Review of Codonopsis Radix biological activities: A plant of traditional Chinese tonic.

ETHNOPHARMACOLOGICAL RELEVANCE: Codonopsis Radix, commonly known as Dangshen in Chinese, is frequently used to treat deficiencies of spleen and lung Qi, gastrointestinal discomfort, fatigue, asthmatic breathing, sallow complexion, lack of strength, shortness of breath, deficiencies of both Qi and blood, as well as impairments to both Qi and body fluids in suboptimal health status. AIM OF THE REVIEW: This review systematically expounds on the modern pharmacological studies related to the use of Codonopsis Radix in invigorating Qi and nourishing the body in recent years. The aim is to provide theoretical research and reference for the in-depth and systematic exploration and development of the applications of Codonopsis Radix in the fields of food and medicine. MATERIALS AND METHODS: This study employs "Codonopsis Radix," "Codonopsis," and "Dangshen" as keywords to gather pertinent information on Codonopsis Radix medicine through electronic searches of classical literature and databases such as PubMed, Elsevier, Google Scholar, Wiley, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and Baidu Scholar. RESULTS: From previous studies, activities such as immune system modulation, gastrointestinal motility regulation, cardiac function revitalization, lung function improvement, blood circulation enhancement, aging process deceleration, learning and memory augmentation, fatigue resistance enhancement, and liver and kidney damage protection of Codonopsis Radix have been reported. Recognized as an important medicine and food homologous traditional Chinese herbal remedy for supplementing deficiencies, its mode of action is multi-elemental, multi-systemic, multi-organ, multi-mechanistic, and multi-targeted. Furthermore, the benefits of its tonic surpass its therapeutic value, establishing it as an extraordinary preventive and therapeutic medicine. CONCLUSIONS: With its long history of traditional applications and the revelations of contemporary pharmacological research, Codonopsis Radix exhibits great potential as both a therapeutic agent and a dietary supplement for further research in medicine, nutrition, and healthcare.

Codonopsis Radix Inhibits the Inflammatory Response and Oxidative Stress in Chronic Obstructive Pulmonary Disease Mice through Regulation of the Nrf2/NF-κB Signaling Pathway.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a nonspecific chronic inflammatory lung disease with no known cure. Codonopsis Radix (CR) has been shown to exhibit anti-inflammatory and antioxidant effects. Therefore, this study aimed to investigate the potential anti-inflammatory effects of different CR varieties on COPD mice. METHODS: Sixty male-specified pathogen-free grade C57BL/6J mice were randomly divided into 6 groups, 10 mice in each group. The COPD mice model was induced by cigarette smoke extract combined with lipopolysaccharide, and the mice in each group were given corresponding drugs. Lung function was assessed in all mice. Lung tissues were stained with hematoxylin-eosin, Masson, and periodic acid-Schiff stains, and serum levels of interleukin (IL)-8 and tumor necrosis factor (TNF)-α were detected using an ELISA. Further, serum and lung tissue levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by colorimetric assay. Network pharmacology and molecular docking were used to predict signaling pathways, which were validated by Western blot analysis. RESULTS: Compared with the COPD group, the mice in each dosing group of CR exhibited significant reductions in serum IL-8 and TNF-α levels, serum and lung tissue MDA levels, and pathological lung tissue damage, alongside elevations in lung function and SOD levels (p < 0.01). Western blot analysis also indicated significant downregulation of p-p65/p65 and p-IκB-α/IκB-α protein expression, alongside significant upregulation of Nrf2 protein expression in the lung tissues of mice treated with CR (p < 0.01). CONCLUSION: In summary, CR effectively enhances lung function, minimizes lung tissue damage, and inhibits inflammation and oxidative stress in mice with COPD. Additionally, these findings suggest that inhibition of the Nrf2/NF-κB axis may be a key mechanism of action of CR in the alleviation of COPD.

[Genetic testing and clinical analysis of a patient with Dilated cardiomyopathy due to variant of FLNC gene].

