[Effect and mechanism of leonurine on pressure overload-induced cardiac hypertrophy in rats].

To investigate the effects of leonurine(Leo) on abdominal aortic constriction(AAC)-induced cardiac hypertrophy in rats and its mechanism. A rat model of pressure overload-induced cardiac hypertrophy was established by AAC method. After 27-d intervention with high-dose(30 mg·kg~(-1)) and low-dose(15 mg·kg~(-1)) Leo or positive control drug losartan(5 mg·kg~(-1)), the cardiac function was evaluated by hemodynamic method, followed by the recording of left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVESP), as well as the maximum rate of increase and decrease in left ventricular pressure(±dp/dt_(max)). The degree of left ventricular hypertrophy was assessed based on heart weight index(HWI) and left ventricular mass index(LVWI). Myocardial tissue changes and the myocardial cell diameter(MD) were measured after hematoxylin-eosin(HE) staining. The contents of angiotensin Ⅱ(AngⅡ) and angiotensin Ⅱ type 1 receptor(AT1 R) in myocardial tissue were detected by ELISA. The level of Ca~(2+) in myocardial tissue was determined by colorimetry. The protein expression levels of phospholipase C(PLC), inositol triphosphate(IP3), AngⅡ, and AT1 R were assayed by Western blot. Real-time quantitative PCR(qRT-PCR) was employed to determine the mRNA expression levels of ß-myosin heavy chain(ß-MHC), atrial natriuretic factor(ANF), AngⅡ, and AT1 R. Compared with the model group, Leo decreased the LVSP, LVEDP, HWI, LVWI and MD values, but increased ±dp/dt_(max) of the left ventricle. Meanwhile, it improved the pathological morphology of myocardial tissue, reduced cardiac hypertrophy, edema, and inflammatory cell infiltration, decreased the protein expression levels of PLC, IP3, AngⅡ, AT1 R, as well as the mRNA expression levels of ß-MHC, ANF, AngⅡ, AT1 R, c-fos, and c-Myc in myocardial tissue. Leo inhibited AAC-induced cardiac hypertrophy possibly by influencing the RAS system.

Tanshinone IIA alleviates brain damage in a mouse model of neuromyelitis optica spectrum disorder by inducing neutrophil apoptosis.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD), an autoimmune astrocytopathic disease associated with the anti-aquaporin-4 (AQP4) antibody, is characterized by extensive necrotic lesions primarily located on the optic nerves and spinal cord. Tanshinone IIA (TSA), an active natural compound extracted from Salvia miltiorrhiza Bunge, has profound immunosuppressive effects on neutrophils. OBJECTIVE: The present study aimed to evaluate the effect of TSA on NMOSD mice and explore the underlying mechanisms. Mice were initially administered TSA (pre-TSA group, n = 20) or vehicle (vehicle group, n = 20) every 8 h for 3 days, and then NMOSD model was induced by intracerebral injection of NMOSD-immunoglobulin G (NMO-IgG) and human complement (hC). In addition, post-TSA mice (n = 10) were administered equal dose of TSA at 8 h and 16 h after model induction. At 24 h after intracerebral injection, histological analysis was performed to assess the inhibitory effects of TSA on astrocyte damage, demyelination, and neuroinflammation in NMOSD mice, and western blotting was conducted to clarify the effect of TSA on the NF-κB and MAPK signaling pathways. Furthermore, flow cytometry and western blotting were conducted to verify the proapoptotic effects of TSA on neutrophils in vitro. RESULTS: There was a profound reduction in astrocyte damage and demyelination in the pre-TSA group and post-TSA group. However, prophylactic administration of TSA induced a better effect than therapeutic treatment. The number of infiltrated neutrophils was also decreased in the lesions of NMOSD mice that were pretreated with TSA. We confirmed that prophylactic administration of TSA significantly promoted neutrophil apoptosis in NMOSD lesions in vivo, and this proapoptotic effect was mediated by modulating the caspase pathway in the presence of inflammatory stimuli in vitro. In addition, TSA restricted activation of the NF-κB signaling pathway in vivo. CONCLUSION: Our data provide evidence that TSA can act as a prophylactic agent that reduces NMO-IgG-induced damage in the mouse brain by enhancing the resolution of inflammation by inducing neutrophil apoptosis, and TSA may serve as a promising therapeutic agent for neutrophil-associated inflammatory disorders, such as NMOSD.

