Treatment with a combination of myricitrin and exercise alleviates myocardial infarction in rats via suppressing Nrf2/HO-1 antioxidant pathway.

Myocardial infarction (MI) is the primary source of death in cardiovascular diseases. Myricitrin (MYR) is a phenolic compound known for its antioxidant properties. This study aimed to investigate the impact of MYR alone or combined with exercise on a rat model of MI and its underlying mechanism. Sprague-Dawley rats were randomized into 5 groups: sham-operated (Sham), MI-sedentary (MI-Sed), MI-exercise (MI-Ex), MI-sedentary + MYR (MI-Sed-MYR) and MI-exercise + MYR (MI-Ex-MYR). MI was induced through ligation of left anterior descending coronary artery. The treatment with exercise or MYR (30 mg/kg/d) gavage began one week after surgery, either individually or in combination. After 8 weeks, the rats were assessed for cardiac function. Myocardial injuries were estimated using triphenyltetrazolium chloride, sirius red and Masson staining. Changes in reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), apoptosis and Nrf2/HO-1 pathway were analyzed by ROS kit, JC-1 kit, TUNEL assay, Western blot and immunohistochemistry. Both MYR and exercise treatments improved cardiac function, reduced infarct size, suppressed collagen deposition, and decreased myocardial fibrosis. Additionally, both MYR and exercise treatments lowered ROS production induced by MI, restored ΔΨm, and attenuated oxidative stress and apoptosis in cardiomyocytes. Importantly, the combination of MYR and exercise showed greater efficacy compared to individual treatments. Mechanistically, the combined intervention activated the Nrf2/HO-1 signaling pathway. These findings suggest that the synergistic effect of MYR and exercise may offer a promising therapeutic approach for alleviating MI.

Light scattering of a uniform uniaxial anisotropic sphere by an on-axis high-order Bessel vortex beam.

Analytical solutions to the scattering of a uniform uniaxial anisotropic sphere illuminated by an on-axis high-order Bessel vortex beam (HOBVB) are investigated. Using the vector wave theory, the expansion coefficients of the incident HOBVB in terms of the spherical vector wave functions (SVWFs) are obtained. According to the orthogonality of the associated Legendre function and exponential function, more concise expressions of the expansion coefficients are derived. It can reinterpret the incident HOBVB faster compared with the expansion coefficients of double integral forms. The internal fields of a uniform uniaxial anisotropic sphere are proposed in the integrating form of the SVWFs by introducing the Fourier transform. The differences of scattering characteristics of a uniaxial anisotropic sphere illuminated by a zero-order Bessel beam, Gaussian beam, and HOBVB are exhibited. Influences of the topological charge, conical angle, and particle size parameters on the angle distributions of the radar cross section are analyzed in detail. The scattering and extinction efficiencies varied with the particle radius, conical angle, permeability, and dielectric anisotropy are also discussed. The results provide insights into the scattering and light-matter interactions and may find important applications in optical propagation and optical micromanipulation of biological and anisotropic complex particles.

Sites and Regulation of L-Type Ca2+ Channel Cav1.2 Phosphorylation in Brain.

Cav1.2 channel phosphorylation plays an important role in regulating neuronal plasticity by action potential-dependent Ca2+ entry. Most studies of Cav1.2 regulation by phosphorylation have been reported in heart and muscles. Here, we identified phosphorylation sites of neuronal Cav1.2 channel protein purified from rat brain using mass spectrometry. The functional characterization of these phosphorylation sites showed altered voltage-dependent biophysical properties of the channel, without affecting current density. These results show that neuronal Cav1.2 channel is regulated by phosphorylation in a complex mechanism involving multiple phosphorylation sites.

Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study. / ä¸åŒç»´æŒå‰‚é‡æž¸æ©¼é ¸å’–å•¡å› å¯¹è¾ åŠ©é€šæ°”æ—©äº§å„¿çš„ç–—æ•ˆè¯„ä¼°ï¼šä¸€é¡¹åˆæ­¥å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS: This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.

