Enhanced polysaccharide production through quorum sensing system in Cordyceps militaris.

This study aimed to enhance extracellular polysaccharide (EPS) production in Cordyceps militaris by constructing a quorum sensing (QS) system to regulate the expression of biosynthetic enzyme genes, including phosphoglucomutase, hexokinase, phosphomannomutase, polysaccharide synthase, and UDP-glucose 4-epimerase genes. The study found higher EPS concentrations in seven recombinant strains compared to the wild-type C. militaris, indicating that the overexpression of key enzyme genes increased EPS production. Among them, the CM-pgm-2 strain exhibited the highest EPS production, reaching a concentration of 3.82 ± 0.26 g/L, which was 1.52 times higher than the amount produced by the wild C. militaris strain. Additionally, the regulatory effects of aromatic amino acids on the QS system of the CM-pgm-2 strain were investigated. Under the influence of 45 mg/L tryptophan, the EPS production in CM-pgm-2 reached 4.75 ± 0.20 g/L, representing a 1.90-fold increase compared to wild C. militaris strains. This study provided an effective method for the large-scale production of EPSs in C. militaris, and opened up new avenues for research into fungal QS mechanisms.

Chemical and activity investigation on metabolites from the endophytic fungus Penicillium macrosclerotiorum isolated from Ilex pubescens Hook. et Arn.

Penicillium macrosclerotiorum was isolated for the first time from the leaves of Ilex pubescens Hook. et Arn (VSN-2022-03-18-001) and found to produce bioactive compounds. Seven compounds were obtained from the fermentation broth and mycelia of P. macrosclerotiorum and identified as palmitic acid (1), methyl 6-acetyl-5,7,8-trihydroxy-4-methoxy-2-naphthoate (2), ergosterol (3), daidzein (4), oleuropein (5), pedunculoside (6) and acteoside (7). Compounds 3, 4 and 7 exhibited antioxidant activity against diphenyl picryl hydrazinyl with IC50 values of 58.06, 2.58 and 12.01 µg/mL, respectively. Compounds 3, 5 and 7 exhibit inhibitory activity against Escherichia coli with MIC values of 0.78, 3.13 and 3.13 mg/mL, while compounds 2, 3, 4, 5, 6 and 7 exhibited inhibitory effect on Candida albicans with MIC values of 0.20, 0.20, 0.39, 0.63, 0.78 and 0.78 mg/mL, respectively. Furthermore, Compound 4 effectively inhibited HepG2 cells, showing an IC50 of 34.03 µg/mL.

NETs: an extracellular DNA network structure with implication for cardiovascular disease and cancer.

Cardiovascular (CV) diseases and tumors are best known for its high morbidity and mortality worldwide. There is a growing recognition of the association between CV diseases and tumorigenesis. In addition to CV damage caused by anti-tumor drugs and tumor-induced organ dysfunction, CV events themselves and their treatment may also have a role in promoting tumorigenesis. Therefore, Therefore, the diagnosis and treatment of the two kinds of diseases have entered the era of clinical convergence. Emerging evidence indicates significant biologic overlap between cancer and CV diseases, with the recognition of shared biologic mechanisms. Neutrophil extracellular traps (NETs) represent an immune mechanism of neutrophils promoting the development of tumors and their metastasis. It has been recently demonstrated that NETs exist in various stages of hypertension and heart failure, exacerbating disease progression. At present, most studies focus on the biological role of NETs in CV diseases and tumor respectively, and there are relatively few studies on the specific regulatory mechanisms and effects of NETs in cardiovascular diseases associated with tumors. In this narrative review, we summarize some recent basic and clinical findings on how NETs are involved in the pathogenesis of cardiovascular diseases associated with tumors. We also highlight that the development of treatments targeting NETs may be one of the effective ways to prevent and treat cardiovascular diseases associated with tumors.

Engineered Bacillus subtilis Biofilm@Biochar living materials for in-situ sensing and bioremediation of heavy metal ions pollution.

