Mechanism of action of icaritin on uterine corpus endometrial carcinoma based on network pharmacology and experimental evaluation.

Background: Uterine corpus endometrial carcinoma (UCEC) belongs to a group of epithelial malignant tumors. Icaritin is the main active compound of Epimedii Folium. Icaritin has been utilized to induce UCEC cells to death. Methods: We wished to identify potential targets for icaritin in the treatment of UCEC, as well as to provide a groundwork for future studies into its pharmacologic mechanism of action. Network pharmacology was employed to conduct investigations on icaritin. Target proteins were chosen from the components of icaritin for UCEC treatment. A protein-protein interaction (PPI) network was established using overlapping genes. Analyses of enrichment of function and signaling pathways were undertaken using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively, to select "hub genes". Finally, experiments were carried out to ascertain the effect of icaritin on endometrial cancer (HEC-1-A) cells. Results: We demonstrated that icaritin has bioactive components and putative targets that are therapeutically important. Icaritin treatment induced sustained activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt pathway) and inhibited growth of HEC-1-A cells. Conclusion: Our data provide a rationale for preclinical and clinical evaluations of icaritin for UCEC therapy.

Incidence and related clinical factors of falls among older Chinese veterans in military communities: a prospective study.

[Purpose] The aim of this study was to determine fall incidence and explore clinical factors of falls among older Chinese veterans in military communities. [Subjects and Methods] We carried out a 12-month prospective study among 13 military communities in Beijing, China. Fall events were obtained by self-report to military community liaisons and monthly telephone interviews by researchers. [Results] Among the final sample of 447 older veterans, 86 fell once, 25 fell twice or more, and 152 falls occurred altogether. The incidence of falls and fallers were 342/1,000 person-years and 249/1,000 person-years. In Cox regression models, independent clinical factors associated with falls were visual acuity (RR=0.47), stroke (RR=2.43), lumbar diseases (RR=1.73), sedatives (RR=1.80), fall history in the past 6 months (RR=2.77), multiple chronic diseases (RR=1.53), multiple medications (RR=1.34), and five-repetition sit-to-stand test score (RR=1.41). Hearing acuity was close to being statistically significant. [Conclusion] The incidences of falls and fallers among older Chinese veterans were lower than those of Hong Kong and western countries. The clinical risk factors of falls were poor senses, stroke, lumbar diseases, taking sedatives, fall history in the past 6 months, having multiple chronic diseases, taking multiple medications, and poor physical function. The preventive strategies targeting the above risk factors are very significant for reducing falls.

Factors Associated with Performance-based Physical Function of Older Veterans of the PLAAF: A Pilot Study.

[Purpose] This study investigated the factors associated with performance-based physical function of older veterans of the People's Liberation Army Air Force of China (PLAAF). [Subjects and Methods] A cross-sectional survey of 146 older veterans of the PLAAF was carried out. Their physical function was measured using the Chinese Mini-Physical Performance Testing (CM-PPT). The demographics and health status (including physical measures, blood chemical tests, chronic diseases, and number of morbidities) were collected from health examination reports and computer records of case history. Cognition was measured using the Mini-Mental Status Examination (MMSE). [Results] In multiple linear regressions, age, MMSE, Parkinsonism, and chronic obstructive pulmonary disease were independently associated with CM-PPT, while previous stroke and albumin level reached borderline statistical significance. The association between the number of morbidities and CM-PPT was significant after adjustment for MMSE and demographics. The CM-PPT of low (0 or 1), medium (2 to 4) and high count (5 or more) morbidities were 11.3±3.9, 10.2±4.1, 6.1±3.8 respectively, and the difference among these three groups was significant. [Conclusion] Some modified conditions and the number of chronic diseases might be associated with the physical function of older veterans of the PLAAF.

[Identification of novel genes related to glioma by oligonucleotide microarray].

