Anti-rheumatoid Arthritis Effect of Kaejadan via Analgesic and Antiinflammatory Activity in vivo and in vitro.

Although Kaejadan (KJD), an herbal cocktail of three medicinal plants (Lithospermum erythrorhizon, Cinnamomum loureirii, and Salvia miltiorrhiza), has been traditionally used for the treatment of rheumatoid arthritis, its scientific evidence is not fully understood. Hence, we investigated antiinflammatory and analgesic mechanism of KJD in vivo and in vitro. Kaejadan suppressed the number of writhing responses in mice treated by acetic acid and showed antinociceptive effect by tail-flick test. Kaejadan abrogated serotonin or carrageenan or Freund's complete adjuvant (FCA)-induced paw edema and also reduced the level of Evans Blue for vascular permeability. Furthermore, KJD effectively reduced the positive responses for C-reactive protein and rheumatoid arthritis test in FCA-treated rats. Of note, KJD inhibited the level of lipid peroxide malondialdehyde and enhanced the level of superoxide dismutase in the hepatic tissues of FCA-treated rats. Additionally, KJD abrogated the levels of IL-1ß and IL-6 in lipopolysaccharide and IFN-γ-exposed RAW 264.7 cells. Also, KJD reduced the expression of cyclooxygenase 2 or inducible nitric oxide synthase at protein and mRNA levels in IFN-γ and lipopolysaccharide-exposed RAW 264.7 cells. Overall, our findings demonstrate that KJD exerts antiinflammatory and analgesic effects via enhancement of antioxidant activity and inhibition of proinflammatory cytokines. Copyright © 2017 John Wiley & Sons, Ltd.

Apoptotic Effect of Astragalin in Melanoma Skin Cancers via Activation of Caspases and Inhibition of Sry-related HMg-Box Gene 10.

Though Astragalin (kaempferol-3-glucoside) contained in Paeonia lactiflora and other plants was known to have anti-oxidant, antiinflammatory, and anti-tumor activity, the anti-tumor mechanism of Astragalin has never been reported in melanomas until now. Thus, in the present study, the underlying apoptotic mechanism of Astragalin isolated from Aceriphyllum rossii was elucidated in A375P and SK-MEL-2 melanoma cells. Astragalin exerted cytotoxicity in A375P and SK-MEL-2 cells in a concentration-dependent manner. Also, Astragalin significantly increased the number of TdT-mediated dUTP nick end labeling positive cells and sub-G1 population as a feature of apoptosis in A375P and SK-MEL-2 cells compared with untreated control. Consistently, western blotting revealed that Astragalin activated caspase 9/3 and Bax, cleaved poly (ADP-ribose) polymerase, and attenuated the expression of cyclin D1, Mcl-1, and Sry-related HMg-Box gene 10 (SOX10) in A375P and SK-MEL-2 cells. Of note, ectopic expression of SOX10 reduced the apoptotic ability of Astragalin to inhibit proliferation, cleave poly (ADP-ribose) polymerase, and caspase 3 in A375P and SK-MEL-2 melanoma cells. Overall, our findings provide evidence that Astragalin induces apoptosis in A375P and SK-MEL-2 melanoma cells via activation of caspase9/3 and inhibition of SOX10 signaling. Copyright © 2017 John Wiley & Sons, Ltd.

Apoptotic Effect of Sanggenol L via Caspase Activation and Inhibition of NF-κB Signaling in Ovarian Cancer Cells.

In the present study, the underlying apoptotic mechanism of sanggenol L was elucidated in ovarian cancer cells. Sanggenol L showed cytotoxic and antiproliferative effect in A2780, SKOV-3, and OVCAR-3 ovarian cancer cells in a concentration-dependent fashion. Consistently, sanggenol L increased sub-G1 phase population and early and late apoptotic portion in ovarian cancer cells. Also, sanggenol L activated caspase9/3, suppressed the phosphorylation of IκBα and p65 NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), attenuated the expression of Cyclin D1, and cleaved poly(adenosine diphosphate ribose -ribose) polymerase in SKOV-3, A2780, and OVCAR-3 cells. Furthermore, sanggenol L blocked nuclear translocation of NF-κB and also attenuated the expression of NF-κB related genes such as c-Myc, Cyclin D1, and Bcl-X L, Bcl-2, in lipopolysaccharide-treated SKOV-3 cells. Overall, our findings for the first time suggest that sanggenol L induces apoptosis via caspase activation and inhibition of NF-κB/IκBα phosphorylation as a potent chemotherapeutic agent for ovarian cancers.

