Suppressive Effect of Matrine on Tumor Invasion in N-Butyl-N-(4-Hydroxybutyl)Nitrosamine-Induced Urinary Bladder Carcinogenesis.

AIMS: This study was designed to investigate the mechanisms and suppressive effects of matrine on the development of urinary bladder cancers induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in rats. METHODS: Male Sprague-Dawley rats were given BBN (200 mg/rat) twice a week for a period of 8 weeks. Oral administration of matrine (50 and 100 mg/kg) was started 1 week before BBN exposure for 35 weeks. Half of each bladder was histopathologically analyzed and the remainder was extracted for protein analysis by Western blot. RESULTS: The bladders of BBN-treated rats demonstrated progression from epithelial hyperplasia to papillary urothelial neoplasia and even poorly differentiated invasive cancer. Matrine (50 and 100 mg/kg) treatment decreased the formation of large bladder tumors by 31.6 and 21.1%, respectively. An incidence of cancer cells was detected in rats given BBN [70% (14/20)] and matrine [50 mg/kg: 68.4% (13/19) and 100 mg/kg: 57.9% (11/19), respectively]. The frequency of invasive tumors in the matrine treatment groups [50 mg/kg: 15.4% (2/13), 100 mg/kg: 9.1% (1/11)] was significantly lower than in the BBN-alone group [57% (8/14)]. Furthermore, oral administration of matrine (50 and 100 mg/kg) markedly attenuated the BBN-induced upregulation of bladder cyclooxygenase-2 (COX-2) expression and the elevation of bladder cytosolic phospholipase A2 (cPLA2) levels. Although the contents of 15-prostaglandin dehydrogenase (PGDH), which degrades PGE2, were dramatically reduced by BBN, matrine exerted no effects on reduced PGDH contents. CONCLUSION: Our results suggest that matrine suppressed bladder tumor invasion in a rat model, and this might be primarily mediated through regulation of the protein contents, COX-2 and cPLA2 in the bladder.

Morphological and clinical feasibility of C3 pedicle screw instrumentation in patients with congenital C2-3 fusion.

PURPOSE: Congenital C2-3 fusion (C2-3CF) is often involved in patients with atlantoaxial dislocation, and posterior occipitocervical fixation surgery is usually required. Hypoplasia of C2 pedicle is common in such patients, making C2 pedicle screws (PS) instrumentation inapplicable. Because of congenital fusion, C3PS instrumentation would be an ideal alternative for it will not sacrifice an additional motion segment; however, the morphological and clinical feasibility has not been previously reported. METHODS: We included 42 C2-3CF patients to this study and evaluated pedicle trajectories of C2 and C3 using a three-dimensional CT. Clinical applications of C3PS instrumentation were evaluated and followed. RESULTS: Among the 42 patients, 23 (54.8%) and 8 (19.0%) had C2 and C3 pedicle trajectory diameters <4.0 mm, respectively. The bisection line of the fused C2-3 lamina was used to represent the superior border of C3 articular mass; the entry point of C3 pedicle was located at 3 mm inferior to the assumed superior border and 3.2 mm medial to the lateral border. Bilateral C3PS instrumentations were successfully adopted in 22 patients. No spinal cord or vertebral artery injury occurred; postoperative CT showed a trajectory breach rate of 17.4% for C3PS. After mean of 3.6-year follow-up, no implant failure was documented. CONCLUSIONS: C3PS instrumentation is morphologically and clinically feasible for a large proportion of patients with C2-3CF and can serve as another reliable alternative for C2PS instrumentation. Preoperative evaluation of pedicle trajectory of C2-3CF with three-dimensional CT is highly valuable in the choice of proper fixation methods.

[Protective effect of oxymatrine on chronic heart failure and ADMA metabolism pathway in isoproterenol-induced chronic heart failure in rats].

