[Alterations in the intestinal microbiota of preterm infants with neurodevelopmental impairments: a prospective cohort study]. / ç¥žç»å‘è‚²æŸå®³æ—©äº§å„¿è‚ é“èŒç¾¤å˜åŒ–çš„å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To investigate the difference in intestinal microbiota between preterm infants with neurodevelopmental impairment (NDI) and those without NDI. METHODS: In this prospective cohort study, the preterm infants who were admitted to the neonatal intensive care unit of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from September 1, 2019 to September 30, 2021 were enrolled as subjects. According to the assessment results of Gesell Developmental Scale at the corrected gestational age of 1.5-2 years, they were divided into two groups: normal (n=115) and NDI (n=100). Fecal samples were collected one day before discharge, one day before introducing solid food, and at the corrected gestational age of 1 year. High-throughput sequencing was used to compare the composition of intestinal microbiota between groups. RESULTS: Compared with the normal group, the NDI group had a significantly higher Shannon diversity index at the corrected gestational age of 1 year (P<0.05). The principal coordinate analysis showed a significant difference in the composition of intestinal microbiota between the two groups one day before introducing solid food and at the corrected gestational age of 1 year (P<0.05). Compared with the normal group, the NDI group had a significantly higher abundance of Bifidobacterium in the intestine at all three time points, a significantly higher abundance of Enterococcus one day before introducing solid food and at the corrected gestational age of 1 year, and a significantly lower abundance of Akkermansia one day before introducing solid food (P<0.05). CONCLUSIONS: There are significant differences in the composition of intestinal microbiota between preterm infants with NDI and those without NDI. This study enriches the data on the characteristics of intestinal microbiota in preterm infants with NDI and provides reference for the microbiota therapy and intervention for NDI in preterm infants.

Orcinol glucoside targeted p38 as an agonist to promote osteogenesis and protect glucocorticoid-induced osteoporosis.

BACKGROUND: Glucocorticoids (GC)-induced osteoporosis (GIOP) is the most common cause of secondary osteoporosis, which leads to an increased risk of fracture in patients. The inhibition of the osteoblast effect is one of the main pathological characteristics of GIOP, but without effective drugs on treatment. PURPOSE: The aim of this study was to investigate the potential effects of orcinol glucoside (OG) on osteoblast cells and GIOP mice, as well as the mechanism of the underlying molecular target protein of OG both in vitro osteoblast cell and in vivo GIOP mice model. METHODS: GIOP mice were used to determine the effect of OG on bone density and bone formation. Then, a cellular thermal shift assay coupled with mass spectrometry (CETSA-MS) method was used to identify the target of OG. Surface plasmon resonance (SPR), enzyme activity assay, molecular docking, and molecular dynamics were used to detect the affinity, activity, and binding site between OG and its target, respectively. Finally, the anti-osteoporosis effect of OG through the target signal pathway was investigated in vitro osteoblast cell and in vivo GIOP mice model. RESULTS: OG treatment increased bone mineral density (BMD) in GIOP mice and effectively promoted osteoblast proliferation, osteogenic differentiation, and mineralization in vitro. The CETSA-MS result showed that the target of OG acting on the osteoblast is the p38 protein. SPR, molecular docking assay and enzyme activity assay showed that OG could direct bind to the p38 protein and is a p38 agonist. The cellular study found that OG could promote p38 phosphorylation and upregulate the proteins expression of its downstream osteogenic (Runx2, Osx, Collagen Ⅰ, Dlx5). Meanwhile, it could also inhibit the nuclear transport of GR by increasing the phosphorylation site at GR226 in osteoblast cell. In vivo GIOP mice experiment further confirmed that OG could prevent bone loss in the GIOP mice model through promoting p38 activity as well as its downstream proteins expression and activity. CONCLUSIONS: This study has established that OG could promote osteoblast activity and revise the bone loss in GIOP mice by direct binding to the p38 protein and is a p38 agonist to improve its downstream signaling, which has great potential in GIOP treatment for targeting p38. This is the first report to identify OG anti-osteoporosis targets using a label-free strategy (CETSA-MS).

