1.Research progress of chemical composition of taxane in Taxus canadensis and medicine source crisis solution.
Chun YANG ; Ling-Yi KONG ; Jun-Song WANG
China Journal of Chinese Materia Medica 2014;39(11):1961-1971
Taxus canadensis distributed mainly in North America, such as northern Minnesota, Newfoundland, south to Wisconsin and Pennsylvania. Its composition has been shown to be very different from other species, and in recent years, some new skeletons also have been found in Canada yew. Through analysis of the taxanes content on various Taxus plants containing taxanes, the results showed a higher content of taxol in T. canadensis. Based on the current research on T. canadensis (from the research results of the author in recent years, as well as from studies of scholars in the field), the paper outlined the research progress in recent years on the chemical constituents of taxane of T. canadensis and the spectral characteristics of various types of compounds. Besides, this paper analyzed the present research about solutions for the taxol drug source crisis.
Animals
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Bridged-Ring Compounds
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chemical synthesis
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chemistry
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pharmacology
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Humans
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Molecular Structure
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Plant Extracts
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chemical synthesis
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chemistry
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pharmacology
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Plants, Medicinal
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chemistry
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Taxoids
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chemical synthesis
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chemistry
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pharmacology
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Taxus
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chemistry
2.Inhibitory effects of small interference RNA targeting vascular endothelial growth factor on oxygen-induced retinal neovascularization
Yi-chun, KONG ; Bei, SUN ; Kan-xing, ZHAO ; Mei, HAN ; Yu-chuan, WANG
Chinese Journal of Experimental Ophthalmology 2013;31(9):823-828
Background Arresting the overexpression of vascular endothelial growth factor (VEGF) will be a new approach to the inhibition of neovascularization.RNA interference (RNAi) can inhibit the expression of specific gene,and its application in eye has little interference to other gene expression.Objective This study was to investigate the effect of small interference RNA (siRNA) targeting VEGF on the expression of VEGF and retinal neovascularization in oxygen-induced retinopathy (OIR) model.Methods psi-HITM/enhanced green fluorescent protein (EGFP)/VEGF siRNA was designed and prepared in vitro.Mouse endothelioma (EOMA) were cultured in DMEM without antibiotic and divided into 5 groups.The cells were incubated in DMEM only in the blank control group;while 1 μl of LipofectamineTM 2000 + psi-HITM/EGFP,1 μl LipofectamineTM 2000 + 40,50 or 60 nmol/L of psi-HITM/EGFP/VEGF siRNA was added into DMEM in the negative control group and siRNA groups,respectively.The expression of VEGF mRNA and protein was detected by real time PCR (RT-PCR) and Western blot.The optimal effective concentration of VEGF siRNA was assessed.OIR models were established in 48 7-day-old C57BL/6J mice by raising them at an oxygen concentration of (75±2) % for 5 days and then to normal air.The mice were randomized into the model group,null vector group and VEGF siRNA group.1 μl of a mixture of psi-HITM/EGFP or VEGF siRNA (60 nmol/L) and LipofectamineTM 2000 was intravitreally injected,respectively,in the null vector group and VEGF siRNA group.The normal mice were used as the normal control group.Expression of VEGF mRNA and protein in the mouse retinas was detected by RT-PCR and Western blot,respectively,and FITC-dextran stretched retinal preparation was examined to evaluate the neovascularization,and retinal sections were examined to quantify the number of vascular endothelial cell nuclei extending beyond the internal limiting