OBJECTIVE: To investigate the protective effects of oxymatrine on chronic heart failure induced by isoproterenol (ISO) and to observe its effects on ADMA metabolism pathway in ISO-induced chronic heart failure in rats. METHOD: Male Sprague-Dawley rats were given oxymatrine (100,50 mg kg-1) orally for 14 days. Heart failure was induced in rats by subcutaneous injection of isoproterenol (5 mg kg-1 d-1 ) at the 8th day for 1 week. Serum parameters, haemodynamic parameters, Heart weight, and histopathological variables were analysed. Expression of protein levels were measured by Western blot. RESULT: Oxymatrine (100,50 mg kg-1) significantly attenuated serum content of cTn I, improved left ventricle systolic and diastolic function and left ventricular remodeling, reduced the ISO-induced myocardial pathological changes compared with ISO group. In addition, oxymatrine (100,50 mg kg-1) significantly reduced serum level of ADMA (P <0. 01), normalize the reduced dimethylarginine dimethylaminohydrolase 2 (DDAH2) expression (P <0. 01) , but had no effect on the isoproterenol-induced upregulated protein arginine methyltransferases 1 expression. CONCLUSION: Oxymatrine could ameliorate the experimental ventricular remodeling in ISO-induced chronic heart failure in rats and the mechanism involved in reducing serum content of ADMA and increased DDAH2 expression.

The value of dual-layer spectral detector CT in preoperative T staging of laryngeal and hypopharyngeal squamous cell carcinoma.

PURPOSE: To explore the optimal kiloelectron voltage (keV) of virtual monochromatic images (VMIs) of dual-layer spectral detector computed tomography (DLSCT) to display laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) and its diagnostic performance for preoperative T staging of LHSCC. METHODS: A total of 67 LHSCC patients were included, and the contrast between the tumor and sternocleidomastoid muscle (SM), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and image noise of 40-100 keV VMIs and conventional polyenergetic images (CIs) were evaluated. The image quality of the CI and 40-100 keV VMI was evaluated by a five-point method. The VMI with the best image quality was screened out, and the accuracy of the optimal keV VMI and CI for T staging was assessed using clinical T staging as the reference standard. RESULTS: The contrast between the tumor and SM, SNR, CNR and subjective image quality scores of LHSCC on 40-50 keV VMIs were higher than those on CIs (P < 0.05); the image noises of 40-100 keV VMIs were lower than those of CIs (P < 0.05). The 40 keV VMI had the highest SNR, CNR and subjective score of image quality. The accuracy rates of the 40 keV VMI and CI for T staging of LHSCC were 0.86 and 0.63 (P < 0.001), respectively. CONCLUSION: The image quality of 40-50 keV VMI is higher than that of CI, and the diagnostic accuracy of 40 keV VMI is better than that of CI, which is most suitable for preoperative T staging of LHSCC.

Use of CT-derived radiomic features to preoperatively identify invasive mucinous adenocarcinoma in solitary pulmonary nodules ≤3 cm.

Objective: In this study, we aimed to utilize computed tomography (CT)-derived radiomics and various machine learning approaches to differentiate between invasive mucinous adenocarcinoma (IMA) and invasive non-mucinous adenocarcinoma (INMA) preoperatively in solitary pulmonary nodules (SPN) ≤3 cm. Methods: A total of 538 patients with SPNs measuring ≤3 cm were enrolled, categorized into either the IMA group (n = 50) or INMA group (n = 488) based on postoperative pathology. Radiomic features were extracted from non-contrast-enhanced CT scans and identified using the least absolute shrinkage and selection operator (LASSO) algorithm. In constructing radiomics-based models, logistic regression, support vector machines, classification and regression trees, and k-nearest neighbors were employed. Additionally, a clinical model was developed, focusing on CT radiological features. Subsequently, this clinical model was integrated with the most effective radiomic model to create a combined model. Performance assessments of these models were conducted, utilizing metrics such as the area under the receiver operating characteristic curve (AUC), DeLong's test, net reclassification index (NRI), and integrated discrimination improvement (IDI). Results: The support vector machine approach showed superior predictive efficiency, with AUCs of 0.829 and 0.846 in the training and test cohorts, respectively. The clinical model had AUCs of 0.760 and 0.777 in the corresponding cohorts. The combined model had AUCs of 0.847 and 0.857 in the corresponding cohorts. Furthermore, compared to the radiomic model, the combined model significantly improved performance in both the training (DeLong test P = 0.045, NRI 0.206, IDI 0.024) and test cohorts (P = 0.029, NRI 0.125, IDI 0.032), as well as compared to the clinical model in both the training (P = 0.01, NRI 0.310, IDI 0.09) and test cohorts (P = 0.047, NRI 0.382, IDI 0.085). Conclusion: the combined model exhibited excellent performance in distinguishing between IMA and INMA in SPNs ≤3 cm.

