Quercetagetin inhibits macrophage-derived chemokine in HaCaT human keratinocytes via the regulation of signal transducer and activator of transcription 1, suppressor of cytokine signalling 1 and transforming growth factor-ß1.

BACKGROUND: Inflammatory chemokines, such as macrophage-derived chemokine (MDC/CCL22), are elevated in the serum and lesioned skin of patients with atopic dermatitis (AD), and are ligands for C-C chemokine receptor 4, which is predominantly expressed on T helper 2 lymphocytes, basophils and natural killer cells. We have previously reported that quercetagetin has an inhibitory activity on inflammatory chemokines, which is induced by interferon (IFN)-γ and tumour necrosis factor (TNF)-α, occurring via inhibition of the signal transducer and activator of transcription 1 (STAT1) signal. OBJECTIVES: To investigate the specific mechanisms of quercetagetin on the STAT1 signal. METHODS: We confirmed the inhibitory activity of quercetagetin on MDC and STAT1 in HaCaT keratinocytes. The interaction between STAT1 and IFN-γR1 was investigated using immunoprecipitation. The small interfering RNA approach was used to investigate the role of suppressor of cytokine signalling 1 (SOCS1) and transforming growth factor (TGF)-ß1 induced by quercetagetin. RESULTS: Quercetagetin inhibited the expression of MDC at both the protein and mRNA levels in IFN-γ- and TNF-α-stimulated HaCaT human keratinocytes. Moreover, quercetagetin inhibited the phosphorylation of STAT1 through upregulation of SOCS1. Increased expression of SOCS1 disrupted the binding of STAT1 to IFN-γR1. Furthermore, quercetagetin augmented the expression of TGF-ß1, which is known to modulate the immune response and inflammation. CONCLUSIONS: These results suggest that quercetagetin may be a potent inhibitor of the STAT1 signal, which could be a new molecular target for anti-inflammatory treatment, and may thus have therapeutic applications as an immune modulator in inflammatory diseases such as AD.

The α-isoform of class II phosphoinositide 3-kinase is necessary for the activation of ERK but not Akt/PKB.

Phosphoinositide 3-kinases (PI3Ks) are key enzymes that activate intracellular signaling molecules when a number of different growth factors bind to cell surface receptors. PI3Ks are divided into three classes (I, II, III), and enzymes of each class have different tissue specificities and physiological functions. The α-isoform (PI3K-C2α) of class II PI3Ks is considered ubiquitous and preferentially activated by insulin. Our previous study showed that suppression of PI3K-C2α leads to apoptotic cell death. The aim of this study is to determine whether depletion of PI3K-C2α affects ERK or PKB/Akt activity following stimulation with serum and insulin growth factors in Chinese hamster ovary cells expressing human insulin receptors (CHO-IR) and human HepG2 liver cells. Different antisense oligonucleotides (ODNs), which were designed based on the sequence of the C2 domain of the human PI3K-C2α gene, were transfected into cells to inhibit PI3K-C2α expression. Insulin- or serum-induced stimulation of ERK was significantly suppressed by depletion of PI3K-C2α, whereas phosphorylation of IRS-1 and the stimulation of PKB/Akt by insulin were not affected. The number of apoptotic cells was also increased by depletion of PI3K-C2α protein levels. Taken together, our data indicate that PI3K-C2α may be a crucial factor in the stimulation of ERK activity in response to serum or insulin, whereas it is less important for the stimulation of PKB/Akt activity in response to insulin.

Effects of Asparagus officinalis extracts on liver cell toxicity and ethanol metabolism.

Asparagus officinalis is a vegetable that is widely consumed worldwide and has also long been used as a herbal medicine for the treatment of several diseases. Although A. officinalis is generally regarded as a supplement for the alleviation of alcohol hangover, little is known about its effects on cell metabolism. Therefore, this study was conducted to analyze the constituents of the young shoots and the leaves of asparagus and to compare their biochemical properties. The amino acid and inorganic mineral contents were found to be much higher in the leaves than the shoots. In addition, treatment of HepG2 human hepatoma cells with the leaf extract suppressed more than 70% of the intensity of hydrogen peroxide (1 mM)-stimulated DCF fluorescence, a marker of reactive oxygen species (ROS). Cellular toxicities induced by treatment with hydrogen peroxide, ethanol, or tetrachloride carbon (CCl(4)) were also significantly alleviated in response to treatment with the extracts of A. officinalis leaves and shoots. Additionally, the activities of 2 key enzymes that metabolize ethanol, alcohol dehydrogenase and aldehyde dehydrogenase, were upregulated by more than 2-fold in response to treatment with the leaf- and shoot extracts. Taken together, these results provide biochemical evidence of the method by which A. officinalis exerts its biological functions, including the alleviation of alcohol hangover and the protection of liver cells against toxic insults. Moreover, the results of this study indicate that portions of asparagus that are typically discarded, such as the leaves, have therapeutic use.

