Effectiveness of mobile health interventions for pregnant women with gestational diabetes mellitus: a systematic review and meta-analysis.

Gestational diabetes mellitus is a growing global health problem. Inadequate management during pregnancy can lead to maternal and foetal complications. Currently, mobile health (mHealth) delivers healthcare services, playing an increasingly important role in the management of blood glucose in GDM. This study aimed to systematically evaluate the effectiveness of mHealth intervention in pregnant women with GDM. Based on randomised controlled trials of mHealth application in GDM patients searched from the database, literature screening, data extraction, and quality evaluation were conducted independently by two researchers. Statistical analysis was performed using Review Manager 5.4 software. The review included 27 studies with a total of 3483 patients. The results showed a significant improvement in glycemic control. In addition, mHealth interventions could reduce the occurrence of adverse pregnancy outcomes and improve self-management ability. In a subgroup analysis, recording of delivery mode and WeChat combined phone call indicated significant differences with mHealth interventions. It was suggested that mHealth interventions imposed a positive effect on glycemic control and reduction of adverse pregnancy outcomes in GDM patients. Our results demonstrated that the application of mHealth interventions can act as an effective and feasible approach to self-management to promote the self-management level and awareness of GDM patients.

Zizaane-Type Sesquiterpenoids and Their Rearranged Derivatives from Agarwood of an Aquilaria Plant.

Nine new sesquiterpenoids (1-9) were isolated from ethyl ether extract of agarwood originated from Aquilaria sp., including three novel sesquiterpenoids (1-3) derived from zizaane, together with six zizaane-type sesquiterpenoids (4-9). All structures were unambiguously elucidated based on 1D and 2D NMR spectra as well as by HRESIMS data. The absolute configuration of sesquiterpenoids was determined by comparison of the experimental and computed ECD spectra. In vitro anti-inflammatory assessment showed that compound 9 exhibited inhibition of NO production in LPS-stimulated RAW264.7 cells with an IC50 value of 62.22 ± 1.27 µM.

Sesquiterpenoids and 2-(2-phenylethyl)chromones respectively acting as α-glucosidase and tyrosinase inhibitors from agarwood of an Aquilaria plant.

The ethyl ether extract of agarwood from an Aquilaria plant afforded six new sesquiterpenoids, Agarozizanol A - F (1-6), together with four known sesquiterpenoids and six known 2-(2-phenylethyl)chromones. Their structures were elucidated via detailed spectroscopic analysis, X-ray diffraction, and comparisons with the published data. All the isolates were evaluated for the α-glucosidase and tyrosinase inhibitory activities in vitro. Compounds 5, 7, 8, and 10 showed significant inhibition of α-glucosidase with IC50 values ranging between 112.3 ± 4.5 and 524.5 ± 2.7 µM (acarbose, 743. 4 ± 3.3 µM). Compounds 13 and 14 exhibited tyrosinase inhibitory effect with IC50 values of 89.0 ± 1.7 and 51.5 ± 0.6 µM, respectively (kojic acid, 46.1 ± 1.3). In the kinetic studies, compounds 5 and 14 were found to be uncompetitive inhibitors for α-glucosidase and mixed type inhibitors for tyrosinase, respectively. Furthermore, molecular docking simulations revealed the binding sites and interactions of the most active compounds with α-glucosidase and tyrosinase.

Identification and characterization of drought-responsive CC-type glutaredoxins from cassava cultivars reveals their involvement in ABA signalling.