OBJECTIVE: To explore the genetic basis for a patient with Dilated cardiomyopathy. METHODS: A patient admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University in April 2022 was selected as the study subject. Clinical data and family history of the patient was collected. Targeted exome sequencing was carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of the American College of Medical Genetics and Genomics (ACMG). RESULTS: DNA sequencing revealed that the patient has harbored a heterozygous c.5044dupG frameshift variant of the FLNC gene. Based on the ACMG guidelines, the variant was predicted to be likely pathogenic (PVS1+PM2_Supporting+PP4). CONCLUSION: The heterozygous c.5044dupG variant of the FLNC gene probably underlay the pathogenesis in this patient, which has provided a basis for the genetic counseling for his family.

Quality Assessment and Classification of Codonopsis Radix Based on Fingerprints and Chemometrics.

In China, Codonopsis Radix (CR) is frequently consumed both as food and medicine. Here, a comprehensive strategy based on fingerprinting and chemometric approaches was created to explore the influence of origins, storage time and kneading processing on the quality of CR. Firstly, high-performance liquid chromatography with diode array detection was used to obtain the fingerprints of 35 batches of CR from six different origins and 33 batches of CR from varying storage times or kneading procedures. Secondly, chemometric methods including similarity analysis (SA), principal component analysis (PCA), hierarchical clustering analysis (HCA), and two-way orthogonal partial least square with discriminant analysis (O2PLS-DA) were used to evaluate the differences of chemical components in CR so as to identify its source and reflect its quality. Moreover, 13 and 16 major compounds were identified as marker compounds for the discrimination of CR from different origins, storage time and kneading processing, respectively. Furthermore, the relative content of the marker components and the exact content of Lobetyolin were measured, indicating that the contents of these components vary significantly between various CR samples. Meanwhile, the chemical components of CR were identified using Mass spectrometry. According to the findings of our investigation, the quality of CR from Gansu was the best, followed by Shanxi and then Sichuan. The quality of CR from Chongqing and Guizhou was poor. At the same time, the quality of CR was the best when it was kneaded and stored for 0 years, indicating that the traditional kneading process of CR is of great significance. Conclusively, HPLC fingerprint in conjunction with chemical pattern recognition and component content determination can be employed to differentiate the raw materials of different CR samples. Additionally, it is also a reliable, comprehensive and prospective method for quality control and evaluation of CR.

Higher serum tissue inhibitor of metalloproteinase-1 predicts atrial fibrillation recurrence after radiofrequency catheter ablation.

Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) levels is strongly associated with cardiac extracellular matrix accumulation and atrial fibrosis. Whether serum levels of TIMP-1 are associated with atrial fibrillation (AF) recurrence following radiofrequency catheter ablation (RFCA) remains unknown. Materials and methods: Serum TIMP-1 levels of patients with AF before they underwent initial RFCA were measured using ELISA. Univariate and multivariate-adjusted Cox models were constructed to determine the relationship between TIMP-1 levels and AF recurrence. Multivariate logistic regression analyses were performed to determine predictors of AF recurrence. Results: Of the 194 enrolled patients, 61 (31.4%) had AF recurrence within the median 30.0 months (interquartile range: 16.5-33.7 months) of follow-up. These patients had significantly higher baseline TIMP-1 levels than those without AF recurrence (129.8 ± 65.7 vs. 112.0 ± 51.0 ng/ml, P = 0.041). The same was true of high-sensitivity C-reactive protein (3.9 ± 6.0 vs. 1.9 ± 2.8 ng/ml, P = 0.001). When a TIMP-1 cutoff of 124.15 ng/ml was set, patients with TIMP-1 ≥ 124.15 ng/ml had a higher risk of recurrent AF than those with TIMP-1 < 124.15 ng/ml (HR, 1.961, 95% CI, 1.182-2. 253, P = 0.009). Multivariate Cox regression analysis revealed that high TIMP-1 was an independent risk factor for AF recurrence. Univariate Cox regression analysis found that substrate modification surgery does not affect AF recurrence (P = 0.553). Subgroup analysis revealed that female sex, age < 65 years, hypertension (HTN), body mass index (BMI) ≥ 24 kg/m2, CHA2DS2-VASc score < 2, HAS-BLED score < 3, and EHRA score = 3 combined with high TIMP-1 level would perform well at predicting AF recurrence after RFCA. Conclusion: Elevated preoperative TIMP-1 levels are related to a higher risk of AF recurrence and can independently predict AF recurrence following RFCA.

