[Anti-tumor mechanism of total saponins of Paridis Rhizoma on inducing ferroptosis of breast cancer MCF-7 cells].

This study aims to investigate the mechanism of total saponins of Paridis Rhizoma in inducing the ferroptosis of MCF-7 cells and provide a theoretical basis for the clinical treatment of breast cancer with total saponins of Paridis Rhizoma. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the effects of different concentrations of total saponins of Paridis Rhizoma on the proliferation of MCF-7 cells. A phase contrast inverted microscope was used to observe the morphological changes of MCF-7 cells. The colony formation assay was employed to test the colony formation of MCF-7 cells. The lactate dehydrogenase(LDH) release test was conducted to determine the cell membrane integrity of MCF-7 cells. The cell scratch assay was employed to examine the migration of MCF-7 cells. After that, the level of reactive oxygen species(ROS) in MCF-7 cells was observed by an inverted fluorescence microscope, and the content of Fe~(2+) in MCF-7 cells was detected by the corresponding kit. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of MCF-7 cells. Western blot was employed to determine the expression of ferroptosis-related proteins, such as p53, solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long-chain family member 4(ACSL4), and transferrin receptor protein 1(TFR1) in MCF-7 cells. The results showed that 1.5, 3, 4.5, 6, 7.5, and 9 µg·mL~(-1) total saponins of Paridis Rhizoma significantly inhibited the proliferation of MCF-7 cells, with the IC_(50) of 4.12 µg·mL~(-1). Total saponins of Paridis Rhizoma significantly damaged the morphology of MCF-7 cells, leading to the formation of vacuoles and the gradual shrinkage and detachment of cells. Meanwhile, total saponins of Paridis Rhizoma inhibited the colony formation of MCF-7 cells, destroyed the cell membrane(leading to the release of LDH), and shortened the migration distance of MCF-7 cells. Total saponins of Paridis Rhizoma treatment significantly increased the content of ROS, induced oxidative damage, and led to the accumulation of Fe~(2+) in MCF-7 cells. Furthermore, total saponins of Paridis Rhizoma changed the mitochondrial structure, increased the mitochondrial membrane density, led to the decrease or even disappear of ridges, promoted the expression of p53 protein, down-regulated the expression of SLC7A11 and GPX4, and up-regulated the expression of ACSL4 and TFR1. In summary, total saponins of Paridis Rhizoma can significantly inhibit the proliferation and migration of MCF-7 cells and destroy the cell structure by inducing ferroptosis.

Medical malpractice in hospitals-how healthcare staff feel.

Introduction: Literature is limited on quantified acute stress reaction, the impact of event scale on medical staff when facing medical malpractice (MMP), and how to individually care for staff. Methods: We analyzed data in the Taichung Veterans General Hospital from October 2015 to December 2017, using the Stanford Acute Stress Reaction Questionnaire (SASRQ), the Impact of Event Scale-Revised (IES-R), and the medical malpractice stress syndrome (MMSS). Results and Discussion: Of all 98 participants, most (78.8%) were women. Most MMPs (74.5%) did not involve injury to patients, and most staff (85.7%) indicated receiving help from the hospital. The internal-consistency evaluations of the three questionnaires showed good validity and reliability. The highest score of IES-R was the construct of intrusion (30.1); the most severe construct of SASRQ was "Marked symptoms of anxiety or increased arousal," and the most were having mental and mild physical symptoms for MMES. A higher total IES-R was associated with younger age (<40 y/o), and more severe injury on patients (mortality). Those who indicated receiving very much help from the hospital were those having significantly lower SASRQ sores. Our study highlighted that hospital authorities should regularly follow up on staff's response to MMP. With timely interventions, vicious cycles of bad feelings can be avoided, especially in young, non-doctor, and non-administrative staff.

[Identification of lncrnas associated with aniline toxicity in male bladder cancer and construction of tumor risk prediction models].

