Inhibition of caffeine biosynthesis in tea (Camellia sinensis) and coffee (Coffea arabica) plants by ribavirin

The effects of ribavirin, an inhibitor of inosine-5'-monophosphate (IMP) dehydrogenase, on [8-(14)C]inosine metabolism in tea leaves, coffee leaves and coffee fruits were investigated. Incorporation of radioactivity from [8-(14)C]inosine into purine alkaloids, such as theobromine and caffeine, guanine residues of RNA, and CO(2) was reduced by ribavirin, while incorporation into nucleotides, including IMP and adenine residues of RNA, was increased. The results indicate that inhibition of IMP dehydrogenase by ribavirin inhibits both caffeine and guanine nucleotide biosynthesis in caffeine-forming plants. The use of IMP dehydrogenase-deficient plants as a potential source of good quality caffeine-deficient tea and coffee plants is discussed.     

The effects of two levels of caffeine ingestion on excess postexercise oxygen consumption in untrained women

The effects of two levels of caffeine ingestion (5 mg.kg-1, CAF1, and 10 mg.kg-1, CAF2) on postexercise oxygen consumption was investigated in six untrained women aged 20.5 (SEM 0.5) years. After a test to determine maximal oxygen consumption (VO2max) each subject underwent three test sessions at 55% VO2max either in a control condition (CON) or with the CAF1 or CAF2 dose of caffeine. During exercise, oxygen consumption was found to be significantly higher in the CAF1 and CAF2 trials, compared to CON (P < 0.05). During the hour postexercise, oxygen consumption in CAF1 and CAF2 remained significantly higher than in CON (P < 0.05). At all times throughout the exercise, free fatty acid (FFA) concentrations were significantly higher in the caffeine trials than in CON. The FFA concentrations 1 h postexercise (+60 min) were further elevated above resting values for all three trials. Caffeine ingestion caused the greatest elevation above resting levels being 1.89 (SEM 0.19) mmol.l-1 and 1.96 (SEM 0.22) mmol.l-1 for the CAF1 and CAF2 trials, respectively. This was significantly higher (P < 0.0001) than the CON level which was 0.97 (SEM 0.19) mmol.l-1. Respiratory exchange ratio (R) values became significantly lower (P < 0.05) in CAF1 and CAF2 compared to CON at the onset of exercise and continued to decrease during the activity. Throughout the recovery period, R values were significantly lower for both caffeine trials compared to CON. The results of this study would suggest that caffeine is useful in significantly increasing metabolic rate above normal levels in untrained women during, as well as after, exercising at 55% VO2max.     

红茶对2型糖尿病小鼠肠道菌群分布的影响

探讨红茶对2型糖尿病（T2DM）小鼠肠道菌群分布的影响,为研究红茶在代谢性疾病的辅助治疗机制提供参考。

构建 T2DM小鼠模型,将其随机分为模型组（T2DM组）和茶水饲喂组（T2DM_T组）,取健康小鼠作为对照组（Control组）,每组各15只。实验终点收集3组小鼠粪便进行宏基因组测序,分析组间菌群差异;同时进行肝脏组织形态学检查,观察组织病理学改变。

与Control组和T2DM组相比,T2DM_T组拟杆菌门（F = 21.056,P＜0.001）、邓肯氏菌属（F = 13.330,P = 0.001）、乳杆菌属（F = 36.546,P＜0.001）和粘液乳杆菌属（F = 43.813,P＜0.001）的相对丰度增加,担子菌门（F = 8.676,P = 0.005）、Muribaculum（F = 8.151,P = 0.006）和肠球菌属（F = 4.271,P = 0.040）的相对丰度降低。与T2DM组小鼠相比,T2DM_T组小鼠肝细胞排列较为紧密,细胞空泡变性程度有所减弱。

红茶在一定范围内能调节T2DM模型小鼠肠道菌群结构和相对丰度,红茶水喂饲可减缓造模所致的T2DM小鼠肝脏细胞的损伤,其具体作用机制值得深入研究和探讨。

     

Coffee and tea consumption and risk of leukaemia in an adult population: A reanalysis of the Italian multicentre case-control study