Advances in the study of egg activation of higher plants.

Fertilization in higher plants induces many structural and physiological changes in the fertilized egg, and represents the transition from the haploid female gamete to the diploid zygote, the first cell of a sporophyte. Some changes are induced extremely rapidly following fusion with sperm cells and are the preclusions of egg activation. This review focuses on the early changes that occur in the egg after fusion with sperm cells, but before nuclear fusion. Reported changes include cell shrinkage, cell wall formation, polarity change, oscillation in Ca2+ concentration, and DNA synthesis. In addition, the current understanding of egg activation is summarized and the possible functional relevance of the changes is explored.

Analytical Solutions for Multi-Time Scale Fractional Stochastic Differential Equations Driven by Fractional Brownian Motion and Their Applications.

In this paper, we investigate analytical solutions of multi-time scale fractional stochastic differential equations driven by fractional Brownian motions. We firstly decompose homogeneous multi-time scale fractional stochastic differential equations driven by fractional Brownian motions into independent differential subequations, and give their analytical solutions. Then, we use the variation of constant parameters to obtain the solutions of nonhomogeneous multi-time scale fractional stochastic differential equations driven by fractional Brownian motions. Finally, we give three examples to demonstrate the applicability of our obtained results.

[Correlation analysis between foliar endophytic fungi of Salvia miltiorrhiza and effective components].

The aim of this study was to comprehensively investigate the correlations between foliar fungal endophyte communities and effective components accumulations in Salvia miltiorrhiza. Foliar samples of S. miltiorrhiza were collected in 5 different areas. Their fungal endophyte communities and effective component contents were determined by denaturing gradient gel electrophoresis (DGGE) and high performance liquid chromatography (HPLC), respectively. The results showed that, for characteristics of foliar fungal endophyte communities and effective component contents, there were both similarities and differences among the five samples. Correlation analysis of DGGEs' band and 24 effective components revealed a significant correlations (P < 0.01). For examples, 4 bands (15, 18, 23 and 26) were all significantly correlated with the accumulations of caffeic acid, salvianolic acid B, salvianolic acid C and dihydrotanshinone I.

Ryanodine receptor 2 contributes to hemorrhagic shock-induced bi-phasic vascular reactivity in rats.

AIM: Ryanodine receptor 2 (RyR2) is a critical component of intracellular Ca(2+) signaling in vascular smooth muscle cells (VSMCs). The aim of this study was to investigate the role of RyR2 in abnormal vascular reactivity after hemorrhagic shock in rats. METHODS: SD rats were hemorrhaged and maintained mean arterial pressure (MAP) at 40 mmHg for 30 min or 2 h, and then superior mesenteric arteries (SMA) rings were prepared to measure the vascular reactivity. In other experiments, SMA rings of normal rats and rat VSMCs were exposed to a hypoxic medium for 10 min or 3 h. SMA rings of normal rats and VSMCs were transfected with siRNA against RyR2. Intracellular Ca(2+) release in VSMCs was assessed using Fura-2/AM. RESULTS: The vascular reactivity of the SMA rings from hemorrhagic rats was significantly increased in the early stage (30 min), but decreased in the late stage (2 h) of hemorrhagic shock. Similar results were observed in the SMA rings exposed to hypoxia for 10 min or 3 h. The enhanced vascular reactivity of the SMA rings exposed to hypoxia for 10 min was partly attenuated by transfection with RyR2 siRNA, whereas the blunted vascular reactivity of the SMA rings exposed to hypoxia for 3 h was partly restored by transfection with RyR2 siRNA. Treatment with the RyR agonist caffeine (1 mmol/L) significantly increased Ca(2+) release in VSMCs exposed to hypoxia for 10 min or 3 h, which was partially antagonized by transfection with RyR2 siRNA. CONCLUSION: RyR2-mediated Ca(2+) release contributes to the development of bi-phasic vascular reactivity induced by hemorrhagic shock or hypoxia.