Analysis of radiation force on a uniaxial anisotropic sphere by dual counter-propagating Gaussian beams.

Based on Maxwell's stress tensor and the generalized Lorenz-Mie theory, a theoretical approach is introduced to study the radiation force exerted on a uniaxial anisotropic sphere illuminated by dual counter-propagating (CP) Gaussian beams. The beams propagate with arbitrary direction and are expanded in terms of the spherical vector wave functions (SVWFs) in a particle coordinate system using the coordinate rotation theorem of the SVWFs. The total expansion coefficients of the incident fields are derived by superposition of the vector fields. Using Maxwell stress tensor analysis, the analytical expressions of the radiation force on a homogeneous absorbing uniaxial anisotropic sphere are obtained. The accuracy of the theory is verified by comparing the radiation forces of the anisotropic sphere reduced to the special cases of an isotropic sphere. In order to study the equilibrium state, the effects of beam parameters, particle size parameters, and anisotropy parameters on the radiation force are discussed in detail. Compared with the isotropic particle, the equilibrium status is sensitive to the anisotropic parameters. Moreover, the properties of optical force on a uniaxial anisotropic sphere in a single Gaussian beam trap and Gaussian standing wave trap are compared. It indicates that the CP Gaussian beam trap may more easily capture or confine the anisotropic particle. However, the radiation force exerted on an anisotropic sphere exhibits very different properties when the beams do not propagate along the primary optical axis. The influence of the anisotropic parameter on the radiation force by CP Gaussian beams is different from that of a single Gaussian beam. In summary, even for anisotropic particles, the Gaussian standing wave trap also exhibits significant advantages when compared with the single Gaussian beam trap. The theoretical predictions of radiation forces exerted on a uniaxial anisotropic sphere by dual Gaussian beams provide effective ways to achieve the improvement of optical tweezers as well as the capture, suspension, and high-precision delivery of anisotropic particles.

DKK1 inhibits breast cancer cell migration and invasion through suppression of ß-catenin/MMP7 signaling pathway.

BACKGROUND: DKK1 has been reported to act as a tumor suppressor in breast cancer. However, the mechanism of DKK1 inhibits breast cancer migration and invasion was still unclear. METHODS: Western blot and real time PCR was used to detect the expression of DKK1, ß-catenin and MMP7 in breast cancer cells. Wound scratch assay and transwell assay was employed to examine migration and invasion of breast cancer cell. RESULTS: DKK1 overexpression dramatically inhibits breast cancer cell migration and invasion. Knockdown of DKK1 promotes migration and invasion of breast cancer cells. DKK1 suppressed breast cancer cell migration and invasion through suppression of ß-catenin and MMP7 expression. XAV-939, an inhibitor of ß-catenin accumulation could reverse DKK1 silencing-induced MMP7 expression in breast cancer cells. Meanwhile, XAV-939 also could reverse the increase in the cell number invaded through Matrigel when DKK1 was knockdown. Furthermore, depletion of MMP7 also could reverse DKK1 knockdown-induced increase in the cell number invaded through Matrigel. CONCLUSIONS: DKK1 inhibits migration and invasion of breast cancer cell through suppression of ß-catenin/MMP7 pathway, our findings offered a potential alternative for breast cancer prevention and treatment.

Suppression of epidermal growth factor receptor-mediated ß-catenin nuclear accumulation enhances the anti-tumor activity of phosphoinositide 3-kinase inhibitor in breast cancer.