BACKGROUND: CC-type glutaredoxins (GRXs) are plant-specific glutaredoxin, play regulatory roles in response of biotic and abiotic stress. However, it is not clear whether the CC-type GRXs are involve in drought response in cassava (Manihot esculenta), an important tropical tuber root crop. RESULTS: Herein, genome-wide analysis identified 18 CC-type GRXs in the cassava genome, of which six (namely MeGRXC3, C4, C7, C14, C15, and C18) were induced by drought stress in leaves of two cassava cultivars Argentina 7 (Arg7) and South China 124 (SC124). Exogenous abscisic acid (ABA) application induced the expression of all the six CC-type GRXs in leaves of both Arg7 and SC124 plants. Overexpression of MeGRXC15 in Arabidopsis (Col-0) increases tolerance of ABA on the sealed agar plates, but results in drought hypersensitivity in soil-grown plants. The results of microarray assays show that MeGRXC15 overexpression affected the expression of a set of transcription factors which involve in stress response, ABA, and JA/ET signalling pathway. The results of protein interaction analysis show that MeGRXC15 can interact with TGA5 from Arabidopsis and MeTGA074 from cassava. CONCLUSIONS: CC-type glutaredoxins play regulatory roles in cassava response to drought possibly through ABA signalling pathway.

Transient receptor potential vanilloid type 4 channels mediate Na-K-Cl-co-transporter-induced brain edema after traumatic brain injury.

Na+ -K+ -2Cl- co-transporter (NKCC1) plays an important role in traumatic brain injury (TBI)-induced brain edema via the MAPK cascade. The transient receptor potential vanilloid type 4 (TRPV4) channel participates in neurogenic inflammation, pain transmission, and edema. In this study, we investigated the relationship between NKCC1 and TRPV4 and the related signaling pathways in TBI-induced brain edema and neuronal damage. TBI was induced by the calibrated weight-drop device. Adult male Wistar rats were randomly assigned into sham and experimental groups for time-course studies of TRPV4 expression after TBI. Hippocampal TRPV4, NKCC1, MAPK, and PI-3K cascades were analyzed by western blot, and brain edema was also evaluated among the different groups. Expression of hippocampal TRPV4 peaked at 8 h after TBI, and phosphorylation of the MAPK cascade and Akt was significantly elevated. Administration of either the TRPV4 antagonist, RN1734, or NKCC1 antagonist, bumetanide, significantly attenuated TBI-induced brain edema through decreasing the phosphorylation of MEK, ERK, and Akt proteins. Bumetanide injection inhibited TRPV4 expression, which suggests NKCC1 activation is critical to TRPV4 activation. Our results showed that hippocampal NKCC1 activation increased TRPV4 expression after TBI and then induced severe brain edema and neuronal damage through activation of the MAPK cascade and Akt-related signaling pathway.

Amplification and overexpression of PSCA at 8q24 in invasive micropapillary carcinoma of breast.

PURPOSE: Invasive micropapillary carcinoma (IMPC) of the breast has distinct histological features and molecular genetic profiles. Gains/amplifications of 8q24 are found associated with IMPC. Although the prostate stem cell antigen (PSCA) gene is located at chromosome 8q24, and found over-expressed in prior studies, its prognostic values and biological significance in IMPC have not been well studied. METHODS: Fluorescence in situ hybridization (FISH) was used to assess the frequencies of PSCA copy number gains in IMPC, invasive ductal carcinoma of no special type (IDC-NST), and invasive lobular carcinoma (ILC) samples. The protein expression levels of PSCA were examined in 56 IMPC, 72 IDC-NST, and 56 ILC samples using immunohistochemical analysis. RESULTS: PSCA gene amplification was detected in 45.2% (14/31) of the IMPC, 28.1% (9/32) of the IDC-NST, and none (0/25) of the ILC. PSCA protein expression was observed in 58.9% (33/56), 40.3% (29/72), and 3.6% (2/56) of IMPC, IDC-NST, and ILC samples, respectively. The concordant rate of the immunohistochemistry and FISH data was 85.2%. PSCA gene amplification highly correlated with its protein overexpression (rs = 0.687, P < 0.001), suggesting that gene amplification is an important mechanism involved in PSCA overexpression. Our univariate analysis showed that the patients with PSCA-positive IMPC had a decreased disease-free survival (DFS) compared to PSCA-negative IMPC patients (P = 0.003). Our multivariate analysis confirmed the worse DFS in PSCA-positive IMPC patients (P = 0.022). CONCLUSIONS: Our results indicate that PSCA may be an attractive target in the 8q24 amplicon and that it may serve as a molecular marker of metastasis and recurrence in IMPC. The differential expression of PSCA may be associated with cell adhesion. Detection of PSCA protein and gene amplification may help manage and predict the prognosis of IMPC patients.

