PURPOSE: Breast cancer (BC) is one of the most common malignant tumors, affecting a significant number of women worldwide. MicroRNAs (miRNAs) have been reported to play important roles in tumorigenesis. The aim of this study was to determine the roles of miR-182-5p in BC progression. MATERIALS AND METHODS: The expressions of miR-182-5p and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) were measured in BC tissues and cells by quantitative real-time polymerase chain reaction or Western blot. Cell proliferation and invasion were detected by cell counting kit-8 assay and trans-well assay, respectively. The interaction between miR-182-5p and PTEN was probed by bioinformatics analysis, luciferase activity, and RNA immunoprecipitation. A murine xenograft model was established to investigate the role of miR-182-5p in BC progression in vivo. RESULTS: An abundance of miR-182-5p was noted in BC tissues and cells. High expression of miR-182-5p was associated with poor survival. Abrogation of miR-182-5p inhibited cell proliferation and invasion in BC cells. Interestingly, PTEN was indicated as a target of miR-182-5p, and its restoration reversed miR-182-5p-mediated promotion of proliferation and invasion of BC cells. Moreover, depletion of miR-182-5p suppressed tumor growth via up-regulating PTEN expression in the murine xenograft model. CONCLUSION: MiR-182-5p exhaustion blocked cell proliferation and invasion by regulating PTEN expression, providing a novel therapeutic avenue for treatment of BC.
Blotting, Western ; Breast Neoplasms ; Breast ; Carcinogenesis ; Cell Count ; Cell Proliferation ; Chromosomes, Human, Pair 10 ; Computational Biology ; Female ; Heterografts ; Humans ; Immunoprecipitation ; Luciferases ; MicroRNAs ; Real-Time Polymerase Chain Reaction ; RNA

Human health has been severely threatened by malignant tumors continuously.Rational and effective drug use provides an effective means for the treatment of malignant tumors,and is expected to become an important way to solve the problem of tumor treatment in the future.In recent years,with the escalation of new cancer theories and the emergence of clinical drug resistance,innovative research and development of anti-cancer drugs has always been a hot spot and focus in cancer research.Among them,the discovery of novel anti-cancer drugs from natural compound is of top priority due to its strong anti-cancer efficacy and the abundant drug resources.Therefore,it is imperative to systematically summarize the cutting-edge advancements of the natural products and their potential pharmacological mechanisms according to the characteristics of tumor progression,and put forward the new directions and trends for further development of anti-cancer natural products in the future.Specifically,the research advancements on anti-cancer effect of natural products were reviewed,focusing on both the traditional and innovative application.We hope this review could bring the light on the research path of the natural anti-cancer products clearly and comprehensively,and also provide inspirations for innovative,safer and more effective anti-cancer drug development and exploration.
Antineoplastic Agents ; pharmacology ; Biological Products ; pharmacology ; Humans ; Neoplasms ; drug therapy ; Research

This paper was mainly to discuss the potential role and mechanism of Lianhua Qingwen Capsules(LHQW) in inhibiting pathological inflammation in the model of acute lung injury caused by bacterial infection. For in vitro study, the mRNA expression of MCP-1 in RAW264.7 cells and THP-1 cells, the content of MCP-1 in cell supernatant, as well as the effect of LHQW on chemotaxis of macrophages were detected. For in vivo study, mice were randomly divided into 7 groups, including normal group, model group(LPS 5 mg·kg~(-1)), LHQW 300, 600 and 1 200 mg·kg~(-1)(low, middle and high dose) groups, dexamethasone 5 mg·kg~(-1) group and penicillin-streptomycin group. Then, the anal temperature was detected two hours later. Dry weight and wet weight of lung tissues in mice were determined; TNF-α and MCP-1 levels in alveolar lavage fluid and MCP-1 in serum were detected. In addition, the infiltration of alveolar macrophages was also observed and the infiltration count of alveolar macrophages was measured by CCK-8 method. HE staining was also used to observe the inflammatory infiltration of lung tissues in mice. Both of the in vitro and in vivo data consistently have confirmed that: by down-regulating the expression of MCP-1, LHWQ could efficiently decrease the chemotaxis of monocytes toward the pulmonary infection foci, thus blocking the disease development in ALI animal model.
Acute Lung Injury ; microbiology ; Animals ; Bacterial Infections ; drug therapy ; Bronchoalveolar Lavage Fluid ; Capsules ; Chemokine CCL2 ; metabolism ; Chemotaxis ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Lipopolysaccharides ; Lung ; Macrophages ; drug effects ; Mice ; RAW 264.7 Cells ; Random Allocation ; THP-1 Cells ; Tumor Necrosis Factor-alpha ; metabolism