membrane (ILM).Results The in vitro transfection test showed that the expression of VEGF mRNA and protein in the EOMA cells was significantly different among the blank control group,negative control group and 40,50,60 nmol/L VEGF siRNA groups (F =148.890,P < 0.001; F =306.960,P < 0.001),and the expression of VEGF mRNA was lower in different concentrations of VEGF siRNA groups than that in the blank control group (t=73.950,119.890,156.480,all at P<0.001).Also,the expression of VEGF protein was less in different concentrations of VEGF siRNA groups than that in the blank control group (t =15.452,23.344,42.119,all at P<0.001).The optimal inhibitory concentration of VEGF siRNA was 60 nmol/L.In vivo study determined that compared to the model group and null vector group,the non-perfusion zones and neovascular net in the retina were decreased,and the number of vascular endothelial cell nuclei extending beyond the ILM was less in the VEGF siRNA group.The relative expression level of VEGF mRNA in the retinas was 1.23±0.18,4.02±0.16,3.98±0.19 and 1.98±0.12 in the normal control group,model group,null vector group and VEGF siRNA group,respectively,with a significant difference among them (F=369.780,P<0.001),and the relative expression levels of VEGF mRNA in the model group and null vector group were higher than that in the normal control group (t=37.880,37.336,both P<0.001),and the expression of VEGF mRNA in the VEGF siRNA group declined by 50.8% (t=10.183,P<0.001).The difference in the expression levels of VEGF protein also was assayed among the various groups (F=408.980,P<0.001),and VEGF level in the retina was lowered by 68.0% in the VEGF siRNA group compared to the model group (t =11.473,P<0.001).However,VEGF level in the VEGF siRNA group remained at a high level in comparison with the normal control group (t =2.422,P<0.001).Conclusions Intravitreal injection of VEGF siRNA can attenuate retinal neovascularization by effectively downregulate the expression VEGF mRNA and protein in the retina.
3.Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin: Creation of an unnatural analogue with improved anticancer properties.
Dexiu YAN ; Jemma ARAKELYAN ; Teng WAN ; Ritvik RAINA ; Tsz Ki CHAN ; Dohyun AHN ; Vladimir KUSHNAREV ; Tsz Kiu CHEUNG ; Ho Ching CHAN ; Inseo CHOI ; Pui Yi HO ; Feijun HU ; Yujeong KIM ; Hill Lam LAU ; Ying Lo LAW ; Chi Seng LEUNG ; Chun Yin TONG ; Kai Kap WONG ; Wing Lam YIM ; Nikolay S KARNAUKHOV ; Richard Y C KONG ; Maria V BABAK ; Yudai MATSUDA
Acta Pharmaceutica Sinica B 2024;14(1):421-432
A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.
4.Economic burden of coronary heart disease and stroke attributable to hypertension in China.
Yi ZHAI ; Jian-Ping HU ; Ling-Zhi KONG ; Wen-Hua ZHAO ; Chun-Ming CHEN
Chinese Journal of Epidemiology 2006;27(9):744-747
OBJECTIVE1) To estimate annual direct medical costs of coronary heart disease (CHD) and stroke attributable to hypertension among Chinese adults aged 35-74 years in China, 2) to analyze the correlation between the hypertension awareness and hypertension treatment rate.
METHODS2003 National Health Services Survey (n = 93 018) was used to derive direct medical costs including costs for outpatient visits, physician services, inpatient stays, rehabilitation services, nurses fees, and medications. The medical costs of CHD and stroke attributable to hypertension were estimated by multiplying population attributable risk proportion by corresponding disease costs. Using 2002 National Nutrition and Health Survey (n = 148 804), the prevalence of hypertension awareness and hypertension treatment rate in 132 survey sites were calculated. Correlation was used to analyze the correlation between the two variables.
RESULTSThe direct medical costs of hypertension, CHD and stroke were 20.2, 15.7 and 24.3 billion Yuan, respectively. The medical costs attributable to hypertension were estimated at 19.1 billion Yuan (RMB), accounting for 47.7% of the total medical costs of the two chronic diseases. The prevalence of hypertension awareness is highly correlated with hypertension treatment rate (r = 0.9777, P < 0.0001).
CONCLUSIONThe economic burden of CHD and stroke attributable to hypertension is very high, reaching about 50% of the total medical costs of the two diseases. The prevalence of hypertension awareness could be used as an important indicator to evaluate the effectiveness of hypertension prevention and control at community level.