Isoliquiritigenin alleviates experimental autoimmune encephalomyelitis by modulating inflammatory and neuroprotective reactive astrocytes.

Multiple sclerosis (MS) is an autoimmune-mediated chronic inflammatory demyelinating disease of the central nervous system (CNS) that poses significant treatment challenges. Currently, it is believed that inflammatory and neuroprotective reactive astrocytes, along with other resident CNS cells and immune cells, contribute to the pathophysiology of MS. In our study, we found that isoliquiritigenin (ILG), a bioactive chalcone compound, significantly reduces the clinical scores of experimental autoimmune encephalomyelitis (EAE) by 44 % (P < 0.05). Additionally, ILG significantly decreases the pathological scores of spinal cord inflammation and demyelination by 61 % and 65 %, respectively (both P < 0.0001). Furthermore, ILG affects the populations of CD4, Th1, Th17, and Treg cells in vivo. More importantly, ILG significantly promotes the activation of astrocytes in EAE (P < 0.0001). Additionally, ILG treatment indirectly inhibits inflammatory reactive astrocytes and promotes neuroprotective reactive astrocytes. It reduces spleen levels of TNFα, IL1α, C1qa, IL1ß, and IL17A by 95 % (P < 0.001), 98 % (P < 0.01), 46 % (P < 0.05), 97 % (P < 0.001), and 60 % (P < 0.001), respectively. It also decreases CNS levels of TNFα, IL1α, C1qa, IL1ß, and IL17A by 53 % (P < 0.05), 88 % (P < 0.05), 64 % (P < 0.01), 57 % (P < 0.05), and 60 % (P < 0.001), respectively. These results indicate that ILG exerts an immunoregulatory effect by inhibiting the secretion of pro-inflammatory cytokines. Consequently, ILG inhibits inflammatory reactive astrocytes, promotes neuroprotective reactive astrocytes, alleviates inflammation and improves EAE. These findings provide a theoretical basis and support for the application of ILG in the prevention and treatment of MS.

Treatment of Degenerative Lumbar Scoliosis with Oblique Lumbar Interbody Fusion in Conjunction with Unilateral Pedicle Screw Fixation via the Wiltse Approach.

OBJECTIVE: To evaluate the clinical outcomes of oblique lumbar interbody fusion (OLIF) in conjunction with unilateral pedicle screw fixation (UPSF) via the Wiltse approach in treating degenerative lumbar scoliosis (DLS). METHODS: The article is a retrospective analysis. Twelve patients with DLS who underwent combined OLIF and UPSF between July 2017 and December 2018 were included. The study included 2 male and 10 female patients, with a mean age at the time of the operation of 67.2 ± 9.1 years. The surgical characteristics and complications were evaluated. The clinical and radiological data such as the correction of deformity, coronal and sagittal profile were analyzed. RESULTS: The mean follow-up time of the study was 26.8 ± 1.8 months. At the final follow-up, all patients who underwent combined OLIF and UPSF achieved statistically significant improvements in coronal Cobb angle (from 19.6° ± 4.8° to 6.9° ± 3.8°, P < 0.01), distance between the C7 plumb line and central sacral vertebral line (from 2.5 ± 1.7 cm to 0.9 ± 0.6 cm, P < 0.01), sagittal vertebral axis (from 4.3 ± 4.3 cm to 1.5 ± 1.0 cm, P = 0.03), lumbar lordosis (from 29.4° ± 8.6° to 40.8° ± 5.8°, P < 0.01), pelvic tilt (from 27.6° ± 10.8° to 18.3° ± 7.0°, P < 0.01), pelvic incidence-lumbar lordosis mismatch (from 23.3° ± 10.5° to 11.9° ± 8.4°, P < 0.01), and cross-sectional area of the dural sac (from 87.33 ± 39.41 mm2 to 124.70 ± 39.26 mm2 , P < 0.01). The visual analogue score for back and leg pain and Oswestry Disability Index of all patients significantly improved postoperatively (P < 0.01). One case of lumbar plexus injury was found after surgery. During the follow-up period, one patient had cage subsidence. A fusion rate of 100% and good positioning of the pedicle screws were achieved in all patients at the final follow-up. CONCLUSION: OLIF in conjunction with UPSF is a safe and effective minimally invasive procedure for correcting both coronal and sagittal deformities, as it results in an improved quality of life in patients with DLS.

