A Review: A concept of tissue adaptation to hypoxia (i. e. hypoxic preconditioning) was developed and its corresponding animal models were reproduced in 1966s. The methods of model reproduction in rat, rabbit, and mouse in particular and the main results are briefly introduced in this review. The tolerance to hypoxia of preconditioned animals is significantly increased. Regular changes in animals' behavior, neurophysiology, respiratory and circulatory physiology, neuron morphology in vivo and function of brain and spinal cord in vitro are briefly demonstrated. The protective effects in vivo and in vitro of homogenate extract taken from the brain of preconditioned animals, neurochemicals and molecular neurobiological alterations are briefly presented. The essence and significance of tissue adaptation to hypoxia/hypoxic preconditioning are discussed in the review in terms of evolution and practical implication.
Animals ; Brain ; metabolism ; physiology ; Disease Models, Animal ; Hypoxia ; metabolism ; Mice ; Rabbits ; Rats

OBJECTIVETo explore the effect of Bushen Tiaojing Recipe (BTR) on the quality of oocytes, reproductive hormones, and the expression of bone morphogenetic protein-15 (BMP15) of in vitro fertilization-embryo transfer (IVF-ET) patients.

METHODSSixty infertility patients who prepared for IVF-ET were assigned to two groups according to the treatment order, the treatment group [20 cases, treated with BTR + controlled ovarian hyperstimulation (COH)] and the control group (treated with COH alone, 40 cases). Age, the time limit for infertility, basal follicle-stimulating hormone (bFSH) concentration, usage days and the dosage of gonadotropins (Gn), serum levels of estradiol (E2), luteotropic hormone (LH), and progesterone (P) on the HCG injection day, the number of retrieved occytes, the fertilization rate, the number of embryos, the high quality embryo rate, and the clinical pregnancy rate were compared. Concentrations of follicle-stimulating hormone (FSH), LH, E2, testosterone (T), and P in the follicular fluid were detected via chemiluminescence microparticle immunoassay. The mRNA and protein expression of BMP-15 in mature granulosa cells was detected by real-time fluorescent PCR and Western blot.

RESULTSThirty-two patients were pregnant and the total pregnancy rate was 53.3%. Of them, 19 were pregnant and the total pregnancy rate was 47.5% in the control group, while 20 were pregnant and the total pregnancy rate was 65.0% in the treatment group. But there was no statistical difference between the two groups (P > 0.05). Compared with the control group, the Gn dosage was lower and the high quality embryo rate was higher in the treatment group, showing statistical difference (P < 0.05). There was no statistical difference in serum concentrations of E2, LH, or P on the HCG injection day, the number of retrieved oocytes, or the fertilization rate (P > 0.05). Compared with the control group, FSH concentrations in the follicular fluid were significantly lower and LH concentrations were significantly higher in the treatment group (P < 0.05). The LH concentrations in the follicular fluid were significantly higher in pregnant patients than non-pregnant patients, showing statistical difference (P < 0.05).There was no statistical difference in E2, T, or P concentrations (P > 0.05). The mRNA and protein expression of BMP-15 in granulosa cells was higher in the treatment group than in the control group (P < 0.05). It was also higher in pregnant patients than non-pregnant patients, showing statistical difference (P < 0.05).

CONCLUSIONDuring the IVF-ET process, BTR could elevate the quality of oocytes, and increase the sensitivity of ovarian follicles to exogenous Gn, which was correlated with the mRNA and protein expression of BMP-15 in granulosa cells, and changing concentrations of FSH and LH.

Adult ; Bone Morphogenetic Protein 15 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Embryo Transfer ; Estradiol ; blood ; metabolism ; Female ; Fertilization in Vitro ; Follicle Stimulating Hormone ; metabolism ; Follicular Fluid ; metabolism ; Humans ; Luteinizing Hormone ; blood ; metabolism ; Oocytes ; drug effects ; Pregnancy ; Progesterone ; blood ; metabolism ; Testosterone ; metabolism ; Young Adult

OBJECTIVETo study the relationship between collgen (Col) IV, VEGF secreted by the tumor cells and vasculogenic mimicry (VM).