OBJECTIVE: Aniline poisoning is considered to be an important factor mediating the development and progression of male bladder cancer,and long non-coding RNA(lncRNA)has also been shown to affect the prognosis of male bladder cancer.Therefore,this study intended to screen and identify lncrnas associated with highly sensitive aniline poisoning of male bladder cancer,and to construct a tumor risk prediction model accordingly. METHODS: Gene expression and clinical data from 410 tissues were downloaded from the Cancer Genome Atlas(TCGA),and all samples were randomly divided into training and testing groups.Lncrnas associated with aniline poisoning were distinguished.We then performed univariate COX and multivariate COX regressions,in parallel with LASSO regression,to establish a lncRNA risk model associated with aniline poisoning.Kaplan-Meier curve,scatterplot,C-index,ROCcurve,nomogram,PCAanalysis,and univariate and multivariate Cox regression were used to test the accuracy of the risk model and predict patient survival. RESULTS: Seven lncrnas associated with aniline poisoning(LINC01184, LINC00513,LINC02443,SMARCA5-AS1,BDNF-AS,SOD2-OT1,HYI-AS1)were screened and identified,and based on this,a risk prediction model with high sensitivity to the malignant progression of bladder cancer was constructed.It is also verified that the model can effectively predict the overall survival(OS)of the test group and the whole cohort at different stages. CONCLUSIONS: We identified 7 lncrnas associated with aniline poisoning and established a novel risk model of lncrnas associated with aniline poisoning,which provides new insights for prognosis assessment and may guide the comprehensive treatment of male bladder cancer.

[Effect of Mobile Health for Standardized Management on Women with Gestational Diabetes Mellitus].

Objective To explore the performance of mobile health platform for standardized management of pregnant women with gestational diabetes mellitus(GDM). Methods A randomized controlled trial was conducted,in which 295 women with GDM were randomized into two groups(traditional management group and mobile health management group)by a computer-generated sequence.The traditional management group accepted standardized GDM management,and the mobile health management group was supplemented by mobile health management based on the standardized management.The glycemic control rate and the incidences of low birth weight,macrosomia,preterm birth,premature rupture of membranes,postpartum hemorrhage after cesarean section,neonatal asphyxia,malformation,and admission to the neonatal intensive care unit were compared between the two groups. Results The glycemic control rate in mobile health management group was significantly higher than that in the traditional management group [(67.22±22.76)% vs.(60.69±21.28)%,P=0.004].The incidences of low birth weight,macrosomia,preterm birth,premature rupture of membranes,postpartum hemorrhage after cesarean section,neonatal asphyxia,malformation,and admission to the neonatal intensive care unit demonstrated no significant differences between groups(all P > 0.05). Conclusions Mobile health applied in standardized management is conducive to the glycemic control of GDM women,whereas it does not significantly improve the pregnancy outcomes.Due to the short time of intervention,the effects of mobile health on pregnancy outcomes need further study.

The Small GTPase OsRac1 Forms Two Distinct Immune Receptor Complexes Containing the PRR OsCERK1 and the NLR Pit.

Plants employ two different types of immune receptors, cell surface pattern recognition receptors (PRRs) and intracellular nucleotide-binding and leucine-rich repeat-containing proteins (NLRs), to cope with pathogen invasion. Both immune receptors often share similar downstream components and responses but it remains unknown whether a PRR and an NLR assemble into the same protein complex or two distinct receptor complexes. We have previously found that the small GTPase OsRac1 plays key roles in the signaling of OsCERK1, a PRR for fungal chitin, and of Pit, an NLR for rice blast fungus, and associates directly and indirectly with both of these immune receptors. In this study, using biochemical and bioimaging approaches, we revealed that OsRac1 formed two distinct receptor complexes with OsCERK1 and with Pit. Supporting this result, OsCERK1 and Pit utilized different transport systems for anchorage to the plasma membrane (PM). Activation of OsCERK1 and Pit led to OsRac1 activation and, concomitantly, OsRac1 shifted from a small to a large protein complex fraction. We also found that the chaperone Hsp90 contributed to the proper transport of Pit to the PM and the immune induction of Pit. These findings illuminate how the PRR OsCERK1 and the NLR Pit orchestrate rice immunity through the small GTPase OsRac1.