Upregulation of Death Receptor 5 and Production of Reactive Oxygen Species Mediate Sensitization of PC-3 Prostate Cancer Cells to TRAIL Induced Apoptosis by Vitisin A.

BACKGROUND/AIMS: Although Vitisin A, derived from wine grapes, is known to have cytotoxic, anti-adipogenic, anti-inflammatory and antioxidant effects, the underlying antitumor mechanism has not been investigated in prostate cancer cells to date. In the present study, the apoptotic mechanism of Vitisin A plus TNF-related apoptosis-inducing ligand (TRAIL) in prostate cancer cells was elucidated. METHODS: The cytotoxicity of Vitisin A and/or TRAIL against PC-3, DU145 and LNCaP prostate cancer cells was measured by MTT colorimetric assay. Annexin V-FITC Apoptosis Detection kit was used to detect apoptotic cells by flow cytometry. Intracellular levels of ROS were measured by flow cytometry using 2070-diacetyl dichlorofluorescein (DCFDA). RESULTS: Combined treatment with Vitisin A and TRAIL enhanced cytotoxicity and also increased sub-G1 population in PC-3 cells better than DU145 or LNCap prostate cancer cells. Similarly, Annexin V and PI staining revealed that combination increased early and late apoptosis in PC-3 cells compared to untreated control. Consistently, combination attenuated the expression of pro-caspases 7/8, DcR1, Bcl-XL or Bcl-2 and activated caspase 3, FADD, DR5 and DR4 in PC-3 cells. Also, combination increased DR5 promoter activity compared to untreated control. Furthermore, combination increased the production of reactive oxygen species (ROS) and DR5 cell surface expression. The ROS inhibitor NAC and silencing of DR5 by siRNA transfection inhibited the ability of combination to induce PARP cleavage and generate ROS. CONCLUSION: These findings provide evidence that Vitisin A can be used in conjunction with TRAIL as a potent TRAIL sensitizer for synergistic apoptosis induction via upregulation of DR5 and production of ROS in prostate cancer cells.

Inhibition of protein kinase C α/ßII and activation of c-Jun NH2-terminal kinase mediate glycyrrhetinic acid induced apoptosis in non-small cell lung cancer NCI-H460 cells.

Though glycyrrhetinic acid (GA) from Glycyrrhiza glabra was known to exert antioxidant, antifilarial, hepatoprotective, anti-inflammatory and anti-tumor effects, the antitumor mechanism of GA was not clearly elucidated in non-small cell lung cancer cells (NSCLCCs). Thus, in the present study, the underlying apoptotic mechanism of GA was examined in NCI-H460 NSCLCCs. GA significantly suppressed the viability of NCI-H460 and A549 non-small lung cancer cells. Also, GA significantly increased the sub G1 population by cell cycle analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells in a concentration dependent manner in NCI-H460 non-small lung cancer cells. Consistently, GA cleaved poly (ADP-ribosyl) polymerase (PARP), caspase 9/3, attenuated the expression of Bcl-XL, Bcl-2, Cyclin D1 and Cyclin E in NCI-H460 cells. Interestingly, GA attenuated the phosphorylation of protein kinase C (PKC) α/ßII and extracellular activated protein kinase (ERK) as well as activated the phosphorylation of PKC δ and c-Jun NH2-terminal kinase in NCI-H460 cells. Conversely, PKC promoter phorbol 12-myristate 13-acetate (PMA) and JNK inhibitor SP600125 reversed the cleavages of caspase 3 and PARP induced by GA in NCI-H460 cells. Overall, our findings suggest that GA induces apoptosis via inhibition of PKC α/ßII and activation of JNK in NCI-H460 non-small lung cancer cells as a potent anticancer candidate for lung cancer treatment.

