Animals ; Antineoplastic Agents ; therapeutic use ; Benzamides ; Dasatinib ; Drug Resistance, Neoplasm ; drug effects ; Fusion Proteins, bcr-abl ; genetics ; metabolism ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; metabolism ; Piperazines ; therapeutic use ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyrimidines ; pharmacology ; therapeutic use ; Thiazoles ; pharmacology ; therapeutic use

Objective: To explore the effect and its mechanism of atorvastatin on cerebral vasospasm after subarachnoid hemorrhage (SAH) in rats. Methods: Sixty male Wistar rats were randomly allocated into four groups: pretreatment group (n = 20), they were fed atorvastatin 10 mg/kg/d for 15 days before the model was made; treatment group (n = 20), they were fed atorvastatin 10 mg/kg at the same day the model was made and continued for 2 days; isotonic saline group (n = 10), instead of atorvastatin, they were fed the same volume of isotonic saline for 15 days before the model was made; and normal control group (n = 10). The SAH model was made by injection of autoblood into cistern magna in rats. On the second day after the model was made, their lipid levels were measured, and neurological deficit scores were assessed; the diameter of basilar artery was measured automatically by the image analysis system after hematoxylin-eosin staining; the levels of serum intercellular adhesion molecule-1 (ICAM-1), interleukin 1 (IL-1) and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA); and ICAM-1 and leucocyte function-associated antigen 1 (LFA-1) messenger RNA (mRNA) expression in basilar artery were determined by reverse transcription-polymerase chain reaction (RT-PCR). Results: The lipid levels in all groups showed no significant differences. The neurologic function scores in the pretreatment group, treatment group and normal control group were 24.3 ± 2.6, 22.0 ± 2.9 and 27.0 ± 0.0, respectively. In comparison with the isotonic saline group (14.2 ± 3.2), there were significant differences (P < 0.05). The diameter of basilar artery in the pretreatment group (169 ± 14 μm) showed significant differences (P < 0.01) with that in the treatment group (146 ± 12 μm) and isotonic saline group (138 ± 18 μm), while no significant differences (P > 0. 05) between the pretreatment group and the normal control group (182 ± 14) μm. The results of ELISA showed that ICAM-1 , LFA-1 and IL-6 expression in the pretreatment group was significantly lower (P < 0.01) than those in the treatment and isotonic saline groups; The results of RT-PCR showed that the expression of ICAM-1 and IL-6 mRNA in the pretreatment group was significantly lower than that in the treatment and isotonic saline groups. Conclusion: Atorvastatin clearly relieves basilar artery vasospasm after subarachnoid hemorrhage (SAH) and improves neurologic function in rats. The mechanism may be associated with its inhibiting the inflammatory reaction after SAH, weakening the interaction between ICAM-1 and LFA-1, and it is not associated with the lowering of lipid levels.

Angiolymphoid Hyperplasia with Eosinophilia ; pathology ; Child, Preschool ; Humans ; Male

Hypoxia occurs in chronic and acute vascular diseases and tumor formation. The ability of tumor cells to maintain a balance between an adaptation to hypoxia and cell death is regulated by a family of transcription factors called hypoxia-inducible factor 1 (HIF-1). Tumor hypoxia mediated by HIF-1 would facilitate the likelihood of resistance to chemotherapy and radiotherapy, proliferation, metastasis and the invasive potential; all of which culminate in a decrease in patient survival. And HIF-1 alpha subunit decides the activity of HIF-1, which is regulated by oxygen. So understanding the role of HIF in signal pathway, drug resistance mechanism and its feature is crucial for developing novel anticancer therapies. In recent years, more attentions have focused on HIF-1 alpha inhibitors. It is expected that development of more potent and selective HIF inhibitors will provide an effective treatment of cancer and other HIF-related diseases. So we will focus on the biological characteristics and mechanism of HIF-1 to review currently studied HIF-1 inhibitors.
Cell Death ; Humans ; Hypoxia-Inducible Factor 1 ; antagonists & inhibitors ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; metabolism ; Neoplasms ; drug therapy ; Oxygen ; metabolism ; Signal Transduction

Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Cell Cycle ; drug effects ; physiology ; Cyclin-Dependent Kinases ; antagonists & inhibitors ; metabolism ; Cyclins ; metabolism ; Flavonoids ; pharmacology ; therapeutic use ; Humans ; Neoplasms ; drug therapy ; metabolism ; pathology ; Piperidines ; pharmacology ; therapeutic use ; Purines ; pharmacology ; therapeutic use ; Staurosporine ; analogs & derivatives ; pharmacology ; therapeutic use