The relationship between plasma taurine levels in early pregnancy and later gestational diabetes mellitus risk in Chinese pregnant women.

Taurine is a sulfur-containing amino acid that plays an important role in glucose homeostasis. However, it remains unknown whether the plasma concentration of taurine affects the risk of later gestational diabetes mellitus (GDM) development. We recruited 398 singleton-pregnancy women and followed up them during the course of pregnancy. We measured the plasma concentrations of taurine based on blood samples collected at nine-week gestation on average and obtained the data regarding both mothers and their infants from medical records. There was a significant increment in the mean value of HOMA-ß across the tertiles of plasma taurine in multiparous women rather than in primiparous women. After adjustment for confounders, an increase of plasma taurine was nominally and significantly associated with a decrease risk of GDM; moreover, women with plasma taurine concentrations in the lowest tertile and in the second tertile had a higher risk of GDM than did those with plasma taurine in the top tertile in multiparous women other than primiparous women. Plasma taurine level seems to be associated with insulin secretion in early pregnancy and be more closely associated with ß-cell function and the risk of GDM development in multiparas in comparison to primiparas.

The Predictive Ability of Two Triglyceride-Associated Indices for Gestational Diabetes Mellitus and Large for Gestational Age Infant Among Chinese Pregnancies: A Preliminary Cohort Study.

BACKGROUND/AIMS: To investigate the potential of maternal first-trimester triglyceride (TG) to high-density lipoprotein cholesterol (TG/HDL-c) ratio, triglyceride glucose index (TyG) and total cholesterol (TC)/HDL-c to predict the risk of later gestational diabetes mellitus (GDM) and large for gestational age (LGA) newborn in Chinese women. METHODS: We included 352 women with a singleton pregnancy, who were followed up prospectively from the first prenatal visit until delivery. Fasting glucose and plasma lipid profiles including TG, TC, HDL-c, and low-density lipoprotein cholesterol (LDL-c) were measured in the first trimester. A binary logistic regression analysis was performed to determine the odds ratios (ORs) and 95% confidence intervals (CIs) of GDM and LGA according to tertiles of those indices, respectively. Receiver-operating characteristic curve (ROC) and areas under the curve (AUC) were employed to evaluate the ability of those indices to predict the risk of GDM and LGA infants, and differences in the AUC values between them were compared. RESULTS: Women with the top tertile of TG/HDL-c or TyG other than TC/HDL-c had a significantly higher risk of GDM (ORTG/HDL-c=2.388, 95% CI 1.026-5.467; ORTyG=3.535, 95% CI 1.483-8.426, respectively) and LGA infant delivery (ORTG/HDL-c=3.742, 95% CI 1.114-12.569; ORTyG=3.011, 95% CI 1.012-8.962, respectively) than women with the lowest tertile of TG/HDL-c or TyG after adjusting for confounders. The AUC of TG/HDL-c and TyG to detect GDM was 0.664 (95% CI 0.595-0.733) and 0.686 (95% CI 0.615-0.756), respectively, and that to detect LGA was 0.646 (95% CI 0.559-0.734) and 0.643 (95% CI 0.552-0.735), respectively (all P < 0.01). There were no statistical differences between TG/HDL-c and TyG in the ability of predicting the risk of GDM or LGA infants. CONCLUSION: Maternal first-trimester TG/HDL-c and TyG are both good indicators in predicting the risk of later GDM and LGA newborn, and it may be useful to evaluate them in early pregnancy.

Associations Between Gestational Diabetes Mellitus Risk and Folate Status in Early Pregnancy and MTHFR C677T Polymorphisms in Chinese Women.

