New phorbol ester derivatives as potent anti-HIV agents.

Tigliane esters show many biological activities, including anti-HIV-1 activity. Our aim in this study was to establish structure-anti-HIV activity relationships for four series of tigliane-type diterpenoids. We synthesized and evaluated 29 new phorbol ester derivatives for anti-HIV activity and for cytotoxicity against human tumor cell lines. Among them, three derivatives, two phorbol-13-monoesters (5d and 5e) and a phorbol-12,13-diester (6a), showed significant anti-HIV activity. We found that better anti-HIV activity was often associated with a shorter acyl ester at C-13. Particularly, compounds with a phenyl ring in the ester side chain exhibited excellent anti-HIV activity and had good safety indexes. Due to its significant anti-HIV potency with a high selectivity index, phorbol-12,13-dicinnamoate (6a) was chosen as the potential candidate for further preclinical trials.

Synthesis and in vitro anticancer activities of biotinylated derivatives of glaucocalyxin A and oridonin.

Fourteen glaucocalyxin A biotinylated derivatives, one glaucocalyxin C biotinylated derivative, and two oridonin biotinylated derivatives were designed and synthesized. Their structures were confirmed from 1H NMR, 13C NMR and HRMS data. The derivatives were evaluated for cytotoxic activities against lung (A549), cervical cancer cell line HeLa derivative (KB), multidrug-resistant KB subline (KB-VIN), triple-negative breast (MDA-MB-231), and estrogen receptor-positive breast (MCF-7) cancer cell lines.[Formula: see text].

Diagnosis and Grading of Prostate Cancer by Relaxation Maps From Synthetic MRI.

BACKGROUND: The interpretation system for prostate MRI is largely based on qualitative image contrast of different tissue types. Therefore, a fast, standardized, and robust quantitative technique is necessary. Synthetic MRI is capable of quantifying multiple relaxation parameters, which might have potential applications in prostate cancer (PCa). PURPOSE: To investigate the use of quantitative relaxation maps derived from synthetic MRI for the diagnosis and grading of PCa. STUDY TYPE: Prospective. SUBJECTS: In all, 94 men with pathologically confirmed PCa or benign pathological changes. FIELD STRENGTH/SEQUENCE: T1 -weighted imaging, T2 -weighted imaging, diffusion-weighted imaging, and synthetic MRI at 3.0T. ASSESSMENT: Four kinds of tissue types were identified on pathology, including PCa, stromal hyperplasia (SH), glandular hyperplasia (GH), and noncancerous peripheral zone (PZ). PCa foci were grouped as low-grade (LG, Gleason score ≤6) and intermediate/high-grade (HG, Gleason score ≥7). Regions of interest were manually drawn by two radiologists in consensus on parametric maps according to the pathological results. STATISTICAL TESTS: Independent sample t-test, Mann-Whitney U-test, and receiver operating characteristic curve analysis. RESULTS: T1 and T2 values of PCa were significantly lower than SH (P = 0.015 and 0.002). The differences of T1 and T2 values between PCa and noncancerous PZ were also significant (P ≤ 0.006). The area under the curve (AUC) of the apparent diffusion coefficient (ADC) value was significantly higher than T1 , T2 , and proton density (PD) values in discriminating PCa from SH and noncancerous PZ (P ≤ 0.025). T2 , PD, and ADC values demonstrated similar diagnostic performance in discriminating LG from HG PCa (AUC = 0.806 [0.640-0.918], 0.717 [0.542-0.854], and 0.817 [0.652-0.925], respectively; P ≥ 0.535). DATA CONCLUSION: Relaxation maps derived from synthetic MRI were helpful for discriminating PCa from other benign pathologies. But the overall diagnostic performance was inferior to the ADC values. T2 , PD, and ADC values performed similarly in discriminating LG from HG PCa lesions. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;52:552-564.

The therapeutic effects of Jaceosidin on lipopolysaccharide-induced acute lung injury in mice.

