(-)-9'-O-(α-l-Rhamnopyranosyl)lyoniresinol from Lespedeza cuneata suppresses ovarian cancer cell proliferation through induction of apoptosis.

Lespedeza cuneata (Dum. Cours.) G. Don. (Fabaceae), known as Chinese bushclover or sericea lespedeza, has been used in traditional medicine to treat diabetes, hematuria, and insomnia, and it has been reported that bioactive compounds from L. cuneata possess various pharmacological properties. However, there has been no study to determine the active compounds from L. cuneata with potential activity against ovarian cancer. This study aimed to isolate cytotoxic compounds from L. cuneata and identify the molecular mechanisms underlying the apoptosis pathway in ovarian cancer cells. Based on cytotoxic activity identified in the screening test, chemical investigation of the active fraction of L. cuneata led to the isolation of nine compounds including four lignanosides (1-4), three flavonoid glycosides (5-7), and two phenolics (8-9). Cytotoxicity and the molecular mechanism were examined by methyl thiazolyl tetrazolium (MTT) assay and Western blot analysis. Of the isolated compounds, (-)-9'-O-(α-l-rhamnopyranosyl)lyoniresinol (3) demonstrated the strongest effect in suppressing A2780 human ovarian carcinoma cell proliferation in a dose-dependent manner, with an IC50 value of 35.40 ±â€¯2.78 µM. Control A2780 cells had normal morphology, whereas cell blebbing, shrinkage, and condensation were observed after treatment with compound 3. Western blotting analysis showed that compound 3 inhibited A2780 human ovarian cancer cell viability by activating caspase-8, caspase-3, and PARP, which contributed to apoptotic cell death. These results suggest that (-)-9'-O-(α-l-rhamnopyranosyl)lyoniresinol (3) has potent anticancer activities against A2780 human ovarian carcinoma cells through the extrinsic apoptotic pathway. Therefore, (-)-9'-O-(α-l-rhamnopyranosyl)lyoniresinol is an excellent candidate for the development of novel chemotherapeutics.

Lignan Glycosides and Flavonoid Glycosides from the Aerial Portion of Lespedeza cuneata and Their Biological Evaluations.

Lespedeza cuneata (Fabaceae), known as Chinese bushclover, has been used in traditional medicines for the treatment of diseases including diabetes, hematuria, and insomnia. As part of a continuing search for bioactive constituents from Korean medicinal plant sources, phytochemical analysis of the aerial portion of L. cuneata led to the isolation of two new lignan glycosides (1,2) along with three known lignan glycosides (3⁻7) and nine known flavonoid glycosides (8⁻14). Numerous analysis techniques, including 1D and 2D NMR spectroscopy, CD spectroscopy, HR-MS, and chemical reactions, were utilized for structural elucidation of the new compounds (1,2). The isolated compounds were evaluated for their applicability in medicinal use using cell-based assays. Compounds 1 and 4⁻6 exhibited weak cytotoxicity against four human breast cancer cell lines (Bt549, MCF7, MDA-MB-231, and HCC70) (IC50 < 30.0 µM). However, none of the isolated compounds showed significant antiviral activity against PR8, HRV1B, or CVB3. In addition, compound 10 produced fewer lipid droplets in Oil Red O staining of mouse mesenchymal stem cells compared to the untreated negative control without altering the amount of alkaline phosphatase staining.

The relationship between psychosocial functioning and resilience and negative symptoms in individuals at ultra-high risk for psychosis.

OBJECTIVE: Decline in psychosocial functioning seems to be a core feature in schizophrenia across various phases of the disorder. Little is known about the relationship between psychosocial functioning and protective factors or psychopathologies in individuals in the prodrome phase of psychosis. We aimed to investigate whether psychosocial functioning is impaired in individuals in the putative prodromal phase of schizophrenia, and, if so, to identify factors associated with compromised psychosocial functioning. METHOD: Sixty participants at ultra-high risk (UHR) for psychosis and 47 healthy controls were recruited. All subjects were assessed in terms of psychosocial functioning using the Quality of Life Scale. A clinical assessment of psychopathology and protective factors, including resilience and coping style, was also conducted. RESULTS: Psychosocial functioning in UHR participants was found to be compromised; this dysfunction was associated with negative symptoms, adaptive coping, and resilience. In addition, baseline resilience was lower among those in the UHR group who converted to frank psychosis than among those who did not. CONCLUSIONS: These findings imply that treatment strategies for individuals at UHR for psychosis should be comprehensive, promoting resilience as well as targeting the reduction of positive and negative symptoms to foster social reintegration and recovery.