PURPOSE: Red blood cell (RBC) folate indicates long-term folate intake, and methylenetetrahydrofolate reductase (MTHFR) gene is the main gene affecting folate status. Increasing evidence suggests an association between gestational diabetes mellitus (GDM) and increased folate levels. Whether RBC folate concentrations in the first trimester of pregnancy or polymorphisms of MTHFR C677T (rs1801133) affect GDM risk in Chinese pregnant women remains unknown. Therefore, we analyzed the associations of RBC folate concentrations and rs1801133 polymorphisms with GDM risk among pregnant women in China. METHODS: A total of 366 women with a singleton pregnancy were followed prospectively from their first prenatal visit to delivery. RBC folate concentrations and rs1801133 polymorphisms were assessed during the first trimester of pregnancy. Binary logistic regression analyses were performed to determine the odds ratios (ORs) of GDM and 95% confidence intervals (CIs) by using the RBC folate concentration quartiles and rs1801133 polymorphisms. RESULTS: Participants with the TT genotype had the highest RBC folate concentrations. Those with heterozygous or homozygous variants did not have a significantly higher risk of GDM than did women with C alleles. After adjustments for covariates, women in the highest quartile for RBC folate concentration had a higher risk of GDM (adjusted OR = 2.473, 95% CI = 1.013-6.037, P = 0.047) than did those in the lowest quartile, but this association was nonsignificant after adjustment for rs1801133 polymorphisms. CONCLUSION: Higher RBC folate, partly caused by MTHFR 677C→T, may be associated with increased GDM risk, even in early pregnancy. Assessing RBC folate status and appropriately supplementing folate during early pregnancy, particularly for patients with MTHFR 677C→T, may prevent GDM. Further studies with larger populations are warranted.

Circular RNA circTET3 mediates migration of rat vascular smooth muscle cells by targeting miR-351-5p.

Abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) are the pathological basis of hyperplasia during vein graft disease. It remains unknown if circular RNAs (circRNAs) are involved in vein graft disease. In the present study, a rat vein graft model was constructed by the "cuff" technique, and whole transcriptome deep sequencing was applied to identify differential circRNAs in the grafted vein compared to the control. We identified a novel circRNA, named circTET3, whose structure was verified by Sanger sequencing and RNase R digestion. CircTET3 was increased in the grafted vein and stably located in the cytoplasm as detected by fluorescence in situ hybridization. Knockdown of circTET3 suppressed VSMC migration by acting as an endogenous miR-351-5p sponge detected by RNA pull-down and dual-luciferase reporter assays. PTPN1 was the targeted gene due to the competitive binding of circTET3 to miR-351-5p. This regulatory pathway may serve as a potential therapeutic avenue against intimal hyperplasia in vein graft disease.

Single-cell analyses reveal functional classification of dendritic cells and their potential roles in inflammatory disease.

Dendritic cells (DCs) have crucial roles in immune-related diseases. However, it is difficult to explore DCs because of their rareness and heterogeneity. Although previous studies had been performed to detect the phenotypic characteristics of DC populations, the functional diversity has been ignored. Using a combination of flow cytometry, single-cell quantitative PCR, and bioinformatic analysis, we depicted the DC panorama with not only phenotypic but also functional markers. Functional classification of DCs in mouse lymphoid tissue (spleen) and nonlymphoid tissue (liver) was performed. The results revealed that expression of macrophage scavenger receptor 1 ( MSR1) and C-C motif chemokine receptors ( CCR) 1, CCR2, and CCR4 were elevated in liver DCs, suggesting increased lipid uptake and migration abilities. The enriched expression of costimulatory molecule CD80, TLR9, and TLR adaptor MYD88 in spleen DCs indicated a more-mature phenotype, enhanced pathogen recognition, and T-cell stimulation abilities. Furthermore, we compared DCs in the atherosclerotic mouse models with healthy controls. In addition to the quantitative increase in DCs in the liver and spleen of the apolipoprotein E-knockout ( ApoE-/-) mice, the functional expression patterns of the DCs also changed at the single-cell level. These results promote our understanding of the participation of DCs in inflammatory diseases and have potential applications in DC clinical assessment.-Shi, Q., Zhuang, F., Liu, J.-T., Li, N., Chen, Y.-X., Su, X.-B., Yao, A.-H., Yao, Q.-P., Han, Y., Li, S.-S., Qi, Y.-X., Jiang, Z.-L. Single-cell analyses reveal functional classification of dendritic cells and their potential roles in inflammatory disease.

