The inhibitory effect of Licochalcone B on the triple negative breast cancer cell MDA-MB-231 and its mechanism / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨甘草查尔酮B（LCB）对三阴性乳腺癌（TNBC）MDA-MB-231细胞的抑制作用及其机制。方法: 常规培养MDA-MB-231细胞，用不同浓度LCB处理后，采用CCK-8法、免疫荧光法、FCM和WB法分别检测MDA-MB-231细胞的增殖活力、细胞核内DNA双链断裂标志物γ-H2AX的表达，以及细胞周期和周期调控、丝裂原活化蛋白激酶（MAPK）、内质网应激信号途径相关蛋白的表达水平。结果: LCB能显著抑制乳腺癌MDA-MB-231细胞的增殖活力（P<0.05），使γ-H2AX阳性细胞数和蛋白表达水平均显著升高（均P<0.05）、G2/M和S期的细胞数量均明显增加（均P<0.05）、MAPK家族主要成员细胞外调节激酶1/2（ERK1/2）和p38MAPK蛋白的磷酸化水平均显著上调（均P<0.05），还使内质网应激途径相关蛋白Bip、ATF4和CHOP的表达均显著上调（均P<0.05）。结论: LCB能够显著抑制MDA-MB-231细胞的增殖活力、诱导DNA损伤和细胞周期阻滞于G2/M和S期，LCB对MDA-MB-231细胞的抑制作用可能与其激活MAPK和内质网应激信号通路相关。

lncRNA OIP5-AS1 targets ROCK1 to promote cell proliferation and inhibit cell apoptosis through a mechanism involving miR-143-3p in cervical cancer

Opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) is one kind of cytoplasmic long non-coding RNA (lncRNA), which has been demonstrated to play a critical function in multiple cancers. However, the detailed mechanism of OIP5-AS1 in the regulation of cervical cancer progression is still obscure. Here, we demonstrated that lncRNA OIP5-AS1 was upregulated in cervical cancer and was correlated with poor prognosis by bioinformatics studies. OIP5-AS1 depletion inhibited cell proliferation and promoted cell apoptosis in cervical cancer cells. Furthermore, we clarified that ROCK1 was the downstream effector of OIP5-AS1 and OIP5-AS1 acted as a molecular sponge of miR-143-3p. Finally, we verified that OIP5-AS1 exerted its function in the regulation of cervical cancer progression via interacting with miR-143-3p to regulate ROCK1 expression. Our study revealed novel mechanisms about how lncRNA OIP5-AS1 executed its function in cervical cancer and thus provided potential therapeutic targets for the disease.

Baicalin suppresses Propionibacterium acnes-induced skin inflammation by downregulating the NF-κB/MAPK signaling pathway and inhibiting activation of NLRP3 inflammasome

Acne is a kind of common, chronic skin condition caused by the inflammation of the sebaceous glands in hair follicles. Recent studies have demonstrated that baicalin (BA) possesses potential anti-inflammatory properties. In this study, we evaluated the anti-inflammatory activity of BA in vitro and in vivo. Heat-killed Propionibacterium acnes-induced THP-1 cells and live P. acnes-injected male Sprague Dawley rats were used for establishing the acne model. The rate of ear swelling was calculated, and the severity was determined by hematoxylin and eosin staining. The production of cytokines [interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF-α)] in the cell supernatant and ear tissue homogenates was measured by ELISA. Protein levels of JNK, ERK, P38, IκBα, P65, Nod-like receptor pyrin domain-containing 3 (NLRP3), pro-caspase-1, and IL-1β in THP-1 cells and ear tissues were detected by western blotting. NLRP3 and IL-1β were detected by immunohistochemistry, and the NLRP3, IL-1β and pro-caspase-1 mRNAs were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The results showed that BA decreased the expression of pro-inflammatory cytokines in vitro and in vivo. Moreover, BA down-regulated the phosphorylation of JNK, ERK1/2, and κBα and inhibited the nuclear translocation of p65. Furthermore, BA inhibited the activation of NLRP3 inflammasome, at both the gene and protein levels. Taken together, the results demonstrated that BA might exert its anti-inflammatory activity by inhibiting NF-κB/MAPK signaling pathways and consequently suppressing the activation of the NLRP3 inflammasome both in vivo and in vitro.

Experimental study of peripheral-blood pro-surfactant protein B for screening non-small cell lung cancer

Abstract Purpose: To evaluate the possibility of using peripheral-blood presurfactant protein B (Pro-SFTPB) for screening non-small cell lung cancer (NSCLC). Methods: A total of 873 healthy volunteers and 165 lung cancer patients hospitalized in the Fifth People's Hospital of Dalian were tested Pro-SFTPB once every half year from January 2014 to September 2015. The healthy volunteers were also conducted spiral computed tomography (CT) examination once every year. The data were then com-pared and statistically analyzed. Results: The positive expression rate of Pro-SFTPB in NSCLC was significantly higher than that in healthy volunteers, and significantly higher in lung adenocarcinoma than in squamous cell carcinoma; additionally, the expression rate was increased with the in-crease of smoking index, and the intergroup differences showed statistical signifi-cance (p≤0.05). The positive rate of newly diagnosed lung cancer was 29.55%, higher than healthy volunteers (22.34%), but there was no significant difference (p>0.05). Conclusion: Pro-SFTPB is over expressed in non-small cell lung cancer, especially in lung adeno-carcinoma, but it can't be used as a clinical screening tool for lung cancer.