Phosphoinositide 3-kinase (PI3K) signaling is frequently deregulated in breast cancer and plays a critical role in tumor progression. However, resistance to PI3K inhibitors in breast cancer has emerged, which is due to the enhanced ß-catenin nuclear accumulation. Until now, the mechanisms underlying PI3K inhibition-induced ß-catenin nuclear accumulation remains largely unknown. In the present study, we found inhibition of PI3K with LY294002 promoted ß-catenin nuclear accumulation in MCF-7 and MDA-MB-231 breast cancer cells. Combining PI3K inhibitor LY294002 with XAV-939, an inhibitor against ß-catenin nuclear accumulation, produced an additive anti-proliferation effect against breast cancer cells. Subsequent experiments suggested ß-catenin nuclear accumulation induced by PI3K inhibition depended on the feedback activation of epidermal growth factor receptor (EGFR) signaling pathway in breast cancer cells. Inhibition of EGFR phosphorylation with Gefitinib enhanced anti-proliferation effect of PI3K inhibitor LY294002 in MCF-7 and MDA-MB-231 cells. Taken together, our findings may elucidate a possible mechanism explaining the poor outcome of PI3K inhibitors in breast cancer treatment.

Doppler ultrasonographic and clinical features of middle aortic syndrome.

OBJECTIVES: To discuss Doppler ultrasonographic and clinical features of middle aortic syndrome (MAS). MATERIALS AND METHODS: Doppler ultrasonographic images and clinical dates of 11 patients with MAS confirmed by angiography were retrospectively analyzed from January 2004 to September 2016. RESULTS: The median age of 11 patients was 10 years (1-39 years). Ten patients presented with hypertension, only 2 cases presented with symptomatic intermittent claudication, and 1 case presented with abdominal pain. The ultrasonographic features of 11 patients with MAS included: (a) Gray-scale image showed significant segmental narrowing of the aorta in 9 cases. (b) Color Doppler demonstrated aliasing in the suspicious narrowed vessels of all cases. (c) On Spectral Doppler image, peak systolic velocity in the location of aorta coarctation was significantly elevated (range, 2.3~4.8 m/s). When infrarenal aorta was involved, a tardus-parvus waveform was only seen in the distal aorta. When suprarenal or inter-renal aorta was involved, a tardus-parvus pattern was seen in the distal aorta as well as renal artery. CONCLUSIONS: Significant segmental narrowing and a tardus-parvus waveform are the important ultrasonographic features in patients with MAS, the latter may be more reliable. Doppler ultrasound can be used as a simple screening method, especially for children and adolescents suspected of having a vascular cause of refractory hypertension.

[7-hydroxy sulfonation of liquiritigenin by recombinant SULT1A3 enzyme and HEK-SULT1A3 cells].

In this study,liquiritigenin sulfonation was characterized using recombinant human sulfotransferases( SULTs). The chemical structure of liquiritigenin sulfate was determined by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS). Then model fitting and parameter estimation were performed using the Graphpad Prism V5 software. Various SULT enzymes( SULT1 A1,1 A2,1 A3,1 B1,1 C2,1 C4,1 E1 and 2 A1) were able to catalyze the formation of liquiritigenin-7-O-sulfate. Sulfonation of liquiritigenin-7-hydroxy( 7-OH) by these eight SULT enzymes consistently displayed the classical Michaelis-Menten profile. According to the intrinsic clearance( CLint) value,the sulfonation rates of liquiritigenin-7-OH by expressed SULT enzymes followed the following rank order: SULT1 C4 > SULT1 A3 > SULT1 E1 > SULT1 A1 > SULT1 A2 > SULT1 B1 >SULT1 C2>SULT2 A1. Further,liquiritigenin-7-O-sulfonation was significantly correlated with the SULT1 A3 protein levels( P<0. 05).Then,human embryonic kidney( HEK) 293 cells over expressing SULT1 A3( named as HEK-SULT1 A3 cells) were conducted. As a result,liquiritigenin-7-O-sulfate( L-7-S) was rapidly generated upon incubation of the cells with liquiritigenin. Consistent with SULT1 A3,sulfonation of liquiritigenin-7-OH in HEK-SULT1 A3 cells also followed the Michaelis-Menten kinetics. The derived Vmaxvalues was( 0. 315±0. 009) µmol·min-1·g-1,Kmwas( 7. 04±0. 680) µmol·L-1,and CLintwas( 0. 045±0. 005) L·min-1·g-1. Moreover,the sulfonation characters of liquiritigenin( 7-OH) in SULT1 A3 were strongly correlated with that in HEK-SULT1 A3 cells( P<0. 001).The results indicated that HEK-SULT1 A3 cells have shown the catalytic function of SULT1 A3 enzymes. In conclusion,liquiritigenin was subjected to efficient sulfonation,and SULT1 A3 enzyme plays an important role in the sulfonation of liquiritigenin-7-OH. Significant sulfonation should be the main reason for the low bioavailability of liquiritigenin. In addition,HEK-SULT1 A3 cells were conducted and successfully used to evaluate liquiritigenin sulfonation,which will provide an appropriate tool to accurately depict the sulfonation disposition of liquiritigenin in vivo.