China ; Coronary Disease ; economics ; etiology ; Cost of Illness ; Data Collection ; Health Care Costs ; statistics & numerical data ; Humans ; Hypertension ; complications ; Stroke ; economics ; etiology
5.The role of dietary factors in chronic disease control in China.
Chun-Ming CHEN ; Wen-Hua ZHAO ; Zheng-Xiong YANG ; Yi ZHAI ; Yang-Feng WU ; Ling-Zhi KONG
Chinese Journal of Epidemiology 2006;27(9):739-743
OBJECTIVETo examine the association of dietary patterns with chronic diseases and their indicators.
METHODSUsing the data from 2002 National Nutrition and Health Survey, we divided the subjects into clusters according to their dietary patterns classified by different percentage of energy intake from cereal foods, carbohydrate and fat, respectively. The analysis of variance was used to identify the difference in chronic disease prevalence across clusters of subjects while controlling for age, gender and geographic regions. Logistic regression analysis was applied to calculate the odd ratios (OR) for association of chronic disease and each dietary pattern, after adjusted for age, gender, region, energy intake, leisure time.
RESULTSThe higher percentage of energy intake from cereals was significantly associated with lower body mass index (BMI), lower total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C). While it was significantly associated with lower risk for overweight/obesity, hypertension, high total cholesterol, high triglyceride (TG) and high LDL-C, but the prevalence of underweight was significantly higher in the cluster of subjects with cereal energy share more than 75%. The higher percentage of energy intake from fat was significantly associated with higher BMI, higher total cholesterol and higher LDL-C, which accordingly, was significantly associated with higher risk for overweight/obesity, hypertension, high total cholesterol, triglyceride and high LDL-C.
CONCLUSIONOur study confirmed the important role of dietary pattern in chronic disease control; in particular, appropriate percentage of energy intake from fat and cereals/carbohydrates are beneficial to control and prevention of chronic diseases.
China ; epidemiology ; Chronic Disease ; epidemiology ; prevention & control ; Diet ; Dietary Carbohydrates ; Dietary Fats ; Humans ; Nutrition Surveys ; Odds Ratio
6.Studies on biotransformation of arbutin by 4-hydroxy phenol in hairy root of Polygonum multiflorum.
Chun-yan YAN ; Zhang ZHANG ; Rong-min YU ; Ling-yi KONG
China Journal of Chinese Materia Medica 2007;32(3):192-195
OBJECTIVETo study the biotransformation of arbutin by 4-hydroxy phenol in hairy root of Polygonum multiflorum.
METHOD4-hydroxy phenol was used as substrate, the standard curve was made by HPLC, and the influences of the co-culture time, the concentration of substrate added and the volume of culture flasks on biotransformation of arbutin were measured by the index of the production yield and transform rate of arbutin.
RESULTArbutin could be detected from both of the cultures and medium. The correlation curve of arbutin: Y = 440740X - 1.473 (r = 0.9997). The production yield (2.22 g x L(-1)) and conversion ratio (81.45%) of arbutin reached the maximum amount as co-culture time at 72 h, substrate added in medium for 1100 mg x L(-1). Furthermore a large-scale culture of 3 L was also successful in our experiment.
CONCLUSIONIt was firstly to biosynthesis arbutin in hairy root of P. multiflorum. The production yield and trasfer rate of arbutin were increased largely. And large-scale production (3 L culture flask) of arbutin was achieved in the experiment and it would be valuable for the industrial production of arbutin by biotechnological method in the future.
Arbutin ; biosynthesis ; Biotransformation ; Hydroquinones ; metabolism ; Plant Roots ; growth & development ; metabolism ; Plants, Medicinal ; growth & development ; metabolism ; Polygonum ; growth & development ; metabolism ; Tissue Culture Techniques
7.Scene-trait coping style of military rescuers in Wenchuan earthquake.