[Study on inhibitory effect of lycium pigment on lipopolysaccharide-induced uveitis in rats and its mechanism].

OBJECTIVE: To investigate the inhibitory effect of lycium pigment on lipopolysaccharide (LPS)-induced uveitis in rats and its mechanism. METHOD: The rat uveitis model was established by 30-day oral administration of lycium pigment (50, 100, 200 mg x kg(-1)) and footpad injection of LPS. Ocular tissues were collected for a histopathological inspection. The protein, nitric oxide and ADMA in aqueous humor, level of inducible nitric oxide synthase (iNOS) in retina, activities of serum total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and content of malondialdehyde (MDA) were determined by using Western blot, ELISA and biochemical methods. RESULT: According to the pathological study, lycium pigment (50, 100, 200 mg x kg(-1)) could notably reduce the inflammatory cell infiltration around corpus ciliare matrix of uveitis rats, and the concentration of protein and nitric oxide, and increased ADMA in aqueous humor. Lycium pigment (100, 200 mg x kg(-1)) could significantly inhibit the expression of iNOS in ocular tissues. In addition, lycium pigment (100, 200 mg x kg(-1)) also decrease the activities of serum T-AOC, SOD, GSH-PX, and the content of lipid peroxide MDA. CONCLUSION: Lycium pigment has the inhibitory effect on LPS-induced uveitis in rats. Its mechanism is related to the regulation of nitric oxide/ADMA pathway and the improvement of oxidation resistance.

Associations between the kynurenine pathway and the brain in patients with major depressive disorder-A systematic review of neuroimaging studies.

Previous studies have indicated that an imbalance in the kynurenine (KYN) pathway is an important pathophysiological mechanism of depression. Several studies have reported that an imbalance in the KYN pathway and its metabolites is associated with abnormalities in cerebral structure and function in depression, but the available evidence has been inconsistent. In this review, we systematically reviewed and integrated the findings concerning the associations between the KYN pathway and the brain in patients with major depressive disorder (MDD). A total of 22 neuroimaging studies were ultimately included in the present study. The neuroimaging modalities used in the studies included structural magnetic resonance imaging (MRI), diffusion tensor imaging, functional MRI, magnetic resonance spectroscopy, arterial spin labelling and positron emission tomography. The results revealed that an imbalance in the KYN pathway was associated with structural and functional abnormalities in several brain regions in patients with MDD. The brain regions most frequently associated with an imbalance in the KYN pathway were cortical regions (i.e., anterior cingulate cortex and orbitofrontal cortex), subcortical regions (i.e., striatum, thalamus and amygdala) and white matter fibres (i.e., inner capsule and left superior longitudinal tract). Our study provides robust evidence that cerebral abnormalities associated with the KYN pathway may be the underlying pathophysiological mechanisms of MDD. Future prospective studies are needed to further elucidate the causal relationships between the imbalanced KYN pathway and cerebral abnormalities in patients with MDD.

Achieving safe and high-performance gastrointestinal tract spectral CT imaging with small-molecule lanthanide complex.