Prediction model for successful induction of labor by cervical strain elastography diagnosed at late-term pregnancy in nulliparous women: a prospective cohort study.

BACKGROUND: The use of cervical strain elastography for nulliparous women during late-term pregnancy remains unclear. This study assesses the predictive value of late-term cervical strain elastography for successful induction of labor (IOL) in nulliparous women. METHODS: This single-centered, prospective study included 86 patients undergoing IOL between January 2020 and March 2022. Univariate and multivariate analyses were conducted to identify predictive factors for successful IOL. The predictive values were assessed using the area under receiver operating characteristic (ROC) curves. RESULTS: IOL was successful in 58 patients. The hardness ratio and cervical length were significantly associated with successful late-term IOL in nulliparous women. The predictive value of the combination of hardness ratio and cervical length was higher than that of cervical length alone. CONCLUSIONS: The hardness ratio and cervical length assessed by cervical strain elastography during late-term pregnancy are predictors of the success of IOL in nulliparous women. The predictive value of the combination of hardness ratio and cervical length was higher than that of cervical length alone.

Ultrasound-Indicated Cervical Cerclage Efficacy Between 16 and 28 Weeks of Gestation in Twin Pregnancy: Retrospective Cohort Study.

Objective: The aim of this study is to determine if cervical cerclage administration reduces the preterm birth (PTB) rate at a gestational age (GA) of 16-28 weeks in women with twin pregnancy. Methods: This is a retrospective cohort study on asymptomatic twin pregnancy with an ultrasound-identified cervix length (CL) of ≦25 mm. The patients were divided into two groups: ultrasound-indicated cerclage (UIC) group and control (expectant management) group. The primary outcome was a PTB rate at <34 weeks. A logistic regression was also performed, and a subgroup analysis stratified by CL and GA at first short cervix diagnosis was planned. Results: In all 320 women, there were no differences in the overall <34-week PTB rates and neonatal outcomes between the UIC group and control group. After performing a multivariate logistic regression analysis, the subgroup analyses were planned. In patients with a CL of ≦15 mm, the <34-week PTB rate was significantly decreased in the UIC subgroup compared with the control subgroup (60.78% vs 78.26%; odds ratio (OR) = 0.43, confidence interval (CI) = 95% [0.22-0.86]; and p = 0.020). In patients with a first short cervix diagnosis GA of ≦24 weeks, the <34-week PTB rate was significantly decreased in the UIC subgroup when compared with the control subgroup (61.54% vs 84.75%; OR = 0.29; CI = 95% [0.13-0.63]; and p = 0.001). Furthermore, compared with the control groups, the UIC groups had higher mean birth weight, lower perinatal mortality, and lower NICU admission, and the differences were statistically significant. Conclusion: UIC could significantly reduce the <34-week PTB rate and improve perinatal outcomes in patients with a CL of ≦15mm or first short cervix diagnosis GA of ≦24 weeks with asymptomatic twin pregnancy during the second trimester.

Cuff-less blood pressure estimation from photoplethysmography signal and electrocardiogram.

In recent studies, the physiological parameters derived from human vital signals are found as the status response of the heart and arteries. In this paper, we therefore firstly attempt to extract abundant vital features from photoplethysmography(PPG) signal, its multivariate derivative signals and Electrocardiogram(ECG) signal, which are verified its statistical significance in BP estimation through statistical analysis t-test. Afterwards, the optimal feature set are obtained by usnig mutual information coefficient analysis, which could investigate the potential associations with blood pressure. The optimized feature set are aid as an input to various machine learning strategies for BP estimation. The results indicates that AdaBoost based BP estimation model outperforms other regression methods. Concurrently, AdaBoost-based model is further analyzed by using the Histograms of Estimation Error and Bland-Altman Plot. The results also indicate the great BP estimation performance of the proposed BP estimation method, and it stays within the Advancement of Medical Instrumention(AAMI) standard. Regarding the British Hypertension Society (BHS), it achieves the grade A for DBP and grade B for MAP. Besides, the experimental result illustrated that our proposed BP estimation method could reduce the MAE and the STD, and improve the r for SBP, MAP and DBP estimation, respectively, which further demonstrates the feasibility of our proposed BP estimation method in this paper.

