Genetically predicted coffee and tea consumption and risk of intracranial aneurysm.

OBJECTIVES: Observational studies have shown associations between coffee and tea consumption and risk of intracranial aneurysm (IA). However, the results are not consistent. We conducted a Mendelian randomization study to clarify whether genetically predicted coffee and tea consumption has a causal effect on IA and its subtypes. METHODS: Genetic variants associated with coffee and tea consumption (cups/day) were obtained from large genome-wide association studies (GWASs), up to 349,376 subjects. Summary-level data for IA were adopted from a GWAS in 79,429 subjects (23 cohorts, 7495 cases, and 71,934 controls). RESULTS: Genetically predicted coffee consumption was associated with a higher risk of any IA and aneurysmal subarachnoid hemorrhage (SAH), but not with unruptured IA. The ORs per 1 cup/day increase in genetically predicted coffee consumption were 1.42 (95% CI: 1.09-1.86; P = 0.010) for IA, 1.51 (95% CI: 1.13-2.03; P = 0.005) for aneurysmal SAH, and 1.20 (95% CI: 0.74-1.96; P = 0.460) for unruptured IA. Genetically predicted tea consumption was not associated with risk of any IA and its subtypes (P > 0.05). The associations remained consistent in sensitivity analyses, and no evidence of pleiotropy was detected. CONCLUSIONS: Our study provides evidence to support that coffee consumption may increase the risk of IA and associated hemorrhage. Coffee should be limited for those at high risk of IA and associated hemorrhage.

Alcohol, Coffee, and Milk Intake in Relation to Epilepsy Risk.

Alcohol, coffee and milk intakes have been explored in relation to epilepsy risk in observational studies; however, the results were not consistent. We performed a Mendelian randomisation (MR) study to evaluate the causality of these relationships. Genetic variants associated with alcohol, coffee and milk intake were adopted as instrumental variables. We obtained the summary data of epilepsy from the International League Against Epilepsy (ILAE) Consortium (15,212 cases and 29,677 controls) and FinnGen consortium (4588 cases and 144,780 controls). Genetically predicted alcohol intake was associated with a higher risk of epilepsy in the ILAE Consortium (odds ratio (OR): 1.22, 95% confidence intervals (CI): 1.02-1.45). The association in the FinnGen consortium remained consistent in direction. Combined analysis of ILAE and FinnGen databases further indicated that genetically predicted alcohol intake was associated with a higher risk of epilepsy (OR = 1.24; 95% CI, 1.06-1.47, p = 0.009). Genetically predicted coffee intake was not related to epilepsy risk, while higher genetically predicted milk intake was related to a lower risk of epilepsy (OR = 0.957; 95% CI, 0.917-0.999, p = 0.044). Our results suggest a detrimental effect of alcohol intake on the risk of epilepsy, while milk intake might be associated with a decreased risk of epilepsy.

Genetically predicted coffee consumption and amyotrophic lateral sclerosis.

Objective: Observational studies have indicated an association between coffee consumption and amyotrophic lateral sclerosis (ALS). Nevertheless, whether the association is causal is still unclear. We conducted a Mendelian randomization study to explore whether coffee consumption is causally related to ALS. Methods: Two genome-wide association studies (GWASs) investigating coffee consumption (n = 129,422 and 375,833, respectively) were adopted to define instrumental variables for coffee consumption (high vs. infrequent/no, 1 cup/day increase, and 50% increase). Summary-level data for ALS were adopted from a large GWAS of ALS with a total of 20,806 cases and 59,804 controls. Results: Genetically predicted higher coffee consumption was not associated with ALS. The ORs were 1.02 (95% CI: 0.93-1.13; p = 0.649) for high vs. infrequent/no, 0.98 (95% CI: 0.84-1.15; p = 0.822) for 1 cup/day increase, 0.97 (95% CI: 0.79-1.19; p = 0.766) for 50% increase. Sensitivity analyses yielded consistent results. No pleiotropic bias and heterogeneity were observed. Conclusion: Using multiple approaches and sensitivity analyses, our MR results show that genetically predicted coffee consumption was not associated with ALS. Further studies are warranted to explore the effect of coffee consumption on ALS progression.