The simultaneous sensing and remediation of multiple heavy metal ions in wastewater or soil with microorganisms is currently a significant challenge. In this study, the microorganism Bacillus subtilis was used as a chassis organism to construct two genetic circuits for sensing and adsorbing heavy-metal ions. The engineered biosensor can sense three heavy metal ions (0.1-75 µM of Pb2+ and Cu2+, 0.01-3.5 µM of Hg2+) in situ real-time with high sensitivity. The engineered B. subtilis TasA-metallothionein (TasA-MT) biofilm can specifically adsorb metal ions from the environment, exhibiting remarkable removal efficiencies of 99.5% for Pb2+, 99.9% for Hg2+and 99.5% for Cu2+ in water. Furthermore, this engineered strain (as a biosensor and absorber of Pb2+, Cu2+, and Hg2+) was incubated with biochar to form a hybrid biofilm@biochar (BBC) material that could be applied in the bioremediation of heavy metal ions. The results showed that BBC material not only significantly reduced exchangeable Pb2+ in the soil but also reduced Pb2+ accumulation in maize plants. In addition, it enhanced maize growth and biomass. In conclusion, this study examined the potential applications of biosensors and hybrid living materials constructed using sensing and adsorption circuits in B. subtilis, providing rapid and cost-effective tools for sensing and remediating multiple heavy metal ions (Pb2+, Hg2+, and Cu2+).

RBM25 regulates hypoxic cardiomyocyte apoptosis through CHOP-associated endoplasmic reticulum stress.

Ischemic heart failure (HF) is one of the leading causes of global morbidity and mortality; blocking the apoptotic cascade could help improve adverse outcomes of it. RNA-binding motif protein 25 (RBM25) is an RNA-binding protein related to apoptosis; however, its role remains unknown in ischemic HF. The main purpose of this study is to explore the mechanism of RBM25 in ischemic HF. Establishing an ischemic HF model and oxygen-glucose deprivation (OGD) model. ELISA was performed to evaluate the BNP level in the ischemic HF model. Echocardiography and histological analysis were performed to assess cardiac function and infarct size. Proteins were quantitatively and locationally analyzed by western blotting and immunofluorescence. The morphological changes of endoplasmic reticulum (ER) were observed with ER-tracker. Cardiac function and myocardial injury were observed in ischemic HF rats. RBM25 was elevated in cardiomyocytes of hypoxia injury hearts and localized in nucleus both in vitro and in vivo. In addition, cell apoptosis was significantly increased when overexpressed RBM25. Moreover, ER stress stimulated upregulation of RBM25 and promoted cell apoptosis through the CHOP related pathway. Finally, inhibiting the expression of RBM25 could ameliorate the apoptosis and improve cardiac function through blocking the activation of CHOP signaling pathway. RBM25 is significantly upregulated in ischemic HF rat heart and OGD model, which leads to apoptosis by modulating the ER stress through CHOP pathway. Knockdown of RBM25 could reverse apoptosis-mediated cardiac dysfunction. RBM25 may be a promising target for the treatment of ischemic HF.

Early growth response-1: Key mediators of cell death and novel targets for cardiovascular disease therapy.

Significance: Cardiovascular diseases are seen to be a primary cause of death, and their prevalence has significantly increased across the globe in the past few years. Several studies have shown that cell death is closely linked to the pathogenesis of cardiovascular diseases. Furthermore, many molecular and cellular mechanisms are involved in the pathogenesis of the cardiac cell death mechanism. One of the factors that played a vital role in the pathogenesis of cardiac cell death mechanisms included the early growth response-1 (Egr-1) factor. Recent Advances: Studies have shown that abnormal Egr-1 expression is linked to different animal and human disorders like heart failure and myocardial infarction. The biosynthesis of Egr-1 regulates its activity. Egr-1 can be triggered by many factors such as serum, cytokines, hormones, growth factors, endotoxins, mechanical injury, hypoxia, and shear stress. It also displays a pro-apoptotic effect on cardiac cells, under varying stress conditions. EGR1 mediates a broad range of biological responses to oxidative stress and cell death by combining the acute changes occurring in the cellular environment with sustained changes in gene expression. Future Directions: The primary regulatory role played by the Egr-1-targeting DNAzymes, microRNAs, and oligonucleotide decoy strategies in cardiovascular diseases were identified to provide a reference to identify novel therapeutic targets for cardiovascular diseases.

