Asperuloside suppressing oxidative stress and inflammation in DSS-induced chronic colitis and RAW 264.7 macrophages via Nrf2/HO-1 and NF-κB pathways.

BACKGROUND: Inflammatory bowel diseases (IBDs), which mainly include Crohn's disease (CD) and ulcerative colitis (UC), are chronic idiopathic inflammatory disease of the gastrointestinal tract for which effective pharmacological treatments are lacking or options are very limited. PURPOSE: Here, we aim to investigate the therapeutic effects of an iridoid glycoside, asperuloside (ASP) on mice experimental chronic colitis induced by dextran sulfate sodium (DSS) and further explore underlying mechanisms in vitro and in vivo. METHODS: LPS-treated RAW 264.7 cells showed inflammation and were assessed for various physiological, morphological and biochemical parameters in the absence or presence of ASP. Chronic colitis was induced by 2% DSS in mice, which were used as an animal model to explore the pharmacodynamics of ASP. We detected p65 and Nrf2 pathway proteins via Western blot and RT-PCR analysis, assessed the cytokines TNF-α and IL-6 via ELISA, tested p65 and Nrf2 nuclear translocation via fluorescence. In addition, the docking affinity of ASP and p65 or Nrf2 proteins in the MOE 2015 software. RESULTS: We found that ASP attenuated weight loss, disease activity index (DAI) and colonic pathological damage in colitis mice and restored the expressions of inflammatory cytokines in the colon. In addition, ASP restored antioxidant capacity in DSS-induced chronic colitis mice and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Furthermore, ASP suppressed oxidative stress through increasing Nrf2, HO-1 and NQO-1 proteins expressions, and down-regulated nuclear levels of p65 to inhibit DSS-induced colonic oxidative stress and inflammation. Validation of the molecular docking results also indicated that ASP interacts with Nrf2 or p65 proteins. In summary, ASP improved DSS-induced chronic colitis by alleviating inflammation and oxidative stress, activating Nrf2/HO-1 signaling and limiting NF-κB signaling pathway, which may be an effective candidate for the treatment of IBD.

Characteristics of Blood Transfusion During Induction Remission in Children With Acute Lymphoblastic Leukemia: A Single-Center Retrospective Investigation.

OBJECTIVE: To investigate the allogeneic blood transfusion (ABT) characteristics of children with acute lymphoblastic leukemia (ALL) in different risk stratification during vincristine, daunorubicin, L-asparaginase and prednisone (VDLP) induction remission. SUBJECTS AND METHODS: By referring to electronic medical records, the demographic characteristics, diagnosis, test, and treatment information including ABT were collected. According to the risk stratification of the CCCG-ALL-2015 protocol, ABTs between groups were compared, and the differences were statistically analyzed. RESULTS: One hundred sixty-three newly treated children with ALL were enrolled in this study, who received 643.5 U of red blood cells and 377.6 U of platelets (PLTs) during the VDLP. The amount of ABT in the intermediate-risk (IR) group (n=102) was significantly higher than that in the low-risk group (n=61), which were reflected in the red blood cells in the first half of VDLP (P=0.033) and the PLTs in the second half of VDLP (P<0.001). Meanwhile, the PLT counts in the IR group were significantly lower in the same period. The time node was bounded by the minimal residual disease test on the 19th day. CONCLUSIONS: Children in the IR group or with unsatisfactory induction may need more ABTs during the VDLP, and the relatively low PLT counts seem to contribute to this. The results of this study can provide a basis for patient blood management, as well as a reference for studying the long-term effects of ABT on children with ALL.

Protective roles and mechanisms of polysaccharides from Dendrobium officinal on natural aging-induced premature ovarian failure.

This study was designed to investigate the pharmacological effects and mechanisms of polysaccharides from Dendrobium officinal (DOP) on premature ovarian failure (POF) in natural aging mice. Fifteen months old female mice (n  =  28) and young adult female mice (n  =  14, 6 weeks) were used. DOP (70 mg/kg) was administrated to mice by oral gavage for 10 weeks and the protection effects of DOP on ovaries were investigated in vivo. The results showed that DOP reduced body weight, ovary and uterus/body weight parameters to normal level and alleviated ovarian pathological damage. Moreover, DOP could reduce pro-inflammatory cytokines (TNF-α, IL-6) and MDA levels and improve estradiol, SOD, GSH-Px, T-AOC and IL-10 levels in serum. These results suggested that DOP may alleviate the damage caused by aging through the inhibition of the nuclear factor -κB (NF-κB) and p53/Bcl-2-mediate signaling pathways. Moreover, we found that DOP can increase the numbers of mitochondria and endoplasmic reticulum. Moreover, DOP increased the numbers of different stages of follicular cells and improved mitochondrial membrane potential in ovaries. These results indicated that DOP may relieve ovarian damage through the protection of mitochondria in the ovaries. These findings suggest that DOP may be a promising drug for treating POF caused by natural aging in females.