Li-Yi ZHANG ; Xin-Yang SUN ; Ling-Ming KONG ; De-Hua TU ; Liang ZHANG ; Guang-Yao LI ; Zi-Xiang SONG ; Chun-Xia CHEN ; Gao-Feng YAO ; Jie SHI
Chinese Journal of Applied Physiology 2014;30(6):538-543
OBJECTIVEThis study aimed to explore the scene-trait coping style of military rescuers in Wenchuan earthquake in an effort to provide scientific evidences for mental intervention program for Chinese military personnel.
METHODSBy cluster sampling, a total of 151 military rescuers and 331 control servicemen were administered the military personnel scene-trait coping style scale (MPSTCSS).
RESULTSAll active coping factor scores, and passive coping factor scores of affection, health and economy in the rescuer group were significantly higher than those in control group (P < 0.05). The 21-above age subgroup, the 3-year plus service subgroup, and the officer subgroup had significantly higher active coping factor scores on military tasks, military experience and personal development than those of the 21-below age subgroup, 3-year minus service subgroup and the soldier subgroup, respectively (P < 0.05 or P < 0.01).
CONCLUSIONThe earthquake relief servicemen can cope with stressful situations better than control group by taking active coping style. The officers, servicemen older than 21 years, and servicemen with more service duration than 3 years could usually take active coping style.
Adaptation, Psychological ; Disasters ; Earthquakes ; Humans ; Military Personnel ; psychology ; Stress, Psychological
8.Effects of vitamin E on expression of PS-1 and production of Abeta in the hippocampus of female senile rats.
Ya-kun KONG ; Lan-chun YAO ; Chang-zhu LU ; Yi SUN ; Jiang NI
Chinese Journal of Applied Physiology 2007;23(2):237-240
AIMTo observe the expression of Presenilin-1 (PS-1) and production of amyloid beta-protein (Abeta) in hippocampus of female senile rats and to investigate the effect of vitamin E(VE) on preventing Alzheimer's disease after menopause.
METHODSThe animal model was established using female senile rats. Experimental groups (n=8) were respectively given different doses of VE(5 mg/kg, 15 mg/kg, 60 mg/kg) per day. The expression of PS-1 in hippocampus was detected by immunohistochemistry, the level of Abeta in hippocampus was measured by Radioimmunoassay, and neuronal ultrastructure in hippocampal DG area was observed using transmission electron microscope.
RESULTSThe expression of PS-1 in rat hippocampus of senile control group was stronger than that of adult control group. PS-1 expressed weakly in three medication groups along with augmentation of dosage. The levels of Abeta were found to correlate statistically with the expression of PS-1. The content of Abeta in VE groups was significantly decreased compared to that in senile control group (P < 0.01). There were some changes in the neuronal ultrastructure of senile rats. Neurons were gradually recovered in VE groups.
CONCLUSIONVE may depress the production of Abeta by regulating the expression of PS-1, reducing neuronal injuries. VE may play a role in neuronal protection.
Aging ; Alzheimer Disease ; metabolism ; Amyloid beta-Peptides ; metabolism ; Animals ; Female ; Hippocampus ; drug effects ; metabolism ; Presenilin-1 ; metabolism ; Rats ; Rats, Wistar ; Vitamin E ; pharmacology
9.Sexual dimorphisms of dopaminergic neurons in rat substantia nigra.