Asteroid Hyalosis (AH) is a common clinical disease,which has been considered a benign disorder as it rarely impairs visual acuity.It was often discovered when the patient was treated for other eye diseases.The mechanism was unclear.Its characteristic B-ultrasound property makes the B-ultrasound a very helpful diagnostic technique.In the case of the patients with other fundus diseases associated with AH,optical coherence tomography (OCT) and fluorescein angiography (FA) may be used to reduce the interference from asteroid bodies,therefore improve the fundus visibility.Recent studies have shown that AH can incorporate with many other eye diseases.For example,in patients with cataracts,asteroid hyalosis can cause surface calcification of silicone plate intraocular lenses,which in most cases may lead to the need for explantation of the calcified intraocular lenses.The efficacy of pars plana vitrectomy (PPV),the removal of some,or all,of the eye`s vitreous humor for AH remains controversial.In this paper,we provide a review of the recent literature on AH disease: the etiology,diagnosis and treatment.We hope to thus improve the awareness and outcomes of AH disease.

In recent years the interaction between host and gut microbiota has attracted increasing attention. However, intestinal flora dysbiosis may lead to many diseases, and there is increasing evidence that the intestinal microbiota in patients with chronic kidney disease (CKD) is associated with the pathophysiological status of the host. "Gut-kidney axis" provides a better explanation of the two-way communication between intestinal flora and CKD. Impaired kidney function leads to dysbiosis of intestinal flora and an altered intestinal flora can damage the intestinal mucosal barrier and facilitate the entry into the bloodstream of harmful bacteria, which can induce chronic inflammation and thus accelerate renal injury. In addition, the accumulation of nephrotoxic metabolites from an altered intestinal flora can aggravate CKD in the "gut-kidney axis". Among them, p-cresol sulfate, indoxyl sulfate and trimethylamine oxide are the most widely studied metabolites of nephrotoxicity, and their renal toxicity has been widely confirmed in basic research and clinical studies. Current studies show that the intestinal microbiota-metabolite network is closely related to the occurrence and development of chronic kidney disease. Thus, intervention in the intestinal microbiota may provide a new approach to the prevention and treatment of chronic kidney disease.

E2F transcription factor 1 (E2F1) is a major member of the E2F transcription factor family and participates in a wide range of physiological regulatory processes, such as cell cycle, survival, apoptosis, and metabolism. It is proved that the activity of E2F1 is related to the G1/S phase regulation of the cell cycle dependent on tumor suppressor retinoblastoma protein (RB). Recent studies have shown that E2F1 is highly expressed in prostate cancer cells, manifested as an oncogene, and its expression level is closely related to the occurrence, development, and poor clinical prognosis of prostate cancer. Androgen receptor (AR) is the main driving factor for the growth and progression of prostate cancer, and the changes of AR pathway play a key role in the pathological progression of prostate cancer. This article provide a systematic and comprehensive summary on recently published articles to review the role of the E2F1 pathway in prostate cancer.

Histone deacetylase (HDAC) is usually abnormally overexpressed, which mainly leads to the transcriptional repression of tumor suppressor genes. Histone deacetylase inhibitors (HDIs) exert anti-tumor biological effects by regulating nucleosome structure, inhibiting HDAC activity, and controlling the expression of tumor suppressor genes. There are currently 5 drugs on the market, but only for peripheral T-cell lymphoma and cutaneous T-cell lymphoma. In solid tumors, most of the HDAC inhibitors used have failed to achieve effective therapeutic effects. Phosphoinositide 3-kinase (PI3K) is the starting node of the PI3K-AKT-mTOR signaling pathway, which plays a very important role in the proliferation, migration, invasion, and differentiation of tumor cells. The abnormal activation of PI3K is closely related to the occurrence and development of tumors, and the combined use of HDAC and PI3K inhibitors and HDAC/PI3K dual-target inhibitors show synergistic anticancer activity. This article introduces the anti-tumor clinical and preclinical research progress of representative HDAC inhibitors and PI3K inhibitors, as well as HDAC/PI3K dual-target inhibitors.

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
Animals ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Hypoxia-Inducible Factor 1 ; metabolism ; Lignans ; pharmacology ; Mice, Nude