Examining biopsychosocial predictors of risk for cognitive impairment among a racially diverse sample of men who have sex with men living with HIV.

Background: Cognitive decline among people living with HIV (PLWH) is growing concern as world populations become increasing older including higher proportions of PLWH. It is vitally important to understand psychosocial predictors of age-related cognitive decline men who have sex with men (MSM) living with HIV. Objectives: The current study seeks to examine psychosocial risk factors the contribute to the risk of age-related cognitive impairment as measured by Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score in a racially diverse sample of MSM living with HIV. Design: The present analysis utilizes data from the baseline (n = 196) and 6-month follow-up (n = 135) time points of a longitudinal cohort study of PLWH. Methods: Using a self-report survey, we examine the associations between psychosocial predictors (e.g. trauma, mental health, chronic pain, sleep disturbance, etc.) and risk of dementia using the CAIDE risk score. Analyses include linear and logistic regression. Results: In adjusted model stress, chronic pain, Black racial identity, and having a sexual identity that is bisexual or another category are all positively associated with CAIDE scores. Childhood sexual abuse history was negatively associated with CAIDE scores indicating a protective effect. Sleep disorder has a positive association with CAIDE scores after adjusting for the baseline CAIDE scores. Conclusion: These results indicate modifiable correlates of cognitive risk (stress and chronic pain). Interventions should seek to address these comorbid factors including the consideration of minority stress and stigma. Interventions should seek to reach Black and bisexual men living with HIV, including possible cultural tailoring to interventions and messaging. Lastly, future research should examine the impact of variation within childhood sexual abuse histories to better understand their association with cognitive impairment later in life. This may include considering the nature, severity, and potential treatment of trauma symptoms.

What makes middle-aged or older people who have HIV more likely to have memory problems later in life? We asked a racially diverse group of gay and bisexual men who have HIV. Why was the study done? Older people are becoming a larger portion of our communities including older people living with HIV. It's important to understand what makes older people more likely to have memory problems as they age including older people living with HIV. What did the researchers do? We asked 196 middle-aged and older adults who have HIV to answer questions about their health including things that we know might make them more likely to have memory problems later in life. What did the researchers find? We found that having more stress or reoccurring pain was related to being more likely to have memory problems later in life. People who have trouble sleeping were more likely to have memory problems later in life. We also found that Black people were more likely to have memory problems later in life. People who had been abused sexually as children were less likely to have memory problems later in life. What do the findings mean? These findings help us understand things that may make someone more likely to have memory problems later in life. These include things that could be changed like reoccurring pain and troubles sleeping. It also highlighted that Black people may need more support to prevent memory problems later in life.

JAK2/STAT5 signaling pathway mediates Bojungbangdocktang enhanced hematopoiesis.

Bojungbangdocktang (BJBDT) is a medicinal herbal cocktail that has been used for cancer prevention and treatment in traditional Korean medicine. In the current study, BJBDT was demonstrated to regulate hematopoiesis. BJBDT significantly increased the expression of hematopoietic cytokines interleukin (IL)-3, stem cell factor (SCF), granulocyte-macrophage-colony stimulating factor (GM-CSF), thrombopoietin (TPO) and erythropoietin (EPO) at the level of mRNA and secretion in hematopoietic stem cells (HSCs). Additionally, BJBDT enhanced the phosphorylation of Janus activated kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) and STAT binding to gamma interferon activated sites (GAS) in HSCs. Furthermore, BJBDT significantly enhanced the growth rate of granulocyte erythrocyte monocyte macrophage colony-forming units (CFU-GEMM) and erythroid burst forming units (BFU-E) in vitro. Moreover, BJBDT increased the level of EPO at mRNA in kidney and plasma, and the numbers of erythroid-specific antigen Ter-119(+) erythroid cells in mice with aplastic anemia induced by 20% benzene. Consistently, histochemical staining revealed BJBDT increased the bone marrow and stromal cells as well as decreased macrophages and adipocytes in bone marrow tissues of mice with aplastic anemia. Taken together, the results suggest that BJBDT can enhance hematopoiesis via hematopoietic cytokine-mediated JAK2/STAT5 pathway as a potent hematopoietic candidate. Copyright © 2010 John Wiley & Sons, Ltd.