Empirically derived dietary patterns and ovarian cancer risk: a meta-analysis.

Dietary patterns, which reflect overall diet and possible nutrient and food interactions, have been reported to be related to ovarian cancer (OC) risk. However, studies on the relationship between dietary patterns and OC risk have been inconsistent. Thus, we carried out a systematic meta-analysis to assess the relationship between dietary patterns and the risk of OC. Relevant studies are identified by searching the Medline and Embase electronic databases up to December 2016. The Cochrane Q statistic and the I statistical were used to evaluate heterogeneity. A total of 22 studies fulfilled the inclusion criteria and were included in this meta-analysis. There was evidence of a decreased risk for OC in the highest versus the lowest categories of healthy dietary pattern [odds ratio (OR)=0.86; 95% confidence interval (CI): 0.74-0.99; P=0.04]. An increased risk of OC was shown for the highest versus the lowest category of a western-style dietary pattern (OR=1.19; 95% CI: 1.01-1.41; P=0.04). No significant association with OC risk was observed in the highest versus the lowest category of a heavy drinking pattern (OR=0.89; 95% CI: 0.67-1.19; P=0.42). The results of this meta-analysis suggest that a healthy dietary pattern is associated with reduced risk for OC and a western-style dietary pattern is associated with an increased risk of OC. Further studies are needed to confirm our results.

Mitigation of Cd accumulation in paddy rice (Oryza sativa L.) by Fe fertilization.

Cadmium uptake in rice is believed to be mediated by the Fe transport system. Phyto-available Cd can be changed by Fe fertilization of substrates. This work investigated whether and how Fe fertilization affects mitigation of Cd accumulation in paddy rice. A 90-d soil column experiment was conducted to study the change of Cd and Fe availability in soil after Fe fertilization (ionic and chelated Fe). A low-Cd accumulating cultivar (TY116) and a high-Cd accumulating cultivar (JY841) were grown in two Cd-polluted paddy soils amended with chelated Fe fertilizers. Additionally, both cultivars were grown in hydroponics to compare Fe-related gene expression in EDDHAFe-deficient and EDDHAFe-sufficient roots. The column experiment showed that EDTANa2Fe(II) and EDDHAFe(III) fertilization had a better mitigation effect on soil Cd availability compared to FeSO4·7H2O. Moreover, the field experiment demonstrated that these two chelated fertilizations could reduce Cd concentrations in brown rice by up to 80%. Iron concentrations in the brown rice were elevated by Fe chelates. Compared to EDDHAFe(III), EDTANa2Fe(II) fertilization had a stronger mitigation effect by generating more EDTANa2Cd(II) in the soil solution to decrease phyto-available Cd in the soil. While EDDHAFe(III) fertilization could increase soil pH and decrease soil Eh which contributed to decreasing phyto-available Cd in a contaminated soil. In the hydroponic experiment, Fe sufficiency significantly reduced Cd concentrations in above-ground organs. In some cases, the expression of OsIRT1, OsNRAMP1 and OsNRAMP5 was inhibited under Fe sufficiency relative to Fe deficiency conditions. These results suggest that mitigation of rice Cd by Fe chelate fertilization results from a decrease in available Cd in substrates and the inhibition of the expression of several Fe-related genes in the IRT and NRAMP families.

A variation on chloroplast development: the bizonoplast and photosynthetic efficiency in the deep-shade plant Selaginella erythropus.