Acute lung injury (ALI) results from various factors including uncontrolled pulmonary inflammation, oxidative damage and the over-activated complement with high mortality rates. Jaceosidin was a flavonoid compound with significant anti-complement activity. We aimed to investigate the therapeutic effects of Jaceosidin on ALI induced by lipopolysaccharide (LPS). Mice were orally administrated with Jaceosidin (15, 30 and 60 mg/kg) after LPS challenge. 24 h after LPS challenge, Jaceosidin could significantly decrease the lung wet-to-dry weight (W/D) ratio and the protein concentration in bronchoalveolar lavage fluid (BALF). Jaceosidin could down-regulate the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), together with up-regulation the levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) in BALF. Jaceosidin could significantly decrease the levels of myeloperoxidase (MPO), cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB), COX-2 mRNA and NF-κB p65 mRNA together with increasing the activity of catalase (CAT). Additionally, Jaceosidin attenuated lung histopathological changes, inhibited the expressions of COX-2 and NF-κB p65 and reduced complement deposition with decreasing the levels of complement 3 (C3) and complement 3c (C3c) in serum. These data suggest that Jaceocidin may dampen the inflammatory response and decrease the levels of complement together with the antioxidant activity following LPS-induced ALI.

Associations between renal function, hippocampal volume, and cognitive impairment in 544 outpatients.

Background: Cognitive impairment and brain atrophy are common in chronic kidney disease patients. It remains unclear whether differences in renal function, even within normal levels, influence hippocampal volume (HCV) and cognition. We aimed to investigate the association between estimated glomerular filtration rate (eGFR), HCV and cognition in outpatients. Methods: This single-center retrospective study enrolled 544 nonrenal outpatients from our hospital. All participants underwent renal function assessment and 3.0 T magnetic resonance imaging (MRI) in the same year. HCV was also measured, and cognitive assessments were obtained. The correlations between eGFR, HCV, and cognitive function were analyzed. Logistic regression analysis was performed to identify the risk factors for hippocampal atrophy and cognitive impairment. Receiver-operator curves (ROCs) were performed to find the cut-off value of HCV that predicts cognitive impairment. Results: The mean age of all participants was 66.5 ± 10.9 years. The mean eGFR of all participants was 88.5 ± 15.1 mL/min/1.73 m2. eGFR was positively correlated with HCV and with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Univariate and multivariate logistic regression analysis showed Age ≥ 65 years, eGFR < 75 mL/min/1.73 m2, Glucose ≥6.1 mmol/L and combined cerebral microvascular diseases were independent risk factors for hippocampal atrophy and Age ≥ 65 years, left hippocampal volume (LHCV) <2,654 mm3 were independent risk factors for cognitive impairment in outpatients. Although initial unadjusted logistic regression analysis indicated that a lower eGFR (eGFR < 75 mL/min/1.73 m2) was associated with poorer cognitive function, this association was lost after adjusting for confounding variables. ROC curve analysis demonstrated that LHCV <2,654 mm3 had the highest AUROC [(0.842, 95% CI: 0.808-0.871)], indicating that LHCV had a credible prognostic value with a high sensitivity and specificity for predicting cognitive impairment compared with age in outpatients. Conclusion: Higher eGFR was associated with higher HCV and better cognitive function. eGFR < 75 mL/min/1.73 m2 was an independent risk factor for hippocampal atrophy after adjusting for age. It is suggested that even eGFR < 75 mL/min/1.73 m2, lower eGFR may still be associated with hippocampal atrophy, which is further associated with cognitive impairment. LHCV was a favorable prognostic marker for predicting cognitive impairment rather than age.

Diagnostic efficacy of complexity metrics from cardiac MRI myocardial segmental motion curves in detecting late gadolinium enhancement in myocardial infarction patients.

Background: Myocardial segmental motion is associated with cardiovascular pathology, often assessed through myocardial strain features. The stability of the motion can be influenced by myocardial fibrosis. This research aimed to explore the complexity metrics (CM) of myocardial segmental motion curves, observe their correlation with late gadolinium enhancement (LGE) transmural extension (TE), and assess diagnostic efficacy combined with segmental strains in different TE segments. Methods: We included 42 myocardial infarction patients, dividing images into 672 myocardial segments (208 remote, 384 viable, and 80 unviable segments based on TE). Radial and circumferential segmental strain, along with CM for motion curves, were extracted. Correlation between CM and LGE, as well as the potential distinguishing role of CM, was evaluated using Pearson correlation, univariate linear regression (F-test), multivariate regression analysis (T-test), area under curve (AUC), machine learning models, and DeLong test. Results: All CMs showed significant linear correlation with TE (P < 0.001). Six CMs were correlated with TE (r > 0.3), with radial frequency drift (FD) displayed the strongest correlation (r = 0.496, P < 0.001). Radial and circumferential FD significantly differed in higher TE myocardium than in remote segments (P < 0.05). Radial FD had practical diagnostic efficacy (remote vs. unviable AUC = 0.89, viable vs. unviable AUC = 0.77, remote vs. viable AUC = 0.65). Combining CM with segmental strain features boosted diagnostic efficacy than models using only segmental strain features (DeLong test, P < 0.05). Conclusions: The CM of myocardial motion curves has been associated with LGE infarction, and combining CM with strain features improves the diagnosis of different myocardial LGE infarction degrees.