BACKGROUND: Non-intrusive imaging of gastrointestinal (GI) tract using computed tomography (CT) contrast agents is of the most significant issues in the diagnosis and treatment of GI diseases. Moreover, spectral CT, which can generate monochromatic images to display the X-ray attenuation characteristics of contrast agents, provides a better imaging sensitivity for diagnose inflammatory bowel disease (IBD) than convention CT imaging. METHODS: Herein, a convenient and one-pot synthesis method is provided for the fabrication of small-molecule lanthanide complex Holmium-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (Ho-DOTA) as a biosafe and high-performance spectral CT contrast agent for GI imaging with IBD. In vivo CT imaging was administered with both healthy mice and colitis mice induced by dextran sodium sulfate. RESULTS: We found that Ho-DOTA accumulated in inflammation sites of large intestines and produced high CT contrast compared with healthy mice. Both in vitro and in vivo experimental results also showed that Ho-DOTA provided much more diagnostic sensitivity and accuracy due to the excellent X-ray attenuation characteristics of Ho-DOTA compared with clinical iodinate agent. Furthermore, the proposed contrast media could be timely excreted from the body via the urinary and digestive system, keeping away from the potential side effects due to long-term retention in vivo. CONCLUSION: Accordingly, Ho-DOTA with excellent biocompatibility can be useful as a potential high-performance spectral CT contrast agent for further clinical imaging of gastrointestinal tract and diagnosis of intestinal system diseases.

Hybrid FeWO4-Hyaluronic Acid Nanoparticles as a Targeted Nanotheranostic Agent for Multimodal Imaging-Guided Tumor Photothermal Therapy.

Background: Development of versatile nanoplatform still remains a great challenge due to multistep synthesis and complicated compositions. Therefore, it is significant to develop a facile method to synthesize a nanocomposite to achieve multimodal imaging and even imaging-guided cancer therapeutics. Methods and Results: In our study, hyaluronic acid-functionalized iron (II) tungstate nanoparticles (HA-FeWO4 NPs) were successfully synthesized as a versatile nanoplatform by a facile one-pot hydrothermal procedure. The formed multifunctional HA-FeWO4 NPs were investigated via a series of characterization techniques, which demonstrated good biocompatibility, excellent dispersion, low cytotoxicity, active tumor-targeting ability and high photothermal efficiency. Furthermore, tumor was clearly visualized by HA-FeWO4 NPs with multimodal imaging of infrared thermal imaging, magnetic resonance imaging, computed tomography imaging in 4T1 tumor bearing mice. More importantly, HA-FeWO4 could achieve multimodal imaging-guided photothermal therapy of 4T1 tumors. Conclusion: The constructed HA-FeWO4 NPs have great potential as ideal nanotheranostic agents for multimodal imaging and even imaging-guided cancer theranostics in biological systems.

Effects of oxymatrine and matrine on left ventricular contractility using pressure-volume relationship analysis in anesthetized rats.

The purpose of this study was to investigate the effects of oxymatrine and matrine on integrated cardiac function in rats using pressure-volume loop analysis. A pressure-volume loop catheter was advanced into the left ventricle in anesthetized rats. Steady-state hemodynamic and load-independent parameters were recorded before and after oxymatrine or matrine injection. Oxymatrine (200 mg/kg) and matrine (50, 100 mg/kg) significantly increased the preload recruitable stroke work, slope of maximal systolic pressure increase (dP/dtmax) - end-diastolic volume relationship, end-systolic elastance and volume axis intercept (V0), which are load-independent parameters. Furthermore, the observed increased cardiac efficiency, along with the decreased ventricular arterial coupling, pressure volume area and potential energy, reflect improved mechanoenergetics in oxymatrine (200 mg/kg) and matrine (25, 50 or 100 mg/kg) treated rats respectively. In addition, matrine (25, 50 mg/kg) decreased end-systolic volume and end-diastolic volume, and increased ejection fraction; matrine at 100 mg/kg further decreased end-systolic volume, end-diastolic volume, stroke volume and stroke work, shortened the time constant of left ventricular pressure decay, and increased dP/dtmax, and heart rate. These results suggest that both oxymatrine and matrine enhance left ventricular contractility and improve cardiac mechanical function. As the dose of matrine was much lower than that of oxymatrine, the effect of matrine on myocardial contractility was stronger than that of oxymatrine.

Alterations in white matter microarchitecture in adolescents and young adults with major depressive disorder: A voxel-based meta-analysis of diffusion tensor imaging.