METHODS158 bi-phase differential malignant tumor specimens were alloted and made into tissue microarray. These tissue microarray sections were stained with CD31, periodic acid-Schiff (PAS) and Col IV. Subsequently, distributive trait of Col IV and the difference of VEGF expression were analyzed.

RESULTSThe basement membrane of VM was PAS and Col IV positive. The expression of VEGF in bi-phase differential malignant tumor with VM was less than that in those without VM. The difference of VEGF expression in malignant melanoma and alveolar rhabdomyosarcoma was significant (P < 0.05).

CONCLUSIONCollgen IV and periodic acid-Schiff positive material take part in constructing the basement membrane of vasculogenic mimicry. The difference of the VEGF expression proves that vasculogenic mimicry can sustain the tumor blood supply.

Collagen Type IV ; analysis ; Humans ; Immunohistochemistry ; Neoplasms ; blood supply ; chemistry ; pathology ; Periodic Acid-Schiff Reaction ; Vascular Endothelial Growth Factor A ; analysis

In adipose tissues from sreater omentum of patients with type 2 diabetes,the mRNA and protein expressions of human rearranged immunoglobulin?light chain (HSIGVL) 022 were measured by the fluorescent quantitative RT-PCR and immunohistochemistry respectively.The results showed that mRNA and protein levels of HSIGVL022 were up-regulated in patients with type 2 diabetes.The mRNA level of HSIGVL022 was linearly correlated with insulin resistance index,suggesting that this gene may play a role in the pathogenesis of insulin resistance and type 2 diabetes.

OBJECTIVEBone-marrow derived mesenchymal stem cells (BMSC) have the potential to differentiate into endothelial cells. The aim of the study was to investigate the induction process of BMSC by B16 melanoma cells in vitro and to analyze the role of VEGF-a in the process.

METHODSA co-culture system containing BMSC and B16 melanoma cells based on transwell indirect model was established, and the induction process of BMSC by B16 melanoma cells was studied in vitro.

RESULTSBMSC were isolated from the bone marrow of C57 mice. BMSC expressed CD105, CD90, CD73, CD44 and CD166, and acquired expressin of endothelial phenotype markers including VEGFR-1, VEGFR-2 and Factor VIII after co-culture with B16 melanoma cells for 48 hours. The expression level of VEGFR-2 would be double and Factor VIII threefold more by extending the co-culture time to 72 hours. In the co-culture system, B16 melanoma cells also up-regulated the expression of VEGF-a.

CONCLUSIONSVEGF-a plays a significant role in the differentiation of BMSC into cells of endothelial phenotype, therefore, is important to tumor angiogenesis.

Animals ; Bone Marrow Cells ; cytology ; metabolism ; Cell Differentiation ; Cell Line, Tumor ; Coculture Techniques ; Endothelial Cells ; cytology ; metabolism ; Factor VIII ; metabolism ; Male ; Melanoma, Experimental ; metabolism ; pathology ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Mice ; Mice, Inbred C57BL ; Pilot Projects ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVETo investigate the mode of angiogenesis between highly invasive malignant melanoma and poorly invasive malignant melanoma by immunohistochemistry and periodic acid-Schiff stain (PAS) and to discuss whether the tumor cells in highly invasive malignant melanoma carry vasculogenic mimicry through self-metamorphosis, thus acquiring blood supply to sustain their growth.

METHODSThirty cases of highly invasive malignant melanoma and 30 cases of poorly invasive malignant melanoma were retrieved and reprocessed as tissue microarray for further investigations. The tissue microarray sections were then stained with CD34 and PAS; and the positivity rates were compared.

RESULTSThere was a significant difference between CD34 and PAS staining in highly invasive malignant melanoma (P < 0.01). The difference was not statistically significant in poorly invasive malignant melanoma (P > 0.05).