Effect of sacubitril/valsartan or valsartan on ventricular remodeling and myocardial fibrosis in perimenopausal women with hypertension.

OBJECTIVE: To evaluate the impact of sacubitril/valsartan on blood pressure (BP), ventricular structure, and myocardial fibrosis compared with valsartan in perimenopausal hypertensive women. METHODS: This prospective, randomized, actively controlled, open-label study included 292 women with perimenopausal hypertension. They were randomly divided into two groups: sacubitril/valsartan 200 mg once daily and valsartan 160 mg once daily for 24 weeks. The relevant indicators of ambulatory BP, echocardiography, and myocardial fibrosis regulation were assessed at baseline and at 24 weeks. RESULTS: The 24-h mean SBP after 24 weeks of treatment was 120.08 ±â€Š10.47 mmHg in the sacubitril/valsartan group versus 121.00 ±â€Š9.76 mmHg in the valsartan group ( P  = 0.457). After 24 weeks of treatment, there was no difference in central SBP between the sacubitril/valsartan and valsartan groups (117.17 ±â€Š11.63 versus 116.38 ±â€Š11.58, P  = 0.568). LVMI in the sacubitril/valsartan group was lower than that in the valsartan group at week 24 ( P  = 0.009). LVMI decreased by 7.23 g/m 2 from the baseline in the sacubitril/valsartan group and 3.70 g/m 2 in the valsartan group at 24 weeks ( P  = 0.000 versus 0.017). A statistically significant difference in LVMI between the two groups was observed at 24 weeks after adjusting for the baseline LVMI ( P  = 0.001). The levels of α-smooth muscle actin (α-SMA), connective tissue growth factor (CT-GF) and transforming growth factor-ß (TGF-ß) were reduced in the sacubitril/valsartan group compared with the baseline ( P  = 0.000, 0.005, and 0.000). LVMI between the two groups was statistically significant at 24 weeks after correcting for confounding factors 24-h mean SBP and 24-h mean DBP ( P  = 0.005). The LVMI, serum TGF-ß, α-SMA, and CT-GF remained statistically significant between the two groups after further correcting the factors of age, BMI, and sex hormone levels ( P  < 0.05). CONCLUSION: Sacubitril/valsartan could reverse ventricular remodeling more effectively than valsartan. The different effects of these two therapies on ventricular remodeling in perimenopausal hypertensive women might be because of their different effects on the down-regulation of fibrosis-related factors.

Metal-Binding Proteins Cross-Linking with Endoplasmic Reticulum Stress in Cardiovascular Diseases.

The endoplasmic reticulum (ER), an essential organelle in eukaryotic cells, is widely distributed in myocardial cells. The ER is where secreted protein synthesis, folding, post-translational modification, and transport are all carried out. It is also where calcium homeostasis, lipid synthesis, and other processes that are crucial for normal biological cell functioning are regulated. We are concerned that ER stress (ERS) is widespread in various damaged cells. To protect cells' function, ERS reduces the accumulation of misfolded proteins by activating the unfolded protein response (UPR) pathway in response to numerous stimulating factors, such as ischemia or hypoxia, metabolic disorders, and inflammation. If these stimulatory factors are not eliminated for a long time, resulting in the persistence of the UPR, it will aggravate cell damage through a series of mechanisms. In the cardiovascular system, it will cause related cardiovascular diseases and seriously endanger human health. Furthermore, there has been a growing number of studies on the antioxidative stress role of metal-binding proteins. We observed that a variety of metal-binding proteins can inhibit ERS and, hence, mitigate myocardial damage.