BackgroundCoffee and tea are the most frequently consumed beverages in the world. Their potential effect on the risk of developing different types of malignancies has been largely investigated, but studies on leukaemia in adults are scarce.MethodsThe present investigation is aimed at evaluating the potential role of regular coffee and tea intake on the risk of adult leukaemia by reanalysing a large population based case-control study carried out in Italy, a country with a high coffee consumption and a low use of green tea. Interviewed subjects, recruited between 1990 and 1993 in 11 Italian areas, included 1771 controls and 651 leukaemia cases. Association between Acute Myeloid Leukaemia (AML), Acute Lymphoid Leukaemia, Chronic Myeloid Leukaemia, Chronic Lymphoid Leukaemia, and use of coffee and tea was evaluated by standard logistic regression. Odds Ratios (OR) were estimated adjusting for the following potential confounders: gender, age, residence area, smoking habit, educational level, previous chemotherapy treatment, alcohol consumption and exposure to electromagnetic fields, radiation, pesticides and aromatic hydrocarbons.ResultsNo association was observed between regular use of coffee and any type of leukaemia. A small protective effect of tea intake was found among myeloid malignancies, which was more evident among AML (OR = 0.68, 95%CI: 0.49–0.94). However, no clear dose-response relation was found.ConclusionThe lower risk of leukaemia among regular coffee consumers, reported by a few of previous small studies, was not confirmed. The protective effect of tea on the AML risk is only partly consistent with results from other investigations.     

Association of CELSR2, APOB100, ABCG5/8, LDLR,and APOE polymorphisms and their genetic risks with lipids among the Thai subjects

BackgroundHypercholesterolemia is a common cardiovascular risk factor. The aim of this study was to investigate the association of CELSR2 (rs629301), APOB100 (rs1367117), ABCG5/8 (rs6544713), LDLR (rs6511720), and APOE (rs429358, rs7412) polymorphisms, and their genetic risk scores with lipids among Thai subjects.MethodsA total of 459 study subjects (184 males, and 275 females) were enrolled. Blood pressure, serum lipids, and fasting blood sugar were measured. CELSR2 (rs629301), APOB100 (rs1367117), ABCG5/8 (rs6544713), and LDLR (rs6511720) polymorphisms were analyzed using PCR-HRM. APOE (rs429358, rs7412) polymorphism was analyzed using PCR-RFLP.ResultsTotal cholesterol (TC) levels were significantly higher in APOB100 AA genotype compared with GG, or AA + AG genotypes in total subjects. In addition, significantly higher concentrations of TC and low density lipoprotein cholesterol (LDL-C) were observed in APOE4 carriers compared to APOE2 carriers in total subjects, males, and females. The significantly higher concentrations of TC were observed in APOE4 carriers compared to APOE3 carriers in females. Moreover, the concentrations of TC, and LDL-C were significantly increased with genetic risk scores of APOB100, and APOE polymorphisms in total subjects, and females. There was no association between CELSR2 (rs629301), ABCG5/8 (rs6544713), and LDLR (rs6511720) polymorphisms and serum lipids.ConclusionAPOB100 (rs1367117), and APOE (rs429358, rs7412) but not CELSR2 (rs629301), ABCG5/8 (rs6544713), and LDLR (rs6511720) polymorphisms were associated with serum lipids. The cumulative risk alleles of APOB100 (rs1367117), and APOE (rs429358, rs7412) polymorphisms could enhance the elevated concentrations of TC, and LDL-C, and they may be used to predict severity of hypercholesterolemia among Thai subjects.     

Coffee and tea consumption during pregnancy and risk of childhood acute myeloid leukemia: A Childhood Leukemia International Consortium (CLIC) study