Tanshinone IIA Ameliorates CNS Autoimmunity by Promoting the Differentiation of Regulatory T Cells.

Tanshinone IIA (TSA), an important natural lipophilic diterpene compound from the traditional Chinese herb Salvia miltiorrhiza Bunge, has long been widely used for the prevention and treatment of various diseases because of its anti-inflammatory activities; however, the anti-inflammatory mechanism remains unknown. In the present work, we examined the effects of TSA on experimental autoimmune encephalomyelitis (EAE), a model of autoreactive T/B cell-mediated central nervous system (CNS) autoimmunity. The data showed that TSA significantly attenuates the severity of EAE when administered at the pre-onset and peak of clinical disease. In vivo, the protective effects of TSA on EAE mice are correlated with diminished inflammatory infiltration, demyelination, and GM-CSF-producing CD4+ T cells in the spinal cord and selectively increased regulatory T (Treg) cell frequencies in both the spinal cord and spleen. We further confirm that TSA can promote the polarization of naïve CD4+ T cells into Treg cells both by targeting dendritic cells (DCs) to drive transforming growth factor ß1 (TGF-ß1) upregulation and by directly targeting naïve CD4+ T cells in vitro. Most importantly, we showed that TSA-induced Treg cells display an effective suppressive activity at a level comparable to TGF-ß1-polarized Treg Cells in vitro and in vivo. Taken together, our data provide evidence that TSA can promote Treg cell differentiation, and TSA may have a promising application as a therapeutic agent for the treatment of neuroinflammatory diseases.

Two-dimensional Co-Seismic Surface Displacements Field of the Chi-Chi Earthquake Inferred from SAR Image Matching.

The Mw=7.6 Chi-Chi earthquake in Taiwan occurred in 1999 over the Chelungpu fault and caused a great surface rupture and severe damage. Differential Synthetic Aperture Radar Interferometry (DInSAR) has been applied previously to study the co-seismic ground displacements. There have however been significant limitations in the studies. First, only one-dimensional displacements along the Line-of-Sight (LOS) direction have been measured. The large horizontal displacements along the Chelungpu fault are largely missing from the measurements as the fault is nearly perpendicular to the LOS direction. Second, due to severe signal decorrelation on the hangling wall of the fault, the displacements in that area are un-measurable by differential InSAR method. We estimate the co-seismic displacements in both the azimuth and range directions with the method of SAR amplitude image matching. GPS observations at the 10 GPS stations are used to correct for the orbital ramp in the amplitude matching and to create the two-dimensional (2D) co-seismic surface displacements field using the descending ERS-2 SAR image pair. The results show that the co-seismic displacements range from about -2.0 m to 0.7 m in the azimuth direction (with the positive direction pointing to the flight direction), with the footwall side of the fault moving mainly southwards and the hanging wall side northwards. The displacements in the LOS direction range from about -0.5 m to 1.0 m, with the largest displacement occuring in the northeastern part of the hanging wall (the positive direction points to the satellite from ground). Comparing the results from amplitude matching with those from DInSAR, we can see that while only a very small fraction of the LOS displacement has been recovered by the DInSAR mehtod, the azimuth displacements cannot be well detected with the DInSAR measurements as they are almost perpendicular to the LOS. Therefore, the amplitude matching method is obviously more advantageous than the DInSAR in studying the Chi-Chi earthquake. Another advantage of the method is that the displacement in the hanging wall of the fault that is un-measurable with DInSAR due to severe signal decorrelation can almost completely retrieved in this research. This makes the whole co-seismic displacements field clearly visible and the location of the rupture identifiable. Using displacements measured at 15 independent GPS stations for validation, we found that the RMS values of the differences between the two types of results were 6.9 cm and 5.7 cm respectively in the azimuth and the range directions.

Atmospheric Effects on InSAR Measurements and Their Mitigation.