Down-Regulation of Laminin (LN)- α5 is Associated with Preeclampsia and Impairs Trophoblast Cell Viability and Invasiveness Through PI3K Signaling Pathway.

BACKGROUND/AIMS: Preeclampsia (PE) is a gestational disorder defined as hypertension and proteinuria, which is deemed a major cause of maternal and neonatal mortality and morbidity worldwide. The aim of this study was to investigate the expression patterns of placental laminin (LN)-α5 expression in normal and PE pregnancies, as well as evaluating the effects of LN-α5 on trophoblast proliferation, apoptosis, and invasion. METHODS: LN-α5 expression levels were examined by reverse-transcriptase polymerase chain reaction (RT-PCR), and further confirmed by western blotting and immunofluorescence staining. Cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry. Cell invasion was assessed by matrigel-based transwell assay. LN-α5 DNA methylation in placentas was determined by bisulfite sequencing PCR (BSP). RESULTS: LN-α5 expression levels in PE placentas were significantly lower than that of normal pregnancies. Deficiency in LN-α5 expression resulted in decreased trophoblast proliferation and invasion but increased cell apoptosis, meanwhile, PI3K/AKT/mTOR signaling pathway was impaired by LN-α5 silencing. LN-α5 promoter methylation didn't show significant difference between PE and normal placentas. CONCLUSION: LN-α5 downregulation is associated with PE placenta and impairs trophoblast viability and invasiveness, which could be a causative factor of PE pathogenesis.

[Change in serum intestinal fatty acid binding protein and its significance in children with pneumonia and gastrointestinal injury].

OBJECTIVE: To study the change in serum intestinal fatty acid binding protein (IFABP) in children with pneumonia and its correlation with gastrointestinal injury. METHODS: A total of 82 children with community-acquired pneumonia who were treated from January to October, 2015 were enrolled, among whom 34 had mild pneumonia and 48 had severe pneumonia. According to pediatric critical illness score (PCIS), the children with severe pneumonia were further divided into non-critical group (25 patients) and critical group (23 patients). Thirty healthy children who underwent physical examination at outpatient service were enrolled as the control group. ELISA was used to measure serum IFABP level, and the acute gastrointestinal injury (AGI) grade was determined for children with severe pneumonia. Serum IFABP level was compared between groups, and the correlations of IFABP with AGI grade and PCIS were analyzed. RESULTS: The severe pneumonia group showed a significantly higher serum IFABP level than the control group and the mild pneumonia group (P<0.01), and the mild pneumonia group also showed a significantly higher serum IFABP level than the control group (P<0.01). The critical group showed a significantly higher serum IFABP level than the non-critical group (P<0.01). The patients with grade I-IV AGI had significantly higher serum IFABP levels than the control group (P<0.01), and the serum IFABP level increased significantly with the increasing AGI grade (P<0.01). Serum IFABP level was positively correlated with AGI grade (P<0.01) but negatively correlated with PCIS (P<0.01). CONCLUSIONS: Children with pneumonia experience an increased serum IFABP level which can be used as a sensitive indicator for the early diagnosis of gastrointestinal injury and the evaluation of conditions in children with pneumonia.