Fermented blueberry pomace supplementation improves egg quality, liver synthesis, and ovary antioxidant capacity of laying hens.

The present study aimed to investigate the effects of dietary fermented blueberry pomace (FBP) supplementation on production performance, egg quality and nutritional value, plasma biochemical parameters, follicle number, reproductive hormones, lipid metabolism, and antioxidant capacity of laying hens during the late laying period. A total of 320 (345-d-old) Yukou Jingfen No. 8 laying hens were randomly divided into 4 groups, with eight replicates per group and 10 hens per replicate. The birds were fed a basal diet (control group) and a basal diet supplemented with 0.25, 0.5, and 1.0% FBP. The trial lasted 56 d. The results showed that FBP (0.25-1.0%) supplementation increased the egg albumen height and Haugh unit compared with the control group on d 14, while 0.5 to 1.0% FBP increased the eggshell thickness compared with the 0.25% FBP group on d 28 of the trial (P < 0.05). The methionine content in egg white was higher (P < 0.05) in the 1.0% FBP group compared with the 0.25% FBP group. The CAT activity in the ovary was increased (P < 0.05) in the FBP groups compared with the control group, while plasma GSH-PX activity was higher (P < 0.05) in the 1.0% FBP group compared with the 0.25% FBP and 0.5% FBP groups. Dietary FBP supplementation up-regulated (P < 0.05) gene expressions related to lipid metabolism in the liver (ACC, FAS, SCD1, and SREBP1) and yolk precursor synthesis (ESR2 and VTG II). Moreover, CYP11A1 expression in the ovary was up-regulated (P < 0.05) in the FBP groups compared with the control group, as well as in the 0.25% FBP group compared with the 1.0% FBP group. In summary, dietary FBP supplementation improved egg quality and nutritional value, ovarian antioxidant capacity, and yolk precursor synthesis, while 1.0% FBP had better effects than 0.25 and 0.5% doses.

Fermented Aronia melanocarpa pomace improves the nutritive value of eggs, enhances ovarian function, and reshapes microbiota abundance in aged laying hens.

Introduction: There is a decline in the quality and nutritive value of eggs in aged laying hens. Fruit pomaces with high nutritional and functional values have gained interest in poultry production to improve the performance. Methods: The performance, egg nutritive value, lipid metabolism, ovarian health, and cecal microbiota abundance were evaluated in aged laying hens (320 laying hens, 345-day-old) fed on a basal diet (control), and a basal diet inclusion of 0.25%, 0.5%, or 1.0% fermented Aronia melanocarpa pomace (FAMP) for eight weeks. Results: The results show that 0.5% FAMP reduced the saturated fatty acids (such as C16:0) and improved the healthy lipid indices in egg yolks by decreasing the atherogenicity index, thrombogenic index, and hypocholesterolemia/hypercholesterolemia ratio and increasing health promotion index and desirable fatty acids (P < 0.05). Additionally, FAMP supplementation (0.25%-1.0%) increased (P < 0.05) the ovarian follicle-stimulating hormone, luteinizing hormone, and estrogen 2 levels, while 1.0% FAMP upregulated the HSD3B1 expression. The expression of VTG II and ApoVLDL II in the 0.25% and 0.5% FAMP groups, APOB in the 0.5% FAMP group, and ESR2 in the 1% FAMP group were upregulated (P < 0.05) in the liver. The ovarian total antioxidant capacity was increased (P < 0.05) by supplementation with 0.25%-1.0% FAMP. Dietary 0.5% and 1.0% FAMP downregulated (P < 0.05) the Keap1 expression, while 1.0% FAMP upregulated (P < 0.05) the Nrf2 expression in the ovary. Furthermore, 1.0% FAMP increased cecal acetate, butyrate, and valerate concentrations and Firmicutes while decreasing Proteobacteria (P < 0.05). Conclusion: Overall, FAMP improved the nutritive value of eggs in aged laying hens by improving the liver-blood-ovary function and cecal microbial and metabolite composition, which might help to enhance economic benefits.

Improving gut functions and egg nutrition with stevia residue in laying hens.