Mutation of rpoS is Beneficial for Suppressing Organic Acid Secretion During 1,3-Propandiol Biosynthesis in Klebsiella pneumoniae.

In this study, to reduce the formation of organic acid during 1,3-propanediol biosynthesis in Klebsiella pneumoniae, a method combining UV mutagenesis and high-throughput screening with pH color plates was employed to obtain K. pneumoniae mutants. When compared with the parent strain, the total organic acid formation by the mutant decreased, whereas 1,3-propanediol biosynthesis increased after 24 h anaerobic shake flask culture. Subsequently, genetic changes in the mutant were analyzed by whole-genome sequencing and verified by signal gene deletion. Mutation of the rpoS gene was confirmed to contribute to the regulation of organic acid synthesis in K. pneumoniae. Besides, rpoS deletion eliminated the formation of 2,3-butanediol, the main byproduct produced during 1,3-propanediol fermentation, indicating the role of rpoS in metabolic regulation in K. pneumoniae. Thus, a K. pneumoniae mutant was developed, which could produce lower organic acid during 1,3-propanediol fermentation due to an rpoS mutation in this study.

Bioinformatics Analysis Reveals Cell Cycle-Related Gene Upregulation in Ascending Aortic Tissues From Murine Models.

Thoracic aortic aneurysm and dissection (TAAD) is a high-risk aortic disease. Mouse models are usually used to explore the pathological progression of TAAD. In our studies, we performed bioinformatics analysis on a microarray dataset (GSE36778) and verified experiments to define the integrated hub genes of TAAD in three different mouse models. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analyses, and histological and quantitative reverse transcription-PCR (qRT-PCR) experiments were used in our study. First, differentially expressed genes (DEGs) were identified, and twelve common differentially expressed genes were found. Second, genes related to the cell cycle and inflammation were enriched by using GO and PPI. We focused on filtering and validating eighteen hub genes that were upregulated. Then, expression data from human ascending aortic tissues in the GSE153434 dataset were also used to verify our findings. These results indicated that cell cycle-related genes participate in the pathological mechanism of TAAD and provide new insight into the molecular mechanisms of TAAD.

Glycan Biosynthesis Ability of Gut Microbiota Increased in Primary Hypertension Patients Taking Antihypertension Medications and Potentially Promoted by Macrophage-Adenosine Monophosphate-Activated Protein Kinase.

Increasing evidences suggest that the gut microbiota have their contributions to the hypertension, but the metagenomic characteristics and potential regulating mechanisms in primary hypertension patients taking antihypertension drugs are not clear yet. We carried out a metagenomic analysis in 30 primary hypertension patients taking antihypertension medications and eight healthy adults without any medication. We found that bacterial strains from species, such as Bacteroides fragilis, Bacteroides vulgatus, Escherichia coli, Klebsiella pneumoniae, and Streptococcus vestibularis, were highly increased in patients; and these strains were reported to generate glycan, short-chain fatty acid (SCFA) and trimethylamine (TMA) or be opportunistic pathogens. Meanwhile, Dorea longicatena, Eubacterium hallii, Clostridium leptum, Faecalibacterium prausnitzii, and some other strains were greatly decreased in the patient group. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that ortholog groups and pathways related to glycan biosynthesis and multidrug resistance were significantly increased in the patient group, and some of the hub genes related to N-glycan biosynthesis were increased in the patient group, while those related to TMA precursor metabolism and amino acid metabolism both increased and decreased in the patient group. Metabolites tested by untargeted liquid chromatography-mass spectrometry (LC-MS) proved the decrease of acetic acid, choline, betaine, and several amino acids in patients' fecal samples. Moreover, meta-analysis of recent studies found that almost all patients were taking at least one kind of drugs that were reported to regulate adenosine monophosphate-activated protein kinase (AMPK) pathway, so we further investigated if AMPK regulated the metagenomic changes by using angiotensin II-induced mouse hypertensive model on wild-type and macrophage-specific AMPK-knockout mice. We found that the changes in E. coli and Dorea and glycan biosynthesis-related orthologs and pathways were similar in our cohort and hypertensive wild-type mice but reversed after AMPK knockout. These results suggest that the gut microbiota-derived glycan, SCFA, TMA, and some other metabolites change in medication-taking primary hypertension patients and that medications might promote gut microbiota glycan biosynthesis through activating macrophage-AMPK.