Observation of the influences of diosgenin on aging ovarian reserve and function in a mouse model.

BACKGROUND: The aim of this study was to investigate the impact of diosgenin, an important monomer of sapogenins in yams, on ovarian reserve in a natural aging mice model. STUDY DESIGN: This randomized controlled trial included 60 9-month-old C57 naturally aging female mice. Twenty-one mice were assigned to the dio group and were fed a single dose of diosgenin (200 mg/kg/day) suspended in 0.3% CMC. Twenty mice were assigned to the DHEA group and were fed a single dose of DHEA (1.25 mg/kg/day) suspended in 0.3% CMC. The remaining 20 mice were assigned to the old control group and were fed a single dose of 0.3% CMC. Three months later, the reproductive performance of these female mice was determined by evaluating ovarian follicles and oocyte number and quality in IVF and comparing age-matched and young controls. The impact of NOBOX, GDF9 and BMP15 mRNA expression was also evaluated. RESULTS: Diosgenin improves ovarian reserve in naturally aging mice in terms of increasing the number of primary follicles (P < 0.05) and serum levels of AMH (P < 0.05). CONCLUSIONS: Diosgenin could counteract age-associated ovarian dysfunction by improving the ovarian reserve in a natural aging mice model.

Reference values for kaolin-activated thromboelastography in volunteers of Anhui Province in China.

BACKGROUND: The assessment of the coagulation status using thromboelastography (TEG) in Chinese population has less been reported. This study aimed to establish reliable reference values for kaolin-activated TEG in Chinese volunteers. METHODS: A total of 1681 Chinese adult individuals were recruited for this study. The reference individuals were stratified by gender and age, and the TEG values were measured on the basis of strict quality control. The 95% reference values were determined using nonparametric statistical methods. RESULTS: The sex-related 95% reference values were reaction time (R):4.2-8.7 minutes; clotting time (K): 1.2-3.2 minutes; alpha angle (α): 47.0-72.3 degree; maximum amplitude (MA): 49.1-70.5 mm for males, and R: 3.7-9.0 minutes; K: 1.0-3.2 minutes; α: 48.4-74.4 degree; MA: 46.8-72.4 mm for females. Also, the TEG parameters indicated a relatively more hypercoagulable profile in both female and elder groups. CONCLUSIONS: This study established the reference values for kaolin-activated TEG in the target Chinese population, which might provide a reference for both clinical and laboratory studies.

Ursolic acid inhibits proliferation and reverses drug resistance of ovarian cancer stem cells by downregulating ABCG2 through suppressing the expression of hypoxia-inducible factor-1α in vitro.

Hypoxia in tumors is closely related to drug resistance. It has not been verified whether hypoxia-inducible factor-1α (HIF-1α) or ABCG2 is related to hypoxia-induced resistance. Ursolic acid (UA), when used in combination with cisplatin can significantly increase the sensitivity of ovarian cancer stem cells (CSCs) to cisplatin, but the exact mechanism is unknown. The cell growth inhibitory rate of cisplatin under different conditions was evaluated using Cell Counting Kit-8 (CCK-8) in adherence and sphere cells (SKOV3, A2780, and HEY). The expression of HIF-1α and ABCG2 was tested using quantitative PCR, western blotting, and immuno-fluorescence under different culture conditions and treated with UA. Knockdown of HIF-1α by shRNA and LY294002 was used to inhibit the activity of PI3K/Akt pathway. Ovarian CSCs express stemness-related genes and drug resistance significantly higher than normal adherent cells. Under hypoxic conditions, the ovarian CSCs grew faster and were more drug resistant than under normoxia. UA could inhibit proliferation and reverse the drug resistance of ovarian CSC by suppressing ABCG2 and HIF-1α under different culture conditions. HIF-1α inhibitor YC-1 combined with UA suppressed the stemness genes and ABCG2 under hypoxic condition. The PI3K/Akt signaling pathway activation plays an important functional role in UA-induced downregulation of HIF-1α and reduction of ABCG2. UA inhibits the proliferation and reversal of drug resistance in ovarian CSCs by suppressing the expression of downregulation of HIF-1α and ABCG2.