Mendelian randomization study of coffee consumption and age at onset of Huntington's disease.

BACKGROUND & AIM: The association between habitual coffee or caffeine consumption and age at onset (AAO) of Huntington's disease (HD) is unclear. We employed Mendelian randomization to investigate the causal relationship between coffee consumption and AAO of HD. METHODS: The instrumental variable including 14 independent genetic variants associated with coffee consumption was selected from a genome-wide association study (GWAS) meta-analysis of 375,833 individuals of European ancestry. Genetic association estimates for AAO of HD were obtained from the Genetic Modifiers of Huntington's Disease Consortium GWAS meta-analysis including 9064 HD patients of European ancestry. The inverse variance weighted method was used to evaluate the causal estimate and a comprehensive set of analyses tested the robustness of our results. RESULTS: Genetically predicted higher coffee consumption was associated with an earlier AAO of HD (ß = -1.84 years, 95% confidence interval = -3.47 to -0.22, P = 0.026). Results were robust to potential pleiotropy and weak instrument bias. CONCLUSIONS: This genetic study suggests high coffee consumption is associated with an earlier AAO of HD. Coffee is widely consumed and thus our findings, if confirmed, offers a potential way to delay the onset of this debilitating autosomal dominant disease.

Genetically Predicted Coffee Consumption and Risk of Alzheimer's Disease and Stroke.

BACKGROUND: Observational studies have reported that coffee consumption was associated with Alzheimer's disease (AD) and stroke risk. However, the results are inconclusive. OBJECTIVE: We aimed to evaluate whether genetically predicted coffee consumption is associated with AD and stroke using Mendelian randomization (MR) design. METHODS: Summary-level data for AD (n = 54,162), ischemic stroke (n = 440,328), and intracerebral hemorrhage (ICH, n = 3,026) were adopted from publicly available databases. Summary-level data for coffee consumption were obtained from two genome-wide association studies, comprising up to 375,833 subjects. RESULTS: Genetically predicted coffee consumption (cups/day) was associated with an increased risk of AD (OR = 1.26, 95%CI = 1.05-1.51). Moreover, genetically predicted 50%increase of coffee consumption was associated with an increased risk of ICH (OR: 2.27, 95%CI: 1.08-4.78) but a decreased risk of small vessel stroke (OR: 0.71, 95%CI: 0.51-0.996). Estimate for AD and ICH in FinnGen consortium is directionally consistent. Combined analysis of different databases further confirmed that genetically predicted coffee consumption was associated with an increased risk of AD and ICH. In the multivariable MR analysis, genetically predicted coffee consumption retained a stable effect with AD and ICH when adjusting for smoking (p < 0.05), while the association with AD attenuated when adjusting for alcohol use. CONCLUSION: Our results indicate that genetically predicted coffee consumption may be associated with an increased risk of AD and ICH. The underlying biological mechanisms warrant further study.

Effects of phosphite as a plant biostimulant on metabolism and stress response for better plant performance in Solanum tuberosum.