Micronutrient Supplementation during Pregnancy among Mildly and Non-anemic Women: Effects on Iron Status and Hemoglobin.

Objectives: Universal prenatal iron-folic acid and other micronutrient supplements are recommended to prevent anemia during pregnancy, but the evidence of their effect on iron status among women with mild or no anemia is limited. This study is to describe the iron status [serum ferritin (SF), serum transferrin receptor (sTfR), and body iron (BI)] before and after micronutrient supplementation during pregnancy. Methods: Among 834 pregnant women with mild or no anemia (Hb >110 g/L) from a subset of participants in a randomized, double-blind trial in China, women were randomly assigned to daily 400 µg folic acid (FA) (control), folic acid plus 30mg iron (IFA,), or folic acid, iron, plus 13 additional multiple micronutrients (MM) provided before 20 weeks gestation to delivery. Venous blood was collected during study enrollment (<20 weeks gestation) and at 28-32 weeks gestation. Results: At 28-32 weeks gestation , compared to FA group, both the IFA and MM group showed significantly lower prevalence of iron deficiency (ID) no matter which indicator (SF, sTfR, or BI) was used for defining ID. The prevalence of ID at 28-32 weeks gestation for IFA, MM, and FA were 35.3%, 42.7%, and 59.6% respectively using low SF; were 53.6%, 59.9%, and 69.9% respectively using high sTfR; and were 34.5%, 41.2%, and 59.6% respectively using low BI. However, there was no difference on anemia prevalence between FA and IFA or MM groups. Conclusions: Compared to FA alone, prenatal IFA and MM supplements provided to women with no or mild anemia improved later pregnancy iron status but did not affect perinatal anemia.

Low-dose B Vitamins Supplementation Improves Framingham Risk Score: A Double Blind Randomized Controlled Trial in Healthy Chinese Elderly.

Objectives: We investigated whether daily supplementation with low-dose B vitamins in healthy elderly improves Framingham risk score (FRS), a cardiovascular disease predictor. Methods: A double-blind randomized controlled trial was conducted in a rural area of North China during 2007-2012. 390 healthy participants aged 60-74 were randomly allocated to receive daily vitamin C (50 mg; control) or vitamin C plus B vitamins (400 μg folic acid, 2 mg B6, and 10 μg B12) for 12 months. The outcome was FRS. Results: Compared with control, supplementation with B vitamins reduced FRS by 3.7% (mean difference, -0.38; 95% CI -1.06, 0.31; P=0.279) at 6 months, 7.6% (-0.77; 95% CI -1.47, -0.06; P=0.033) at 12 months, but this reduction effect vanished 6 months later after stopping supplementation (-0.7%; -0.07; 95% CI -0.80, 0.66; P=0.855). The reduction in FRS at 12 months after supplementation was more pronounced in individuals with folate deficiency (11.0%; -1.38; 95% CI -2.56, -0.20; P=0.023) than those without folate deficiency (5.0%; -0.47; 95% CI -1.20, 0.26; P=0.206). B vitamins elevated high-density lipoprotein cholesterol by 3.4% (0.04 mmol/L; 95% CI -0.02, 0.10; P=0.155) at 6 months, 9.2% (0.11 mmol/L; 95% CI 0.04, 0.18; P=0.003) at 12 months; the change magnitude declined to 3.3% (0.04 mmol/L; 95% CI -0.02, 0.10; P=0.194) after stopping supplementation, compared with control. Conclusions: Daily supplementation with low-dose B vitamins for 12 months reduced FRS, particularly in healthy elderly with folate deficiency. These reduction effects declined after stopping supplementation, indicating a need for persistent supplementation to maintain the benefits.

Role of nitric oxide in iron-induced toxicity in rat hearts / 生理学报

The aim of the present study was to explore the effect of nitric oxide (NO) on iron-induced toxicity in rat hearts. Langendorff perfused rat heart and enzymatically isolated cardiomyocytes were used. It was shown that lipophilic Fe-HQ reduced the contractile amplitude, velocity and end-diastolic cell length in the cardiomyocyte, while the left ventricular developed pressure (LVDP), +/-dp/dt(max), heart rate and coronary flow showed biphasic alterations, which increased in the first 2 min and then was followed by a decline in isolated perfused rat heart; the contents of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary effluent and the malondialdehyde (MDA) in the myocardium were increased. L-arginine (L-Arg), an NO precursor, reduced the contractile amplitude and end-diastolic cell length in the cardiomyocyte; but reversibly increased LVDP, +/-dp/dt(max), and coronary flow in isolated perfused rat heart. Pretreatment with L-Arg aggravated the Fe-HQ-induced decrease in contractile amplitude, velocity and end-diastolic cell length in the cardiomyocyte; LVDP, +/-dp/dt(max), heart rate and coronary flow were significantly reduced in the perfused heart, and the levels of LDH and CK increased in the coronary effluent. In contrast, the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) blocked the Fe-HQ induced change in contractile amplitude, velocity and end-diastolic cell length in the cardio- myocyte; it inhibited the decrease in LVDP, LVEDP and +/-dp/dt(max), and reduced the LDH and CK. Removing endothelial cells in coronary vessels attenuated the increase in LVDP and +/-dp/dt(max) at the beginning of Fe-HQ perfusion. It is suggested that L-Arg aggravates the iron-induced cardiac dysfunction, NO can mediate the iron-induced toxicity in heart, and endothelial cells in coronary vessels play an important role in the early stage of the effect of iron.