Adolescents and young adults are at a critical stage of life development, and depression can have serious consequences. In recent decades, an increasing number of diffusion tensor imaging (DTI) studies of major depressive disorder (MDD) have reported inconsistent alterations in white matter (WM) microarchitecture. To rule out the confounding effects of age, we conducted a meta-analysis of fractional anisotropy (FA) in adolescents and young adults with MDD to identify abnormalities in WM involved in the pathogenesis of MDD using anisotropic effect-size signed differential mapping (AES-SDM). The pooled meta-analysis revealed significantly lower FA mainly in the corpus callosum (CC) extending to the left anterior thalamic projections (ATP) and left cortico-spinal projection (CSP) in depressed adolescents and young adults than that in healthy controls. A reduction in FA was also identified in the right frontal orbito-polar tract (FOPT) extending to the right inferior fronto-occipital fasciculus (IFOF). In the meta-regression analysis, the mean age of patients, percentage of female patients and duration of depression were not linearly associated with abnormalities in FA. These results constitute robust evidence that abnormalities in WM microarchitecture in the interhemispheric connections and frontal-subcortical neuronal circuits may contribute to the pathogenesis of MDD during adolescence and young adulthood.

Small-Molecule Bi-DOTA Complex for High-Performance CT and Spectral CT Bioimaging.

OBJECTIVES: It is necessary to develop a high-performance and biocompatible contrast agent to accurately diagnose various diseases via in vivo computed tomography (CT) imaging. Here, we synthesized a small molecular Bi-DOTA complex as a high-performance contrast agent for in vitro and in vivo CT bioimaging. MATERIALS AND METHODS: In our study, Bi-DOTA was fabricated through a facile and one-pot synthesis strategy. The formed Bi-DOTA complex was characterized via different techniques. Furthermore, Bi-DOTA was used for in vitro and in vivo CT bioimaging to verify its X-ray attenuation ability, especially in vivo kidney imaging, gastrointestinal tract CT imaging, and spectral CT imaging. RESULTS: A small molecular Bi-DOTA complex with a molecular mass of 0.61 kDa was synthesized successfully, which exhibited outstanding dispersion, good biocompatibility, and superior X-ray attenuation ability. Meanwhile, we showed that the obtained contrast agent was quite biocompatible and safe in the given concentration range as confirmed by in vitro and in vivo cytotoxicity assay. Also, the proposed contrast agent can be rapidly excreted from the body via the urinary system, avoiding the potential side effects caused by long-term retention in vivo. Importantly, Bi-DOTA was successfully used in high-quality in vitro CT imaging, in vivo kidney imaging, gastrointestinal tract CT imaging, and spectral CT imaging. CONCLUSIONS: These superiorities allowed Bi-DOTA to be used as an efficient CT contrast agent and laid down a new way of designing high-performance CT contrast agents with great clinical transformation potential.

Synergistic interaction between matrine and paracetamol in the acetic acid writhing test in mice.

The purpose of this study was to investigate the analgesic interaction between matrine and paracetamol in an acetic acid-induced writhing model in mice. Fifty percent effective dose (ED50) values of the individual drugs were determined, and the different proportions of matrine and paracetamol were assayed using the isobolographic method. Our study demonstrated that both of matrine and paracetamol dose-dependently inhibited the writhing response evoked by acetic acid, and the ED50 values and their 95% confidence intervals against these tonic pain were 21.10 (17.86-24.92) mg/kg and 61.30 (50.71-74.10) mg/kg for matrine and paracetamol, respectively. At the fixed ratios of 1:1, 1:3 and 3:1, the experimental ED50 values of matrine and paracetamol combinations and their 95% confidence intervals were 10.52 (5.14-21.55) mg/kg, 9.13 (4.46-18.70) mg/kg and 4.98 (4.17-5.95) mg/kg, respectively, their theoretical ED50 values and 95% confidence intervals were 41.20 (36.31-46.74) mg/kg, 51.25 (44.19-59.44) mg/kg and 31.15 (27.25-35.60) mg/kg, and the experimental ED50 values of matrine and paracetamol combination were significantly lower than their calculated theoretical ED50 values (all P < 0.01), as revealed by isobolographic analysis. Furthermore, the experimental regression line was also significantly different from the calculated additive equal-effect line over the range of the tested doses (all P < 0.01). Our results suggest that the combination of matrine with paracetamol exerts analgesic synergistic interactions in a mouse acetic acid-induced writhing model, thereby offering a possible therapeutic alternative for the clinical management of inflammatory pain.