Hypertension assessment based on feature extraction using a photoplethysmography signal and its derivatives.

Objective.Long-term abnormal blood pressure (BP) can lead to various cardiovascular diseases; therefore, it is significant to assess BP status as a preventative measure. In this study, a feature-extraction-based approach is proposed and performed on an open clinical trial dataset.Approach.Firstly, a complete ensemble of empirical mode decomposition with an adaptive noise algorithm and wavelet threshold analysis is applied to eliminate the noise interference from an original photoplethysmography (PPG) signal compared to other signal filters. Considering the strong connection between hypertension and diabetes, an analysis of variance test with a 95% confidence interval is firstly carried out to select these leading extracted morphological features, which are uniquely related to hypertension, from the PPG signal and its derivatives. Subsequently a variety of classification models are evaluated at different BP levels and their performances are compared.Main results and Significance.The test results demonstrate that the support vector machine classification model achieves a greater performance compared to other explored models in this paper, with accuracy of 78%, 87% and 88% for cases including normal versus prehypertension subjects, normotension versus hypertension subjects and non-hypertension versus hypertension subjects, respectively, which further illustrates the great potential of the proposed method in hypertension assessment.

[Comparison of the effect and safety of Er:YAG laser combined with fluoride and methylene blue-photodynamic therapy on caries prevention].

OBJECTIVE: To compare the anti-caries effect and safety of Er:YAG laser combined with fluoride and methylene blue-photodynamic therapy (MB-PDT). METHODS: A total of 28 rat dental caries models were established and randomly divided into seven groups: photodynamic therapy (PDT) group, laser combined with fluoride group, laser group, sodium fluoride group, and 0.9% saline control group. Spectrophotometric optical density was used to reflect the growth of Streptococcus mutans. Laser-induced fluorescence diagnostic (LF) instrument was utilized to detect the demineralization degree of dental caries. Histopathological sections were employed to observe the damage of dental pulp and buccal mucosa. RESULTS: The optical density (OD) value of the PDT and combination groups was significantly lower than that of other treatment groups (P<0.05). An increase in LF value and demineralization occurred in varying degrees with different treatment methods. Histopathological observation showed that pulp and buccal mucosa injury was more obvious in the combination group of 70 mw·cm⁻² and Er:YAG laser group compared with other groups. CONCLUSIONS: Under the same parameters, the combined group and PDT have good germicidal efficacy, but PDT has fewer adverse reactions and less damage. It is an effective and safe method for caries prevention.

The Tumor-Associated Macrophage-M2-Cancer Cell Complex and the Observation of Heterogeneous Modification of the Morphological Structure of Lung Adenocarcinoma.

OBJECTIVE: The aim of this study was to investigate the effect of the tumor-associated macrophage-m2-cancer cell complex (TAM-M2-CC) on the heterostructural modification of lung adenocarcinoma. METHODS: The expression of CD163+/CD68+ in macrophages in the microenvironment of 161 cases of lung adenocarcinoma was identified by dual immunohistochemistry, and the association between a TAM-M2-CC and its growth, as well as the histological changes in lung adenocarcinoma cells, was assessed. RESULTS: The morphological change of lung adenocarcinoma was related to the number of m2 phenotypes of the macrophages in the microenvironment of lung adenocarcinoma. TAM-M2-CCs were involved in the process of cancer cell recognition, association, and reconstruction. CONCLUSION: The microenvironment of lung adenocarcinoma can affect the phenotypic distinction of macrophages, and the polarization recruitment, zombification, and formation of a TAM-M2-CC, which can also affect the local differentiation of lung adenocarcinoma to a certain extent. The applicable pathogenesis needs to be verified and studied further.

Hyperpolarization-activated cation currents in medium-size dorsal root ganglion cells are involved in overactive bladder syndrome in rats.