OBJECTIVE: To identify the genes differentially expressed in development of human glioma, and to study the expression of some genes in different grade gliomas. METHODS: Oligonucleotide microarray (including 218 genes related to neural system development) was adopted and hybridized with probes which were prepared from the total RNAs of glioma specimens and normal brain tissues. Differentially expressed genes between the normal tissues and glioma tissues were assayed after scanning oligonuceltide microarray with ScanArray 4000, and some of these genes such as smad1, Hmp19 and TRIP3 were verified by real-time quantitative PCR(real-time-Q-PCR) method. RESULTS: In comparison with the genes in the normal brain tissue, 5 down-regulated and 5 up-regulated genes in glioma specimens were revealed by means of microarrays, and the expression of smad1, Hmp19 and TRIP3 were verified by real-time-Q-PCR assay. CONCLUSION: Multiple genes play important roles in development of glioma. cDNA microarray technology is a powerful technique in screening for differentially expressed genes between glioma tissues and normal brain tissues. This study is helpful for judgement of invasion and prognosis of gliomas, and provides more target genes for targeted therapy.

Effects of dietary supplementation of certain nutrients on maze performance and biochemical indices in mice after exposure to high +Gz.

OBJECTIVE: To explore the possible effects of nutritional supplements on brain function as reflected by Water Maze test performance in mice after +Gz exposure. METHOD: Mice were arranged into control group (group A), +Gz group without nutritional supplementation (group B) and +Gz plus nutritional supplementation group (group C). Each group contains 12 mice. Mice in group A were not exposed to +Gz while mice in both group B and group C were exposed to 8 min + 10 Gz. Distilled water was gavaged to group B mice 3 h before +Gz exposure. On the day before +Gz exposure pyridoxol fortified water was given and 3 h before exposure mixed amino acids solution were gavaged to group C mice. Water Maze test was done and scores were recorded in all groups. After the Water Maze test was completed, blood was collected through the eyes for serum amino acid determinations and brain tissue was collected by decollation for monoamine determination and gamma-glutamyl transferase (GGT) activity evaluation. RESULT: After +Gz exposure, longer completion time and more mistakes were observed in Water Maze test in group B as compared with group A and a trend of improvement in group C was noticed. The ratio of brain 5-HT to dopamine (DA) was significantly reduced in group C as compared with group B. Gamma glutamyl transferase (GGT) activity in brain tissue in group C and group B increased significantly. CONCLUSION: High sustained +Gz exposure significantly reduces Water Maze test performance in mice (longer completion time and more mistakes). It seems that there is a trend of improvement in Water Maze performance in mice in dietary nutritional supplementation group, which might be due to significant reduction in ratio of brain 5-HT to DA in mice with nutritional supplementation.

[Effects of nutritional intervention on brain functions and its related biochemical indexes in mice exposed to high +Gy].

OBJECTIVE: To study the effects of nutritional intervention on changes of monoamines in rats brain, certain amino acids in rats serum and maze behaviors caused by high +Gy exposure. METHOD: The mice were arranged into control group (Group A), +Gy group (Group B) and +Gy nutritional intervention group (group C). Group A was not exposed to +Gy. Both Group B and group C were exposed to +10 Gy for 8 min. Three hours before +Gy exposure distilled water was given to mice in group B by gavage. The day before exposure pyridoxal fortified water was given and 3 h before exposure mixed amino acids solution were given by gavage to group C. Maze test scores were recorded for all groups. After the maze test was completed, blood was collected through the eyes for serum amino acids and brain tissue was collected by decollation for monoamines and gamma-glutamyl transferase (GGT) activity determinations. RESULT: After +Gy exposure maze test scores and brain NE concentrations decreased and abnormal behaviors were found. While other monoamine transmitters increased significantly. In group C maze behaviors improved and biochemical changes induced by +Gy exposure alleviated. CONCLUSION: High +Gy exposure can induce changes of neural transmitters coming from nutritional metabolites in central nervous system. As a result, brain functions are affected. Nutritional intervention can alleviate this negative effect to some extent.