Mining salt stress-related genes in Spartina alterniflora via analyzing co-evolution signal across 365 plant species using phylogenetic profiling.

With the increasing number of sequenced species, phylogenetic profiling (PP) has become a powerful method to predict functional genes based on co-evolutionary information. However, its potential in plant genomics has not yet been fully explored. In this context, we combined the power of machine learning and PP to identify salt stress-related genes in a halophytic grass, Spartina alterniflora, using evolutionary information generated from 365 plant species. Our results showed that the genes highly co-evolved with known salt stress-related genes are enriched in biological processes of ion transport, detoxification and metabolic pathways. For ion transport, five identified genes coding two sodium and three potassium transporters were validated to be able to uptake Na+. In addition, we identified two orthologs of trichome-related AtR3-MYB genes, SaCPC1 and SaCPC2, which may be involved in salinity responses. Genes co-evolved with SaCPCs were enriched in functions related to the circadian rhythm and abiotic stress responses. Overall, this work demonstrates the feasibility of mining salt stress-related genes using evolutionary information, highlighting the potential of PP as a valuable tool for plant functional genomics. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00125-5.

Edible and Medicinal Progress of Cryptotympana atrata (Fabricius) in China.

As an important resource insect, the Cryptotympana atrata is widely distributed in the eastern and central parts of China. The cicada slough is one of the traditional crude drugs in East Asia, and the main component is polysaccharide, which has the functions of anti-convulsion, relieving asthma and improving lipid metabolism. The parasitoid fungus Cordyceps cicadae, which grows inside the cicada nymphs and forms the fruiting bodies on the surface of the host's carcass, is also known as the "cicada flower" in China. The Cordyceps cicadae is another old, traditional Chinese medicine, which has been used as a tonic and medicine to nourish and regulate human immunity for centuries. For the further development and utilization of the golden cicada, this paper summarized the C. atrata from the aspects of their biological characteristics, distribution area, life cycle, history of edible and medicinal use, edible methods and nutritional compositions; emphatically introduced the edible and potential medicinal value of the C. atrata; and specifically expounded the research progress of its application. As one popular insect food, the prospects for the development of C. atrata have also been put forward, especially in artificial breeding technology, food safety risk assessment and medicinal value utilization.

Investigating of zein-gum arabic-tea polyphenols ternary complex nanoparticles for luteolin encapsulation: Fabrication, characterization, and functional performance.

Luteolin has extensive biological effects, but its low water-solubility and oral bioavailability have restricted its application. In this study, we successfully prepared new zein-gum arabic (GA)-tea polyphenols (TP) ternary complex nanoparticles (ZGTL) as a delivery system to encapsulate luteolin using an anti-solvent precipitation method. Consequently, ZGTL nanoparticles showed negatively charged smooth spherical structures with smaller particle size and higher encapsulation ability. X-ray diffraction revealed the amorphous state of luteolin in the nanoparticles. Hydrophobic, electrostatic, and hydrogen bonding interactions contributed to the formation and stability of ZGTL nanoparticles, as indicated by fluorescence and Fourier transform infrared spectra analyses. The inclusion of TP improved the physicochemical stability and luteolin retention rate of ZGTL nanoparticles by forming more compact nanostructures under different environmental conditions, including pH, salt ion concentration, temperature, and storage. Additionally, ZGTL nanoparticles exhibited stronger antioxidant activity and better sustainable release capacity under simulated gastrointestinal conditions due to TP incorporation. These findings demonstrate that ZGT complex nanoparticles have potential applications as an effective delivery system for encapsulating bioactive substances in food and medicine fields.

Herb-drug interaction of Xingnaojing injection and Edaravone via pharmacokinetics, mixed inhibition of UGTs, and molecular docking.