BACKGROUND: To investigate the functions of the hyperpolarization-activated cation currents in medium-size dorsal root ganglion cells in a rat model of overactive bladder syndrome. METHODS: Rats with OAB were screened using a urodynamic testing device. The whole-cell patch clamp technique was used to investigate changes in excitability and hyperpolarization-activated cation current (Ih) of medium-size cells in the L6 dorsal root ganglia (DRG) of the OAB rats. Intrathecal injection of the specific Ih inhibitor ZD7288 was used to investigate changes of voiding function and Ih of medium-size cells in the L6 DRG. RESULTS: The urinary bladder weight of the OAB rats was significantly increased (p < 0.01); However, 7 days after intrathecally administration of ZD7288 (2 µM), the weight of rat bladder was significantly reduced (p < 0.01). The excitability of the medium-size cells in the L6 DRG of the OAB rats was significantly increased, and the number of action potentials elicited by a 500 pA stimulus was also markedly increased. Furthermore, ZD7288 significantly reduced the excitability of the medium-size DRG cells. The medium-size cells in the DRG of the OAB rats had a significantly increased Ih current density, which was blocked by ZD7288. CONCLUSIONS: The Ih current density significantly increased in medium-size cells of the L6 DRG in the OAB model. A decrease of the Ih current was able to significantly improve the voiding function of the OAB rats, in addition to lowering their urinary bladder weight. Our finding suggested that the observed increase of Ih current in the medium-size DRG neurons might play an important role in the pathological processes of OAB.

Pinolenic acid ameliorates oleic acid-induced lipogenesis and oxidative stress via AMPK/SIRT1 signaling pathway in HepG2 cells.

Pinolenic acid (PLA), a natural compound isolated from pine nut oil, has been reported to exert bioactivity against lipid anabolism. Nonetheless, the underlying mechanisms still poorly elucidated. The aim of this study is to comprehensively demonstrate the effects of PLA on oleic acid (OA)-induced non-alcoholic fatty liver disease (NAFLD) and their relationship with the lipid metabolic regulation. The results demonstrated that treatment with PLA dramatically inhibited lipid accumulation, oxidative stress as well as inflammatory responses induced by oleic acid in HepG2 cells. PLA also obviously decreased the levels of cellular triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA), reactive oxygen species (ROS) and nitric oxide (NO). As well as PLA stilled promoted the antioxidant enzymes activity including superoxide dismutase (SOD) and glutathione peroxidase (GPX). Furthermore, PLA could increase the expressions of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase1 (HO-1) to alleviate oxidative damage. It also could reduce lipogenesis-related transcription factors expression, such as sterol regulatory element-binding protein 1 (SREBP1c), fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1). PLA treatment resulted in increasing phosphorylation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-α (PPARα) expression. However, pretreatment with compound C (inhibitor of AMPK) inhibited the effect of PLA on promoting the expression of p-AMPK, SIRT1 and PPARα for lipolysis. Taken together, these results demonstrated that PLA possessed the potential to prevent lipid accumulation in OA-induced HepG2 cells via upregulating the AMPK/SIRT1 signaling pathway, which supported the development of new drug candidate against non-alcoholic steatohepatitis.

An Efficient Strategy Based on Liquid-Liquid Extraction With Acid Condition and HSCCC for Rapid Enrichment and Preparative Separation of Three Caffeoylquinic Acid Isomers From Mulberry Leaves.

Morus alba L. is a medicinal plant that contains a high amount of caffeoylquinic acids such as 3-caffeoylquinic acid (3-CQA), 5-caffeoylquinic acid (5-CQA) and 4-caffeoylquinic acid (4-CQA). This study aimed to establish a fast and efficient method for separating caffeoylquinic acids from mulberry leaves by using high-speed countercurrent chromatography coupled with macroporous resin. D101 resin showed better adsorption and desorption capacity for three caffeoylquinic acids among six macroporous resin adsorbents. The contents of 3-CQA, 5-CQA and 4-CQA reached for 4.77%, 18.95% and 9.84% through one cycle of D101 resin, which were 3.13-fold, 4.57-fold and 4.78-fold more than those in crude extracts, respectively. With a two-phase solvent system of ethyl acetate-water (1:1, V/V), >93% purity of target compounds were obtained in one cycle during 150 min with the recovery yields of 80.59%, 99.56% and 94.21% for 3-CQA, 5-CQA and 4-CQA, respectively. The structural identification of target compounds was carried out by ESI-MS, 1H NMR and 13C NMR spectra. The present result represented an easy and efficient separation strategy for the utilization of mulberry resource.