Honokiol induces cell cycle arrest and apoptosis via inhibiting class I histone deacetylases in acute myeloid leukemia.

Honokiol, a constituent of Magnolia officinalis, has been reported to possess potent anti-cancer activity through targeting multiple signaling pathways in numerous malignancies including acute myeloid leukemia (AML). However, the underlying mechanisms remain to be defined. Here, we report that honokiol effectively decreased enzyme activity of histone deacetylases (HDACs) and reduced the protein expression of class I HDACs in leukemic cells. Moreover, treatment with proteasome inhibitor MG132 prevented honokiol-induced degradation of class I HDACs. Importantly, honokiol increased the levels of p21/waf1 and Bax via triggering acetylation of histone in the regions of p21/waf1 and Bax promoter. Honokiol induced apoptosis, decreased activity of HDACs, and significantly inhibited the clonogenic activity of hematopoietic progenitors in bone marrow mononuclear cells from patients with AML. However, honokiol did not decrease the activity of HDACs and induce apoptosis in normal hematopoietic progenitors from unbilicial cord blood. Finally, honokiol dramatically reduced tumorigenicity in a xenograft leukemia model. Collectively, our findings demonstrate that honokiol has anti-leukemia activity through inhibiting HDACs. Thus, being a relative non-toxic agent, honokiol may serve as a novel natural agent for cancer prevention and therapy in leukemia.

EGCG inhibits properties of glioma stem-like cells and synergizes with temozolomide through downregulation of P-glycoprotein inhibition.

RATIONAL: Combination therapy to inhibit cancer stem cells may have important clinical implications. Here, we examine the molecular mechanisms by which epigallocatechin gallate (EGCG), a bioactive polyphenol in green tea, inhibits the stem cell characteristics of glioma stem-like cells (GSLCs) and synergizes with temozolomide (TMZ), a DNA-methylating agent commonly used as first-line chemotherapy in gliomas. GSLCs were enriched from the human glioblastoma cell line U87 using neurosphere culture. Cells were analyzed using flow cytometry, quantitative PCR, and western blotting. Compared to U87 cells, a higher percentage of U87 GSLCs remained in the G0/G1 phase, with downregulation of the cell-cycle protein CylinD1 and overexpression of stem cell markers CD133 and ALDH1. The drug-resistance gene ABCB1 (but not ABCG2 or MGMT) also showed high mRNA and protein expression. The resistance index of U87 GSLCs against TMZ and carmustine (BCNU) was 3.0 and 16.8, respectively. These results indicate that U87 GSLCs possess neural stem cell and drug-resistance properties. Interestingly, EGCG treatment inhibited cell viability, neurosphere formation, and migration in this cell model. EGCG also induced apoptosis, downregulation of p-Akt and Bcl-2, and cleaving PARP in a dose-dependent manner. Importantly, EGCG treatment significantly downregulated P-glycoprotein expression but not that of ABCG2 or MGMT and simultaneously enhanced sensitivity to TMZ. Our study demonstrates that the use of EGCG alone or in combination with TMZ may be an effective therapeutic strategy for glioma.

Two new compounds from the plant endophytic fungus Pestalotiopsis versicolor.

A new coumarin, 4,6-dihydroxy-7-formyl-3-methylcoumarin (1), and an α-pyrone derivative, 6-[(7S,8R)-8-propyloxiran-1-yl]-4-methoxy-pyran-2-one (2), together with four known α-pyrone derivatives (3-6), were isolated from the broth extract of the plant endophytic fungus Pestalotiopsis versicolor. Their structures were elucidated by extensive spectroscopic analysis and by comparison of the chemical shift values with those of related known compounds.

Epithelial-to-mesenchymal transition is involved in BCNU resistance in human glioma cells.