BACKGROUND: Xingnaojing injection (XNJ) is a famous emergency Traditional Chinese medicine (TCM) derived from the classical Chinese prescription named An-Gong-Niu-Huang Pill. XNJ is often used along with Edaravone injection (EDA) to treat acute ischemic stroke, they have a synergistic effect in improving patients' blood coagulation and neurological function. However, this combination also causes herb-drug interactions (HDIs), raising the risk of adverse reactions. At present, little is known about the pharmacokinetics and potential mechanism of XNJ combined with EDA. PURPOSE: This study investigates the pharmacokinetics and potential mechanism of the HDIs between XNJ and EDA. STUDY DESIGN AND METHODS: The pharmacokinetic interactions between XNJ and EDA were studied by GC-MS in rats, and the inhibition of XNJ and (-)-borneol on UDP-glucuronosyltransferase (UGTs) were assayed by LC-MS/MS in vitro. In vitro-in vivo extrapolation (IVIVE) and molecular docking were performed to reveal the potential for HDIs. RESULTS: The AUC0-∞ of (-)-borneol was increased by 1.25-fold in group EDA+XNJ 10 min later, and the Cmax of edaravone was increased by 1.6-fold in group XNJ+EDA 10 min later (p < 0.05). XNJ and (-)-borneol inhibited UGTs-mediated edaravone metabolism in HLM and RLM with a similar inhibitory intensity, in which both of them have stronger inhibition in RLM. These findings demonstrated that (-)-borneol in XNJ mainly exerted UGTs inhibition, which was consistent with the pharmacokinetic assays. (-)-Borneol moderately inhibited UGT2B7 and UGT1A6 by a mixed inhibition mechanism, with Ki values of 101.393 and 136.217 µM, respectively. Due to the blood concentration of injection was dramatically increased, the HDIs caused by the inhibitory effect of XNJ on UGTs should be highly emphasized. The binding energies of (-)-borneol and edaravone toward UGT2B7 were -6.254 and -6.643 kcal/mol, and the scores towards UGT1A6 were -5.220 and -6.469 kcal/mol, respectively. Moreover, (-)-borneol has similar free energies to many drugs metabolized by UGT2B7 and UGT1A6. CONCLUSIONS: (-)-Borneol modulates the pharmacokinetic behavior of edaravone via mixed inhibition of UGT2B7 and UGT1A6. It provides a theoretical basis for the synergistic effect of XNJ and EDA combinations in clinical practice. When XNJ is used along with UGT2B7 and UGT1A6 substrates, it should be used clinically with caution.

[Research progress of Angelicae Sinensis Radix and predictive analysis on its quality markers].

Angelicae Sinensis Radix, as a medicinal and edible Chinese medicinal herb, is widely used in clinical practice. It is mainly cultivated in Minxian, Tanchang, Zhangxian and Weiyuan counties of Gansu province. In recent years, with the comprehensive and in-depth study of Angelicae Sinensis Radix in China and abroad, its chemical composition, pharmacological effects and application and development have attracted much attention. In this study, the chemical composition, traditional efficacy, and modern pharmacological effects of Angelicae Sinensis Radix were summarized. On this basis, combined with the core concept of quality markers(Q-markers), the Q-markers of Angelicae Sinensis Radix were discussed from the aspects of mass transfer and traceability and chemical composition specificity, availability, and measurability, which provided scientific basis for the quality evaluation of Angelicae Sinensis Radix.

Clinical Application of the Classical Theory of Traditional Chinese Medicine in Diabetic Nephropathy.

Objective: To explore the clinical application of the classical theory of traditional Chinese medicine (TCM) in diabetic nephropathy (DN). Methods: A total of 100 patients with DN treated in our hospital from May 2019 to June 2021 were included. The patients were randomly assigned to the control group and the study group. The control group received routine treatment, and the study group was treated with the classical theory of TCM. The efficacy, TCM syndrome score, urine proteinuria (UTP), urine albumin-creatinine ratio (UACR), plasma albumin (ALB), hemoglobin A1c (HbA1C), fasting blood glucose (FBG), blood urea nitrogen (BUN), creatinine (Cr), and treatment safety were compared between the two groups. Results: In comparison to the curative effect, the study group was significantly effective in 34 cases, effective in 12 cases, and ineffective in 4 cases, and the effective rate was 92.00%; the control group was significantly effective in 16 cases, effective in 18 cases, and ineffective in 16 cases, and the effective rate was 68.00%. The effective rate in the study group was higher compared to the control (P < 0.05). In comparison to the TCM syndrome scores, there exhibited no significant difference before treatment (P > 0.05), but after treatment, the TCM syndrome scores of the two groups decreased, and the TCM syndrome scores of the study group were lower compared to the control at 6 weeks, 12 weeks, 24 weeks, and 36 weeks of treatment (P < 0.05). There exhibited no significant difference in the indexes of UTP and UACR before treatment, but the indexes of UTP and UACR in the two groups decreased after treatment, and the indexes of UTP and UACR in the study group were lower compared to the control at 6 and 12 weeks after treatment. There was no significant difference in the indexes of ALB, HbA1C, and FBG before treatment, but after treatment, the indexes of ALB increased, the indexes of HbA1C and FBG decreased in both groups, and the indexes of HbA1C and FBG i4n the study group were lower compared to the control, while the index of ALB in the study group was higher. The indexes of BUN and Cr were compared, and there was no significant difference before treatment, but after treatment, the indexes of BUN and Cr in the two groups decreased, and the indexes of BUN and Cr in the study group were lower compared to the control (P < 0.05). In terms of the treatment safety of the two groups, there was no abnormality in blood, urine, stool routine, and liver and kidney function examination in the study group. No obvious adverse reactions were found in all patients. There were 1 case of abnormal liver function and 2 cases of rash in the control group, and there exhibited no significant difference (P > 0.05). Conclusion: Under the guidance of classical theory, the optimization scheme of comprehensive treatment of TCM may improve renal function by improving metabolic disorders, vascular lesions, neurotrophic disorders, antioxidant stress, and other ways to repair nerve injury, improving the changes of TCM syndromes, signs, and indicators of patients, and delay the progress of DN.