Food availability represents a major worldwide concern due to population growth, increased demand, and climate change. Therefore, it is imperative to identify compounds that can improve crop performance. Plant biostimulants have gained prominence because of their potentials to increase germination, productivity and quality of a wide range of horticultural and agronomic crops. Phosphite (Phi), an analog of orthophosphate, is an emerging biostimulant used in horticulture and agronomy. The aim of this study was to uncover the molecular mechanisms through which Phi acts as a biostimulant with potential effects of overall plant growth. Field and greenhouse experiments, using 4 potato cultivars, showed that following Phi applications, plant performance, including several physio-biochemical traits, crop productivity, and quality traits, were significantly improved. RNA sequencing of control and Phi-treated plants of cultivar Xingjia No. 2, at 0 h, 6 h, 24 h, 48 h, 72 h and 96 h after the Phi application for 24 h revealed extensive changes in the gene expression profiles. A total of 2856 differentially expressed genes were identified, suggesting that multiple pathways of primary and secondary metabolism, such as flavonoids biosynthesis, starch and sucrose metabolism, and phenylpropanoid biosynthesis, were strongly influenced by foliar applications of Phi. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses associated with defense responses revealed significant effects of Phi on a plethora of defense mechanisms. These results suggest that Phi acted as a biostimulant by priming the plants, that was, by triggering dynamic changes in gene expression and modulating metabolic fluxes in a way that allowed plants to perform better. Therefore, Phi usage has the potential to improve crop yield and health, alleviating the challenges posed by the need of feeding a growing world population, while minimizing the agricultural impact on human health and environment.

Higher tea consumption is associated with decreased risk of small vessel stroke.

BACKGROUND & AIM: Observational studies have reported that tea consumption is associated with risk of stroke. However, this observed association is inconsistent, and whether this observed association is due to confounding factors or reverse causation remains unclear. Thus, we applied a two-sample mendelian randomization (MR) approach to determine whether genetically predicted tea consumption is causally associated with risk of stroke, ischemic stroke (IS), and IS subtypes. METHODS: UK Biobank available data (349,376 samples of European ancestry) was used to identify single nucleotide polymorphisms associated with tea consumption (cups/day). The summary statistics for stroke, IS, and IS subtypes were obtained from the MEGASTROKE consortium with 40,585 stroke cases and 406,111 controls. RESULTS: We found that genetically predicted an extra daily cup of tea consumption was casually associated with a reduced risk of small vessel stroke (odds ratio (OR), 0.79; 95% confidence interval (CI), 0.69-0.91; P = 0.001), but not with cardioembolic stroke (OR, 0.97; 95% CI, 0.86-1.09; P = 0.582), large artery stroke (OR, 0.95; 95% CI, 0.82-1.10; P = 0.506), stroke (OR, 1.00; 95% CI, 0.95-1.06; P = 0.889) or IS (OR, 0.95; 95% CI, 0.89-1.01; P = 0.083). CONCLUSIONS: Our study provided evidence that genetically predicted an extra daily cup of tea consumption is causally associated with a reduced risk of small vessel stroke.

Exogenous phosphite application alleviates the adverse effects of heat stress and improves thermotolerance of potato (Solanum tuberosum L.) seedlings.

Phosphite (Phi), an analog of phosphate (Pi) anion, is emerging as a potential biostimulator, fungicide and insecticide. Here, we reported that Phi also significantly enhanced thermotolerance in potatoes under heat stress. Potato plants with and without Phi pretreatment were exposed to heat stress and their heat tolerance was examined by assessing the morphological characteristics, photosynthetic pigment content, photosystem II (PS II) efficiency, levels of oxidative stress, and level of DNA damage. In addition, RNA-sequencing (RNA-Seq) was adopted to investigate the roles of Phi signals and the underlying heat resistance mechanism. RNA-Seq revealed that Phi orchestrated plant immune responses against heat stress by reprograming global gene expressions. Results from physiological data combined with RNA-Seq suggested that the supply of Phi not only was essential for the better plant performance, but also improved thermotolerance of the plants by alleviating oxidative stress and DNA damage, and improved biosynthesis of osmolytes and defense metabolites when exposed to unfavorable thermal conditions. This is the first study to explore the role of Phi in thermotolerance in plants, and the work can be applied to other crops under the challenging environment.

Translocation of phosphite encourages the protection against Phytophthora infestans in potato: The efficiency and efficacy.