Genome-wide characterization and expression analysis enables identification of abiotic stress-responsive MYB transcription factors in cassava (Manihot esculenta).

The myeloblastosis (MYB) transcription factor superfamily is the largest transcription factor family in plants, playing different roles during stress response. However, abiotic stress-responsive MYB transcription factors have not been systematically studied in cassava (Manihot esculenta), an important tropical tuber root crop. In this study, we used a genome-wide transcriptome analysis to predict 299 putative MeMYB genes in the cassava genome. Under drought and cold stresses, many MeMYB genes exhibited different expression patterns in cassava leaves, indicating that these genes might play a role in abiotic stress responses. We found that several stress-responsive MeMYB genes responded to abscisic acid (ABA) in cassava leaves. We characterize four MeMYBs, namely MeMYB1, MeMYB2, MeMYB4, and MeMYB9, as R2R3-MYB transcription factors. Furthermore, RNAi-driven repression of MeMYB2 resulted in drought and cold tolerance in transgenic cassava. Gene expression assays in wild-type and MeMYB2-RNAi cassava plants revealed that MeMYB2 may affect other MeMYBs as well as MeWRKYs under drought and cold stress, suggesting crosstalk between MYB and WRKY family genes under stress conditions in cassava.

Assessment of dual-probe Her-2 fluorescent in situ hybridization in breast cancer by the 2013 ASCO/CAP guidelines produces more equivocal results than that by the 2007 ASCO/CAP guidelines.

Dual-probe fluorescence in situ hybridization (D-FISH) is a widely accepted method to determine the gene amplification status of human epidermal growth factor receptor 2 (Her-2). In 2013, the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) updated the guidelines on the Her-2 testing for invasive breast cancer (BCa). The interpretation criteria for D-FISH changed accordingly. In this study, we compared the Her-2 FISH statuses based on the 2013 and 2007 ASCO/CAP guidelines in 1931 cases of BCa with Her-2 D-FISH testing at our hospital. We analyzed the clinicopathologic features of cases with equivocal results by the 2013 ASCO/CAP guidelines. Although the guideline update significantly improved the detection rate of Her-2 amplification, it also significantly increased the rate of equivocal results, posing a dilemma for clinical management. The equivocal results had a good reproducibility. The distribution of D-FISH-equivocal cases did not correlate with Her-2 status by immunohistochemistry, suggesting that Her-2 D-FISH equivocality may not reflect Her-2 overexpression. Compared with Her-2-negative cases by D-FISH, Her-2 D-FISH-equivocal cases had higher Ki67 expression, higher histological grade, more frequent lymph node metastasis, and lower estrogen receptor α expression, indicating a group of BCa with worse prognosis. The clinical significance of Her-2-equivocal results by D-FISH warrants further investigation.

[Effect of Modified Guipi Decoction on Blood Pressure and Quality of Life in Hypertension Patients Complicated Depression].

