[Epidemiological Features of Lung Cancer Mortality between 1990 and 2016 in Xuanwei City,Yunnan Province].

Objective To describe the trend of lung cancer mortality in Xuanwei City,Yunnan Province,from 1990 to 2016 and provide scientific evidence for the prevention and control of lung cancer in Xuanwei.Methods Mortality data from the 2nd(year 1990-1992)and 3rd(year 2004-2005)Retrospective Survey on Causes of Death,and the Routine Death Registration System(year 2011-2013 and 2014-2016)in Xuanwei were used in this study.We calibrated the missing report of the mortality data for the corresponding periods,calculated the crude mortality rates,standardized mortality rates and corresponding 95% CI of different types of lung cancers in the above four periods.Results The crude mortality rates of all lung cancers in Xuanwei for these four periods(1990-1992,2004-2005,2011-2013,and 2014-2016)were 34.0/100 000,89.8/100 000,102.3/100 000 and 87.2/100 000 respectively.The standardized morality rate of lung cancer remain high in Xuanwei although it has been decreasing since 2004.Morality rates of lung cancer for most age groups showed decreasing trends.The decrease has been statistically significant in the ≤ 40 year group since 2014.Except for Longchang,the standardized mortality rates have decreased in all other townships with high lung cancer prevalence.Conclusions Although the mortality rate of lung cancer remains high in Xuanwei,it has shown a decreasing trend since 2004.The decrease in lung cancer mortality in populations younger than 40 years is statistically significant.

[Icariin and its pharmaceutical efficacy: research progress of molecular mechanism].

Icariin is one of the key active components of Epimedium species, which is most widely applied to supplement the kidney in traditional Chinese medicine. Scientific research has found that icariin possesses extensive therapeutic effects such as protecting neurons from injury, promoting growth of neuronal synapse, improving sexual dysfunction and bone morphogenesis, as well as anti-inflammation, anti-tumor and anti-depression functions. Considering that molecular mechanism is the fundamental basis for pharmaceutical efficacy of icariin, in this article, the authors retrospectively retrieved 122 scientific papers recorded in the PubMed database with "icariin" in the title from January 1, 1995 to January 5, 2011. It was found that icariin has been closely highlighted in the intervention of p38 mitogen-activated protein kinases and phosphatidylinositol 3-kinase/Akt signal pathways, inhibition of phosphodiesterase 5, and regulation of nuclear receptors. Besides, the authors also discussed the main orientation for molecular mechanism of icariin in future research.

[Effects of active ingredients in three kidney-tonifying Chinese herbal drugs on gene expression profile of bone marrow stromal cells from a rat model of corticosterone-induced osteoporosis].

OBJECTIVE: To observe the effects of icariin, psoralen and oleanolic acid, the three active ingredients of Yinyanghuo (Herba Epimedii Brevicornus), Buguzhi (Fructus Psoraleae) and Nuzhenzi (Fructus Ligustri Lucidi), respectively, on gene expression profile of bone marrow stromal cells (BMSCs) from rats with corticosterone-induced osteoporosis. METHODS: Fifty Sprague-Dawley rats were randomly divided into normal control group, untreated group, icariin group, psoralen group and oleanolic acid group (the last three groups are called treatment groups). Rats in untreated group and treatment groups were subcutaneously injected with corticosterone once a day for 14 d while rats in normal control group were injected isodose of olive oil. Rats in the treatment groups were intragastrically administered with icarrin, or psoralen, or oleanolic acid at 20 mg/(kg·d), respectively, 5 d prior to modeling for 19 d. The body weight of rats was recorded on the 1st, 4th, 7th, 11th, and 14th day after modeling, respectively. All rats were sacrificed and the fourth lumbar vertebrae were harvested for micro-CT scanning to evaluate bone mass. BMSCs were obtained ex vivo by the methods of bone marrow adherent culture. The mRNAs of BMSCs were detected by using gene chip technique on the 7th day of culture. RESULTS: There was no significant difference in body weight of rats between untreated group and treatment groups. Micro-CT showed no significant difference in lumbar vertebral morphometry between the untreated and the normal control, or the untreated and treatment groups. In microarray, icariin, psoralen and oleanolic acid changed expressions of 11, 12 and 15 genes compared to the normal level, respectively. These three active ingredients all acted on 5 genes involving osteoblast differentiation, cell cycle regulation, cell metabolism and Notch signal pathway. CONCLUSION: Traditional Chinese herbal drugs with the effect of tonifying the kidney may promote BMSCs to differentiate into osteoblasts by regulating BMSCs cycles and cell metabolism, and show therapeutic effect on osteoporosis. However, the exact mechanisms need to be further studied.

Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5.

Neural stem cells (NSCs) harbor the potential to differentiate into neurons, astrocytes, and oligodendrocytes under normal conditions and/or in response to tissue damage. NSCs open a new way of treatment of the injured central nervous system and neurodegenerative disorders. Thus far, few drugs have been developed for controlling NSC functions. Here, the effect as well as mechanism of oleanolic acid (OA), a pentacyclic triterpenoid, on NSC function was investigated. We found OA significantly inhibited neurosphere formation in a dose-dependent manner and achieved a maximum effect at 10 nM. OA also reduced 5-ethynyl-2'-deoxyuridine (EdU) incorporation into NSCs, which was indicative of inhibited NSC proliferation. Western blotting analysis revealed the protein levels of neuron-specific marker tubulin-ßIII (TuJ1) and Mash1 were increased whilst the astrocyte-specific marker glial fibrillary acidic protein (GFAP) decreased. Immunofluorescence analysis showed OA significantly elevated the percentage of TuJ1-positive cells and reduced GFAP-positive cells. Using DNA microarray analysis, 183 genes were differentially regulated by OA. Through transcription factor binding site analyses of the upstream regulatory sequences of these genes, 87 genes were predicted to share a common motif for Nkx-2.5 binding. Finally, small interfering RNA (siRNA) methodology was used to silence Nkx-2.5 expression and found silence of Nkx-2.5 alone did not change the expression of TuJ-1 and the percentage of TuJ-1-positive cells. But in combination of OA treatment and silence of Nkx-2.5, most effects of OA on NSCs were abolished. These results indicated that OA is an effective inducer for NSCs differentiation into neurons at least partially by Nkx-2.5-dependent mechanism.

Mechanisms Underlying the Antiproliferative and Prodifferentiative Effects of Psoralen on Adult Neural Stem Cells via DNA Microarray.

Adult neural stem cells (NSCs) persist throughout life to replace mature cells that are lost during turnover, disease, or injury. The investigation of NSC creates novel treatments for central nervous system (CNS) injuries and neurodegenerative disorders. The plasticity and reparative potential of NSC are regulated by different factors, which are critical for neurological regenerative medicine research. We investigated the effects of Psoralen, which is the mature fruit of Psoralea corylifolia L., on NSC behaviors and the underlying mechanisms. The self-renewal and proliferation of NSC were examined. We detected neuron- and/or astrocyte-specific markers using immunofluorescence and Western blotting, which could evaluate NSC differentiation. Psoralen treatment significantly inhibited neurosphere formation in a dose-dependent manner. Psoralen treatment increased the expression of the astrocyte-specific marker but decreased neuron-specific marker expression. These results suggested that Psoralen was a differentiation inducer in astrocyte. Differential gene expression following Psoralen treatment was screened using DNA microarray and confirmed by quantitative real-time PCR. Our microarray study demonstrated that Psoralen could effectively regulate the specific gene expression profile of NSC. The genes involved in the classification of cellular differentiation, proliferation, and metabolism, the transcription factors belonging to Ets family, and the hedgehog pathway may be closely related to the regulation.

Different molecular targets of Icariin on bMSCs in CORT and OVX -rats.

Icariin (ICA) is an active component of Herba Epimedium effective in preventing osteoporosis. Bone mesenchymal stem cells (bMSCs) are an important target by which ICA promotes osteogenesis. However, its molecular mechanisms are poorly defined. In the present study, we induced osteoporosis in rats by corticosterone (CORT) and ovariectomy (OVX), treated both with ICA for 2 weeks or 3 months. As results, both models displayed bone loss tendency within 2 weeks and a significant bone loss after 3 months. ICA promoted bMSCs diffenentiation from CORT rat, and increased the secretion of osteocalcin, collagen I, runt-related transcription factor 2 in OVX model. Gene profile revealed a marked shift of gene expression by ICA, with much more significance in CORT rats. These potential molecular targets were involved in cell communication, adhesion, cycle and cytokines secretion. But very few genes overlapped in these two models, suggesting the effects and molecular mechanisms of ICA on osteoporosis might be pathogenesis-dependent. However, the Notch signaling pathway was common in both models, and should be paid close attention to for further study.