Chemotherapy has been considered as an effective treatment for malignant glioma; however, it becomes increasingly ineffective with tumor progression. Epithelial-to-mesenchymal transition (EMT) is a process whereby cells acquire morphologic and molecular alterations that facilitate tumor metastasis and progression. Emerging evidence associates chemoresistance with the acquisition of EMT in cancer. However, it is not clear whether this phenomenon is involved in glioma. We used the previously established human glioma cell lines SWOZ1, SWOZ2 and SWOZ2-BCNU to assess cellular morphology, molecular changes, migration and invasion. We found that BCNU-resistant cells showed multiple drug resistance and phenotypic changes consistent with EMT, including spindle-shaped morphology and enhanced pseudopodia formation. Decreased expression of the epithelial adhesion molecule E-cadherin and increased expression of the mesenchymal marker vimentin were observed in BCNU-resistant SWOZ1 and SWOZ2-BCNU cells compared to SWOZ2 cells. Migratory and metastatic potentials were markedly enhanced in SWOZ1 and SWOZ2-BCNU cells compared to SWOZ2 cells. These data suggest that there is a possible link between drug resistance and EMT induction in glioma cells. Gaining further insight into the mechanisms underlying chemoresistance and EMT may enable the restoration of chemosensitivity or suppression of metastasis.

Regional subsidence monitoring and prediction along high-speed railways based on PS-InSAR and LSTM.

The rapid construction of high-speed railways in China has forced more and more routes to pass through slow subsidence zones caused by groundwater extraction or underground mining. It is crucial to carry out deformation monitoring and prediction those areas along high-speed railways to ensure the safe operation. Twenty-nine periods of Sentinel-1A data between Taiyuan South Station and Taigu East Station were first processed using the PS-InSAR technique, and the ground subsidence sequences at ten typical points were selected. Then the Variational modal decomposition (VMD) was combined with the Adaptive Boosting Algorithm (AdaBoost), and the VMD-LSTMAda-LSTMAda model was constructed by combining the long short-term memory (LSTM) model for the prediction of regional ground subsidence along the high-speed railway. The results show that the cumulative subsidence within the 200 m buffer of the line centreline is - 37.58 - 89.19 mm, and the annual average subsidence rate is - 26.57 - 82.63 mm/y. The proposed model can reduce the complexity of the deformation sequence and combines with AdaBoost to improve the prediction accuracy of the LSTM model. It performs well in terms of RMSE, MAE, MAPE, and R2 at the two feature points (3703: RMSE = 0.82 mm, MAE = 0.25 mm, MAPE = 6.31%, and R2 = 0.94; 522: RMSE = 1.32 mm, MAE = 0.46 mm, MAPE = 4.92%, R2 = 0.95). The model improves the accuracy of regional subsidence prediction along the high-speed railway.

Amygdalin and exercise training exert a synergistic effect in improving cardiac performance and ameliorating cardiac inflammation and fibrosis in a rat model of myocardial infarction.

This study investigated the effects of amygdalin (AMY, a cyanogenic glycoside widely distributed in the fruits and seeds of Rosaceae plants) on cardiac performance and ventricular remodeling in a rat model of myocardial infarction (MI). We also investigated whether the combination of AMY with exercise training (ExT) has a beneficial synergistic effect in treating MI rats. MI was induced by the ligation of the left anterior descending coronary artery in male SD rats. ExT or AMY treatment was started 1 week after MI and continued for 1 week (short-term) or 8 weeks (long-term). Cardiac function was evaluated by echocardiographic and hemodynamic parameters. Heart tissues were harvested and subjected to 2,3,5-triphenyl-tetrazolium chloride, Masson's trichrome, hematoxylin-eosin, and immunohistochemical staining. Gene expression was determined by quantitative polymerase chain reaction. Western blot gave a qualitative assessment of protein levels. AMY or ExT improved cardiac function and reduced infarct size in MI rats. AMY or ExT also suppressed myocardial fibrosis and attenuated inflammation in the infarct border zone of hearts from MI rats, as evidenced by inhibition of collagen deposition, inflammatory cell infiltration, and pro-inflammatory markers (interleukin 1ß, interleukin 6, tumor necrosis factor-α, and cyclooxygenase 2). Notably, the effects of AMY combined with ExT were superior to those of AMY alone or ExT alone. Mechanistically, these beneficial functions were correlated with the inhibition of MI-induced activation of the transforming growth factor-ß/Smad pathway. Collectively, AMY and ExT exert a synergistic effect on improving cardiac performance and ameliorating cardiac inflammation and fibrosis after MI, and the effects of long-term intervention were better than short-term intervention.