This study aimed to investigate the effect of stevia residue (STER) on the production performance, egg quality and nutrition, antioxidant ability, immune responses, gut morphology and microbiota of laying hens during the peak laying period. A total of 270 Yikoujingfen NO. 8 laying hens (35 wk of age) were randomly divided into 5 treatments. The control group fed a basal diet and groups supplemented with 2, 4, 6, and 8% STER. The results showed that STER significantly increased egg production, the content of amino acids (alanine, proline, valine, ornithine, asparagine, aspartic acid, and cysteine) in egg whites, and decreased the yolk color (P < 0.05). Additionally, STER significantly increased acetate, HOMOγ linolenic acid and cis-13, 16-docosadienoic acid levels in egg yolk (P < 0.05). IL-2, IL-4, and IL-10 levels in serum significantly increased by STER (P < 0.05), while IL-1ß significantly decreased (P < 0.05). STER also increased total antioxidant activity (T-AOC) in the liver and estradiol level in the oviduct (P < 0.05), but decreased the cortisol level in the oviduct (P < 0.05). For the intestinal morphology, the jejunal villus height and crypt-to-villus (V:C) significantly increased by STER (P < 0.05). STER increased the relative abundance of Actinobacteriota (P < 0.05), while deceased Proteobacteria, Desulfobacterota, and Synergistota (P < 0.05). In conclusion, STER improved egg production, quality and nutrition, improved the immune responses, antioxidant capabilities, estrogen level, gut morphology, and increased the relative abundance of beneficial bacteria while decreased the harmful bacteria. Among all treatments, 4 and 6% STER supplementation yielded the most favorable results in terms of enhancing production performance, egg nutrition, gut health, and immune capabilities in laying hens.

Jian Gan powder ameliorates immunological liver injury in mice by modulating the gut microbiota and metabolic profiles.

BACKGROUND: Immunological liver injury (ILI) is a common liver disease associated with the microbiota-gut-liver axis. Jian Gan powder (JGP) exhibits both protective and therapeutic effects on hepatitis virus-induced ILI in the clinic. However, the underlying mechanisms remain elusive. The aim of this study is to investigate the hepatoprotective effects and associated mechanisms of JGP in the context of gut microbiota, utilizing a mouse model of ILI. METHODS: The mouse model was established employing Bacillus Calmette-Guérin (BCG) plus lipopolysaccharide (LPS). Following treatment with JGP (7.5, 15, or 30 g/kg), serum, liver, and fresh fecal samples were analyzed. 16S rRNA gene sequencing and untargeted metabolomics profiling were performed to assess the role of JGP on the gut microbiota and its metabolites. RESULTS: JGP treatment markedly reduced serum IFN-γ, IL-6, IL-22, and hepatic p-STAT3 (phosphorylated transducer and activator of transcription-3) expression. In contrast, JGP increased the percentage of proliferating cell nuclear antigen-positive liver cells in treated mice. Fecal 16S rRNA gene sequencing revealed that JGP treatment restored the levels of Alloprevotella, Burkholderia-Caballeronia-Paraburkholderia, Muribaculum, Streptococcus, and Stenotrophomonas. Additionally, metabolomics analysis of fecal samples showed that JGP restored the levels of allylestrenol, eplerenone, phosphatidylethanolamine (PE) (P-20:0/0:0), sphingomyelin (SM) d27:1, soyasapogenol C, chrysin, and soyasaponin I. CONCLUSIONS: JGP intervention improves ILI by restoring gut microbiota and modifying its metabolic profiles. These results provide a novel insight into the mechanism of JGP in treating ILI and the scientific basis to support its clinical application.

Dietary Chinese herbal formula supplementation improves yolk fatty acid profile in aged laying hens.