Inotodiol inhibits cells migration and invasion and induces apoptosis via p53-dependent pathway in HeLa cells.

BACKGROUND: Inonotus obliquus, namely as Chaga mushroom, is a medicinal and edible fungus, which is widely used in food and medical fields. Inotodiol, a natural lanostane-type triterpenoid with remarkable pharmacological activities, was isolated from Inonotus obliquus, which its potential anti-tumor molecular mechanism was elaborated poorly. PURPOSE: The aim of the present study was to investigate the effect of Inotodiol on HeLa cell migration, invasion and apoptosis through p53-dependent pathway. STUDY DESIGN AND METHODS: The potential mechanisms of Inotodiol on HeLa cell anti-metastatic and pro-apoptosis via wound healing assay, trans-well invasion assay, flow cytometry, caspase-3 activity assay and western blot analysis were studied, as well as the involvement of p53 signaling pathway in anti-metastatic and pro-apoptosis of Inotodiol. Besides, the function of tumor suppressor p53 was further verified by small interfering RNA. RESULTS: Firstly, the cell viability assay showed that low-concentration of Inotodiol had no cytotoxicity to HeLa cells and whereas the concentration above 25 µM significantly inhibited HeLa cell growth and even induced apoptosis. This result was further demonstrated by cell proliferation and morphology assay. Secondly, in vitro wound healing and trans-well invasion assays reported that low-concentration treatment of Inotodiol significantly inhibited cells migration and invasion in a dose-dependent manner, the western blot analysis of matrix mettalloprotinase-2 (MMP2) and matrix mettalloprotinase-9 (MMP9) levels were also decreased. Moreover, Inotodiol notably induced tumor cell apoptosis by Annexin-V-FITC apoptosis assay, which is associated with activation pro-apoptotic proteins of PARP, cleaved caspase-3 and Bax expression, inhibition anti-apoptotic protein Bcl-2 expression. Finally, the anti-tumor activity of Inotodiol was attenuated by silencing p53 tumor suppressor, the result revealed that pre-treatment with p53-specific small interfering RNA (si-p53) markedly inhibited Intodiol-indeuced HeLa cell apoptosis and decreased the caspase-3 activity. What is more, the inhibitory effect of Inotodiol on tumor migration and invasion was blocked under p53 knockdown. CONCLUSION: To sum up, the present study indicated that Inotodiol possessed the potential to prevent malignant tumor migration and invasion, and it might be a natural active compound candidate for clinical treatment of human cervical cancer.

2'O-galloylhyperin attenuates LPS-induced acute lung injury via up-regulation antioxidation and inhibition of inflammatory responses in vivo.

2'O-galloylhyperin, an active flavonol glycoside compound with remarkable anti-immune activity, was isolated from Pyrola [P. incarnata Fisch.]. However, the evidence of anti-inflammatory activity in pulmonary diseases was still not convincing. The aim of the present study was (1) to investigate the effect of 2'O-galloylhyperin on LPS-induced acute lung injury in mice, and (2) to identify the mechanisms of attenuation of inflammatory responses. The results demonstrated that 2'O-galloylhyperin significantly reduced LPS-induced inflammation damage in a dose-dependent manner. After LPS challenge, treatment with 2'O-galloylhyperin reduced the production of pro-inflammatory cytokines and chemokines, and also improved LPS-induced lung histopathology changes. 2'O-galloylhyperin also increased the activities of antioxidant enzymes, including SOD and GSH-Px to maintain cellular redox homeostasis. Furthermore, 2'O-galloylhyperin inhibited translocation of nuclear factor (NF-κB) activation and suppressed phosphorylation of MAPK signaling pathway consisting of p38, ERK, JNK. In addition, 2'O-galloylhyperin enhanced heme oxygenase-1 (HO-1) expression to block LPS-induced inflammation via activating nuclear factor-crythroid 2-related factor (Nrf2). Moreover, 2'O-galloylhyperin induced adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation. 2'O-galloylhyperin attenuated LPS-induced acute lung injury by inhibiting the MAPK and NF-κB signaling pathways, presumably related to up-regulation of the AMPK and Nrf2 signaling pathways. Furthermore, 2'O-galloylhyperin is a potential protective antioxidant to protect lung tissues from the acute injury.