Molecular Characterization of Lignite Extracts of Methanol and Carbon Disulfide/N-Methyl-2-pyrrolidone by High-Resolution Mass Spectrometry.

CS2/N-methyl-2-pyrrolidone (NMP) could extract much more substance from coals than any other solvents. Investigation on the molecular composition of CS2/NMP extracts from lignite is significant for the understanding of high extraction yield and the clean utilization of coal. The methanol-soluble portions from lignites and CS2/NMP extracts of lignites were characterized by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. The yield of CS2/NMP extracts from lignite was quite higher than that of methanol extracts. Furthermore, the yield of methanol-soluble portions from CS2/NMP extracts was far more than that of methanol extracts from lignite. At the level of molecular composition, the relative content of heteroatom compounds with more oxygen atoms, longer side chain, and higher condensation in the CS2/NMP extract was also higher than that in the methanol extract. Despite great difference in the yield and the relative content of components, the distributions of species, molecular weight, carbon number, and double-bond equivalent were similar to those of most organic molecules for the methanol extract and methanol-soluble portions from the CS2/NMP extract. These phenomena suggested that organic molecules with similar structure but different composition, nonuniformly distributed in the coal matrix, were released more in the CS2/NMP extract compared to the single methanol extract.

Molecular Characterization of Soluble Components in the Lignite by Sequential Solvent Extraction via Continuously Reducing Particle Size.

A lignite was subjected to sequential solvent extraction via continuously reducing particle size from around 20 to more than 200 mesh. Five sets of n-hexane and methanol extracts from the particles were characterized by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS) and gas chromatography-mass spectrometry. The total extract yield for lignite when using hexane and methanol as solvents could reach to 0.98 and 15.12%, respectively. The results showed that more molecules with a similar structure but different composition could be extracted by continuously reducing the particle size of the residues, indicating the nonuniform distribution of the low-solubility molecules trapped in the coal particles. The extracts were abundant in branched long-chain aliphatic moieties and oxygen-containing compounds. With the increasing of the extraction degree, the content of alkanes in the extracts decreased rapidly. On the contrary, the content of the compounds with higher condensation and more oxygen atoms increased. It should be noted that polycyclic aromatic hydrocarbons were almost steadily present in all the extraction steps. The molecular composition and distribution of organic molecules in the lignite provide clues to the understanding of coal structure, which is significant for the environmental emission and development of processing techniques for the clean and high value-added utilizations of such a low-rank and abundant coal resource.

Regulation of Pyruvate Formate Lyase-Deficient Klebsiella pneumoniae for Efficient 1,3-Propanediol Bioproduction.

Anaerobic growth defect of pyruvate formate lyase (PFL)-deficient Klebsiella pneumoniae limits its industrial application, and the reason for this growth defect was analyzed in this study. The obtained evidences, combined with normal intracellular redox status and no further inhibition by adhE deletion, strongly suggested that growth defect in PFL-deficient K. pneumoniae was probably caused by lack of carbon flux from pyruvate to acetyl-CoA (AcCoA). Correspondingly, the anaerobic growth of PFL-deficient K. pneumoniae was promoted by deletion of pdhR, a negative transcriptional regulator gene for AcCoA generation. Through the regulation of pdhR deletion, the PFL-deficient K. pneumoniae exhibited highly efficient 1,3-propanediol production. Besides, in a 2-L fed-batch fermentation process, the cell growth of PFL-deficient K. pneumoniae strain almost recovered, when compared with that of the normal strain, and the 1,3-propanediol yield increased by 14%, while the byproducts acetate and 2,3-butanediol contents decreased by 29% and 24%, respectively.