Interferometric Synthetic Aperture Radar (InSAR) is a powerful technology for observing the Earth surface, especially for mapping the Earth's topography and deformations. InSAR measurements are however often significantly affected by the atmosphere as the radar signals propagate through the atmosphere whose state varies both in space and in time. Great efforts have been made in recent years to better understand the properties of the atmospheric effects and to develop methods for mitigating the effects. This paper provides a systematic review of the work carried out in this area. The basic principles of atmospheric effects on repeat-pass InSAR are first introduced. The studies on the properties of the atmospheric effects, including the magnitudes of the effects determined in the various parts of the world, the spectra of the atmospheric effects, the isotropic properties and the statistical distributions of the effects, are then discussed. The various methods developed for mitigating the atmospheric effects are then reviewed, including the methods that are based on PSInSAR processing, the methods that are based on interferogram modeling, and those that are based on external data such as GPS observations, ground meteorological data, and satellite data including those from the MODIS and MERIS. Two examples that use MODIS and MERIS data respectively to calibrate atmospheric effects on InSAR are also given.

Platelet-derived growth factor-ß expression in rabbit models of cerebral vasospasm following subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH), one of the serious types of stroke incurred by bleeding into the space surrounding the brain, occurs when brains are deprived of oxygen by various factors, particularly an interruption to the blood supply or a ruptured aneurysm. Cerebral vasospasm (CVS) is one of the most common complications of SAH. It has been proposed that platelet­derived growth factor (PDGF) is involved in CVS. The aim of the present study was to analyze expression of PDGF in rabbit models of CVS. Post-SAH CVS rabbit models were created using endovascular puncture and employed to analyze the expression patterns of PDGF by enzyme-linked immunosorbent assay and immunohistochemistry. The results indicated that the creation of the rabbit model of CVS induced using endovascular puncture was successful and demonstrated the double phase changes observed in human CVS. The acute stage started at 12 h post-SAH with narrowing of the vascular lumen diameter. This narrowing appeared again on the seventh day in delayed CVS alongside increased thickness of vessel walls. PDGF-ß expression was observed in vascular smooth muscle cells of the rabbit models. PDGF-ß was expressed as early as 3 h post-SAH, it was evident after 1 day and reached a peak in 7 days, suggesting that PDGF-ß is involved in the early stages of CVS. In the current study, it was confirmed that PDGF-ß expression was present in the rabbit models of CVS, which may aid the elucidation of the pathogenesis of CVS, and also provide useful information for diagnosis and treatment of CVS.

A temporary self-expanding metallic stent for malignant colorectal obstruction.

AIM: To investigate the clinical safety and efficacy of a temporary self-expanding metallic stent (SEMS) for malignant colorectal obstruction. METHODS: From September 2007 to June 2012, 33 patients with malignant colorectal obstruction were treated with a temporary SEMS. The stent had a tubular configuration with a retrieval lasso attached inside the proximal end of the stent to facilitate its removal. The SEMS was removed one week after placement. Clinical examination, abdominal X-ray and a contrast study were prospectively performed and both initial and follow-up data before and at 1 d, 1 wk, and 1 mo, 3 mo, 6 mo and 12 mo after stent placement were obtained. Data collected on the technical and clinical success of the procedures, complications, need for reinsertion and survival were analyzed. RESULTS: Stent placement and removal were technically successful in all patients with no procedure-related complications. Post-procedural complications included stent migration (n = 2) and anal pain (n = 2). Clinical success was achieved in 31 (93.9%) of 33 patients with resolution of bowel obstruction within 3 d of stent removal. Eleven of the 33 patients died 73.81 ± 23.66 d (range 42-121 d) after removal of the stent without colonic re-obstruction. Clinical success was achieved in another 8 patients without symptoms of obstruction during the follow-up period. Reinsertion of the stent was performed in the remaining 12 patients with re-obstruction after 84.33 ± 51.80 d of follow-up. The mean and median periods of relief of obstructive symptoms were 97.25 ± 9.56 d and 105 ± 17.43 d, respectively, using Kaplan-Meier analysis. CONCLUSION: Temporary SEMS is a safe and effective approach in patients with malignant colorectal obstruction due to low complication rates and good medium-term outcomes.

The inhibitory effect of Binens bipinnata L. extract on U14 tumour in mice.