2'-O-Galloylhyperin Isolated From Pyrola incarnata Fisch. Attenuates LPS-Induced Inflammatory Response by Activation of SIRT1/Nrf2 and Inhibition of the NF-κB Pathways in Vitro and Vivo.

2'-O-galloylhyperin, a major compound of Pyrola incarnata Fisch., possesses a variety of biological and pharmacological activities, including anti-oxidative and anti-inflammatory activities. Nevertheless, the underlying molecular mechanisms of 2'-O-GH in microbial infection and sepsis are not clear. In this study, we investigated the anti-inflammatory effects of 2'-O-GH. We found that 2'-O-GH significantly reduced the production of TNF-α, IL-6, and nitric oxide (NO), suppressed the expression levels of iNOS, blocked the translocation of NF-κB from the cytosol to nucleus, and decreased the MAPK activation in LPS-activated RAW 264.7 cells. 2'-O-GH also enhanced the nuclear translocation of Nrf2 and up-regulated the expression of heme oxygenase-1 (HO-1) and SIRT1. In addition, the administration of 2'-O-GH attenuated the TNF-α and IL-6 production in the serum, infiltration of inflammatory cells, liver tissue damage, and the mortality rate of LPS-challenged mice. Moreover, 2'-O-GH significantly upregulated Nrf2 and SIRT1 expression and inhibited the inflammatory responses in the liver of septic mice. The collective data indicate that 2'-O-GH could potentially be a novel functional food candidate in the treatment of sepsis.

Quercetin attenuates myocardial ischemia-reperfusion injury via downregulation of the HMGB1-TLR4-NF-κB signaling pathway.

The goal of this study was to assess the ability of quercetin (Qu) to protect against myocardial ischemia-reperfusion injury. Cardiac injury was assessed in the context of global ischemia of isolated hearts, coronary artery ligated rats, and H9C2 cells. Qu was shown to significantly inhibit inflammatory cytokine production in coronary artery occlusion-induced rats, isolated hearts, and H9C2 cells. Electrocardiographic analysis revealed a restoration of the ST segment to normal levels following treatment of Qu. Triphenyltetrazolium chloride (TTC) staining and pathological analysis showed that Qu could significantly alleviate myocardial injury in vivo. Furthermore, ex vivo analyses showed improved recovery of heart function in response to Qu, characterized by enhanced myocardial contractility and coronary flow in isolated hearts. From a mechanistic standpoint, these effects appeared to be mediated through the HMGB1-related pathway, with expression of downstream targets significantly downregulated in rats, isolated hearts, and H9C2 cells following Qu treatment. Taken together, these data demonstrate the protective effects of Qu against myocardial injury via inhibition of the HMGB1 pathway in a myocardial ischemia-reperfusion injury (I/R) model.

Captopril inhibits calpain­mediated apoptosis of myocardial cells in diabetic rats and improves cardiac function.