Chinese herbal formula (CHF) has the potential to improve the performance of aged laying hens through integrated regulation of various physiological functions. The present study aimed to investigate the effects of dietary CHF supplementation on the yolk fatty acid profile in aged laying hens. A total of 144 healthy 307-day-old Xinyang black-feather laying hens were randomly allocated into two groups: a control group (CON, fed a basal diet) and a CHF group (fed a basal diet supplemented with 1% CHF; contained 0.30% Leonurus japonicus Houtt., 0.20% Salvia miltiorrhiza Bge., 0.25% Ligustrum lucidum Ait., and 0.25% Taraxacum mongolicum Hand.-Mazz. for 120 days). The fatty acid concentrations in egg yolks were analyzed using a targeted metabolomics technology at days 60 and 120 of the trial. The results showed that dietary CHF supplementation increased (p < .05) the concentrations of several saturated fatty acids (SFA, including myristic acid and stearic acid), monounsaturated fatty acids (MUFA, including petroselinic acid, elaidic acid, trans-11-eicosenoic acid, and cis-11-eicosenoic acid), polyunsaturated fatty acids (PUFA, including linolelaidic acid, linoleic acid, γ-linolenic acid, α-linolenic acid, 11c,14c-eicosadienoic acid, eicosatrienoic acid, homo-γ-linolenic acid, arachidonic acid, and docosapentaenoic acid), and fatty acid indexes (total MUFA, n-3 and n-6 PUFA, PUFA/SFA, hypocholesterolemic/hypercholesterolaemic ratio, health promotion index, and desirable fatty acids) in egg yolks. Collectively, these findings suggest that dietary CHF supplementation could improve the nutritional value of fatty acids in egg yolks of aged laying hens, which would be beneficial for the production of healthier eggs to meet consumer demands.

Chinese herb ultrafine powder supplementation improves egg nutritional value and quality in laying hens.

This study evaluates the effects of dietary Chinese herb ultrafine powder (CHUP) supplementation in late-phase laying hens on the quality and nutritional values of eggs. A total of 576 Xinyang black-feather laying hens (300-day-old) were randomly allocated into eight groups for a 120-day feeding trial. Each group contained eight replicates with nine hens per replicate. The experimental groups included the control (basal diet) and different levels of CHUP groups (details in 'Materials and methods'). The results showed that the eggshell strength was increased (p < 0.05) in the L, LF, L-LF, L-T, and LF-T groups on day 60 of the trial. In addition, the plasma estradiol level in the L-LF, LF-T, and L-LF-T groups and unsaturated fatty acids concentrations in egg yolk of the CHUP groups (except LF-T group) were increased, whereas total cholesterol (T, L-LF, L-T, and L-LF-T groups) in egg yolk and the atherogenicity (T, L-T, and L-LF-T groups) and thrombogenicity (T, L-LF, L-T, and L-LF-T groups) indexes were decreased (p < 0.05) on day 60 of the trial compared with the control group. Moreover, bitter amino acids in egg albumen were decreased (p < 0.05) in the L-LF group on day 60 and the L-LF-T group on day 120 of the trial. Collectively, these findings indicate that dietary CHUP supplementation could improve eggshell quality and increase plasma reproductive hormone, fatty acid and amino acid composition, and nutritional values of eggs, especially L-LF and L-LF-T.

Synthesis and anti-HIV activities of phorbol derivatives.

In this study, 37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated, building upon our previous synthesis of 51 phorbol derivatives. 12-Para-electron-acceptor-trans-cinnamoyl-13-decanoyl phorbol derivatives stood out, demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia formation. These derivatives exhibited a higher safety index compared with the positive control drug. Among them, 12-(trans-4-fluorocinnamoyl)-13-decanoyl phorbol, designated as compound 3c, exhibited the most potent anti-HIV-1 activity (EC50 2.9 nmol·L-1, CC50/EC50 11 117.24) and significantly inhibited the formation of syncytium (EC50 7.0 nmol·L-1, CC50/EC50 4891.43). Moreover, compound 3c is hypothesized to act both as an HIV-1 entry inhibitor and as an HIV-1 reverse transcriptase inhibitor. Isothermal titration calorimetry and molecular docking studies indicated that compound 3c may also function as a natural activator of protein kinase C (PKC). Therefore, compound 3c emerges as a potential candidate for developing new anti-HIV drugs.

Cerebral hypometabolism mediates the effect of stroke volume on cognitive impairment in heart failure patients.