OBJECTIVE: To study the effect of Modified Guipi Decoction (MGD) on blood pressure and quality of life (QOL) in hypertension patients complicated depression. METHODS: Totally 245 hypertension patients complicated depression were randomly assigned to the treatment group (125 cases, treated with MGD) and the control group (120 cases, treated with Sertraline). Final recruited qualified patients were 117 cases in the treatment group and 111 cases in the control group. The therapeutic course for all was 4 weeks. Changes of blood pressure, scores rated by Hamilton Depression Scale-17 (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), short-form 36 health survey questionnaire (SF-36), and Treatment Emergent Symptom Scale (TESS) were observed before and after treatment, thereby judging their efficacies. RESULTS: (1) Compared with before treatment in the same group, systolic and diastolic blood pressures significantly decreased in the treatment group after 2 weeks of treatment; systolic blood pressure significantly-decreased after 2 weeks of treatment and diastolic blood pressure significantly decreased after 3 weeks of treatment in the control group (all P < 0.05, P < 0.01). Decreased valley values of systolic and diastolic blood pressures at week 2, 3, and 4 after treatment were obviously higher than those at week 1 after treatment in the two groups (P < 0.05, P < 0.01). Compared with the control group at week 4 after treatment, valley value of systolic blood pressure obviously decreased in the treatment group (P <0. 01). Decreased valley values of systolic and diastolic blood pressures in the treatment group were higher than those of the control group (P <0. 01). The success rate of target blood pressure was 60. 7% (71/117 cases) in the treatment group and 42. 3% (47/111 cases) in the control group, with statistical difference (χ² = 7.6781, P < 0.01). (2) Compared with before treatment in the same group, the score of HAMD-17 at week 2, 3, and 4 after treatment all decreased in the two groups (P < 0.01). Compared with the control group, the score of HAMD-17 at week 4 after treatment decreased more obviously in the treatment group, with higher difference in decreased value (P < 0.05). The effective rate was 79.5% (93/117) in the treatment group, higher than that in the control group [66.7% (74/111); χ² = 4.7741, P < 0.05]. (3) Compared with before treatment in the same group, the score of HAMA at week 1, 2, 3, and 4 after treatment all obviously decreased in the two groups (P <0. 05, P <0. 01). Compared with the control group, the score of HAMA at week 3 and 4 after treatment decreased more obviously in the treatment group, with higher difference in decreased value (P < 0.05, P < 0.01). (4) After 4 weeks of treatment, except physical function in the control group, SF-36 total score and the score for each factor were obviously higher in the two groups (P < 0.05, P < 0.01). MGD showed superior effect in improving physical function, physical activity, overall health, emotion activity, and health changes to that of Sertraline (P < 0.05, P < 0.01). (5) The incidence of insomnia, tremor, liability to agitation, dizziness was obviously less in the treatment group than in the control group (P < 0.05). CONCLUSIONS: MGD had favorable clinical effect on hypertension patients complicated depression. Meanwhile, it also could improve their blood pressure and QOL.

NKCC1 mediates traumatic brain injury-induced hippocampal neurogenesis through CREB phosphorylation and HIF-1α expression.

Traumatic brain injury (TBI) is one of the most prevalent causes of worldwide mortality and morbidity. We previously had evidenced that TBI induced Na-K-2Cl co-transporter (NKCC1) upregulation in hippocampus. Here, we aim to investigate the role of NKCC1 in TBI-induced neurogenesis and the detailed mechanisms. The TBI-associated alternations in the expression of NKCC1, HIF-1α, VEGF, MAPK cascade, and CREB phosphorylation were analyzed by Western blot. TBI-induced neurogenesis was determined by immuno-fluorescence labeling. Chromatin immunoprecipitation was used to elucidate whether HIF-1α would activate VEGF gene after TBI. We found that the level of hippocampal NKCC1 and VEGF began to rise 8 h after TBI, and both of them reached maxima at day 7. Along with the upregulation of NKCC1 and VEGF, MAPK cascade was activated and hippocampal neurogenesis was promoted. Administration of CREB antisense oligonucleotide significantly attenuated the expression of HIF-1α, while HIF-1α antisense oligonucleotide exhibited little effect on the expression of CREB. However, HIF-1α antisense oligonucleotide administration did effectively suppress the expression of VEGF. Our results of the chromosome immunoprecipitation also indicated that HIF-1α could directly act on the VEGF promoter and presumably would elevate the VEGF expression after TBI. All these results have illustrated the correlation between NKCC1 upregulation and TBI-associated neurogenesis. The pathway involves the activation of Raf/MEK/ERK cascade, CREB phosphorylation, and HIF-1α upregulation, and finally leads to the stimulation of VEGF expression and the induction of neurogenesis.

Neonatal glucocorticoid treatment increased depression-like behaviour in adult rats.

Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Previous studies suggested that neonatal DEX treatment altered brain development and cognitive function. It has been recognized that the amygdala is involved in emotional processes and also a critical site of neuronal plasticity for fear conditioning. Little is known about the possible long-term adverse effect of neonatal DEX treatment on amygdala function. The present study was aimed to evaluate the possible effect of neonatal DEX treatment on the synaptic function of amygdala in adult rats. Newborn Wistar rats were subjected to subcutaneous tapering-dose injections of DEX (0.5, 0.3 and 0.1 mg/kg) from post-natal day one to three, PN1-PN3. Animals were then subjected to a forced swimming test (FST) and electrophysiological recording aged eight weeks. The results of the FST showed neonatal DEX treatment increased depression-like behaviour in adulthood. After acute stress evoking, the percentage of time spent free floating is significantly increased in the DEX treated group compared with the control animals. Furthermore, neonatal DEX treatment elevated long-term potentiation (LTP) response and the phosphorylation level of MAPK in the lateral nucleus of amygdala (LA). Intracerebroventricular infusion of the MAPK inhibitor, PD98059, showed significant rescue effects including reduced depression-like behaviour and restoration of LTP to within normal range. In conclusion, our results suggested that MAPK signalling cascade in the LA plays an important role in the adverse effect of neonatal DEX treatment on amygdala function, which may result in adverse consequences in adult age, such as the enhancement of susceptibility for a depressive disorder in later life.

[Tumor genetic heterogeneity].

Although the majority of spontaneous tumors derive from a single cell, people have come to realize intra-tumor heterogeneity of individual tumors. Human cancers frequently display substantial difference in phenotypic features, such as the degree of differentiation, cell proliferation rate, invasion and metastatic potential, response to therapy and many other aspects. Molecular biology studies have confirmed the occurrence of new mutations during the process of tumor progression, which provide more powerful evidences to show the existence of intra-tumor genetic heterogeneity. This re-view will focus on recent major advances in the study of tumor genetic heterogeneity. Considering that genetic heterogene-ity analysis can provide important information to indicate how long normal cells transform into tumor cells and how to spread and migrate, we firstly describe experimental evidences of intra-tumor genetic heterogeneity. Then we discuss the research value of genetic diversity in the evolutionary history of human individual tumor, introduce the two modes of the genetic heterogeneity - cancer stem cell model and the clonal evolution model, and summarize the implications of in-tra-tumor heterogeneity studies in metastasis and therapy. In addition, the article presents the research methods of genetic heterogeneity, including specific gene and genome-wide level, pointing out their strengths and limitations.

Genetic heterogeneity of HER2 in breast cancer: impact on HER2 testing and its clinicopathologic significance.

In 2009, ASCO/CAP expanded its human epidermal growth factor receptor type 2 (HER2) testing guideline to define HER2 genetic heterogeneity (GH). However, the clinical significance of GH is unclear. We investigated the impact of HER2 GH on HER2 testing and studied its clinicopathologic significance. Paraffin-embedded tumor tissues of surgical resections of 617 non-consecutive breast carcinoma patients were studied by routine HER2 fluorescence in situ hybridization (FISH). HER2 GH was evaluated, and the results were correlated with HER2 protein expression by immunohistochemistry and HER2 gene amplification by FISH, and with various clinicopathologic parameters. HER2 GH was observed in 15.2 % (94/617) of the patients. It was associated with low-to-middle level of HER2 expression, and with none-to-low level of HER2 gene amplification. Among the 17 patients with equivocal HER2 FISH results, 35.3 % (6/17) of tumors displayed GH. In contrast with HER2-positive tumors without GH, tumors with HER2 GH demonstrated significant association with lower histologic grade, smaller tumor size, and proclivity to hormone receptor expression. HER2 GH is a substantial cause of equivocal HER2 testing results of breast cancer by FISH. Tumors with HER2 GH showed that biologic features resemble more of HER2-negative tumors than HER2-positive tumors without GH. The findings indicate a need of the guidelines to clarify whether tumors with HER2 GH truly benefit from HER2-targeted therapy of breast cancer.

Indomethacin protects rats from neuronal damage induced by traumatic brain injury and suppresses hippocampal IL-1ß release through the inhibition of Nogo-A expression.