CONCLUSIONVasculogenic mimicry exists in some cases of highly invasive malignant melanoma. It is possible that the tumor cells can acquire blood supply to sustain growth and metastasize via this mechanism.

Antigens, CD34 ; analysis ; Antigens, Neoplasm ; Humans ; Immunohistochemistry ; Keratins ; analysis ; Melanoma ; blood supply ; metabolism ; pathology ; Melanoma-Specific Antigens ; Neoplasm Proteins ; analysis ; Neovascularization, Pathologic ; metabolism ; pathology

OBJECTIVETo observe the peripheral neurotoxicity of 1-bromopropane (1-BP) by developing an animal model of peripheral neuropathy through oral administration of 1-BP.

METHODSForty male Wistar rats were randomly and equally divided into low-dose group (200 mg/kg), medium-dose group (400 mg/kg), high-dose group (800 mg/kg), and control group. The rats in the low-dose, medium-dose, and high-dose groups were orally given 1-BP (dissolved in corn oil), while the rats in the control group were orally given an equal volume of corn oil. The oral administration (0.2 ml/100 g BW) was performed once per day, 5 days per week, for 16 consecutive weeks. Neurobehavioral indices including gait score, hindlimb grip strength, and hindlimb landing foot splay were recorded periodically. Hematological and biochemical parameters were also measured during and after 1-BP exposure.

RESULTSThe gait scores were significantly higher in the high-dose group (after 8 ∼ 16 weeks of 1-BP exposure), medium-dose group (after 14 ∼ 16 weeks of 1-BP exposure), and low-dose group (after 15 ∼ 16 weeks of 1-BP exposure) than in the control group (P < 0.05, P < 0.01). Compared with the control group, the high-dose group showed significantly decreased hindlimb grip strength after 9, 12, and 14 weeks of 1-BP exposure (P < 0.05, P < 0.01), with the hindlimbs paralyzed after 16 weeks of 1-BP exposure. After 16 weeks of 1-BP exposure, the hindlimb grip strengths of rats in the medium-dose and low-dose groups were decreased to 72.6% and 91.2% of the control value (P < 0.01, P < 0.05). Compared with the control group, the high-dose group showed significantly increased hindlimb landing foot splay after 12, 14, and 16 weeks of 1-BP exposure, and the medium-dose group showed significantly increased hindlimb landing foot splay after 14 and 16 weeks of 1-BP exposure (P < 0.05, P < 0.01). The high-dose and medium-dose groups showed significantly higher serum alanine aminotransferase (ALT) activity than the control group after 8 weeks of 1-BP exposure, and so did the low-dose group after 16 weeks of 1-BP exposure (P < 0.01).

CONCLUSIONThe nervous system is sensitive to the toxic effect of 1-BP, and 1-BP exposure can induce peripheral neuropathy in rats.

Animals ; Disease Models, Animal ; Hydrocarbons, Brominated ; administration & dosage ; toxicity ; Male ; Peripheral Nervous System Diseases ; chemically induced ; physiopathology ; Rats ; Rats, Wistar

OBJECTIVETo explore if vasculogenic mimicry (VM) exists in hepatocellular carcinoma (HCC) and to explain the clinical significance of VM.

METHODSNinety-nine HCC resection specimens with complete clinical and prognostic data were collected. Immunohistochemical staining of CD31 and CD105, hepatocyte and PAS staining of the histological preparations were conducted to explore if VM exists in those HCC.

RESULTS12.12% (12 specimens) of the 99 specimens exhibited evidence of VM. One of 40 HCC specimens (2.5%) which belong to Edmondson pathologic grade I-II exhibited VM; 11 of 59 HCC specimens which belong to Edmondson pathologic grade III-VI (18.64%) exhibited VM, the low differentiated HCC (grade III-VI) exhibited more VM specimens than the high differentiated HCC (grade I-II) (chi2=4.416, P < 0.05). The biological behavior of VM was assessed and the stages of the cancers, using the TNM (tumor, node, metastases) classification criteria, were analyzed. These parameters of the VM and non-VM groups were compared. The mean TNM stage of the VM group was not more advanced than that of the non-VM group. The hematogenous metastases ( lung, bone, peritoneum et al) between the 2 groups were compared, and in the VM group the hematogenous metastasis rate was higher (chi2=8.873, P < 0.01). Kaplan-Meier actuarial survival curves were used to compare the VM group (n = 12) with the non-VM group (n = 87). Median survival time of the VM group was 9 months and that of the non-VM group was 31 months. The VM group had a lower survival rate than the non-VM group (P < 0.01).