Folic Acid-Conjugated CuFeSe2 Nanoparticles for Targeted T2-Weighted Magnetic Resonance Imaging and Computed Tomography of Tumors In Vivo.

BACKGROUND: Development of new long-circulating contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI) of different biological systems still remains a great challenge. Here, we report the synthesis of folic acid (FA)-targeted CuFeSe2 nano-contrast agent for CT and MRI imaging in vitro and in vivo. METHODS AND RESULTS: In our study, CuFeSe2 was fabricated through a facile and green aqueous reaction and then further aminated through silanization. The amine-functionalized CuFeSe2-NH2 nanoparticles enable the covalent conjugation of folate-conjugated polyethylene glycol (FA-PEG-COOH) as a targeting ligand onto their surface, which could improve the dispersion and endue the targetability of nanoparticles, respectively. The formed multifunctional CuFeSe2-PEG-FA nanoparticles were characterized via different techniques, which exhibited outstanding dispersion, good biocompatibility and excellent FA-targeted capability. Meanwhile, the nanoparticles were quite safe in the given concentration range as confirmed by in vitro and in vivo toxicity assay. Importantly, CuFeSe2-PEG-FA nanoparticles were successfully applied in CT/MRI dual-modality imaging in vitro and in vivo, which showed a better imaging performance and targeted capability. CONCLUSION: Therefore, the constructed CuFeSe2-PEG-FA nanoparticles have a great potential as an efficient contrast agent for dual-modality imaging of different biological systems.

Altered gray matter volume and functional connectivity in patients with herpes zoster and postherpetic neuralgia.

Numerous neuroimaging studies on postherpetic neuralgia (PHN) and herpes zoster (HZ) have revealed abnormalities in brain structure/microstructure and function. However, few studies have focused on changes in gray matter (GM) volume and intrinsic functional connectivity (FC) in the transition from HZ to PHN. This study combined voxel-based morphometry and FC analysis methods to investigate GM volume and FC differences in 28 PHN patients, 25 HZ patients, and 21 well-matched healthy controls (HCs). Compared to HCs, PHN patients exhibited a reduction in GM volume in the bilateral putamen. Compared with HZ patients, PHN patients showed decreased GM volume in the left parahippocampal gyrus, putamen, anterior cingulate cortex, and right caudate and increased GM volume in the right thalamus. However, no regions with significant GM volume changes were found between the HZ and HC groups. Correlation analysis revealed that GM volume in the right putamen was positively associated with illness duration in PHN patients. Furthermore, lower FCs between the right putamen and right middle frontal gyrus/brainstem were observed in PHN patients than in HCs. These results indicate that aberrant GM volumes and FC in several brain regions, especially in the right putamen, are closely associated with chronification from HZ to PHN; moreover, these changes profoundly affect multiple dimensions of pain processing. These findings may provide new insights into the pathophysiological mechanisms of PHN.

Relaxant effects of matrine on aortic smooth muscles of guinea pigs.

OBJECTIVE: To determine whether matrine, a kind of traditional Chinese medicinal alkaloid, can relax the aortic smooth muscles isolated from guinea pigs and to investigate the mechanism of its relaxant effects. METHODS: Phenylephrine or potassium chloride concentration-dependent relaxation response of aortic smooth muscles to matrine was studied in the precontracted guinea pigs. RESULTS: Matrine (1 x 10(-4) mol/L -3.3 x 10(3) mol/L) relaxed the endothelium-denuded aortic rings pre-contracted sub-maximally with phenylephrine, in a concentration-dependent manner, and its pre-incubation (3.3 x 10(-3) mol/L) produced a significant rightward shift in the phenylephrine dose-response curve, but had no effects on the potassium chloride-induced contraction. The anti-contractile effect of matrine was not reduced by the highly selective ATP-dependent K+ channel blocker glibenclamide (10(-5) mol/L), either by the non-selective K+ channel blocker tetraethylammonium (10(-3) mol/L), or by the beta-antagonist propranolol (10(-5) mol/L). In either "normal" or "Ca(2+)-free" bathing medium, the phenylephrine-induced contraction was attenuated by matrine (3.3 x 10(-3) mol/L), indicating that the vasorelaxation was due to inhibition of intracellular and extracellular Ca2+ mobilization. CONCLUSION: Matrine inhibits phenylephrine-induced contractions by inhibiting activation of alpha-adrenoceptor and interfering with the release of intracellular Ca2+ and the influx of extracellular Ca2+.