The objective of this paper was to study the in vitro and in vivo inhibitory effect of Bidens bipinnata L. extract on growth of cervical carcinoma U14 cells. MTT method was used to determine the inhibitory effect of Bidens bipinnata L. extract on U14 tumour cells, and the effects of Bidens bipinnata L. extract on inhibition rate of solid tumour and life prolongation rate of ascites tumour were observed through the establishment of two animal models of mouse cervical carcinoma U14 solid tumour and ascites tumour. In the in vitro MTT assay, the inhibition rate gradually increased with the increase of dose of Bidens bipinnata L. and the extension of time. Its inhibition rate was 70.44% at a concentration of 80µg/L. Solid tumour inhibition rates in the high- and low-dose groups and cisplatin group were 49.13%, 2.26% and 75.72% respectively; life prolongation rates in each ascites tumour group were 63.63%, 34.86% and 87.34% respectively. The Bidens bipinnata L. extract has a certain inhibitory effect on growth of mouse cervical carcinoma U14.

Synergistic antitumor activity of reversine combined with aspirin in cervical carcinoma in vitro and in vivo.

A recent report showed that reversine treatment could induce murine myoblasts dedifferentiation into multipotent progenitor cells and inhibit proliferation of some tumors, and other reports showed that apoptosis of lung adenocarcinoma cells could be induced by aspirin. The aim of the present study was to evaluate the synergistic antitumor effects of reversine and aspirin on cervical cancer. The inhibition rate of reversine and aspirin on cervical cancer cell lines' (HeLa and U14) was determined by MTT method, cell cycle of HeLa and U14 cells was analyzed by FACS, mitochondrial membrane potential of HeLa and U14 was detected using a JC-1 kit. HeLa and U14 colony formation was analyzed by soft agar colony formation assay. The expression of caspase-3, Bcl-2/Bax, cyclin D1 and p21 was detected by qRT-PCR and Western Blotting. Moreover, tumor weight and tumor volume was assessed using a murine model of cervical cancer with U14 cells subcutaneously (s.c.) administered into the neck, separately or combined with drug administration via the intraperitoneal (i.p.) route. The inhibition rate of cells in the combination group (10 µmol/L reversine, 10 mmol/L aspirin) increased significantly in comparison to that when the drugs were used alone (P < 0.05); moreover, this combination could synergistically inhibit the proliferation of five cervical cancer cell lines (HeLa, U14, Siha, Caski and C33A). In the therapeutic mouse model, tumor weight and tumor volume of cervical cancer bearing mice was more reduced when compared with the control agents (P < 0.05) in tumor-bearing mice. The combination of reversine and aspirin exerts synergistic growth inhibition and apoptosis induction on cervical cancers cells.

[CHL prevent colon neoplasms in mice and its selective inhibition on COX-2].

BACKGROUND & OBJECTIVE: Chlorophyllin (CHL) was proved to have strong anti-inducement effect toward many mutagens and epicarcinogens. This study was to explore effect of CHL in preventing colon neoplasms in mice induced by dimethylhydrazine (DMH), and the selective inhibition on cyclooxygenase 2(COX-2). METHODS: The colorectal neoplasms were induced with DMH in mice and the different dose of CHL were administered in different phases, then the prevention of colorectal neoplasms by CHL was examined; The IC50 and growth curve of HT29 cells were measured with MTT method after treated with CHL; The effect of CHL on the expression of COX-1 mRNA and COX-2 mRNA in HT29 cells were measured with RT-PCR method; The effect of CHL on the expression of COX-2 protein and NF-kappaB protein were measured with western blot and immunohistochemistry methods. RESULTS: The incidence of colon cancer, average tumor amount, and percentage of carcinoma in CHL group were significantly lower than those in DMH group (P< .05); CHL could inhibit the growth of HT29 cells. The effects were dose dependent; CHL could selectively inhibit the expression of COX-2mRNA in HT29 cells,the expression of COX-2 protein in colon neoplasms and HT29 cells, and the expression of NF-kappaB protein in colon neoplasms. CONCLUSIONS: CHL could prevent colon neoplasms in mice induced by DMH and the preventive effect related to selective inhibition on COX-2, furthermore, the inhibition of CHL on COX-2 was realized by inhibiting NF-kappaB protein.