Establishment of an Individual-Specific Nomogram for Predicting the Risk of Left Ventricular Hypertrophy in Chinese Postmenopausal Hypertensive Women.

Background and Objectives: The physiological phenomenon peculiar to women, namely menopause, makes the occurrence of left ventricular hypertrophy (LVH) in postmenopausal hypertensive women more characteristic. Less is known about the risk of developing LVH in Chinese postmenopausal hypertensive women. Thus, the present study was intended to design a nomogram for predicting the risk of developing LVH in Chinese postmenopausal hypertensive women. Materials and Methods: Postmenopausal hypertensive women aged between 49 and 68 years were divided into either the training set (n = 550) or the validation set (n = 284) in a 2:1 ratio. Patients in the validation set were followed up for one year. A stepwise multivariable logistic regression model was used to assess the predictors of LVH in postmenopausal women with hypertension. The best-fit nomogram was executed using R software. The calibration and decision curve were employed to verify the predictive accuracy of the nomogram. The results were evaluated in the validation set. Results: Menopause age (OR = 0.929, 95% CI 0.866-0.998, p = 0.044), BMI (OR = 1.067, 95% CI 1.019-1.116, p = 0.005), morning systolic blood pressure (SBP: OR = 1.050, 95% CI 1.032-1.069, p = 0.000), morning diastolic BP (DBP OR = 1.055, 95% CI 1.028-1.083, p = 0.003), angiotensin II receptor blocker (ARB) utilization rate (OR = 0.219, 95% CI 0.131-0.365, p = 0.000), LDL-C (OR = 1.460, 95% CI 1.090-1.954, p = 0.011) and cardio-ankle vascular index (CAVI) (OR = 1.415, 95% CI 1.139-1.757, p = 0.028) were associated with LVH in postmenopausal hypertension patients. The nomogram model was then developed using these variables. The internal validation trial showed that the nomogram model described herein had good performance in discriminating a C-index of 0.881 (95% CI: 0.837-0.924) and high quality of calibration plots. External validation of LVH-predictive nomogram results showed that the area under the ROC curve was 0.903 (95%CI 0.900-0.907). Conclusions: Our results indicate that the risk prediction nomogram model based on menopausal age, BMI, morning SBP, morning DBP, ARB utilization rate, LDL-C and CAVI has good accuracy and may provide useful references for the medical staff in the intuitive and individualized risk assessment in clinical practice.

A preparation strategy for protein-oriented immobilized silica magnetic beads with Spy chemistry for ligand fishing.

Due to the complexity of bioactive ingredients in biological samples, the screening of target proteins is a complex process. Herein, a feasible strategy for directing protein immobilization on silica magnetic beads for ligand fishing based on SpyTag/SpyCatcher (ST/SC)-mediated anchoring is presented. Carboxyl functional groups on the surface of silica-coated magnetic beads (SMBs) were coupled with SC using the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxysulfosuccinimide method, named SC-SMBs. The green fluorescent protein (GFP), as the capturing protein model, was ST-labeled and anchored at a specific orientation onto the surface of SC-SMBs directly from relevant cell lysates via ST/SC self-ligation. The characteristics of the SC-SMBs were studied via electron microscopy, energy dispersive spectroscopy, and Fourier transform infrared spectroscopy. The spontaneity and site-specificity of this unique reaction were confirmed via electrophoresis and fluorescence analyses. Although the alkaline stability of ST-GFP-ligated SC-SMBs was not ideal, the formed isopeptide bond was unbreakable under acidic conditions (0.05 M glycine-HCl buffer, pH 1-6) for 2 h, under 20% ethanol solution within 7 days, and at most temperatures. We, therefore, present a simple and universal strategy for the preparation of diverse protein-functionalized SMBs for ligand fishing, prompting its usage on drug screening and target finding.