Reduced fertility caused by meiotic defects and micronuclei formation during microsporogenesis in xBrassicoraphanus.

BACKGROUND: Hybridization and polyploidization events are important driving forces in plant evolution. Allopolyploids formed between different species can be naturally or artificially created but often suffer from genetic instability and infertility in successive generations. xBrassicoraphanus is an intergeneric allopolyploid obtained from a cross between Brassica rapa and Raphanus sativus, providing a useful resource for genetic and genomic study in hybrid species. OBJECTIVE: The current study aims to understand the cause of hybrid sterility and pollen abnormality in different lines of synthetic xBrassicoraphanus from the cytogenetic perspective. METHODS: Alexander staining was used to assess the pollen viability. Cytogenetic analysis was employed to monitor meiotic chromosome behaviors in pollen mother cells (PMCs). Origins of parental chromosomes in xBrassicoraphanus meiocytes were determined by genome in situ hybridization analysis. RESULTS: The xBrassicoraphanus lines BB#4 and BB#6 showed high rates of seed abortion and pollen deformation. Abnormal chromosome behaviors were observed in their PMCs, frequently forming univalents and inter-chromosomal bridges during meiosis. A positive correlation also exists between meiotic defects and the formation of micronuclei, which is conceivably responsible for unbalanced gamete production and pollen sterility. CONCLUSION: These results suggest that unequal segregation of meiotic chromosomes, due in part to non-homologous interactions, is responsible for micronuclei and unbalanced gamete formation, eventually leading to pollen degeneration and inferior fertility in unstable xBrassicoraphanus lines.

Meiotic Chromosome Stability and Suppression of Crossover Between Non-homologous Chromosomes in xBrassicoraphanus, an Intergeneric Allotetraploid Derived From a Cross Between Brassica rapa and Raphanus sativus.

Hybridization and polyploidization are major driving forces in plant evolution. Allopolyploids can be occasionally formed from a cross between distantly related species but often suffer from chromosome instability and infertility. xBrassicoraphanus is an intergeneric allotetraploid (AARR; 2n = 38) derived from a cross between Brassica rapa (AA; 2n = 20) and Raphanus sativus (RR; 2n = 18). xBrassicoraphanus is fertile and genetically stable, while retaining complete sets of both B. rapa and R. sativus chromosomes. Precise control of meiotic recombination is essential for the production of balanced gametes, and crossovers (COs) must occur exclusively between homologous chromosomes. Many interspecific hybrids have problems with meiotic division at early generations, in which interactions between non-homologous chromosomes often bring about aneuploidy and unbalanced gamete formation. We analyzed meiotic chromosome behaviors in pollen mother cells (PMCs) of allotetraploid and allodiploid F1 individuals of newly synthesized xBrassicoraphanus. Allotetraploid xBrassicoraphanus PMCs showed a normal diploid-like meiotic behavior. By contrast, allodiploid xBrassicoraphanus PMCs displayed abnormal segregation of chromosomes mainly due to the absence of homologous pairs. Notably, during early stages of meiosis I many of allodiploid xBrassicoraphanus chromosomes behave independently with few interactions between B. rapa and R. sativus chromosomes, forming many univalent chromosomes before segregation. Chromosomes were randomly assorted at later stages of meiosis, and tetrads with unequal numbers of chromosomes were formed at completion of meiosis. Immunolocalization of HEI10 protein mediating meiotic recombination revealed that COs were more frequent in synthetic allotetraploid xBrassicoraphanus than in allodiploid, but less than in the stabilized line. These findings suggest that structural dissimilarity between B. rapa and R. sativus chromosomes prevents non-homologous interactions between the parental chromosomes in allotetraploid xBrassicoraphanus, allowing normal diploid-like meiosis when homologous pairing partners are present. This study also suggests that CO suppression between non-homologous chromosomes is required for correct meiotic progression in newly synthesized allopolyploids, which is important for the formation of viable gametes and reproductive success in the hybrid progeny.