To explore the effects of captopril on calpain­mediated apoptosis of myocardial cells and cardiac function in diabetic rats, 30 adult male Sprague­Dawley rats were randomly divided into three groups: Negative control (NC group), untreated diabetic rats (DM group) and diabetic rats treated with captopril (Cap group). Diabetes was induced by streptozotocin injection. Captopril was intragastrically administered at a daily dose of 50 mg/kg for 12 weeks; the NC and DM groups received an equivalent volume of saline. After 12 weeks of treatment, left ventricular systolic pressure (LVSP), left ventricular end­diastolic pressure (LVDEP), maximal rate of left ventricular pressure increase (+dp/dtmax), maximal rate of left ventricular pressure decrease (­dp/dtmax) and left ventricular mass index (LVMI) were measured. The levels of calpain­1, calpain­2, B­cell lymphoma (Bcl)­2, Bcl­2 associated protein X (Bax) and total caspase­3 were detected in cardiac tissue by western blot analysis. The apoptotic index (AI) was assessed with a terminal deoxynucleotidyl transferase­mediated dUTP nick­end labeling assay. The ultrastructure of cardiac tissue was determined by transmission electron microscopy. Compared with the NC group, LVDEP and LVMI were increased, whereas LVSP, +dp/dtmax and ­dp/dtmax were decreased in the DM group. In the Cap group, LVDEP and LVMI were decreased, whereas LVSP, +dp/dtmax and ­dp/dtmax were increased compared with the DM group. Bcl­2 protein expression was decreased, whereas the levels of calpain­1, calpain­2, Bax and total caspase­3 protein were increased in the DM group, compared with the NC group. Cap treatment increased Bcl­2 protein expression and decreased calpain­1, calpain­2, Bax and total caspase­3 protein expression compared with the DM group. Additionally, the AI was increased in the DM group compared with the NC group, and decreased in the Cap group compared with the DM group. Furthermore, ultrastructural examination demonstrated that myocardial cell injury was reduced in the Cap group compared with the DM group. Therefore, captopril improved myocardial structure and ventricular function, by inhibiting calpain­1 and calpain­2 activation, increasing Bcl­2 expression, reducing Bax expression and subsequently inhibiting caspase­3­dependent apoptosis.

Paeonol alleviated acute alcohol-induced liver injury via SIRT1/Nrf2/NF-κB signaling pathway.

In this study, the beneficial effect of paeonol on acute alcohol-induced liver injury and the basic mechanisms were investigated. in vitro, HepG2 cells were treated with paeonol for 24 h before it were exposed to alcohol for 24 h. in vivo, male C57BL/6 mice were used to establish alcohol-induced liver injury models by oral gavage of alcohol (5 g/kg BW). Paeonol pretreatment showed statistically significant reduction in alcohol-induced ROS, MDA, IL-1ß, IL-6, TNF-α, and nitric oxide, while GSH content was retained (P < 0.05). Furthermore, paeonol treatment resulted in the increase of Nrf2 nuclear translocation, the increase of NQO-1 and HO-1 expression, and the suppression of NF-κB p65 nuclear translocation. However, pretreatment with NAM (inhibitor of SIRT1) not only inhibited the effect of paeonol on reducing nuclear translocation of NF-κBp65, but also inhibited the effect of paeonol on promoting the expression of nuclear Nrf2, NQO1 and HO-1. Besides, paeonol pretreatment at test doses significantly ameliorated alcohol-induced edema, hepatocyte necrosis and hepatic cord irregular. These results demonstrated that paeonol has the high potential for relieving acute alcohol-induced liver injury.

Juglone induces apoptosis and autophagy via modulation of mitogen-activated protein kinase pathways in human hepatocellular carcinoma cells.