Oxymatrine prevents the development of monocrotaline-induced pulmonary hypertension via regulation of the NG, NG-dimethyl-L-arginine metabolism pathways in rats.

The purpose of this study was to investigate the potential effect of oxymatrine in monocrotaline-induced pulmonary hypertension and its possible influence on the NG,NG-dimethyl-L-arginine (ADMA) metabolism pathway. Pulmonary hypertension was induced in rats by a single-dose injection of monocrotaline (60 mg/kg). Daily oral administration of oxymatrine (25, 50 and 100 mg/kg) was started on the day following the monocrotaline injection for 28 days. Oxymatrine (50 and 100 mg/kg) significantly attenuated monocrotaline-induced lung and right ventricular hypertrophy, right ventricular systolic pressure elevation, and right ventricular dysfunction. Oxymatrine also reduced the thickening of monocrotaline-induced pulmonary arterial medial wall. Meanwhile, oxymatrine normalized the level of pulmonary asymmetric ADMA and attenuated the upregulated expression of protein arginine methyltransferase 1 (PRMT1). Oxymatrine had no effect on the expression of protein arginine methyltransferase 2 (PRMT2) and NG,NG-Dimethylarginine dimethylaminohydrolase 1 (DDAH1), which were upregulated in monocrotaline-induced pulmonary arterial hypertensive rats. However, the expression of the protein NG,NG-Dimethylarginine dimethylaminohydrolase 2 (DDAH2) did not differ among all groups (all P﹥0.05). These results suggest that oxymatrine may offer protective effects on the development of pulmonary hypertension by ameliorating pulmonary remodeling and modulating the ADMA metabolism pathway.

A meta-analysis on the diagnostic value of diffusion-weighted imaging on ovarian cancer.

PURPOSE: This study systematically evaluated the potential influences of diffusion- weighted imaging (DWI) on the initial diagnosis, clinical decision making and diagnostic accuracy of ovarian cancer in the follow-up period. METHODS: Literature on the correlation between DWI and diagnosis of ovarian cancer were searched from PubMed, Embase, Cochrane Library, and Web of Science published before January 1, 2019. References in enrolled eligible literature were manually reviewed. Quality assessment on the diagnostic accuracy was performed using the QUADAS scale. Receiver operating characteristics (ROC) curve was depicted using STATA 12.0. Study heterogeneity and its sources were determined. Sensitivity (SEN), specificity (SPF), positive likelihood ratio (+LR), negative likelihood ratio (-LR) and diagnostic odds ratio (DOR) of eligible studies were calculated for depicting forest plot and summary of ROC curve (SROC). The area under the curve (AUC) was calculated. RESULTS: A total of 15 articles involving 930 ovarian cancer cases and 832 control cases were enrolled. DWI was identified to exert a certain diagnostic value on ovarian cancer. The 95%CI of the merged SEN (91%, 95%CI=84-95%), SPF (85%, 95%CI=78-90%), +LR (6.18, 95%CI=4.17-9.15) and -LR (4.05, 95%CI=3.30-4.79) were calculated using the random-effects model due to the slight heterogeneity among these studies. AUC was 0.94 (95%CI=0.91-0.96). Subgroup analysis in Asian population obtained the following results: SEN was 85% (95%CI=78-91%), SPF 83% (95%CI=72-90%), +LR 0.18 (95%CI=0.11-0.27), -LR 3.34 (95%CI=2.60-4.09) and DOR 3.34 (95%CI=2.60-4.09); AUC was 0.91 (95%CI=0.88-0.93). In Caucasian population, SEN was 96% (95%CI=83-99%), SPF 89% (95%CI=84-93%), +LR 41.36 (95%CI=5.95-287.48), -LR 0.06 (95%CI=0.02-0.18) and DOR 5.31(95%CI=3.93-6.69); AUC was 0.94 (95%CI=0.91-0.96). CONCLUSIONS: This meta-analysis proved that DWI exerted a relatively high sensitivity and specificity in diagnosing ovarian cancer, especially in the Caucasian population. This conclusion still needs to be further verified in a multi-center study with a large sample size.

Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat.

The present study was designed to investigate whether fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, would attenuate the acute myocardial infarction in isoproterenol-treated rat model via maintaining activities of endogenous antioxidant enzymes. Hemodynamic and electrocardiograph parameters were monitored and recorded continuously, cardiac marker enzymes and antioxidative parameters of plasma and heart tissues were measured, and histopathological examination of heart tissues was performed. Isoproterenol-treated rats showed lower of left-ventricular systolic pressure (LVSP), maximum (LVdP/dtmax) and minimum rate of developed left ventricular pressure (LVdP/dtmin), and higher of left ventricular end-diastolic pressure (LVEDP), in addition, a significant rise in ST-segment and increase in content of lactate dehydrogenase, glutamic oxalacetic transaminase, creatine kinase and malondialdehyde, as well as fall in activities of glutathione peroxidase, superoxide dismutase and catalase were observed. Oral administration of fluvastatin (5, 10 and 20 mg/kg, respectively) significantly prevented almost all the parameters of isoproterenol-induced heart failure and myocardial injury that mentioned above. The protective role of fluvastatin on isoproterenol-induced myocardial damage was further confirmed by histopathological examination. There was no significant change in heart rate in all experimental groups. Compared with control group, any indexes in sham rats treated with fluvastatin (20 mg/kg) alone were unaltered (all P>0.05). Our results suggest that fluvastatin has a significant effect on the protection of heart against isoproterenol-induced myocardial infarction through maintaining endogenous antioxidant enzyme activities.

Elevated prostaglandin E2 level via cPLA2--COX-2--mPGES-1 pathway involved in bladder carcinogenesis induced by terephthalic acid-calculi in Wistar rats.

To investigate the prostaglandin E2 (PGE2) biosynthetic mechanism in bladder carcinogenesis, we established Wistar rat model of bladder papilloma and transitional cell carcinoma (TCC) induced by 5% terephthalic acid (TPA) treatment. Then, the mRNA level of cytosolic phospholipase A2 (cPLA2), cyclooxygenases (COX)-1 and -2, membrane-bound PGE2 synthases (mPGES)-1 and -2 was detected using reverse transcription polymerase chain reaction (RT-PCR). Immunoblotting was applied to detect the expression of COX-2 protein. Proliferating cell nuclear antigen (PCNA) was determined by immunohistochemistry. In addition, the level of PGE2 was measured by radioimmunoassay (RIA). Bladder papilloma (100%, 8/8) was examined in rats after 24-week treatment, and bladder TCC (80%, 16/20) was found after 48-week treatment. Histopathological changes were not found in control group rats. The incidence of bladder papilloma and TCC in test group was significantly higher than that in control group (P<0.01). The mRNA levels of cPLA2, COX-2 and mPGES-1 in the bladder papilloma and TCC were significantly higher than those in normal bladder (P<0.01), while the mRNA levels of COX-1 and mPGES-2 in TCC were unchanged compared with normal bladder. Bladder TCC exhibited a substantial expression of COX-2 protein. On the contrary, normal bladder tissue barely expresses COX-2 protein. PCNA labeling index (LI) and the level of PGE2 in bladder papilloma are much higher than those in normal bladder (P<0.01), but lower than those in bladder TCC (P<0.05). In conclusion, increasing PGE2 level via cPLA2--COX-2--mPGES-1 pathway may play an important role in rat bladder carcinogenesis. PGE2 may be a biomarker for the development of bladder TCC. cPLA2 and mPGES-1 may be targets for development of novel chemoprevention strategies for bladder TCC.