BackgroundDietary habits during pregnancy have been inconsistently linked to childhood acute myeloid leukemia (AML), given the putative intrauterine onset of the disease as a result of triggering events during the critical period of fetal hematopoiesis. We investigated the potential association of maternal coffee and tea consumption during pregnancy with childhood AML risk, pooling primary data from eight case-control studies participating in the Childhood Leukemia International Consortium.MethodsInformation on coffee and/or tea consumption was available for 444 cases and 1255 age- and sex-matched controls, on coffee consumption for 318 cases and 971 controls and on tea consumption for 388 cases and 932 controls. Categories for cups of daily coffee/tea consumption were created in order to explore potential dose-response associations. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression.ResultsAssociations were found neither in the analysis on coffee or tea nor in the analysis on coffee only consumption (any versus no). A positive association with increasing coffee intake was observed (>1 cup per day; OR: 1.40, 95% CI: 1.03–1.92, increment of one cup per day; OR: 1.18, 95% CI: 1.01–1.39). No associations were observed with tea consumption. Interaction analyses showed non-significant associations between coffee/tea and smoking. Hyperdiploidy was inversely associated with tea consumption, with other cytogenetic markers having no association with coffee/tea.ConclusionGiven the widespread consumption of caffeinated beverages among pregnant women, our finding is of important public health relevance, suggesting adverse effects of maternal coffee consumption during pregnancy in the offspring.     

PGM1 and TF subtypes and C3 polymorphisms in Continental Italy and Sardinia. Data on the world distribution of these genetic markers

PGM1, TF and C3 polymorphisms have been examined in two Italian samples, collected in continental Italy and in Sardinia (Cagliari). The PGM1 and TF subtypes were determined by isoelectric focusing while the C3 was studied by conventional methods. A significant difference in the gene frequencies of PGM1 and TF systems between our two samples has been observed. In addition, data on the world distribution of PGM1, TF and C3 polymorphisms have been presented.     

Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses

Background

L-theanine, an amino acid contained in green tea leaves, is known to block the binding of L-glutamic acid to glutamate receptors in the brain, and has been considered to cause anti-stress effects by inhibiting cortical neuron excitation. Both L-theanine and caffeine, which green tea contains, have been highlighted for their beneficial effects on cognition and mood.

Methods

In this study, we investigated the effects of orally administered L-theanine or caffeine on mental task performance and physiological activities under conditions of physical or psychological stress in humans. Fourteen participants each underwent three separate trials, in which they orally took either L-theanine + placebo, caffeine + placebo, or placebo only.

Results

The results after the mental tasks showed that L-theanine significantly inhibited the blood-pressure increases in a high-response group, which consisted of participants whose blood pressure increased more than average by a performance of a mental task after placebo intake. Caffeine tended to have a similar but smaller inhibition of the blood-pressure increases caused by the mental tasks. The result of the Profile of Mood States after the mental tasks also showed that L-theanine reduced the Tension-Anxiety scores as compared with placebo intake.

Conclusions

The findings above denote that L-theanine not only reduces anxiety but also attenuates the blood-pressure increase in high-stress-response adults.     

Association of different zinc concentrations combined with a fixed caffeine dose on plasma and tissue caffeine and zinc levels in the rat

Because caffeine and tissue levels of Zn are closely related, the objectives of this study were to determine the changes in plasma caffeine levels over a period of 5 h when different concentrations of Zn combined with a fixed concentration of caffeine were injected into the femoral vein of rats and to determine the relationship between tissue levels of caffeine and Zn at 5 h postinjection. Rats were divided into three groups: group 1, 220 μg caffeine; group 2,220 μg caffeine + 8 μg Zn/g body weight (BW); group 3, 220 μg caffeine +16 μg Zn/g BW. Blood from groups 1 and 3 was collected at 3 min, 30 min, 1h, 3h, and 5h to determine the pharmacokinetics of caffeine. All groups were killed at 5 h. Caffeine and Zn concentrations of the brain, kidney, heart, and liver of all groups were determined. The plasma-caffeine curve in group 3 showed a lower concentration at 3 min and a slower caffeine-elimination rate during the first 3 h. Brain and kidney caffeine levels remained constant in all groups, whereas caffeine levels were increased in the heart in group 2 and in the liver in group 3. Zn concentrations in the brain and kidney were lower in group 2 compared with groups 1 and 3 and higher in group 3 compared to groups 1 and 2. Zn concentration in the heart was the same among the three groups but was increased in the liver in group 3 compared to groups 1 and 2. Therefore, we concluded that caffeine combined with Zn affects caffeine pharmacokinetics. With caffeine intake, levels of Zn (16 μg/g BW) that are slightly higher than the daily requirements (12 μg/g BW) may prevent a reduction of Zn in tissue. In addition, caffeine’s effects on Zn concentration among organs are different.     