CONCLUSIONVM exists in HCC, and the higher invasive HCCs exhibit more VM than the less invasive HCCs. The HCC patients in the VM group had a higher rate of hematogenous metastases, a lower survival rate, and a poorer prognosis.

Adult ; Aged ; Carcinoma, Hepatocellular ; blood supply ; metabolism ; pathology ; Female ; Humans ; Liver Neoplasms ; blood supply ; metabolism ; pathology ; Male ; Microcirculation ; Middle Aged ; Neovascularization, Pathologic ; metabolism ; pathology

Six heavy metals, including As, Cu, Hg, Cd, Pb and Cr in Panax notoginseng were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES) combined with wet digestion method. The samples of P. notoginseng were collected in 12 different regions, including Yunnan and Guangxi Province. Green Standards of Foreign Trading Medicinal Plants & Preparations was used as the standard to evaluate the pollution status of As, Cu, Hg, Cd, Pb and Cr in P. notoginseng. The results showed that content of As and Cd exceeded the limit of the standard and the percentage was 32.4% and 29.7%, respectively, while Cu, Hg and Pb were all bellow the limit. The SPSS 16.0 software was used to analyze the data. The occurrence of contained heavy metals has been discussed.
China ; Drug Contamination ; Drugs, Chinese Herbal ; analysis ; Metals, Heavy ; analysis ; metabolism ; Panax notoginseng ; chemistry ; metabolism ; Soil Pollutants ; analysis ; metabolism

OBJECTIVETo investigate the effects of endostatin and doxycycline on microcirculation patterns in melanoma and their molecular mechanisms.

METHODSTo establish mouse B16 melanoma model by subcutaneous injection of B16 melanoma cell suspension. The mice were divided into 3 experimental groups and 1 control group. To treat the mice in the 3 experimental groups with endostatin, doxycycline, endostatin and doxycycline, respectively, and the control group without any treatment. The tumor volume was measured and recorded to make comparison of their growth rate. To assess the expression of MMP-2, MMP-9 and TIMP-2 by immunohistochemical staining. The three microcirculation patterns of endothelium-dependent vessels, mosaic vessels and vasculogenic mimicry were counted. The activity of MMP-2, MMP-9 between different groups was examined by gelatin zymography.

RESULTSTumor growth in the three experimental groups was statistically significantly slower than that in the control group. The expression of MMP-2, MMP-9 and TIMP-2 in each treated group was significantly different with that in the control group. The amount of three microcirculation patterns in three experimental groups was less than that of the control group, and the amount of MV and VM in each experimental group was significantly less than that in the control group. By gelatin zymography, the enzyme activity of MMP-9, actived-MMP-2 and MMP-2/proMMP-2 in ES, DOX and ES + DOX group was lower than that in the control group, but the enzyme activity of pro-MMP-2 among the four groups was not significantly different.

CONCLUSIONThe combined use of doxycycline and endostatin in melanoma can inhibit the expression of MMPs, influencing the formation of different microcirculation patterns in melanoma.

Animals ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Doxycycline ; pharmacology ; Drug Combinations ; Drug Synergism ; Endostatins ; pharmacology ; Female ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Melanoma, Experimental ; blood supply ; enzymology ; pathology ; Mice ; Mice, Inbred C57BL ; Microcirculation ; drug effects ; Microvessels ; pathology ; Neoplasm Transplantation ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism ; Tumor Burden ; drug effects