BACKGROUND: Nogo-A is a member of the reticulon family of membrane-associated proteins and plays an important role in axonal remodeling. The present study aimed to investigate alterations in Nogo-A expression following traumatic brain injury (TBI)-induced inflammation and neuronal damage. METHODS: A weight-drop device was used to deliver a standard traumatic impact to rats. Western blot, RT-PCR and ELISA were used to analyze the expression of Nogo-A and IL-1ß. Nogo-A antisense, and an irrelevant control oligonucleotide was intracerebroventricularly infused. We also performed H & E staining and luxol fast blue staining to evaluate the neuronal damage and demyelination resulting from TBI and various treatments. RESULTS: Based on RT-PCR and western blot analyses, the expression of Nogo-A was found to be significantly upregulated in the hippocampus beginning eight hours after TBI. In addition, TBI caused an apparent elevation in IL-1ß levels and severe neuronal damage and demyelination in the tested animals. All of the TBI-associated molecular and cellular consequences could be effectively reversed by treating the animals with the anti-inflammatory drug indomethacin. More importantly, the TBI-associated stimulation in the levels of both Nogo-A and IL-1ß could be effectively inhibited by a specific Nogo-A antisense oligonucleotide. CONCLUSIONS: Our findings suggest that the suppression of Nogo-A expression appears to be an early response conferred by indomethacin, which then leads to decreases in the levels of IL-1ß and TBI-induced neuron damage.

Effect of MK-801-induced impairment of inhibitory avoidance learning in zebrafish via inactivation of extracellular signal-regulated kinase (ERK) in telencephalon.

N-Methyl-D-aspartate (NMDA) receptors are implicated in a wide range of complex behavioral functions, including cognitive activity. Numerous studies have shown that using the repetitive administration of a noncompetitive NMDA receptor antagonist, MK-801, induces amnesia in rodents. In this study, the effect of a subchronic MK-801 treatment on the cognitive function of zebrafish was evaluated using a novel inhibitory avoidance task. First, we established a new system to investigate the inhibitory avoidance learning of zebrafish where they were trained to refrain from swimming from a shallow compartment to a deep compartment in order to avoid electric shock. Second, we found that blocking NMDA receptors by MK-801 could significantly attenuate the inhibitory avoidance behavior of the zebrafish and alter the telencephalic extracellular signal-regulated kinase (ERK) phosphorylation level 90 min after the inhibitory avoidance training. These results suggest that the formation of long-term emotional memory is possibly mediated by ERK activation in the telencephalon of zebrafish.

Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC.

The aarF domain containing kinase 2 (ADCK2) is a mitochondria-locating protein, important for fatty acid metabolism and coenzyme Q biosynthesis. The bioinformatics results show that elevated ADCK2 transcripts in NSCLC correlate with poor overall survival and poor anti-PD-1/PD-L1 therapy response. ADCK2 is overexpressed in local human NSCLC tissues and various primary and established NSCLC cells. In NSCLC cells, ADCK2 shRNA or CRISPR/Cas9 knockout remarkably suppressed cell viability, proliferation, cell cycle progression, cell mobility, and provoked cell apoptosis. Moreover, ADCK2 depletion disrupted mitochondrial functions in NSCLC cells, causing cytochrome C release, mitochondrial depolarization, DNA damage and ATP reduction. Contrarily, ectopic ADCK2 overexpression promoted NSCLC cell growth. Further studies revealed that ADCK2 depletion inactivated Akt-mTOR signaling in primary NSCLC cells. NSCLC xenograft growth in nude mice was significantly hindered after ADCK2 silencing or knockout. ADCK2 depletion, apoptosis induction and oxidative injury as well as ATP reduction and Akt-mTOR inactivation were detected in ADCK2-silenced or ADCK2-knockout NSCLC xenograft tissues. Together overexpressed ADCK2 is important for the growth of NSCLC cells, representing an important therapeutic molecular oncotarget.

A Novel Laser-Based Zebrafish Model for Studying Traumatic Brain Injury and Its Molecular Targets.

