versus length relationships, suggesting that they are adapted to generate near-maximal tensions over a relatively wide range of preloads (at least 0.85-1.05 L(0)). Thoracic duct exhibited the flattest active tension curve, particularly for peak active tension, in which there was less than a 5% change in peak active tension from 0.75 to 1.30 of optimal length. Femoral lymph vessels were able to withstand the highest estimated pressures, followed by mesenteric and cervical vessels and then thoracic duct. CONCLUSIONS: We conclude that lymph vessels effectively adapt their contractile force to the particular hydrodynamic conditions (transmural pressures and intraluminal flows) that exist in different regions of the lymphatic system.