Icariin improves cognitive deficits and activates quiescent neural stem cells in aging rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Icariin represents an important active component in Herba Epimedii, which is a famous Chinese herbal medicine that is widely used to treat some age-related diseases in oriental countries. OBJECTIVE: The aim of this work was to investigate the effects of icariin on cognitive function in natural aging rats, and then to explore its mechanism by investigating the activation of quiescent neural stem cells (NSCs) in the hippocampus. MATERIALS AND METHODS: Sprague-Dawley rats that were 18 months of age were divided into two groups including treated rats (i.e., icariin was administered from the age of 18 months to 21 months) and control rats (i.e., only saline was administered). The Morris water maze (MWM) tasks were then employed to measure spatial learning and memory. Subsequently, AraC was infused into the brain with osmotic minipumps in order to destroy proliferative stem cells primarily leaving quiescent NSCs. After seven days of recovery, 5-bromodeoxyuridine (BrdU) was co-labeled with markers for NSC to identify NSCs. RESULTS: The results from the MWM indicated that icariin has a beneficial effect on cognitive function in aging rats. In addition, by double-labeling BrdU and glial fibrillary acidic protein (GFAP), our findings indicated that NSC activation is markedly increased in the icariin-treated rats compared to control rats. For example, a much greater increase was produced in BrdU and highly polysialylated neural cell adhesion molecule (PSA-NCAM) and BrdU and Olig2 double-labeled cells following icariin treatment. CONCLUSION: Our findings suggest that icariin represents a promising candidate for the modulation of aging. Therefore, icariin administration may effectively prevent or delay the onset of age-related cognitive degeneration, and its capability to activate quiescent NSCs may potentially be one of its mechanisms.

Oleanolic acid exerts an osteoprotective effect in ovariectomy-induced osteoporotic rats and stimulates the osteoblastic differentiation of bone mesenchymal stem cells in vitro.

OBJECTIVE: Oleanolic acid (OA) and its glycosides have been reported to prevent bone loss by inhibiting the formation of osteoclasts. However, because bone formation and resorption are balanced processes in bone metabolism, no studies have described the effect of OA on osteogenesis. The aim of the present study was to evaluate the osteoprotective effect of OA in rats with ovariectomy (OVX)-induced osteoporosis and to search for the molecular targets of OA in bone mesenchymal stem cells (bMSCs). METHODS: Two-month-old female mice that underwent OVX were treated with OA (20 mg/kg a day). After 2 weeks and after 3 months, bone mass was evaluated by micro-CT, morphometry, and immunohistochemical detection. In addition, the expression of 256 genes was measured via microarray and confirmed by real-time reverse transcription-polymerase chain reaction. The effects of OA on the activities of bMSCs were also observed in vitro using alkaline phosphatase and cell proliferation assays. RESULTS: Micro-CT displayed only a tendency for bone loss at 2 weeks but a decrease in bone mass at 3 months after OVX. OA treatment increased osteoblast number, increasing osteocalcin and runt-related protein 2 protein levels in vivo and facilitating the osteoblastic differentiation of bMSCs in vitro at doses of 10(-6) and 10(-5) M. Gene expression profile analysis revealed that OVX caused a marked dysregulation of gene expression, especially at 2 weeks, some of which was rescued by OA. Few of these genes overlapped, but their functions were involved in the Notch signaling pathway between two phases of the osteoporotic process. CONCLUSIONS: OA exerts an osteoprotective effect in OVX-induced osteoporotic rats and stimulates the osteoblastic differentiation of bMSCs in vitro. The molecular mechanism of this effect might be related to the Notch signaling pathway and requires further investigation.

Alteration of the proteome profile of the pancreas in diabetic rats induced by streptozotocin.

Type 1 diabetes mellitus (T1DM) is receiving increased attention. To obtain a better understanding of the mechanism underlying T1DM, we performed a proteomic study on a rat model induced by streptozotocin. Pancreatic proteins were separated by two-dimensional gel electrophoresis. Eighteen protein spots were differentially expressed (P<0.05) with 2-fold or more increased or decreased intensity in the diabetic rats as compared with controls, of which 11 protein spots were up-regulated and 7 protein spots were down-regulated. These protein spots were successfully identified by liquid chromatography-electrospray ionization tandem mass spectrometry. The 60 kDa heat shock protein, the carbonyl reductase 1 (Cbr1), the hydroxyacyl-CoA dehydrogenase, Δ(3,5),Δ(2,4)-dienoyl-CoA isomerase, the elongation factor 1-δ, the 26S protease regulatory subunit 7 and the transitional endoplasmic reticulum ATPase were up-regulated, while the 78 kDa glucose-regulated protein, peroxiredoxin 4 and plakoglobin were down-regulated. The expression change of Cbr1 which is closely related to diabetic complications was further validated by western blotting. Our results and those of the bioinformatics analysis suggest that oxidative stress, the Wnt pathway, fatty acid degradation and glucose transport may be closely related to T1DM.