Preparation and properties of N-glycosylated chitosan/polyvinyl alcohol hydrogels for use in wound dressings.

Chitosan and its derivatives show potent biocompatibility, biodegradability, antimicrobial activity, hemostatic effects, and wound healing properties. Their application in wound dressings has garnered substantial research interest. In this work, we prepared a drug-loaded hydrogel by mixing N-glycosylated chitosan with polyvinyl alcohol (PVA), followed by loading of ofloxacin. A 2:1 volume ratio of chitosan to PVA was found to be optimal based on swelling and water evaporation rates. The slow-drug-release performance of the blended hydrogel was best when the ofloxacin loading was 5.0%. The ofloxacin-loaded hydrogel shows excellent antimicrobial properties in vitro and wound healing ability in an in vivo rabbit full-thickness excision wound model. The chitosan/PVA blended hydrogel has great potential for use in wound dressings and sustained drug release.

mTOR inhibitor improves testosterone-induced myocardial hypertrophy in hypertensive rats.

Compelling evidence has described that the incidence of hypertension and left ventricular hypertrophy (LVH) in postmenopausal women is significantly increased worldwide. Our team's previous research identified that androgen was an underlying factor contributing to increased blood pressure and LVH in postmenopausal women. However, little is known about how androgens affect LVH in postmenopausal hypertensive women. The purpose of this study was to evaluate the role of mammalian rapamycin receptor (mTOR) signaling pathway in myocardial hypertrophy in androgen-induced postmenopausal hypertension and whether mTOR inhibitors can protect the myocardium from androgen-induced interference to prevent and treat cardiac hypertrophy. For that, ovariectomized (OVX) spontaneously hypertensive rats (SHR) aged 12 weeks were used to study the effects of testosterone (T 2.85 mg/kg/weekly i.m.) on blood pressure and myocardial tissue. On the basis of antihypertensive therapy (chlorthalidone 8 mg/kg/day ig), the improvement of blood pressure and myocardial hypertrophy in rats treated with different dose gradients of rapamycin (0.8 mg/kg/day vs 1.5 mg/kg/day vs 2 mg/kg/day i.p.) in OVX + estrogen (E 9.6 mg/kg/day, ig) + testosterone group was further evaluated. After testosterone intervention, the OVX female rats exhibited significant increments in the heart weight/tibial length (TL), area of cardiomyocytes and the mRNA expressions of ANP, ß-myosin heavy chain and matrix metalloproteinase 9 accompanied by a significant reduction in the uterine weight/TL and tissue inhibitor of metalloproteinase 1. mTOR, ribosomal protein S6 kinase (S6K1), 4E-binding protein 1 (4EBP1) and eukaryotic translation initiation factor 4E in myocardial tissue of OVX + estrogen + testosterone group were expressed at higher levels than those of the other four groups. On the other hand, rapamycin abolished the effects of testosterone-induced cardiac hypertrophy, decreased the systolic and diastolic blood pressure of SHR, and inhibited the activation of mTOR/S6K1/4EBP1 signaling pathway in a concentration-dependent manner. Collectively, these data suggest that the mTOR/S6K1/4EBP1 pathway is an important therapeutic target for the prevention of LVH in postmenopausal hypertensive female rats with high testosterone levels. Our findings also support the standpoint that the mTOR inhibitor, rapamycin, can eliminate testosterone-induced cardiomyocyte hypertrophy.

Rho kinase inhibition ameliorates vascular remodeling and blood pressure elevations in a rat model of apatinib-induced hypertension.