The association between two genetic polymorphisms in ITGB3 and increase risk of venous thromboembolism in cancer patients in Eastern Province of Saudi Arabia

Venous thromboembolism (VTE) is one of the major complications in most cancer patients leading to poor prognosis and short survival. Several common clinical risk factors coexist in cancer patients are used as risk predictive biomarkers to help in the management and prevention of VTE. These include cancer site and stage, chemotherapy regimen and elevated biological markers. However, Genetic polymorphisms in genes controlling coagulation and fibrinolysis are significantly associated with VTE if detected, then they might be more sensitive individual predictive biomarkers for VTE risk assessment. This study was conducted to evaluate the association between ITGB3 rs3809865 and rs5918 with VTE risk as well as monitor the effect of VTE on overall survival of these cancer patients. In this retrospective case-control study, 195 cancer patients’ formalin-fixed paraffin embedded tissue (FFPE) samples were collected (controls n = 157, case n = 38) using the stored data through Jan 2010 to Sep 2018 from King Fahad Specialist Hospital in Dammam. Samples were genotyped using TaqMan genotyping assay, then logistic regression analysis and Chi-square were used to predict the association between risk factors and VTE. Survival Comparison was tested by the log-rank test. Genetic polymorphisms in ITGB3 (rs3809865 and rs5918) found not to be associated with VTE increasing risk in cancer patients (p>0.05). While the advanced stage was potentially increasing the risk of VTE events (OR 5.1 CI 2.01–12.9p = 0.001). Patients with VTE showed a poor overall survival reflected by the median survival rate of only three years compared to seven years for cancer patients without VTE. This study highlighted the potential influence of VTE on prognosis and survival of cancer patients and raised the importance of exploring risk predictive biomarkers in our population. This will improve the risk prediction biomarkers leading to implementing safe and effective thrombosis prophylaxis strategies.     

The use of RAPD markers for detecting genetic diversity,relationship and molecular identification of Chinese elite tea genetic resources [<Emphasis Type="Italic">Camellia sinensis</Emphasis> (L.) O. Kuntze] preserved in a tea germplasm repository

The genetic diversity, relationship and molecular identification of 15 well known, widely planted traditional Chinese elite tea genetic resources [Camellia sinensis (L.) O. Kuntze] preserved in the China National Germplasm Hangzhou Tea Repository in the Tea Research Institute of the Chinese Academy of Agricultural Sciences located in Zhejiang province, China, were investigated using RAPD markers. A total of 1050 bands with an average of 52.5 bands per primer, 70 bands per genetic resource were generated by the 20 selected primers from the 15 tea genetic resources. In the total of 137 amplified products, 129 were polymorphic, corresponding to 94.2% genetic diversity. The relative frequency of polymorphic products was from 0.24 to 0.83, with an average of 0.47. In general, this average frequency was relatively high. The genetic distances among the genetic resources were from 0.16 to 0.62, with an average of 0.37. The 15 tea genetic resources were grouped into three groups by UPGMA cluster analysis based on RAPD data. By using the presence of 20 unique RAPD markers and the absence of 11 unique markers, all the 15 investigated tea genetic resources could be easily identified. RAPD markers provided a practical method not only to evaluate the genetic diversity and relationship, but also to identify tea genetic resources.     

Effects of increasing saturation vapour pressure deficit on growth and ABA levels in black spruce and jack pine

 Plant responses to saturation vapour pressure deficit (SVPD) were studied by subjecting black spruce [Picea mariana (Mill) B.S.P.] and jack pine seedlings (Pinus banksiana Lamb.) to humid (0.3 – 0.8 kPa) or dry (2.0 – 2.5 kPa SVPD) regimes for 4 weeks using a computer-controlled environmental system to control diurnal variation in SVPD. Dry matter accumulation in needles was not altered by increasing SVPD. However, root growth declined by 60% which increased shoot to root ratio and reduced total seedling dry weight in both black spruce and jack pine. Relative growth rate of jack pine also declined to about half the rate of plants grown under humid conditions. In situ root marking studies showed that the decline in root growth of jack pine under the high SVPD was the result of reduced lateral root initiation, whereas root elongation was unaffected by humidity. A 4-week exposure to dry air increased abscisic acid (ABA) levels in needles, but not roots, of jack pine whereas ABA levels in black spruce were not altered. A short (3-day) exposure failed to increase needle ABA levels in either species. These results suggest that the responses of conifers to dry air were not the result of ABA accumulation. Received: 24 March 1996 / Accepted: 30 May 1996     