Multiple extramedullary relapses without bone marrow involvement after second allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia.

EMR without BM involvement after allogeneic HSCT is extremely rare, especially in children; only a few cases have been reported. A two-yr-old boy was diagnosed with AML (M4) and underwent allogeneic HSCT in first complete remission with BM from HLA-matched unrelated donor without GVHD. Four yr later, he had a BM relapse and after induction and consolidation chemotherapy, he received a second HSCT from an unrelated donor using peripheral blood stem cells. His second post-transplant course was complicated by extensive chronic GVHD involving the skin, oral cavity, and lungs, which was treated with tacrolimus and corticosteroid. Two yr later, he noticed a mild swelling in the right cheek area. The BM showed a complete remission marrow and a soft tissue biopsy was compatible with granulocytic sarcoma. PET-CT showed multifocal bone involvements. He received chemotherapy, and the chloromas decreased in size. We report a case of diffuse EMR of AML without BM involvement after a second allogeneic HSCT.

Aqueous extract of Lespedeza cuneata improves male menopause by increase of nitric oxide and dihydrotestosterone.

This study aimed to evaluate the effect of aqueous extract of Lespedeza cuneata (ALC) on men menopause induced erectile dysfunction (ED) and testosterone deficiency syndrome (TDS) in vitro and in vivo. Nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) have been fundamental factors of ED, and free testosterone such as dihydrotestosterone (DHT) has a crucial role in mitigation of TDS. ALC increased the production of NO in a dose-dependent manner in vitro and in vivo. The level of neuronal nitric oxide synthase and cGMP was increased in the ALC group. The level of DHT and 17-beta hydroxysteroid dehydrogenases (17ß-HSD) was also increased in the ALC group. There was no significant change of hepatotoxicity, renal toxicity, lipid metabolism, and glucose. These results suggest that ALC enhanced NO, cGMP and free testosterone which could be developed as a health supplement for improving male menopause.

Coping styles in individuals at ultra-high risk for psychosis: Associations with cognitive appraisals.

Maladaptive coping may play an important role in the manifestation of symptoms, functioning, and overt psychosis onset in individuals at ultra-high risk (UHR) for psychosis. To determine the factors associated with coping strategies, the relationships between cognitive appraisals and coping styles were investigated in UHR individuals. Sixty-five UHR individuals and 83 healthy controls were assessed for coping styles and cognitive appraisals of attribution bias as a primary appraisal and self-efficacy and perceived social support as a secondary appraisal. UHR participants relied more on a passive, tension-reduction coping style and less on an active, problem-focused coping style. These maladaptive coping styles in UHR individuals were significantly associated with their cognitive appraisals of stress. Aberrant attribution style of hostility perception and composite blaming bias were associated with problem-focused coping and tension-reduction, respectively. Perceived social support was related to problem-focused coping, seeking social support, and wishful thinking. General self-efficacy was associated with problem-focused coping. Our findings suggest that cognitive appraisals themselves may be the major determinants of coping styles in UHR individuals. The identified attribution styles, perceived social support, and self-efficacy may provide some clues regarding specialized interventions for the buildup of adaptive coping strategies in UHR individuals.

The Efficacy and Safety of Clonazepam in Patients with Anxiety Disorder Taking Newer Antidepressants: A Multicenter Naturalistic Study.