OBJECTIVES: Hypertension is one of the major adverse effects of tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factors. However, the mechanism underlying TKIs-induced hypertension remains unclear. Here, we explored the role of the RhoA/Rho kinase (ROCK) signaling pathway in elevation of blood pressure (BP) induced by apatinib, a selective TKI approved in China for treatment of advanced or metastatic gastric cancer. A nonspecific ROCK inhibitor, Y27632, was then combined with apatinib and its efficacy in alleviating apatinib-induced hypertension was evaluated. METHODS: Normotensive female Wistar-Kyoto rats were exposed to two different doses of apatinib, or apatinib combined with Y27632, or vehicle for 2 weeks. BP was monitored by a tail-cuff plethysmography system. The mRNA levels and protein expression in the RhoA/ROCK pathway were determined, and vascular remodeling assessed. RESULTS: Administration of either a high or low dose of apatinib was associated with a rapid rise in BP, reaching a plateau after 12 days. Apatinib treatment mediated upregulation of RhoA and ROCK II in the mid-aorta, more significant in the high-dose group. However, ROCK I expression showed no statistically significant differences. Furthermore, the mRNA level of GRAF3 decreased dose-dependently. Apatinib administration was also associated with decreased levels of MLCP, and elevated endothelin-1 (ET-1) and collagen I, which were accompanied with increased mid-aortic media. However, treatment with Y27632 attenuated the above changes. CONCLUSION: These findings suggest that activation of the RhoA/ROCK signaling pathway could be the underlying mechanism of apatinib-induced hypertension, while ROCK inhibitor have potential therapeutic value.

A preparation strategy for protein-oriented immobilized silica magnetic beads with Spy chemistry for ligand fishing / 药物分析学报

Due to the complexity of bioactive ingredients in biological samples,the screening of target proteins is a complex process.Herein,a feasible strategy for directing protein immobilization on silica magnetic beads for ligand fishing based on SpyTag/SpyCatcher(ST/SC)-mediated anchoring is presented.Carboxyl functional groups on the surface of silica-coated magnetic beads(SMBs)were coupled with SC using the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysulfosuccinimide method,named SC-SMBs.The green fluorescent protein(GFP),as the capturing protein model,was ST-labeled and anchored at a specific orientation onto the surface of SC-SMBs directly from relevant cell lysates via ST/SC self-ligation.The characteristics of the SC-SMBs were studied via electron microscopy,energy dispersive spectroscopy,and Fourier transform infrared spectroscopy.The spontaneity and site-specificity of this unique reaction were confirmed via electrophoresis and fluorescence analyses.Although the alkaline stability of ST-GFP-ligated SC-SMBs was not ideal,the formed isopeptide bond was unbreakable under acidic conditions(0.05 M glycine-HCl buffer,pH 1-6)for 2 h,under 20％ethanol solution within 7 days,and at most temperatures.We,therefore,present a simple and universal strategy for the preparation of diverse protein-functionalized SMBs for ligand fishing,prompting its usage on drug screening and target finding.

Effect of free androgen index on blood pressure variability and target organ damage in postmenopausal hypertensive women: findings from a cross-sectional study.