Effects of black tea consumption on plasma catechins and markers of oxidative stress and inflammation in patients with coronary artery disease

We previously demonstrated that black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. To investigate potential mechanisms of this effect, we examined plasma catechins and systemic markers of oxidation, inflammation, and antioxidant protection from 66 subjects enrolled in that study. We collected samples at baseline, 2 h after 450 ml of black tea (acute), after 4 weeks of 900 ml of black tea per day (chronic), and after acute and chronic consumption of water. Total catechins increased 33% after acute tea (P < 0.05) and 29% after chronic tea (P < 0.05). Of individual catechins, plasma epicatechin gallate (ECG) concentration significantly increased with acute tea consumption, and plasma epicatechin (EC) increased with chronic tea consumption. Tea consumption did not improve plasma antioxidant capacity and did not reduce urinary 8-hydroxy-2'-deoxyguanosine, or urinary 8-isoprostane levels. Changes in catechin levels did not correlate with changes in endothelial function, plasma markers of oxidative stress, or C-reactive protein. In contrast, endothelial function at baseline correlated with dietary flavonoid intake (beta = 0.32, P = 0.02) and with baseline plasma EC concentration after adjusting for confounding variables (beta = 0.39, P = 0.03). These findings suggest that the benefits of black tea consumption on endothelial function may not be attributable to tea catechins or a systemic antioxidant or anti-inflammatory effect. Chronic dietary flavonoid status appears to relate to endothelial function, possibly suggesting that other flavonoids or polyphenolic components of tea favorably influence vascular health and risk for cardiovascular disease.     

Effects of caffeine, cumulus cell removal and aging on polyspermy and embryo development on in vitro matured and fertilized ovine oocytes

The objectives of these studies were to determine the effects of cumulus cell removal and caffeine treatment on the development of in vitro matured ovine oocytes aged in vitro until until fertilization. Oocytes were denuded (DO) at 24 h post-onset of maturation (hpm), control cumulus oocyte complexes (COC's) and DO groups were fertilized at 24 hpm or returned to culture in the presence or absence of 10 mM caffeine and fertilized at 30 hpm. Removal of cumulus cells and aging both increased polyspermy, caffeine reduced this increase, however, with the exception of DO's (30 hpm) vs. COC's (24 hpm) the differences were not statistically significant. Aging significantly decreased cleavage between COC groups at 24 hpm and 30 hpm and caffeine did not affect this (68.4%, 73.4%, 74.0% respectively). In contrast, the frequency of cleavage was significantly reduced in the DO (24 hpm) group as compared to COC controls (45.6% vs. 68.4% (P < 0.05)), however, cleavage increased in the DO group on aging (73.4%) and this was not affected by caffeine (73.0%). The percentage of COC's and DO's developing to the blastocyst stage significantly decreased on aging, caffeine treatment of DO's prevented this (31.3%, 12.7% and 29.4% respectively (P < 0.05)) but had no effect on COC's (4.2% vs. 3.9%). Total cell numbers in blastocysts were not statistically different (92.4 ± 5.2, 84.7 ± 3.7 and 80.4 ± 5.8 (P > 0.05)). In summary caffeine treatment of aged COC's had no significant effect on the frequency of development, however, in aged DO's caffeine treatment statistically increased development to blastocyst and lowered the frequency of polyspermy.     