UNLABELLED: • PREMISE OF THE STUDY: Chloroplast development and structure are highly conserved in vascular plants, but the bizonoplast of Selaginella is a notable exception. In the shade plant S. erythropus, each dorsal epidermal cell contains one bizonoplast, while other cells have normal chloroplasts. Our quest was to (1) determine the origin of bizonoplasts, (2) explore developmental plasticity, and (3) correlate developmental changes with photosynthetic activity to provide insights unavailable in other green plants with more constrained development.• METHODS: Bizonoplast development was studied in juvenile prostrate and older erect shoots of S. erythropus. Plastid plasticity was studied in plants cultivated under different light conditions. Chlorophyll fluorescence was measured and correlated with photosynthetic activity.• KEY RESULTS: The bizonoplast originates from a proplastid, forming a distinctive upper zone rapidly after exposure to low light. In the prostrate shoots, the proplastid develops through early stages only. When the shoot becomes erect, the proplastid soon develops into a mature bizonoplast. Erect shoots have significantly higher photosynthetic efficiency than prostrate shoots. No bizonoplasts were found in the plants growing in high light, where 2-4 spheroidal chloroplasts formed, or with light from below.• CONCLUSIONS: The upper zone develops above a normal-looking chloroplast structure to produce a bizonoplast. Bizonoplast developmental plasticity suggests that regular lamellar structure and monoplastidy are adaptations to deep shade environments. Such novel variation in S. erythropus is in stark contrast to known plastid development in other vascular plants, possibly reflecting retention of developmental flexibility in the basal clade, Lycophyta, to which it belongs.

Hollow hydroxyapatite microspheres/chitosan composite as a sustained delivery vehicle for rhBMP-2 in the treatment of bone defects.

Composite scaffold comprised of hollow hydroxyapatite (HA) and chitosan (designated hHA/CS) was prepared as a delivery vehicle for recombinating human bone morphogenetic protein-2 (rhBMP-2). The in vitro and in vivo biological activities of rhBMP2 released from the composite scaffold were then investigated. The rhBMP-2 was firstly loaded into the hollow HA microspheres, and then the rhBMP2-loaded HA microspheres were further incorporated into the chitosan matrix. The chitosan not only served to bind the HA microspheres together and kept them at the implant site, but also effectively modified the release behavior of rhBMP-2. The in vitro release and bioactivity analysis confirmed that the rhBMP2 could be loaded and released from the composite scaffolds in bioactive form. In addition, the composite scaffolds significantly reduced the initial burst release of rhBMP2, and thus providing prolonged period of time (as long as 60 days) compared with CS scaffolds. In vivo bone regenerative potential of the rhBMP2-loaded composite scaffolds was evaluated in a rabbit radius defect model. The results revealed that the rate of new bone formation in the rhBMP2-loaded hHA/CS group was higher than that in both negative control and rhBMP2-loaded CS group. These observations suggest that the hHA/CS composite scaffold would be effective and feasible as a delivery vehicle for growth factors in bone regeneration and repair.

Palmitoylation-dependent membrane localization of the rice resistance protein pit is critical for the activation of the small GTPase OsRac1.

Nucleotide binding domain and leucine-rich repeat (NLR)-containing family proteins function as intracellular immune sensors in both plants and animals. In plants, the downstream components activated by NLR family proteins and the immune response mechanisms induced by these downstream molecules are largely unknown. We have previously found that the small GTPase OsRac1, which acts as a molecular switch in rice immunity, is activated by Pit, an NLR-type resistance (R) protein to rice blast fungus, and this activation plays critical roles in Pit-mediated immunity. However, the sites and mechanisms of activation of Pit in vivo remain unknown. To clarify the mechanisms involved in the localization of Pit, we searched for consensus sequences in Pit that specify membrane localization and found a pair of potential palmitoylation sites in the N-terminal coiled-coil region. Although wild-type Pit was localized mainly to the plasma membrane, this membrane localization was compromised in a palmitoylation-deficient mutant of Pit. The palmitoylation-deficient Pit displayed significantly lower affinity for OsRac1 on the plasma membrane, thereby resulting in failures of the Pit-mediated cell death, the production of reactive oxygen species, and disease resistance to rice blast fungus. These results indicate that palmitoylation-dependent membrane localization of Pit is required for the interaction with and the activation of OsRac1 and that OsRac1 activation by Pit is vital for Pit-mediated disease resistance to rice blast fungus.