Phosphite (Phi)-based fungicides, such as the commercial product Phostrol™, are widely used in potato late blight control. However, the Phi translocation efficiency and the efficacy against pathogen are less discussed. In this study, the Phi concentration were quantified by high performance ion chromatography (HPIC) and the Phi translocation efficiency in potato tissues was evaluated using potato cultivar Russet Burbank with foliar application of the Phostrol solution both under greenhouse and field conditions. In the greenhouse trials, it was found that Phi was translocated from leaves to roots within 3 h and its concentration was significantly increased in the roots 24 h after the Phostrol application. In the field trials, the application rate of Phostrol affected the Phi translocation in potato tubers. To assess the efficacy of Phi against P. infestans, both the inhibition and infection tests were carried out. In the inhibition tests, three most common strains of P. infestans in Canada (US-8, US-23 and US-24) were inoculated on pea agar containing different levels of Phi. In the infection tests, both of detached leaves and whole tubers that received Phi were infected by the three strains of P. infestans. The in vitro tests indicated that the US-8 strain is the most tolerant whereas the US-23 strain is the most sensitive to Phi. Also, the in vivo tests demonstrated the dose-dependent translocation of Phi in potato leaves and tubers decreased the severity of infection by P. infestans. Moreover, potential defense mechanisms related to salicylic acid (SA) and jasmonic acid (JA) pathways that might be activated by Phi were also explored. Overall, the results of the study provided evidences that high Phi translocation efficiency encouraged late blight suppression in potato production.

An environmental approach to correcting iodine deficiency: supplementing iodine in soil by iodination of irrigation water in remote areas.

OBJECTIVE: Iodine deficiency disorders continue to be a severe problem in many parts of Central Asia, causing delayed mental development and cretinism in indigenous populations. In some areas, iodized salt has not succeeded in controlling this problem. In southern Xinjiang Province of China, we tried a new method of supplying iodine to rural populations by dripping potassium iodate into irrigation water canals. By this means iodine was distributed into soil, crops, animals and people. This proved feasible and cost effective; it reached all the people, required no medical expertise, required no continuing effort after the initial dripping, and had the important added benefit of improving livestock production. METHODS: We serially monitored iodine concentrations in soil, crops, animal products and human urine for several years after the last dripping. In a similar project in Inner Mongolia, total soil iodine was determined in addition. Here, iodine concentrations in soil, crops, animals and people have been monitored for 4 years after supplementation. RESULTS: After dripping, total iodine increased two-fold, while soluble iodine increased 4-5-fold. Iodine added to soil is available for more than 4 years after a single application. CONCLUSIONS: Potassium iodate added to soil appears to increase soluble iodine out of proportion to the amount added. This effect and the long persistence of dripped iodate in soil contribute to the efficacy and cost effectiveness of this method of iodine supplementation.

[Clinical and experimental study of treatment of nanmiqing capsule for chronic prostatitis].

OBJECTIVES: To investigate the clinical effect and therapeutic mechanism of Nanmiqing capsule made of rheum palmatum, leech, astragalus memberanaceus on patients with chronic prostatitis(CP). METHODS: Seventy-six CP cases were treated with Nanmiqing, while 32 CP cases were treated with Qianliekang as a control. The changes of EPS were observed pre- and post-treatment. The rat model of CP got by Xiaozhiling inducing were treated with Nanmiqing and Qianliekang respectively. The concentration of endothelin, TXB2, 6-keto-PGF1 alpha and SOD, IgG, IgA in plasma were measured pre- and post-treatment, meanwhile, pathological changes of prostate tissues were observed. RESULTS: The total effective rate was 89.47% in treatment group, which was significantly higher than 71.88% in the control group (P < 0.01). Experimental study for CP rats showed that the Nanmiqing was more effective medicine than Qianliekang (P < 0.01). CONCLUSIONS: Nanmiqing was an effective medicine for CP. The mechanism of clearing heat and resolving toxin, activating blood and removing stasis and reinforcing Qi in chinese medicine could be the explanation of the useful treatment including three therapentic ways.