In the background of the high incidence and high mortality of cardiovascular diseases,atherosclerosis is the main pathological feature of cardiovascular diseases and the core pathological basis for disease progression. In the evolution of atherosclerotic plaques,the rupture of unstable plaques,plaque shedding and formation of thrombosis are the most dangerous parts. In this process,the formation of plaque fibrosis is the core mechanism regulating plaque stability. Additionally,fibrosis reflects dynamic changes in the inflammatory processes and pathological changes. In view of the inflammation regulation and fibrosis regulation,this paper clarified the process of atherosclerotic plaque,explained the roles of relevant inflammatory cells and cytokines in plaque stability,and summed up drug researches related with stable plaque in recent years. In the future,improving the fibrosis will be a new idea for stabilizing plaque in atherosclerosis drug development.
Atherosclerosis ; drug therapy ; pathology ; Cytokines ; Fibrosis ; Humans ; Inflammation ; Plaque, Atherosclerotic ; drug therapy ; pathology ; Thrombosis ; drug therapy ; pathology

Objective: To study the effects of Xiaoyaosan on sexual behavior and inflammatory factors of rat with depression. Methods: The establishing depressive rat models of chronic mild unpredictable stress were established. The rats were randomly divided into model group and Xiaoyaosan group, 15 in each group. The Xiaoyaosan group was given 4.612 5 g/(kg•d) Xiaoyaosan, the blank group and the model group were intragastrically administered with normal saline once daily. After 4 weeks of oral administration, mount frequency and perineal licking numbers to female rats in each experimental group were observed by sexual behavior experiment, and the spleen index and thymus index were calculated. The serum DA, IL-1β, IL-6 levels were tested by Elisa. Results: Compared with the normal group, the mount frequency (4.42 ± 3.91 vs. 11.58 ± 6.54), perineal licking numbers (3.53 ± 3.29 vs. 16.36 ± 10.68) and serum DA levels (14.14 ± 0.71 pg/ml vs. 17.44 ± 4.06 pg/ml) in the model group significantly decreased (P<0.05 or P<0.01), and the thymus index (0.012 4 ± 0.001 8 vs. 0.009 3 ± 0.001 7), serum IL-1β (39.45 ± 11.98 pg/ml vs. 28.62 ± 6.61 pg/ml), IL-6 levels (9.74 ± 1.49 pg/ml vs. 6.40 ± 0.66 pg/ml) significantly increased (P<0.05 or P<0.01). Compared with the model group, the contents of serum DA in Xiaoyaosan group (15.90 ± 1.24 pg/ml vs. 14.14 ± 0.71 pg/ml) increased significantly (P<0.01), and the thymus index (0.009 9 ± 0.001 3 vs. 0.012 4 ± 0.001 8) and IL-6 levels (8.32 ± 0.39 pg/ml vs. 9.74 ± 1.49 pg/ml) decreased significantly (P<0.05). Conclusions The Xiaoyaosan had a therapeutic effect on immune dysfunction and increases the expression of serum dopamine in depressive rats, which may be one of the mechanisms of its anti-depression.

Objective:To explore the molecular mechanism of cantharidin(CTD) in inducing morphological changes and dissociation in human colon cancer HCT116 cells, in order to study the correlation with tumor metastasis and provide a new basis for clinical use of cantharidin. Method:Different concentrations of CTD (0, 2.5, 5, 10, 15, 20 μmol·L^-1) were added to each hole to culture for 7 to 10 days, so as to determine the inhibitory effect of CTD on HCT116 cells; and changes of F-actin cytoskeleton and integrin in HCT116 cells were detected by immunofluorescence staining. Western blot analysis of protein expressions of RhoA,RhoB,RhoC,Cdc42 and Rac1/2/3 of Rho family were performed before and after cantharidin treatment. overexpression of RhoA was constructed by plasmid transient transfection, and effect of 10 μmol·L^-1 cantharidin on the morphology and adhesion of overexpressing cells was also observed. Result:Cantharidin induced cytoskeletal remodeling and decreased integrin content in HCT116 colon cancer cells. RhoA protein was a member of Rho enzyme family with the greatest variation after cantharidin action. The proportion of transfected RhoA cells with green fluorescence was about 60%, the expression of RhoA protein in constructed RhoA overexpression cells was significantly increased, compared with wild-type HCT116 cells (P<0.01). However, cantharidin can act on RhoA overexpressed HCT116 cells, reverse its overexpression(P<0.01), and affect its morphology. Conclusion:Cantharidin can inhibit the expression of RhoA protein, induce the morphological changes of HCT116 cells and weaken the adhesion to the basement, thereby inhibiting cell migration.