Molecular Characterization of Thiols in Fossil Fuels by Michael Addition Reaction Derivatization and Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

Thiols widely occur in sediments and fossil fuels. However, the molecular composition of these compounds is unclear due to the lack of appropriate analytical methods. In this work, a characterization method for thiols in fossil fuels was developed on the basis of Michael addition reaction derivatization followed by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS). Model thiol compound studies showed that thiols were selectively reacted with phenylvinylsulfone and transformed to sulfones with greater than 98% conversions. This method was applied to a coker naphtha, light and heavy gas oils, and crude oils from various geological sources. The results showed that long alkyl chain thiols are readily present in petroleum, which have up to 30 carbon atoms. Large DBE dispersity of thiols indicates that naphthenic and aromatic thiols are also present in the petroleum. This method is capable of detecting thiol compounds in the part per million range by weight. This method allows characterization of thiols in a complex hydrocarbon matrix, which is complementary to the comprehensive analysis of sulfur compounds in fossil fuels.

Identification of multiple ACVRL1 mutations in patients with pulmonary arterial hypertension by targeted exome capture.

Pulmonary artery hypertension (PAH) is characterized as sustained elevation of pressure in the pulmonary vascular system that is attributable to a variety of causes. More than a dozen genes have previously been proposed as being associated with PAH. To examine potential mutations of these genes in patients with PAH, we developed a targeted exome kit containing 22 PAH-associated genes for genetic screens of 80 unrelated patients with PAH. As a result, we identified 16 different mutations in the BMPR2 gene and four different mutations in ACVRL1, the gene for activin receptor-like kinase-1 (ACVRL1). However, no deleterious mutations were found in the remaining 20 genes. In the present study, we provided detailed characterization of the ACVRL1 mutations in four pedigrees, including two novel missense mutations (c.676G>A, p.V226M; c.955G>C, p.G319R) and two recurrent mutations (c.1231C>T, p.R411W; c.1450C>T, p.R484W). Furthermore, we showed that markedly reduced Smad1/5 phosphorylation levels and reduced activities of luciferase reporters in each of the four ACVRL1 mutant-transfected NIH-3T3 cells. Therefore, our findings demonstrated that missense mutations of ACVRL1 identified in the present study significantly affected the bone morphogenetic protein 9 (BMP-9) pathway, implicating PAH pathogenesis. Detailed genotype-phenotype correlation analysis revealed initial symptoms of hereditary haemorrhagic telangiectasia (HHT) in some of the patients, suggesting the importance of sequencing molecular markers for early identification and intervention of individuals at risk for PAH and potential HHT. We developed a customized exome sequencing system to identify mutations in these PAH-associated genes, and found two novel missense mutations and two recurrent mutations in the ACVRL1 gene in four unrelated Chinese families; we also determined hypomorphic alleles using functional studies.

Wide mutation spectrum and frequent variant Ala27Thr of FBN1 identified in a large cohort of Chinese patients with sporadic TAAD.

Genetic etiology in majority of patients with sporadic thoracic aortic aneurysm and dissections (STAAD) remains unknown. Recent GWAS study suggested common variant(s) in FBN1 is associated with STAAD. The present study aims to test this hypothesis and to identify mutation spectrum by targeted exome sequencing of the FBN1 gene in 146 unrelated patients with STAAD. Totally, 15.75% of FBN1 variants in STAAD were identified, including 5 disruptive and 18 missense mutations. Most of the variants were novel. Genotype-phenotype correlation analysis suggested that the maximum aortic diameter in the disruptive mutation group was significantly larger than that in the non-Cys missense mutation group. Interestingly, the variant Ala27Thr at -1 position, which is predicted to change the cleavage site of the signal peptidase of fibrillin-1, was detected in two unrelated patients. Furthermore, genotyping analysis of this variant detected 10 heterozygous Ala27Thr from additional 666 unrelated patients (1.50%), versus 7 from 1500 controls (0.47%), indicating a significant association of this variant with STAAD. Collectively, the identification of the variant Ala27Thr may represent a relatively common genetic predisposition and a novel pathogenetic mechanism for STAAD. Also, expansion of the mutation spectrum in FBN1 will be helpful in genetic counselling for Chinese patients with STAAD.