AIMS: The present study aimed to phenotype the cerebral structural and glucose metabolic alterations in patients with heart failure (HF) using simultaneous positron emission tomography (PET)/magnetic resonance (MR) and to investigate their relationship to cardiac biomarkers and cognitive performance. METHODS AND RESULTS: Forty-two HF patients caused by ischaemic heart disease (mean age 67.2 ± 10.4, 32 males) and 32 age- and sex-matched healthy volunteers (mean age 61.3 ± 4.8, 18 males) were included in this study. Participants underwent simultaneous cerebral fluorine-18 (18 F) fluorodeoxyglucose PET/MR followed by cardiac MR scan, and neuropsychological scores were obtained to assess cognitive performance. The grey matter volume (GMV) and standardized uptake value ratio (SUVR) were calculated to examine cerebral structural and metabolic alterations. Cardiac biomarkers included cardiac MR parameters and cardiac serum laboratory tests. Mediation analysis was performed to explore the associations among cerebral alterations, cardiac biomarkers, and cognitive performance. HF patients demonstrated notable cognitive impairment compared with normal controls (P < 0.001). Furthermore, HF patients exhibited regional brain hypometabolism in the bilateral calcarine cortex, caudate nucleus, thalamus, hippocampus, precuneus, posterior cingulate cortex, lingual and olfactory cortex, and GMV reduction in bilateral thalamus and hippocampus (cluster level at P < 0.05, Gaussian random field correction). The SUVR of the hypometabolic brain regions was correlated with the Montreal Cognitive Assessment (MoCA) scores (r = 0.55, P = 0.038) and cardiac stroke volume (r = 0.49, P = 0.002). Cerebral hypometabolism played a key role in the relationship between the decreased stroke volume and MoCA scores, with a mediation effect of 33.2%. CONCLUSIONS: HF patients suffered cerebral metabolic and structural alterations in regions associated with cognition. The observed correlation between cardiac stroke volume and cognitive impairment underscored the potential influence of cerebral hypometabolism, suggesting that cerebral hypometabolism due to chronic systemic hypoperfusion may significantly contribute to cognitive impairment in HF patients.

Seco-cyclic phorbol derivatives and their anti-HIV-1 activities.

Phorbol esters are recognized for their dual role as anti-HIV-1 agents and as activators of protein kinase C (PKC). The efficacy of phorbol esters in binding with PKC is attributed to the presence of oxygen groups at positions C20, C3/C4, and C9 of phorbol. Concurrently, the lipids located at positions C12/C13 are essential for both the anti-HIV-1 activity and the formation of the PKC-ligand complex. The influence of the cyclopropane ring at positions C13 and C14 in phorbol derivatives on their anti-HIV-1 activity requires further exploration. This research entailed the hydrolysis of phorbol, producing seco-cyclic phorbol derivatives. The anti-HIV-1 efficacy of these derivatives was assessed, and the affinity constant (Kd) for PKC-δ protein of selected seco-cyclic phorbol derivatives was determined through isothermal titration calorimetry. The findings suggest that the chemical modification of cyclopropanols could affect both the anti-HIV-1 activity and the PKC binding affinity. Remarkably, compound S11, with an EC50 of 0.27 µmol·L-1 and a CC50 of 153.92 µmol·L-1, demonstrated a potent inhibitory effect on the intermediate products of HIV-1 reverse transcription (ssDNA and 2LTR), likely acting at the viral entry stage, yet showed no affinity for the PKC-δ protein. These results position compound S11 as a potential candidate for further preclinical investigation and for studies aimed at elucidating the pharmacological mechanism underlying its anti-HIV-1 activity.

Prevalence of mixed dyslipidemia among Australian patients undergoing lipid-modifying therapy.

BACKGROUND: Few studies have assessed the prevalence of mixed dyslipidemia (MD) and the effectiveness of lipid-modifying therapy (LMT) for the treatment of abnormal levels of low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) in Australian clinical practice. OBJECTIVE: To estimate the prevalence of MD in Australian patients undergoing LMT. METHODS: Patients 35 years of age and older undergoing LMT for ≥1 year were enrolled from nine general practice and cardiologist/endocrinologist outpatient clinics in Australia between April 2007 and May 2008. Lipid levels, including LDL-C, HDL-C and TG levels, were prospectively collected at the enrollment date and from patient records one year before LMT was initiated. Normal lipid levels were assessed according to Australian guidelines. Multivariate logistic regression was used to evaluate predictors of normal lipid level attainment. RESULTS: Of 297 patients (mean age 60.1 years; 43% male), the prevalence of MD before LMT was 61%; 93% of patients had elevated LDL-C levels, 17% had low HDL-C levels and 62% had elevated TG levels. Following LMT (98.3% statins), 31% of patients had MD. The prevalence of elevated LDL-C levels, low HDL-C levels and elevated TG levels were 44%, 21% and 42%, respectively. Baseline lipid levels were significant predictors of attainment of normal LDL-C levels (OR 0.42 [95% CI 0.27 to 0.63]) and TG levels (OR 0.26 [95% CI 0.16 to 0.45]). CONCLUSION: Among Australian patients primarily treated with statins, nearly one-third had MD despite LMT. LMT considerably improved LDL-C goal attainment; however, a large proportion of patients did not achieve normal HDL-C and TG levels. Patients may benefit from a more comprehensive approach to lipid management that treats all three lipid risk factors, as suggested in clinical guidelines.