Effects of chlorogenic acid,caffeine, and coffee on behavioral and biochemical parameters of diabetic rats

Mesenchymal stem cells (MSCs) represent a potential therapeutic target for glioma. We determined the molecular mechanism of inhibitory effect of human umbilical cord-derived MSCs (hUC-MSCs) on the growth of C6 glioma cells. We demonstrated that hUC-MSCs inhibited C6 cell growth and modulated the cell cycle to G0/G1 phase. The expression of β-catenin and c-Myc was downregulated in C6 cells by conditioned media from hUC-MSCs, and the levels of secreted DKK1 were positively correlated with concentrations of hUCMSCs-CM. The inhibitory effect of hUC-MSCs on C6 cell proliferation was enhanced as the concentration of DKK1 in hUCMSCs-CM increased. When DKK1 was neutralized by anti-DKK1 antibody, the inhibitory effect of hUC-MSCs on C6 cells was attenuated. Furthermore, we found that conditioned media from hUC-MSCs transfection with siRNA targeting DKK1 mRNA or pEGFPN1-DKK1 plasmid lost or enhanced the abilities to regulate the Wnt signaling in C6 cells. Therefore, hUC-MSCs inhibited C6 glioma cell growth via secreting DKK1, an inhibitor of Wnt pathway, may represent a novel therapeutic strategy for malignant glioma.     

Effects of indole and caffeine on cAMP in the ind1 and cfn1 mutant strains of Schizophyllum commune during sexual development

The ind1 and cfn1 mutations of Schizophyllum commune express resistance to high concentrations of indole and caffeine respectively, and also affect sexual development. To clarify molecular events caused by the mutations, it was investigated how cAMP levels in S. commune strains respond to externally supplied indole and caffeine. Both compounds increased the cAMP levels in wild-type strains under several culture conditions. During sexual development of the ind1 mutant, the cAMP level in an early stage (hyphal aggregation) was highly increased by addition of indole, and the phenomenon disappeared in a later stage (fruit body formation). For the cfn1 mutants, the incremental increase in cAMP levels by addition of caffeine was smaller than that of wild-type strains.     

乙草胺和甲胺磷对农田黑土可培养真菌数量及种群结构的影响

应用传统及PCR-DGGE方法(denaturing gradient gel electrophoresis),分别对不同浓度乙草胺、甲胺磷胁迫下黑土中可培养真菌CFU(colony forming units)、种群丰富度(richness)及种群结构动态变化规律进行了研究.结果表明,在实验室微域条件下,乙草胺对黑土可培养真菌CFU的影响随处理浓度的增加而抑制作用增强,表现出由低浓度(50 mg·kg^-1)时的刺激生长到高浓度(250 mg·kg^-1)时的长期抑制效应;250 mg·kg^-1甲胺磷在8周处理过程中对土壤可培养真菌生长具有显著的刺激效应,使可培养真菌CFU比对照增加10倍,但50和150 mg·kg^-1甲胺磷处理对土壤可培养真菌CFU无显著影响.种群丰富度系数分析结果表明,高、中浓度乙草胺处理可使土壤可培养真菌种群丰富度不可逆地降低.土壤真菌rDNA特异PCR-DGGE聚类分析结果表明,不同浓度乙草胺、甲胺磷处理均不同程度地对土壤可培养真菌的种群组成和结构造成影响,其中甲胺磷尤为显著.     

Effects of chlorogenic acid,caffeine and coffee on components of the purinergic system of streptozotocin-induced diabetic rats

We evaluated the effect of chlorogenic acid (CGA), caffeine (CA) and coffee (CF) on components of the purinergic system from the cerebral cortex and platelets of streptozotocin-induced diabetic rats. Animals were divided into eight groups: control animals treated with (I) water (WT), (II) CGA (5 mg/kg), (III) CA (15 mg/kg) and (IV) CF (0.5 g/kg), and diabetic animals treated with (V) WT, (VI) CGA (5 mg/kg), (VII) CA (15 mg/kg) and (VIII) CF (0.5 g/kg). Our results showed an increase (173%) in adenosine monophosphate (AMP) hydrolysis in the cerebral cortex of diabetic rats. In addition, CF treatment increased adenosine diphosphate (ADP) and AMP hydrolysis in group VIII synaptosomes. Platelets showed an increase in ectonucleotidase activity in group V, and all treatments reduced the increase in adenosine triphosphate and ADP hydrolysis. Furthermore, there was an increase in platelet aggregation of 72% in the diabetic rats, and CGA and CF treatment reduced platelet aggregation by nearly 60% when compared to diabetic rats. In this context, we can suggest that CGA and CF treatment should be considered a therapeutic and scientific target to be investigated in diseases associated with hyperglycemia.