Effects of eugenol on T-type Ca2+ channel isoforms.

Eugenol has been used as an analgesic in dentistry. Previous studies have demonstrated that voltage-gated Na(+) channels and high-voltage-activated Ca(2+) channels expressed in trigeminal ganglion (TG) neurons sensing dental pain are molecular targets of eugenol for its analgesic effects. However, it has not been investigated whether eugenol can affect T-type Ca(2+) channels, which are known to be detected in the afferent neurons. In this report, we investigate how eugenol can influence cloned T-type channel isoforms expressed in HEK293 cells, using whole-cell patch clamp. Application of eugenol inhibited Cav3.1, Cav3.2, and Cav3.3 currents in a concentration-dependent manner with IC50 values of 463, 486, and 708 µM, respectively. Eugenol was found to negatively shift the steady-state inactivation curves of the T-type channel isoforms, but it did not shift their activation curves. In addition, eugenol had little effect on the current kinetics of Cav3.1 and Cav3.2, but it accelerated the inactivation kinetics of Cav3.3 currents. Reduction of channel availability enhanced eugenol inhibition sensitivity for Cav3.1 and Cav3.2, but not for Cav3.3. Moreover, eugenol inhibition of T-type channel isoforms was found to be use dependent. Finally, we show that the T-type currents recorded from rat TG neurons were inhibited by eugenol with a similar potency to Cav3.1 and Cav3.2 isoforms. Taken together, our findings suggest that T-type Ca(2+) channels are additional molecular targets for the pain-relieving effects of eugenol.

Biophysical studies on the interactions of jatrorrhizine with bovine serum albumin by spectroscopic and molecular modeling methods.

The interaction between jatrorrhizine (JAT) and bovine serum albumin (BSA) has been studied. The studies were carried out in a buffer medium at pH 7.4 using fluorescence spectroscopy, UV-vis spectroscopy, and molecular modeling methods. The results of fluorescence quenching and UV-vis absorption spectra experiments indicated the formation of the complex of BSA-JAT. Binding parameters were determined using the Stern-Volmer equation and Scatchard equation. The results of thermodynamic parameters ΔG, ΔH and ΔS at different temperatures indicate that the electrostatic interactions and hydrogen bonds play a major role for JAT-BSA association. Site marker competitive displacement experiments and molecular modeling calculation demonstrating that JAT is mainly located within the hydrophobic pocket of the subdomain IIIA of BSA. Furthermore, The distance between donor (BSA) and acceptor (JAT) was estimated according to fluorescence resonance energy transfer.

[Effects on the secretion of reproductive hormones in adult female rats exposed to lipopolysaccharide in neonatal life].

OBJECTIVE: To explore whether neonatal endotoxin challenge alters reproductive hormone secretion in adult female rats. METHODS: Rats were intraperitoneally injected with lipopolysaccharide (LPS) or normal saline at postnatal days 3 and 5. At Week 12, the animals underwent bilateral oophorectomy and were exposed to LPS or saline. The secretion levels of luteinizing hormone (LH) and estradiol were measured. RESULTS: The LPS injection in adult neonatal saline rats caused the suppressed secretion of LH and estradiol. However, the decreased secretion of both LH and estradiol were much more apparent in adult neonatal LPS-treated rats. CONCLUSION: The neonatal LPS challenge alters the secretions of LH and estradiol during adulthood. And the mechanism may be mediated by epigenetic programming of hypothalamic-pituitary-gonadal axis.