Objective:To study the effect of Shenlian extract (SL extract) on macrophage function and inflammatory resolution in lipid peroxidation inflammatory injury models. Method:The effects of different concentrations of SL extract (2.5, 5.0, 10.0, 20.0 mg·L^-1) on the polarization type, foam formation and chemotactic function of macrophages were detected with RAW264.7 cells induced by oxidized low-density lipoprotein(ox-LDL). Western blot was used to detect pro-inflammatory resolution factor arachidonate 5-lipoxygenase(ALOX5) and inducible inducible nitric oxide synthase(iNOS), and phosphorylated p65 (p-p65) and phosphorylated IκK (p-IκK) in nuclear factor(NF)-κB related signaling pathways. Result:Compared with the control group, ox-LDL enhanced the expressions of M1 macrophage markers TNF-α, IL-1β, iNOS (P<0.01), inhibited the expressions of IL-10 of M2 markers, promoted foam cell formation (P<0.01), induced THP-1 chemotaxis ability, increased the content of MCP-1 (P<0.01), and inhibited the expression of ALOX5.Compared with the model group, SL extract reduced the expressions of TNF-α, IL-1β, and iNOS (P<0.01), increased the expression of IL-10 (P<0.05), and down-regulated the formation of foam of macrophages (P<0.01). In transwell assay, SL extract obviously decreased the MCP-1 secretion and the number of chemotaxis cells (P<0.01), and promoted the increase of the inflammatory resolution factor ALOX5.The phosphorylation of p65 and IκK was inhibited significantly (P<0.01). Conclusion:In the inflammatory damage model of lipid peroxidation, SL extract can regulate the polarization of macrophage, inhibit the chemotaxis and foaming of ox-LDL, increase the inflammatory resolution molecular expression, and improve the state of lipid peroxidation, which may be related to the inhibition of NF-κB signaling pathway.

Objective:To systematically and comprehensively analyze coumarin components in Angelicae Sihensis Radix by an efficient and stable HPLC-Q-TOF-MS/MS method,in order to offer the theoretical basis to develop coumarin,establish the quality control standard and apply in clinic. Method:The separation effect of coumarin components was extracted by adjusting the column,temperature,mobile phase,flow rate,sample concentration and other conditions,and various coumarin components in Angelicae Sihensis Radix were identified by corresponding standards,precise molecular mass,polarity,pyrolysis pattern. Result:In this study,a high-efficiency and stable coumarin separation method was established that can be used to separate complex components,and 14 coumarin components were identified in this study,including phellopterin and osthenol that were rarely reported as effective components in Angelicae Sihensis Radix. Major fragment ions of coumarin components were analyzed. The cleavage in methoxy bond or anisole bond on the parent nucleus was the primary pattern for coumarin components, which was summarized for detecting unknowing coumarins. Conclusion:Abundant coumarins were contained in Angelicae Sihensis Radix. Further qualitative and quantitative analysis of coumarins are conducive to improving the quality standards of Angelicae Sihensis Radix,and providing reference for the development of coumarins and clinical application of Angelicae Sinensis Radix.

Objective The treatment methods for blood blister-like aneurysm remain controversial due to its special patholog-ical structure,the risk of post-operative rebleeding and the high rate of recurrence. The arm of this paper is to access the feasibility and effectiveness of overlapping stent-assisted coiling in the treatment of blood blister-like aneurysms of the internal carotid artery. Methods Form January 2014 to December 2016,we treated 15 patients with blood blister-like aneurysm of the internal carotid artery by stent-assisted coiling in the Department of Neurosurgery,5 with two Enterprise tents,3 with three Enterprise tents,4 with Enter-prise+LVIS tents,and 3 with two LVIS tents. We determined the rate of immediate embolization of aneurysms by Raymond-Roy Occlu-sion Classification(RROC)and analyzed the clinical characteristics,postoperative complications,and follow-up data. Results All the coils and stents were successfully implanted. RROC showed 9 cases of gradeⅠ(60%),4 cases of gradeⅡ(27%),and 2 cases of gradeⅢimmediate occlusion(13%),with the parent arteries unobstructed in all the cases. Thrombosis in the stent was found in 2 cases intraoperatively,slight stent migration in 1 case,and internal carotid artery dissection in the petrous segment in another,but no cer-ebral vasospasm or aneurysm rupture in any case.Delayed cerebral in-farct was observed in 2 cases postoperatively. The patients were fol-lowed up for 2 weeks to 28 months,which showed that 11 of them were cured,2 remained stable and 2 developed further thrombosis,with an MRS score of 0-2 in 12 cases,4 in 1 case,5 in 1 case, and 6 in 1case. Conclusion Overlapping stent-assisted coiling is effective for the treatment of blood blister-like aneurysm by reduc-ing the risks of rebleeding and recurrence.