Peppermint extract improves egg production and quality, increases antioxidant capacity, and alters cecal microbiota in late-phase laying hens.

Introduction: Peppermint contains substantial bioactive ingredients belonging to the phytoestrogens, and its effects on the production of late-laying hens deserve more attention. This study evaluated the effects of dietary peppermint extract (PE) supplementation on egg production and quality, yolk fatty acid composition, antioxidant capacity, and cecal microbiota in late-phase laying hens. Method: PE powder was identified by UPLC-MS/MS analysis. Two hundred and sixteen laying hens (60 weeks old) were randomly assigned to four treatments, each for 28 days: (i) basal diet (control group, CON); (ii) basal diet + 0.1% PE; (iii) basal diet + 0.2% PE; and (iv) basal diet + 0.4% PE. Egg, serum, and cecal samples were collected for analysis. Results: Dietary PE supplementation increased the laying rate, serum triglyceride, immunoglobulin G, and total antioxidant capacity, while 0.2 and 0.4% PE supplementation increased eggshell thickness, serum total protein level, and superoxide dismutase activity of laying hens compared with the CON group (P < 0.05). PE addition in diets increased the C14:0, C18:3n3, C18:3n6, C23:0, C24:0, and C24:1n9 contents in the yolk. In addition, the egg yolk saturated fatty acid content was higher (P < 0.05) in the 0.2 and 0.4% PE groups compared with the CON and 0.1% PE groups. The microbiota analysis revealed that the cecal phylum Proteobacteria was decreased (P < 0.05) in the PE-supplemented groups. A total of 0.4% PE supplementation increased the cecal richness of gram-positive bacteria and decreased the richness of gram-negative and potentially pathogenic bacteria compared with the 0.1% PE group (P < 0.05). Microbial function prediction analysis showed that the cecal microbiota of the PE group was mainly enriched by fatty acid degradation, fatty acid metabolism, amino sugar metabolism, nucleotide sugar metabolism, and other pathways. Regression analysis suggested that 0.28-0.36% PE supplementation was the optimal level for improving egg production and quality, antioxidant capacity, and yolk fatty acid in late-phase laying hens. Discussion: Dietary PE supplementation improved egg production and quality (including yolk fatty acid composition) by increasing serum IgG and antioxidant capacity and modulating the intestinal microbiota in late-phase laying hens.

Dietary supplementation with Chinese herb ultrafine powder improves intestinal morphology and physical barrier function by altering jejunal microbiota in laying hens.

Introduction: Chinese medicinal herbs play important roles in anti-inflammatory, antioxidant, and antibacterial activities. However, the effects of Chinese herb ultrafine powder (CHUP) on laying hens still need to be elucidated. Therefore, this study aimed to evaluate the effects of dietary CHUP supplementation on jejunal morphology, physical barrier function, and microbiota in laying hens. Methods: A total of 576 Xinyang black-feather laying hens (300 days old) were randomly assigned into eight groups, with eight replicates per group and nine hens per replicate. The hens were fed a basal diet (control group) and a basal diet supplemented with 0.5% Leonuri herba (LH group), 0.25% Ligustri lucidi fructus (LF group), 0.25% Taraxaci herba (TH group), 0.5% LH + 0.25% LF (LH-LF group), 0.5% LH + 0.25% TH (LH-TH group), 0.25% LF + 0.25% TH (LF-TH group), and 0.5% LH + 0.25% LF + 0.25% TH (LH-LF-TH group), respectively, for 120 days. Results: The results showed that dietary LH-LF and LH-LF-TH supplementation increased (p < 0.05) the jejunal villus height to crypt depth ratio of laying hens. Dietary LF-TH supplementation up-regulated jejunal claudin-5 expression, while LH supplementation up-regulated jejunal claudin-1 expression and increased the jejunal abundances of potentially beneficial bacteria related to short-chain fatty acids and bacteriocins production, such as Blautia, Carnobacterium, Clostridiales, and Erysipelotrichales (p < 0.05). In addition, dietary LH supplementation enriched (p < 0.05) the tetracycline biosynthesis, butirosin/neomycin biosynthesis, and D-arginine/D-ornithine metabolism, whereas steroid biosynthesis and limonene/pinene degradation were enriched (p < 0.05) in the LH-LF and LH-LF-TH groups. Moreover, Spearman's correlation analysis revealed the potential correlation between the abundance of the jejunal microbiota and jejunal morphology and the physical barrier function of laying hens. Discussion: Collectively, these findings suggest that dietary CHUP supplementation could enhance the beneficial bacteria abundance, physical barrier function, and metabolic function associated with short-chain fatty acids and bacteriocins production. Moreover, combined supplementation of dietary CHUP showed better effects than the sole CHUP supplementation.