OBJECTIVE: This study compared the efficacy and tolerability of clonazepam with other benzodiazepines in patients with anxiety disorders. METHODS: Inclusion criteria were as follows: age >20 years, diagnosis of anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition, text revision (DSM-IV-TR) criteria, taking only one type of antidepressant, and prescribed one of three oral benzodiazepines (alprazolam, clonazepam, or lorazepam). At baseline and week 6, clinical benefit was evaluated using the Clinical Global Impression-Severity Scale (CGI-S), Clinical Global Impression-Anxiety Scale (CGI-anxiety), and Clinical Global Impression-Sleep Scale (CGI-sleep). RESULTS: Among 180 patients, no differences in demographic characteristics among the three benzodiazepine groups were noted. After six weeks of treatment, all benzodiazepine groups showed significant improvements in CGI-S, CGI-anxiety, and CGI-sleep scores (p<0.001). There were no differences in mean changes in CGI-S, CGI-anxiety and CGI-sleep among the three benzodiazepine groups. The incidence of side effects was significantly lower in the clonazepam group than with the other benzodiazepines. The incidences of adverse events for the clonazepam, alprazolam, and lorazepam groups were 26.7% (n=20), 48.4% (n=31), and 43.9% (n=18), respectively. CONCLUSION: The present study suggests that clonazepam is as efficacious as other benzodiazepines for the treatment of various anxiety disorders. Furthermore, the safety profile of clonazepam was superior to the other benzodiazepines in this study.

Constituents of the fruits and leaves of Euodia daniellii.

Four flavonoid glycosides, flavaprin (7), evodioside B (8), vitexin (11), and hesperidin (12), as well as the coumarins bergapten (1), xanthotoxin (2), and isopimpinellin (3), the lignan simplexoside (10), the steroids beta-sitosterol (4) and daucosterol (5), the limonoids isolimonexic acid (6) and limonin (9), and uracil (13) and myo-inositol (14) have been isolated from Euodia daniellii. The structures of these compounds were established from spectral data. Among the isolates, bergapten showed cyclooxygenase-2 inhibitory activity with an IC50 value of 6.2 microg/ml. Flavonoids isolated from this plant exhibited no cytotoxic activity against the human tumor cell lines, A549, SKOV-3, SKMEL-2, XF498, and HCT15.

A case of congenital heminasal hypoplasia with an intranasal cyst: an extremely rare occurrence.

Various congenital nasal deformities can occur because of the complexities of the developmental process. These conditions range from partial deformities of the nose (such as isolated absence of the nasal bones, absence of columella, absence of the septal cartilage, and absence of vomeral bone) to complete absence of the nose. Congenital heminasal hypoplasia is an extremely rare defect of embryogenesis. We present a case of congenital heminasal hypoplasia with an associated dacryocystocele and intranasal cyst. The treatment of congenital dacryocystocele remains controversial. The majority of researchers recommend an initial treatment plan that does not include surgical intervention. Surgical reconstruction of the external nose and inner cavities can be delayed at least until the preschool years, when facial development is nearly complete.

Abnormalities of emotional awareness and perception in patients with obsessive-compulsive disorder.

BACKGROUND: Emotional awareness deficit may play a critical role in the production and maintenance of obsessive-compulsive symptoms and social dysfunction in patients with obsessive-compulsive disorder (OCD). The aim of this study was to investigate characteristics of emotional awareness such as empathy and alexithymia in OCD patients. In addition, we examined whether impaired emotional awareness measured by self-assessment questionnaires was associated with emotional facial recognition ability in OCD patients. METHODS: Study participants included 107 patients with OCD and 130 healthy age- and sex-matched volunteers. The Interpersonal Reactivity Index (IRI) and Toronto Alexithymia Scale-20 were applied as measures of empathy and alexithymia. A subset of 56 patients with OCD additionally performed the emotional perception task of face expression. RESULTS: Patients with OCD scored significantly lower for perspective taking, and significantly higher for personal distress of IRI, and significantly higher for alexithymia compared to normal controls. Impaired emotional awareness such as lower perspective taking and fantasy seeking had a perception bias towards disgust in response to ambiguous facial expressions in OCD patients. LIMITATIONS: The OCD group consisted of patients in different stages of the illness and with different degrees of severity. CONCLUSIONS: OCD involves the impairment of emotional awareness and perception and it may relate to social dysfunction and to impairments in the ability to shift naturally from obsessive thoughts to other thoughts in response to social situations in patients with OCD.