OBJECTIVE: The present study investigated the effects of free androgen index (FAI) on ambulatory blood pressure (ABP) and target organ function in postmenopausal hypertensive women. METHODS: A total of 285 postmenopausal hypertensive women (mean age 54.06 ±â€Š3.61) were admitted to the Department of Hypertension of Lanzhou University Second Hospital between December 2018 and December 2020. According to the serum FAI level, the participants were divided into a low-FAI (<0.15) group, a medium-FAI (0.15-0.2) group, and a high-FAI (>0.2) group. The relationship of FAI with 24-hour ABP, left ventricular mass index (LVMI), and cardio-ankle vascular index (CAVI) was analyzed. RESULTS: The LVMI, CAVI, 24-hour mean systolic blood pressure (SBP), 24-hour SBP coefficient of variation and 24-hour SBP standard deviation, 24-hour SBP average real variation (ARV), and 24-hour diastolic blood pressure (DBP) ARV in high-FAI group were significantly higher than those in low- and medium-FAI groups (P < 0.05). After adjusting for confounding factors, partial correlation analysis showed that FAI was positively correlated with LVMI (r = 0.728, P < 0.001), CAVI (left: r = 0.718, P < 0.001; right: r = 0.742, P < 0.001), 24-hour SBP ARV (r = 0.817, P < 0.001), and 24-hour DBP ARV (r = 0.747, P < 0.001). After adjusting for confounding factors, it was found that LVMI increased by 17.64 g/m2 for every 1 unit increase in FAI. CAVI also increased by 8.983 for every additional unit of FAI. In addition, the results also showed that LVMI and CAVI decreased respectively by 0.198 g/m2 and 0.009 for every 1 unit increase in sex hormone-binding globulin. Multivariable linear regression showed that FAI was an independent risk factor for 24-hour SBP ARV (OR: 20.416, 95% CI 8.143-32.688, P = 0.001) and 24-hour DBP ARV (OR: 16.539, 95% CI 0.472-32.607, P = 0.044). The results also showed that sex hormone-binding globulin was an independent factor of 24-hour SBP ARV (OR: -0.022, 95% CI -0.044 to 0.000, P = 0.048) and 24-hour DBP-ARV (OR: -0.018, 95% CI -0.029 to -0.008, P = 0.001). CONCLUSION: Higher serum FAI levels in postmenopausal hypertensive women indicate abnormal BP regulation and more serious target organ damage. FAI is closely related to 24-hour SBP ARV and 24-hour DBP ARV in postmenopausal hypertensive women.

Effects of hormone replacement therapy on left ventricular diastolic function in postmenopausal women: a systematic review and meta-analysis.

BACKGROUND: Postmenopausal women tend to experience significant changes in left ventricular diastolic function (LVDF). However, there are conflicting reports about LVDF between postmenopausal women on hormone replacement therapy (HRT) and those not on HRT. This meta-analysis is to evaluate the effects of HRT on LVDF in postmenopausal women. METHODS: We conducted a systemic review of randomized controlled trials published up to December 31 2019 using Embase, Pubmed, and the Cochrane library database. RESULTS: Eight studies involving 668 postmenopausal women were identified. Our analysis indicated that the ratio of the peak velocity during early filing to late filling from atrial contraction improvement in HRT group was better than that in placebo group (MD 0.20, 95%CI 0.12 to 0.28). There was a significant reduction in deceleration time and left ventricular mass index in HRT group compared with placebo group (MD -21.01, 95%CI -40.11 to -1.91 vs MD -8.26, 95%CI -14.10 to -2.42). No significant difference was observed in left ventricular end systole diameter (MD 0.80, 95%CI -0.72 to 2.31), left ventricular end diastole diameter (MD -0.07, 95%CI -1.25 to 1.10), left atrial size (MD -0.33, 95%CI -1.34 to 0.68)and the isovolumic relaxation time (MD -12.08, 95%CI -27.65 to 3.5). CONCLUSIONS: Our meta-analysis illustrated that postmenopausal women seem to obtain more beneficial effects from HRT on LVDF, though future studies are required to elucidate the specific mechanisms for this phenomenon.

Comparative efficacy of different types of antihypertensive drugs in reversing left ventricular hypertrophy as determined with echocardiography in hypertensive patients: A network meta-analysis of randomized controlled trials.

Reversing left ventricular hypertrophy (LVH) can reduce the incidence of adverse cardiovascular events. However, there is no clear superiority-inferiority differentiation between angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta-blockers (BB), calcium channel blockers (CCB), and diuretics in reversing LVH in hypertensive patients. To provide further evidence for choosing the optimal antihypertensive drug for improving LVH, we performed a network meta-analysis of randomized controlled trials (RCTs) based on the Cochrane library database, Embase, and Pubmed, and identified 49 studies involving 5402 patients that were eligible for inclusion. It was found that ARB could improve LVH in hypertensive patients more effectively than CCB (MD -4.07, 95%CI -8.03 to -0.24) and BB (MD -4.57, 95%CI -8.07 to -1.12). Matched comparison of renin-angiotensin system inhibitors (RASi) showed that the effect of ACEI in reducing left ventricular mass index (LVMi) was not effective as that of ARB (MD -3.72, 95%CI -7.52 to -0.11). The surface under the cumulative ranking for each intervention indicated that the use of ARB was more effective among the different types of antihypertensive drugs (97%). This network meta-analysis revealed that the use of ARB in antihypertensive therapy could achieve better efficacy in reversing LVH in hypertensive patients.