Traumatic brain injury (TBI) is a major public health problem. Here, we developed a novel model of non-invasive TBI induced by laser irradiation in the telencephalon of adult zebrafish (Danio rerio) and assessed their behavior and neuromorphology to validate the model and evaluate potential targets for neuroreparative treatment. Overall, TBI induced hypolocomotion and anxiety-like behavior in the novel tank test, strikingly recapitulating responses in mammalian TBI models, hence supporting the face validity of our model. NeuN-positive cell staining was markedly reduced one day, but not seven days, after TBI, suggesting increased neuronal damage immediately after the injury, and its fast recovery. The brain-derived neurotrophic factor (Bdnf) level in the brain dropped immediately after the trauma, but fully recovered seven days later. A marker of microglial activation, Iba1, was elevated in the TBI brain, albeit decreasing from Day 3. The levels of hypoxia-inducible factor 1-alpha (Hif1a) increased 30 min after the injury, and recovered by Day 7, further supporting the construct validity of the model. Collectively, these findings suggest that our model of laser-induced brain injury in zebrafish reproduces mild TBI and can be a useful tool for TBI research and preclinical neuroprotective drug screening.

Upregulation of NF-E2-related factor-2-dependent glutathione by carnosol provokes a cytoprotective response and enhances cell survival.

AIM: To explore whether glutathione (GSH) increased through Nrf-2 activation is involved in the cytoprotective effects of carnosol in HepG2 cells. METHODS: Human hepatoma cell line HepG2 were exposed to rosemarry essential oil or carnosol. Cell viability was measured using an Alamar blue assay. The production of intracellular GSH was determined using monochlorobimane. The level of protein or mRNA was examined by Western blotting or RT-PCR, respectively. RESULTS: Rosemarry essential oil (0.005%-0.02%) and carnosol (5 and 10 mol/L) increased the intracellular GSH levels and GSH synthesis enzyme subunit GCLC/GCLM expression. Rosemary essential oil and carnosol increased nuclear accumulation of Nrf2 and enhanced Nrf2-antioxidant responsive element (ARE)-reporter activity. Transfection of the treated cells with an Nrf2 siRNA construct blocks GCLC/GCLM induction. Furthermore, pretreatment of the HepG2 cells with essential oil and carnosol exerted significant cytoprotective effects against H(2)O(2) or alcohol. In TNFα-treated cells, the nuclear translocation and transcriptional activity of NF-κB was abolished for 12 h following carnosol pretreatment. Cotreatment with GSH also suppressed NF-κB nuclear translocation, whereas cotreatment with BSO, a GSH synthesis blocker, blocked the inhibitory effects of carnosol. CONCLUSION: This study demonstrated that Nrf2 is involved in the cytoprotective effects by carnasol, which were at least partially mediated through increased GSH biosynthesis.

[PSCA expression in invasive micropapillary carcinoma of breast].

OBJECTIVE: To study the expression of prostate stem cell antigen (PSCA) at protein and mRNA levels in invasive micropapillary carcinoma of the breast (IMPC) and to analyze the relationship between PSCA expression and clinicopathologic features. METHODS: The expression of PSCA protein was analyzed by immunohistochemistry (LSAB) in 66 cases of IMPC and 67 cases of invasive ductal carcinoma, not otherwise specified (IDC-NOS). The association between PSCA expression and clinicopathologic features was also analyzed in IMPC. Furthermore, RT-PCR was used to detect PSCA mRNA in 10 cases of primary IMPC and 10 cases of primary IDC-NOS with paired normal breast tissues, each from the same subject. RESULTS: Immunohistochemical analysis revealed the overexpression of PSCA in 47 of 66 (71.2%) cases of IMPC and 35 of 67 (52.2%) IDC-NOS. Statistical analysis showed a significant difference of PSCA expression between IMPC and IDC-NOS (P = 0.024). In IMPC, the expression of PSCA was correlated with lymph nodes metastasis (P = 0.039). RT-PCR showed the mRNA level of PSCA was significantly higher in primary IMPC and IDC-NOS tissue than that in paired normal breast tissue (7/10 and 5/10, respectively), and it was also significantly higher in primary IMPC tissue than that in IDC-NOS tissue. CONCLUSION: PSCA might play an important role in lymph node metastasis in IMPC.