Randomized control trial of hand acupuncture for female stress urinary incontinence.

This study was designed to evaluate the effect of Hand acupuncture treatment on the stress urinary incontinence of 52 women randomly assigned to Experimental hand acupuncture treatment group (n = 25) and Control group (n = 27). 11 hand acupuncture points were established as a basic treatment formula. Among them, 5 points on the midline of the palm represent the major acupoints of external genitals, bladder, abdominal aorta, stomach and heart, while the other 6 points were applied as supplementary ones (2 points on the mid line of the palm for adrenal glands and heart, 2 points near the wrist for kidneys and 2 points on the back of the hand for bladder). This basic treatment formula was applied to all subjects in the Experimental group. Additional treatments were given to the subjects with tenderness at ST27, CV4 or SP15, while no treatment to the subjects in Control group for 12 weeks. Assessment was made before and after 12 weeks of clinical study. In the present study, Hand acupuncture treatment significantly reduced the frequency of urinary incontinence compared to Control group. Similarly, the prevalence score of urinary incontinence was significantly reduced up to 37% of Control group in Experimental group. Furthermore, vaginal contraction pressure of the Experimental group was significantly increased 1.6 fold compared to Control group. In addition, Hand acupuncture treatment significantly improved the scores of making friends, sexual life and social community in Experimental group compared to Control group. Overall, these findings suggest that Hand acupuncture can be a potent alternative therapy for stress urinary incontinence.

Beneficial effects of phosphatidylcholine on high-fat diet-induced obesity, hyperlipidemia and fatty liver in mice.

AIMS: Soybean-derived PC is an essential cell membrane phospholipid that is composed of unsaturated fatty acids, including oleic acid. The present study aimed to evaluate the potential alleviation effects of soybean PC on high fat diet (HFD)-induced obesity and its related complications. MAIN METHODS: We fed C57BL/6 mice a HFD for 12 weeks and administered PC orally for 8 or 12 weeks at different doses. At the end of the experiment, blood was prepared for biochemical analysis and leptin ELISA. Aorta, epididymal and mesenteric fat and liver were removed surgically, weighed and observed for histological or immunohistochemical changes. KEY FINDINGS: PC significantly prevented body weight gain and lipid accumulation and alleviated hyperlipidemia by decreasing triglyceride (TG) and total cholesterol (TC) levels and the atherogenic index in serum or by increasing the HDL/TC ratio. Aortic apoE expression and serum leptin levels were suppressed by PC treatment in the HFD-induced obese mouse model. Elevated serum aspartate aminotransferase and alanine aminotransferase levels in HFD-fed mice were decreased in the PC groups. PC treatment significantly decreased HFD-induced liver weight and hepatic lipid accumulation. SIGNIFICANCE: PC treatment alleviated HFD-induced obese status and obesity-related complications such as hyperlipidemic changes that induce cardiovascular disease and NAFLD.

Meta-analysis of Complementary and Alternative Intervention on Menstrual Distress.

PURPOSE: This study was to analyze the effect size of complementary and alternative intervention studies in reference to dysmenorrhea and menstrual distress. METHODS: In order to conduct a meta-analysis, a total of 393 studies were retrieved from the database. Twenty-eight studies that were published from March 2001 to February 2011 were selected. RESULTS: Intervention studies included seven studies on aromatherapy, five on auriculotherapy, three on each Koryo-Sooji-Chim and moxibustion, two on each heat therapy and magnetic therapy and six on other therapy. The effect size of the intervention studies on dysmenorrhea and menstrual distress was greater than 0.48 for Koryo-Sooji-Chim, moxibustion, aromatherapy, auriculotherapy and other therapy. CONCLUSION: This study suggests that drug free therapy can reduce the levels of menstrual distress, despite the small number of intervention studies and randomized controlled trials.