Screening Mutations of MYBPC3 in 114 Unrelated Patients with Hypertrophic Cardiomyopathy by Targeted Capture and Next-generation Sequencing.

Hypertrophic cardiomyopathy (HCM) is a major cause of sudden cardiac death. Mutations in the MYBPC3 gene represent the cause of HCM in ~35% of patients with HCM. However, genetic testing in clinic setting has been limited due to the cost and relatively time-consuming by Sanger sequencing. Here, we developed a HCM Molecular Diagnostic Kit enabling ultra-low-cost targeted gene resequencing in a large cohort and investigated the mutation spectrum of MYBPC3. In a cohort of 114 patients with HCM, a total of 20 different mutations (8 novel and 12 known mutations) of MYBPC3 were identified from 25 patients (21.9%). We demonstrated that the power of targeted resequencing in a cohort of HCM patients, and found that MYBPC3 is a common HCM-causing gene in Chinese patients. Phenotype-genotype analyses showed that the patients with double mutations (n = 2) or premature termination codon mutations (n = 12) showed more severe manifestations, compared with patients with missense mutations (n = 11). Particularly, we identified a recurrent truncation mutation (p.Y842X) in four unrelated cases (4/25, 16%), who showed severe phenotypes, and suggest that the p.Y842X is a frequent mutation in Chinese HCM patients with severe phenotypes.

Positive association of coronary calcium detected by computed tomography coronary angiography with periprocedural myocardial infarction.

BACKGROUND: Periprocedural myocardial infarction (PMI) may occur in approximately 5% to 30% of patients undergoing percutaneous coronary intervention. Whether the morphology of coronary plaque calcium affects the occurrence of PMI is unknown. MATERIALS AND METHODS: A total of 616 subjects with stable angina and normal baseline cardiac troponin I levels who had undergone computed tomography angiography (CTA) were referred to elective percutaneous coronary intervention. The morphology of coronary calcium was determined by CTA analysis. PMI was defined as an elevation in 24-h post-procedural cardiac troponin I levels of > 5 times the upper limit of normal with either symptoms of myocardial ischemia, new ischemic electrocardiographic changes, or documented complications during the procedure. Logistic regression was performed to identify the effect of the morphology of coronary calcium on the occurrence of PMI. RESULTS: According to the presence or morphology of coronary calcium as shown by CTA, 210 subjects were grouped in the heavy calcification group, 258 in the mild calcification group, 40 in the spotty calcification group and 108 in the control group. The dissection rate was significantly higher in the heavy calcification group than in the control group (7.1 % vs. 1.9%, p = 0.03). The occurrence of PMI in the heavy calcification group was significantly higher than that in the control group (OR 4.38, 95% CI 1.80-10.65, p = 0.001). After multivariate adjustment, the risk of PMI still remained significantly higher in the heavy calcification group than in the control group (OR 4.04, 95% CI 1.50-10.89, p = 0.003). CONCLUSIONS: The morphology of coronary calcium determined by CTA may help to predict the subsequent occurrence of PMI. A large amount of coronary calcium may be predictive of PMI.

Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials.