[Changes in plasma levels of atrial natriuretic peptide, endothelin-1 and von Willebrand factor among newborns with persistent pulmonary hypertension].

OBJECTIVE: To investigate the changes in plasma levels of atrial natriuretic peptide (ANP), endothelin-1 (ET-1) and von Willebrand factor (vWF), and their significance among newborns with persistent pulmonary hypertension (PPH). METHODS: Sixty-six newborns with PPH (case group) (mild: 26 cases; moderate: 21 cases; severe: 19 cases), as well as 40 newborns without PPH (control group) who were hospitalized in the same period, were enrolled. The control group underwent echocardiography on admission. The case group underwent echocardiography before treatment (with refractory hypoxemia) and after 7 days of treatment for measurement of pulmonary artery systolic pressure (PASP). Meanwhile, plasma levels of ANP, ET-1 and vWF were measured using ELISA. RESULTS: Before treatment, the case group had significantly higher plasma levels of ANP, ET-1 and vWF than the control group (P<0.05), and these indices increased as PASP rose. After 7 days of treatment, the children with mild or moderate PPH showed normal PASP, and their plasma levels of ANP, ET-1 and vWF were not significantly different from those of control group. The children with severe PPH had significant decreases in all indices, but they were significantly higher than those of the control group. Plasma levels of ANP, ET-1 and vWF were significantly positively correlated with PASP before and after treatment (P<0.01). CONCLUSIONS: Changes in plasma levels of ANP, ET-1 and vWF can reflect PASP in newborns with PPH during treatment. Dynamic monitoring of these indices can help to judge the severity of PPH and guide treatment.

Effect of aqueous extract and fractions of Zhi-Zi-Hou-Pu decoction against depression in inescapable stressed mice: Restoration of monoamine neurotransmitters in discrete brain regions.

CONTEXT: Zhi-Zi-Hou-Pu decoction (ZZHPD) is a traditional prescription which has been used to treat "Yu-syndrome" (depression and melancholia) in Chinese herbal medication. OBJECTIVE: To evaluate antidepressant activities of ZZHPD, its fractions and possible mechanism(s) of action. MATERIALS AND METHODS: ZZHPD (1241, 2482 and 4964 mg/kg), n-butanol fraction (ZH-BA, 1454 mg/kg), cyclohexane fraction (ZH-CH, 17 mg/kg) and aqueous fraction (ZH-AQ, 3493 mg/kg) were administered orally to different groups of mice for seven consecutive days. Forced Swimming Test (FST) and Tail Suspension Test (TST) were conducted 60 min after the last administration to evaluate the antidepressant effect. Norepinephrine, dopamine and 5-hydroxytryptamine levels in discrete brain parts were determined by HPLC-FD immediately after behavioral tests. RESULTS: ZZHPD at 2482, 4964 mg/kg, ZH-BA (1454 mg/kg), ZH-CH (17 mg/kg) or clomipramine hydrochloride (20 mg/kg) significantly (p < 0.05) reduced the duration of immobility in FST and TST without affecting locomotor activities in the open field test. Observed from score plot of principle component analysis of monoamine levels in different groups, the monoamine profile of ZZHPD-treated mice were similar to that of the normal control mice. HPLC-UV analysis indicated that iridoid glycosides, flavones and neolignans might be the active chemicals. DISCUSSION AND CONCLUSION: The results demonstrated significant antidepressant-like effect of ZZHPD in mice which was related to monoaminergic system, ZH-BA and ZH-CH could be the active fractions responsible for the antidepressant effect of ZZHPD.

SOD mimetic improves the function, growth, and survival of small-size liver grafts after transplantation in rats.