Prognostic value of heart failure echocardiography index in HF patients with preserved, mid-ranged and reduced ejection fraction.

BACKGROUND: To investigate the clinical value of heart failure echocardiography index (HFEI) in evaluating the cardiac function and predicting the prognosis of patients with different types of heart failure (HF). METHODS: Four hundred eighty-nine consecutively admitted HF patients were divided into three groups: HF with reduced ejection (HFrEF), HF with mid-range ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). The baseline characteristics and ultrasound indexes were compared between the three groups. The correlation between HFEI and one-year risk of adverse events was compared by multivariate logistic regression. The clinical value of HFEI and plasma level of NT-proBNP in assessing the prognosis of patients with chronic heart failure (CHF) was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: HFEI in HFrEF was significantly higher than that in HFmrEF and HFpEF. Multivariate regression analysis indicated that HFEI and plasma level of NT-proBNP were independent risk factors for predicting the short-time prognosis of HF patients. The ROC curve indicated that the HFEI cutoff level of 3.5 and the plasma NT-proBNP level of 3000 pg/ml predicted a poor prognosis of CHF patients with a sensitivity of 64% and a specificity of 75% vs. 68 and 65%. CONCLUSION: HFEI can comprehensively evaluate the overall cardiac function of patients with various types of HF, and may prove to be an important index of assessing the prognosis of HF patients.

Functional dissection of HGGT and HPT in barley vitamin E biosynthesis via CRISPR/Cas9-enabled genome editing.

BACKGROUND AND AIMS: Vitamin E (tocochromanol) is a lipid-soluble antioxidant and an essential nutrient for human health. Among cereal crops, barley (Hordeum vulgare) contains a high level of vitamin E, which includes both tocopherols and tocotrienols. Although the vitamin E biosynthetic pathway has been characterized in dicots, such as Arabidopsis, which only accumulate tocopherols, knowledge regarding vitamin E biosynthesis in monocots is limited because of the lack of functional mutants. This study aimed to obtain gene knockout mutants to elucidate the genetic control of vitamin E composition in barley. METHODS: Targeted knockout mutations of HvHPT and HvHGGT in barley were created with CRISPR/Cas9-enabled genome editing. High-performance liquid chromatography (HPLC) was performed to analyse the content of tocochromanol isomers in transgene-free homozygous Hvhpt and Hvhggt mutants. KEY RESULTS: Mutagenesis efficiency among T0 regenerated plantlets was 50-65 % as a result of two simultaneously expressed guide RNAs targeting each gene; most of the mutations were stably inherited by the next generation. The transgene-free homozygous mutants of Hvhpt and Hvhggt exhibited decreased grain size and weight, and the HvHGGT mutation led to a shrunken phenotype and significantly lower total starch content in grains. HPLC analysis revealed that targeted mutation of HvHPT significantly reduced the content of both tocopherols and tocotrienols, whereas mutations in HvHGGT completely blocked tocotrienol biosynthesis in barley grains. Transient overexpression of an HvHPT homologue in tobacco leaves significantly increased the production of γ- and δ-tocopherols, which may partly explain why targeted mutation of HvHPT in barley grains did not eliminate tocopherol production. CONCLUSIONS: Our results functionally validated that HvHGGT is the only committed gene for the production of tocotrienols, whereas HvHPT is partly responsible for tocopherol biosynthesis in barley.