Association of high-density lipoprotein cholesterol with incident cardiovascular events in women, by low-density lipoprotein cholesterol and apolipoprotein B100 levels: a cohort study.

BACKGROUND: Prior studies have found inverse associations between high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I levels and cardiovascular disease (CVD). Whether this observation is consistent across low-density lipoprotein cholesterol (LDL-C) levels or total atherogenic particle burden (apolipoprotein B100) is less well-studied, particularly in women. OBJECTIVE: To determine the association between HDL-C or apolipoprotein A-I level and CVD across a range of LDL-C and apolipoprotein B100 values. DESIGN: Prospective cohort study. SETTING: The Women's Health Study, a cohort of U.S. female health professionals. PARTICIPANTS: 26,861 initially healthy women, aged 45 years or older at study entry (1992-1995), who were followed for a mean of approximately 11 years. MEASUREMENTS: Baseline lipids were measured directly, and apolipoproteins were measured with immunoassays. Outcomes were incident total CVD (n = 929), coronary events (n = 602), and stroke (n = 319). RESULTS: In multivariable analyses, HDL-C and apolipoprotein A-I levels were inversely associated with CVD and coronary events but not stroke. Adjusted coronary hazard ratios for decreasing quintiles of HDL-C were 1.00 (reference), 1.23 (95% CI, 0.85 to 1.78), 1.42 (CI, 0.98 to 2.06), 1.90 (CI, 1.33 to 2.71), and 2.19 (CI, 1.51 to 3.19) (P for linear trend < 0.001); corresponding hazard ratios for apolipoprotein A-I were 1.00 (reference), 0.98 (CI, 0.71 to 1.35), 1.02 (CI, 0.72 to 1.44), 1.37 (CI, 0.98 to 1.90), and 1.58 (CI, 1.14 to 2.20) (P for linear trend = 0.005). Consistent inverse associations were found for HDL-C with coronary events across a range of LDL-C values, including among women with low LDL-C levels. No associations were noted for HDL-C or apolipoprotein A-I among women with low apolipoprotein B100 values (<0.90 g/L). LIMITATION: Participants were at low risk for CVD, the number of events in the lowest apolipoprotein B100 stratum was small, only a single baseline measurement was obtained, and residual confounding may have occurred. CONCLUSION: Consistent inverse associations were found for HDL-C with incident coronary events among women with a range of LDL-C values. Among women with low total atherogenic particle burden (apolipoprotein B100 level <0.90 g/L), few events occurred and no associations were seen. PRIMARY FUNDING SOURCE: Merck & Co. and the National Heart, Lung, and Blood Institute and National Cancer Institute, National Institutes of Health.

Isolation and characterization of secondary metabolites from the leaves of Sauropus spatulifolius Beille and their potential biological assays.

Eight new compounds (1-8), along with three known related compounds (9-11) were isolated from the leaves of Sauropus spatulifolius Beille. Their structures and configurations were elucidated by means of spectrometric and the modified Mosher's method. Among the new compounds, compounds 1 and 2 were identified as ethyl 3, 6-anhydro-2-deoxy-ß-D-arabino-hexofuranoside (1) and ethyl 3, 6-anhydro-2-deoxy- hexofuranoside (2). Compounds 3-5 were the 2-acetylpyrrole derivatives and identified as 2-(2-acetyl-1H-pyrrol-1-yl)-4-hydroxybutyric acid (3), methyl 4-(2-acetyl-lH-pyrrol- 1-yl) butanoate (4) and 1, 4-bis (2-acetyl-1H-pyrrol-1-yl) butane (5), respectively. Compound 6 was elucidated as 7-megastigmane-3, 8, 9-triol. Compounds 7, 8 were identified as kaempferol-3-O-2-deoxy-ß-D-glucoside (7) and kaempferol-3-O-ß-D- glucopyranosyl-(1-6)-2-deoxy-ß-D-glucoside (8). In addition, the cytotoxic activities of all the compounds were also evaluated, where compounds 3, 5, 7, 9\10 and 11 exhibited the magnificent inhibition activity on lung fibroblast differentiation induced by TGF-ß1with low toxicity against the RLE-6TN cell.