BACKGROUND: The effect of green tea beverage and green tea extract on lipid changes is controversial. OBJECTIVE: We aimed to identify and quantify the effect of green tea and its extract on total cholesterol (TC), LDL cholesterol, and HDL cholesterol. DESIGN: We performed a comprehensive literature search to identify relevant trials of green tea beverages and extracts on lipid profiles in adults. Weighted mean differences were calculated for net changes in lipid concentrations by using fixed-effects or random-effects models. Study quality was assessed by using the Jadad score, and a meta-analysis was conducted. RESULTS: Fourteen eligible randomized controlled trials with 1136 subjects were enrolled in our current meta-analysis. Green tea consumption significantly lowered the TC concentration by 7.20 mg/dL (95% CI: -8.19, -6.21 mg/dL; P < 0.001) and significantly lowered the LDL-cholesterol concentration by 2.19 mg/dL (95% CI: -3.16, -1.21 mg/dL; P < 0.001). The mean change in blood HDL-cholesterol concentration was not significant. Subgroup and sensitivity analyses showed that these changes were not influenced by the type of intervention, treatment dose of green tea catechins, study duration, individual health status, or quality of the study. Overall, no significant heterogeneity was detected for TC, LDL cholesterol, and HDL cholesterol; and results were reported on the basis of fixed-effects models. CONCLUSION: The analysis of eligible studies showed that the administration of green tea beverages or extracts resulted in significant reductions in serum TC and LDL-cholesterol concentrations, but no effect on HDL cholesterol was observed.

Effect of oral isoflavone supplementation on vascular endothelial function in postmenopausal women: a meta-analysis of randomized placebo-controlled trials.

BACKGROUND: The effect of isoflavone on endothelial function in postmenopausal women is controversial. OBJECTIVE: The objective of this study was to evaluate the effect of oral isoflavone supplementation on endothelial function, as measured by flow-mediated dilation (FMD), in postmenopausal women. DESIGN: A meta-analysis of randomized placebo-controlled trials was conducted to evaluate the effect of oral isoflavone supplementation on endothelial function in postmenopausal women. Trials were searched in PubMed, Embase, the Cochrane Library database, and reviews and reference lists of relevant articles. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. RESULTS: A total of 9 trials were reviewed in the present meta-analysis. Overall, the results of the 9 trials showed that isoflavone significantly increased FMD (WMD: 1.75%; 95% CI: 0.83%, 2.67%; P = 0.0002). Meta-regression analysis indicated that the age-adjusted baseline FMD was inversely related to effect size. Subgroup analysis showed that oral supplementation of isoflavone had no influence on FMD if the age-adjusted baseline FMD was > or = 5.2% (4 trials; WMD: 0.24%; 95% CI: -0.94%, 1.42%; P = 0.69). This improvement seemed to be significant when the age-adjusted baseline FMD levels were <5.2% (5 trials; WMD: 2.22%; 95% CI: 1.15%, 3.30%; P < 0.0001), although significant heterogeneity was still detected in this low-baseline-FMD subgroup. CONCLUSIONS: Oral isoflavone supplementation does not improve endothelial function in postmenopausal women with high baseline FMD levels but leads to significant improvement in women with low baseline FMD levels.

Stretch-activated potassium channels in hypotonically induced blebs of atrial myocytes.

Stress in the lipids of the cell membrane may be responsible for activating stretch-activated channels (SACs) in nonspecialized sensory cells such as cardiac myocytes, where they are likely to play a role in cardiac mechanoelectric feedback. We examined the influence of the mechanical microenvironment on the gating of stretch-activated potassium channels (SAKCs) in rat atrial myocytes. The goal was to examine the role of the cytoskeleton in the gating process. We recorded from blebs that have minimal cytoskeleton and cells treated with cytochalasin B (cyto-B) to disrupt filamentous actin. Histochemical and electron microscopic techniques confirmed that the bleb membrane was largely free of F-actin. Channel currents showed mechanosensitivity and potassium selectivity and were activated by low pH and arachidonic acid, similar to properties of TREK-1. Some patches showed a time-dependent decrease in current that may be adaptation or inactivation, and since this decrease appeared in control cells and blebs, it is probably not the result of adaptation in the cytoskeleton. Cyto-B treatment and blebbing caused an increase in background channel activity, suggesting a transfer of stress from actin to bilayer and then to the channel. The slope sensitivity of gating before and after cyto-B treatment was similar to that of blebs, implying the characteristic change of dimensions associated with channel gating was the same in the three mechanical environments. The mechanosensitivity of SAKCs appears to be the result of interaction with membrane lipids and not of direct involvement of the cytoskeleton.