Icariside II induces apoptosis in U937 acute myeloid leukemia cells: role of inactivation of STAT3-related signaling.

BACKGROUND: The aim of this study is to determine anti-cancer effect of Icariside II purified from the root of Epimedium koreanum Nakai on human acute myeloid leukemia (AML) cell line U937. METHODOLOGY/PRINCIPAL FINDINGS: Icariside II blocked the growth U937 cells in a dose- and time-dependent manner. In this anti-proliferation process, this herb compound rendered the cells susceptible to apoptosis, manifested by enhanced accumulation of sub-G1 cell population and increased the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. Icariside II was able to activate caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) in a time-dependent manner. Concurrently, the anti-apoptotic proteins, such as bcl-x(L) and survivin in U937 cells, were downregulated by Icariside II. In addition, Icariside II could inhibit STAT3 phosphorylation and function and subsequently suppress the activation of Janus activated kinase 2 (JAK2), the upstream activators of STAT3, in a dose- and time-dependent manner. Icariside II also enhanced the expression of protein tyrosine phosphatase (PTP) SH2 domain-containing phosphatase (SHP)-1, and the addition of sodium pervanadate (a PTP inhibitor) prevented Icariside II-induced apoptosis as well as STAT3 inactivation in STAT3 positive U937 cells. Furthermore, silencing SHP-1 using its specific siRNA significantly blocked STAT3 inactivation and apoptosis induced by Icariside II in U937 cells. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated that via targeting STAT3-related signaling, Icariside II sensitizes U937 cells to apoptosis and perhaps serves as a potent chemotherapeutic agent for AML.

Ginsenoside rich fraction of Panax ginseng C.A. Meyer improve feeding behavior following radiation-induced pica in rats.

Panax ginseng is an indigenous medicinal herb and has traditionally been used among Asian population for relief of many human ailments. We investigated the prophylactic role of Korean P. ginseng extract (KG) against X-ray irradiation-induced emesis in an acute rat pica model. Rats were treated with KG (12.5, 25, 50 mg/kg orally at -48, -24 and 0 h) prior to X-ray irradiation (6 Gy), and intake of kaolin and normal food and body weight changes examined as an index of the acute emetic stimulus. Levels of serotonin in small intestine tissue were assessed and histopathology of gastric tissue, small intestine and colon examined specific staining. Pre-treatment with KG (12.5 and 25 mg/kg) reduced X-ray irradiation-induced kaolin intake at 24h. Normal food intake was improved in rats treated with 25 mg/kg KG. The anti-emetic effect of KG was further confirmed on the basis of serotonin release, histopathological findings. Our findings collectively indicate that KG protects against X-ray irradiation-induced acute pica to a moderate extent, leading to improved feeding behavior in rats.

Ethanol extract of Ocimum sanctum exerts anti-metastatic activity through inactivation of matrix metalloproteinase-9 and enhancement of anti-oxidant enzymes.

Ocimum sanctum has been known to possess various beneficial properties including anti-oxidative, anti-inflammatory and anti-cancer activities. In the present study, we investigated that ethanol extracts of O. sanctum (EEOS) had anti-metastatic activity through activation of anti-oxidative enzymes. EEOS exerted cytotoxicity against Lewis lung carcinoma (LLC) cells. Also, EEOS significantly inhibited cell adhesion and invasion as well as activities of matrix metalloproteinase-9 (MMP-9), but not MMP-2, indicating the important role of MMP-9 in anti-metastatic regulation of EEOS. In addition, EEOS significantly reduced the tumor nodule formation and lung weight in LLC-injected mice. Inhibitory effect of EEOS on metastasis was further confirmed by using hematoxylin and eosin (H&E) staining. Notably, we also found that EEOS enhanced activities of anti-oxidative enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in a concentration-dependent manner. Taken together, our findings support that EEOS can be a potent anti-metastatic candidate through inactivation of MMP-9 and enhancement of anti-oxidant enzymes.