Juglone (JG), a naturally-occurring naphthoquinone of Manchurian walnut (Juglans mandshurica) was shown to inhibit proliferation in various tumor types. However, the molecular mechanisms of JG on the induction of apoptosis and autophagy in HepG2 cells have not been examined. Herein, we investigated that JG could inhibit cell proliferation by induction of G2/M phase arrest. Also, occurrence of apoptosis was closely related with loss of mitochondrial membrane potential, the changes of apoptosis-related proteins after treatment with JG. In addition, we found that JG caused autophagy, as evidenced by increased expressions of LC3-II and Beclin-1. Interestingly, inhibition of JG-induced autophagy by 3-methyladenine (3-MA) and wortmannin (WT) significantly decreased apoptosis, whereas the apoptosis inhibitor z-VAD-fmk slightly enhanced autophagy. Furthermore, the induction of autophagy and apoptosis was associated with activation of MAPK family members (p38 and JNK) and production of reactive oxygen species (ROS). Both JNK inhibitor (SP600125) and ROS scavenger (N-acetylcysteine, NAC) could attenuate JG-induced autophagy and apoptosis. However, the p38-specific inhibitor SB203580 enhanced autophagic and apoptotic death. Moreover, the ROS scavenger NAC prevented phosphorylation of both p38 and JNK. Collectively, our data revealed that JG induced G2/M phase arrest, apoptosis, and autophagy through the ROS-dependent signaling pathway.

A pilot study of a cardiovascular virtual endoscopy system based on multi-detector computed tomography in diagnosing tetralogy of Fallot in pediatric patients.

The present study aimed to investigate the capabilities of the cardiovascular virtual endoscopy (VE) system in diagnosing tetralogy of Fallot (TOF) and performing measurements. A total of 37 patients underwent two-dimensional echocardiography (2-DE) and multi-detector computed tomography (MDCT) examinations. The obtained MDCT images were applied to a cardiovascular VE system. Diagnostic time by VE was first studied and compared with MDCT. Subsequently, with surgical findings as the ground truth, the capabilities of VE, 2-DE and MDCT in diagnosing TOF and its complications were investigated. Additionally, measurements on aorta overriding ratio and diameters for the left pulmonary artery, right pulmonary artery and right ventricular outflow tract by 2-DE and VE were analyzed. Diagnostic time by VE was significantly shorter than MDCT (188±42 vs. 303±42 sec, respectively; P<0.0001). VE, MDCT and 2-DE demonstrated comparable diagnostic rates of TOF (35/37 vs. 34/37 vs. 32/37, respectively; P>0.05). Similar findings were demonstrated in diagnosing complications of the muscular ventricular septal defects, patent ductus arteriosus, vagus subclavian artery, right arch, double superior vena cava and pulmonary artery. Furthermore, in diagnosing the atrial septal defect, 2-DE outperformed MDCT and VE (accuracy, 100 vs. 81 vs. 73%, respectively; all P<0.05). In performing relevant measurements, VE outperformed MDCT and 2-DE, particularly in accessing aorta overriding ratios with no intra-operator difference (P=0.3770) and high consistency (r=0.916). In conclusion, cardiovascular VE was demonstrated to have acceptable accuracy in diagnosing TOF, and possess advantages in shortening the diagnostic time and in performing measurements.

Application of cardiovascular virtual endoscopy: a pilot study on roaming path planning for diagnosis of congenital heart diseases in children.

To investigate roaming paths planning for diagnosis of congenital heart diseases (CHD) using a cardiovascular virtual endoscopy (VE) system. Forty children were enrolled. VE system was applied to support in establishing a diagnosis. Performance in diagnosing CHDs by CT, VE using automatically planned roaming paths (VE-auto, objects were treated as left heart system and right heart system), VE using manually planned paths (VE-manual), and VE using automatically planned path for left heart system and manually planned path for right heart system (VE-combined) were studied and compared. Comparable accuracy of 93%, 93%, 95% and 95% was found by CT, VE-auto, VE-manual and VE-combined. However, in diagnosing tetralogy of Fallot, significantly higher performance was found by VEs, compared with CT. For VE-auto, poor performance with an accuracy of 85% and sensitivity of 22% was revealed in diagnosing muscular ventricular septal defect, compared with VE-manual and VE-combined. Compared with VE-manual, VE-combined illustrated comparable diagnostic accuracy on all CHDs; however, significantly smaller diagnostic time was utilized (P < 0.05).Cardiovascular VE system demonstrated considerable clinical value in the diagnosis of CHDs. Left and right heart system should not be modeled as two cavity objects simultaneously. When one of two systems is treated as one object, the other system should be treated as three separate objects when using VE to diagnose CHDs.