BACKGROUND: Small-for-size syndrome (SFSS) may occur when graft volume is less than 45% of the standard liver volume, and it manifests as retarded growth and failure of the grafts and more mortality. However, its pathogenesis is poorly understood, and few effective interventions have been attempted. AIMS: The present study aimed to delineate the critical role of oxidant stress in SFSS and protective effects of a superoxide dismutase mimetic, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), on graft function, growth, and survival in the recipient rats. METHODS: Small size graft liver transplantation (SSGLT) was performed to determine the survival, graft injury, and growth. MnTBAP was administered in SSGLT recipients (SSGLT+MnTBAP). RESULTS: Serum alanine aminotransferase levels were sustained higher in SSGLT recipients, which were correlated with an increased apoptotic cell count and hepatocellular necrosis in liver sections. Malondialdehyde content, gene expression of tumor necrosis factor α and interleukin 1ß, and DNA binding activity of nuclear factor-κB in the grafts were increased significantly in SSGLT recipients compared with sham-operated controls. Both phosphorylated p38 mitogen-activated protein kinase and nuclear c-Jun were increased in SSGLT. All these changes were strikingly reversed by the administration of MnTBAP, with an increase in serum superoxide dismutase activity. Moreover, in situ bromodeoxyuridine incorporation demonstrated that graft regeneration was much more profound in the SSGLT+MnTBAP group than in the SSGLT group. Finally, the survival of recipients with MnTBAP treatments was significantly improved. CONCLUSIONS: Enhanced oxidant stress with activation of the p38/c-Jun/nuclear factor-κB signaling pathway contributes to SFSS-associated graft failure, retarded graft growth, and poor survival. MnTBAP effectively reversed the pathologic changes in SFSS-associated graft failure.

Activation of a Rac GTPase by the NLR family disease resistance protein Pit plays a critical role in rice innate immunity.

The nucleotide-binding domain and leucine-rich repeat-containing (NLR) family proteins recognize pathogen-derived molecules and trigger immune responses in both plants and animals. In plants, the direct or indirect recognition of specific pathogen effectors by NLRs culminates in a hypersensitive response (HR) and the production of reactive oxygen species (ROS), key components of the plant defense response. However, the molecules activated by NLRs and how they induce immune responses are largely unknown. We found that the rice GTPase OsRac1 at the plasma membrane interacts directly with Pit, an NLR protein that confers resistance to the rice blast fungus. OsRac1 contributes to Pit-mediated ROS production as well as the HR and is required for Pit-mediated disease resistance in rice. Furthermore, the active form of Pit induces the activation of OsRac1 at the plasma membrane. Thus, OsRac1 is activated by Pit during pathogen attack and plays a critical role in Pit-mediated immunity in rice.

Hepatic regenerative response in small-sized liver isografts in the rat.

BACKGROUND: To investigate hepatic regenerative response and associated mechanisms in different-size liver grafts in the rat. METHODS: Rat models of different-size-graft liver transplantation (whole, 50%-size, or 30%-size) were established, with a sham operation group serving as a control. Portal pressure, graft injury, interleukin 6 (IL-6), signal transducer and activator of transcription (Stat3), mitogen-activated protein kinase (MAPK), cyclin D1, and proliferating cell nuclear antigen (PCNA) were all assessed. RESULTS: The portal pressure was significantly higher and hepatic injury more severe in the smaller sized groups than in the whole graft group, especially in the 30%-size grafts. Hepatic IL-6 and tumor necrosis factor-alpha (TNF-alpha) levels in the two smaller sized groups were significantly higher than in the whole graft group, while IL-6 levels appeared to be negatively associated with graft sizes. Downstream markers of IL-6, Stat3 and MAPK phosphorylation, cyclin D1, and PCNA expression were also markedly increased in the small-sized grafts compared with the whole grafts, and appeared to positively correlate with early measurements of portal pressure and subsequent hepatic injury. CONCLUSION: Vigorous hepatic regeneration in small-for-size liver grafts may be associated with highly activated IL-6/Stat3 and MAPK signaling, which may in turn correlate with graft size, portal pressure, and hepatic injury.