Yuan-Yi MA ; Shu-Zhen KONG ; Li-Jiang YANG ; Jin-Lan MENG ; Le-Chun LV ; Min HE
Acta Physiologica Sinica 2007;59(6):753-758
There are sex differences in some brain areas in mammalians. Parkinson's disease (PD), caused by the mesencephalic substantia nigra (SN) dopaminergic neuronal loss, displays sexual difference, i.e., the incidence is higher and the symptoms are more intense in males than that in females. However, it has not been known whether sexual dimorphisms exist in the SN. Sixty adult Sprague-Dawley rats were randomly divided into 5 groups: (1) Female intact group (F-INT group); (2) Male intact group (M-INT group); (3) Ovariectomized group (OVX group); (4) Castration group (CAST group); (5) Ovariectomized + estrogen-replaced group (OVX-E(2) group): The rats received sequentially physiological dose of estrogen for 3 d from the 7th day after ovariectomization. P50 auditory evoked potential (P50) was recorded for 14 d from electrodes inserted in the rat right SN in quiet and awake state. After recording, the brain tissues were dissected and the tyrosine hydroxylase (TH)-expressing neurons in the compact zone of the SN were counted using immunohistochemical method. The results showed that the number of TH-positive (TH(+)) cells in the SN of normal male animals was less than that in normal female rats (P<0.05), and the T/C ratio of P50 in normal males was significantly less than that in normal females (P<0.01), indicating that there exists sexual difference in function and structure in the SN. No differences in the T/C ratio of P50 or the number of TH(+) cells were found between M-INT and CAST groups. The T/C ratio of P50 and the number of TH(+) cells in the SN in OVX group were reduced significantly compared with those in F-INT group (P<0.01). There was no significant difference in the T/C ratio of P50 and the number of TH(+) cells in the SN between OVX- E(2) and F-INT groups 15-20 d after estrogen replacement, suggesting that estrogen can promote the survival and functional recovery of dopaminergic neurons in the SN. The results suggest that there exist sex-specific differences in the dopaminergic neurons in the SN structurally and functionally. The difference of estrogen level in cerebra between male and female animals may account for the sexual differences. Endogenous estrogen plays an important role in maintaining the integrity and modulating the functional activity of dopamine system in the SN.
Animals
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Dopaminergic Neurons
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cytology
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Estrogens
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pharmacology
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Evoked Potentials, Auditory
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Female
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Male
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Orchiectomy
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Ovariectomy
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Rats
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Rats, Sprague-Dawley
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Sex Characteristics
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Substantia Nigra
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cytology
10.Effect of nutritional status during infancy and childhood on the risk of overweight and obesity in adulthood.
Wen-hua ZHAO ; Zheng-xiong YANG ; Yi ZHAI ; Ling-zhi KONG ; Chun-ming CHEN
Chinese Journal of Epidemiology 2006;27(8):647-650
OBJECTIVETo examine the association between fetal nutritional status and overweight and obesity in their adulthood and to provide evidence for formulation of the strategy on preventing low birth weight.
METHODSUsing data from 2002 Nationwide Nutrition and Health Survey to set up a case-control method in order to compare body mass index(BMI), prevalence of overweight and obesity as well as to calculate odds ratio of overweight and obesity of case group compared with control group. Three case groups were selected from those who were born in 1959, 1960,1961 respectively, and the controls were those who were born in 1964.
RESULTSThe health consequence of being famines on adulthood was evident in women. Means of BMI in women were significantly higher in three case groups than that in control group(P<0.01). After adjustment on geographic regions, the prevalence of overweight in women was significantly higher in three case groups than that in control group(P< 0.01). The prevalence rates of obesity were significantly higher in 1959, 1960 groups than 1964 group(P< 0.05). The odds ratios of overweight of women in three case groups were 28.9% (95% CI:1.063-1.565), 37.2% (95% CI:1. 136-1.658) and 35.2% (95% CI: 1. 103-1.657) respectively, all higher than that in the control group. The odds ratios of obesity of women born in 1959, 1960 groups were 46.5% (95% CI: 1.088-1.972) and 39.6% (95% CI: 1.039- 1.876) respectively, higher than that in the 1964 group. However, such differences were not found in men.
CONCLUSIONHigher risks of overweight and obesity in women were caused by malnutrition during their fetal lives. A strategy on preventing low birth weight should be formulated by the government to prevent the chronic disease in adulthood.
Adult ; Case-Control Studies ; China ; epidemiology ; Female ; Humans ; Infant Nutritional Physiological Phenomena ; Infant, Low Birth Weight ; Infant, Newborn ; Male ; Nutritional Status ; Obesity ; epidemiology ; Overweight ; epidemiology ; Prevalence ; Risk