Apolipoprotein E genotype in Korean schizophrenic patients.

The apolipoprotein E (APOE) epsilon4 allele is a known risk factor for the development of Alzheimer's disease, however, an association of the APOE genotype with schizophrenia is controversial. We investigated the association in 60 Korean schizophrenic patients and 60 healthy controls. APOE genotypes were identified by reverse hybridization-based line probe assay. There were significant differences in the distribution of APOE genotypes between schizophrenic patients and controls. APOE epsilon2 and epsilon3 allele frequencies in schizophrenic patients were significantly different from those in controls. Our results suggest that APOE alleles seem to be operative in the pathogenesis of schizophrenic disorders.

A new trend in operative technique for intracerebral hemorrhage: a comparative study of stereotactic endoscopic removal and stereotactic catheter drainage.

The development of less invasive methods to evacuate intracerebral hematomas (ICHs) has improved outcome in patients with traumatic brain injury. Eighteen patients with ICHs underwent surgery via one of two methods: stereotactic endoscopic removal (SER) or stereotactic catheter drainage (SCD). The outcome results were then compared. The patient population was composed of 11 men and seven women with a mean age of 53.3 years (range 33-81 years), all suffering from ICH in the basal ganglia. The mean hematoma volume was 34.4 ml (range 23-105 ml). All patients had major neurological deficits, but showed no sign of transtentorial herniation. Ten patients underwent SCD and eight had SER. All procedures were performed within 24 hours of insult. After local anesthesia was induced in the patient, an intracranial pressure (ICP) monitoring catheter and an Otzuki cannula were placed through separate burr holes in the skull. Using the SER technique, the ICH was removed using suction and forceps through the side window of the cannula until the ICP had decreased significantly. Hemostasis was attained by lesioning with a Nd-YAG laser. In the SCD procedure, we placed a silicone catheter into the hematoma to drain it and then added urokinase. The hematoma was drained for 3 to 5 days in the SER method and 7 to 10 days in the SCD method. Rebleeding occurred in one of the early cases in which we used the SER procedure. At follow-up evaluation, the mortality rate was 13% in the SER group and 10% in the SCD group. The patients in whom outcome was most improved from these treatments were those who had been admitted with an impaired level of consciousness. Stereotactic catheter drainage is a precise, safe, and brief procedure with a very low rebleeding rate, but its outcome effect was more delayed than other procedures. Stereotactic endoscopic removal can easily replace SCD, with a similar mortality rate. Both procedures can be accomplished under direct visualization so as to eliminate any undesirable event or outcome.

Modification of high-heeled shoes to decrease pronation during gait.

One of the reasons that high heels may contribute to the formation of halux valgus is that the wearers pronate during propulsion. This pilot study was performed to determine whether relocation of the heel under the counter of a fashion high-heeled pump could change the degree of pronation of the foot during the gait cycle. The authors report that more foot stability was experienced by the subjects when the center of the heel was offset between 2 and 4 mm medial to the center of the heel counter. This study is designed to promote further research into whether the shoe industry should change the design parameters of high-heeled fashion shoes in order to improve foot function.

The effect of culture on the sex differences in schizophrenia.

Cultural influences on sex differences in clinical characteristics and symptomatology of schizophrenia were studied among 369 schizophrenic patients from the United States and Turkey. Male schizophrenics were more likely to be single, and were younger than female schizophrenics at onset of symptoms and when first diagnosed, treated and hospitalised in both cultures. Turkish male and female schizophrenics were more ambivalent, inappropriate, "silly", euphoric, depersonalised, dissociated, mute, conceptually disorganised, and exhibiting more flight of ideas and thought than American male and female schizophrenics. Irrelevant thought and stereotypic behaviour were most severe in Turkish male and American female schizophrenics. Hallucinatory behaviour was most intense in Turkish separated, divorced, or widowed female schizophrenics and American married male schizophrenics. Turkish married female and Turkish separated, divorced, or widowed male schizophrenics were most disoriented. Turkish single female schizophrenics were most mute. Turkish separated, divorced, or widowed male schizophrenics showed most intense stupor behaviour.

Dorsal bunions: a review.

The authors present a review of the literature on dorsal bunion and describe its classification, etiology, predisposing factors, and different methods of treatment. The deformity is functionally limiting during ambulation and cosmetically undesirable for the patient. It is a progressively disabling deformity that requires surgical management.