Shen-Shuai-Ling Formulation Attenuates Renal Interstitial Fibrosis in Chronic Kidney Disease by Regulating SHH-Gli1 Signaling Pathway.

BACKGROUND: Shen-Shuai-Ling Formulation (SSLF) has apparent effects on improving renal function, delaying the progression of chronic kidney disease (CKD). METHODS: Fifty male SD rats were randomly divided into 5 groups: Sham group, Model group, SSLF group, CPN group, and C + S group. The morphological changes and the collagen fibers of the rat kidneys were observed by HE staining. The expression of α-SMA, Col I, SHH, Gli1, and snail1 was detected by Western blot and qPCR. Then, the cells were divided into the control group, SHH group, and SHH + SSLF serum group. RESULTS: Compared with the Model group, the fibrosis in SSLF, CPN, and C + S groups was significantly alleviated. And, compared with those in the Model group, the expression of α-SMA, Col I, SHH, Gli1, Snail in SSLF, CPN, and C + S groups decreased remarkably. CONCLUSIONS: SSLF remarkably improves renal function and alleviates renal interstitial fibrosis in UUO rats.

Prevalence and Risk Factors Comparison of Anterior and Posterior Intracranial Arterial Stenosis.

The prevalence and risk factors of intracranial atherosclerotic stenosis (ICAS) located in the anterior circulation (AC) and posterior circulation (PC) has been scarcely noted in the general population. We aimed to determine ICAS prevalence and risk factor profile of AC and PC in a representative population. Data were from the China Hypertension Survey of Beijing. In total, 4800 people aged 35 years or older were enrolled in this subsurvey for ICAS, and 3954 participants were eligible for analysis. ICAS was assessed by transcranial Doppler. The prevalence of ICAS in AC was much greater than that in PC (11.9% vs. 4.2%), and subjects with ICAS in PC were 3.9 years older than those with ICAS in AC. Multivariable logistics regression showed that the odds of hypertension and diabetes increased by 79% (OR: 1.79, 95% CI: 1.40-2.27) and 35% (OR: 1.35, 95% CI: 1.04-1.75) in those with AC vascular lesions and by 3.35 times (OR: 3.35, 95% CI: 2.49-4.50) and 71% (OR: 1.71, 95% CI: 1.19-2.46) in those with PC vascular lesions compared with those without vascular lesions. Most modifiable vascular risk factors for ICAS appeared to exert similar magnitudes of risk for PC to AC lesions.

Massage Therapy's Effectiveness on the Decoding EEG Rhythms of Left/Right Motor Imagery and Motion Execution in Patients With Skeletal Muscle Pain.

OBJECTIVE: Most of effectiveness assessments of the widely-used Massage therapy were based on subjective routine clinical assessment tools, such as Visual Analogue Scale (VAS) score. However, few studies demonstrated the impact of massage on the Electroencephalograph (EEG) rhythm decoding of Motor imagery (MI) and motion execution (ME) with trunk left/right bending in patients with skeletal muscle pain. METHOD: We used the sample entropy (SampEn), permutation entropy (PermuEn), common spatial pattern (CSP) features, support vector machine (SVM) and logic regression (LR) classifiers. We also used the convolutional neural network (CNN) and attention-based bi-directional long short-term memory (BiLSTM) for classification. RESULTS: The averaged SampEn and PermuEn values of alpha rhythm decreased in almost fourteen channels for five statuses (quiet, MI with left/right bending, ME with left/right bending). It indicated that massage alleviates the pain for the patients of skeletal pain. Furthermore, compared with the SVM and LR classifiers, the BiLSTM method achieved a better area under curve (AUC) of 0.89 for the classification of MI with trunk left/right bending before massage. The AUC became smaller after massage than that before massage for the classification of MI with trunk left/right bending using CNN and BiLSTM methods. The Permutation direct indicator (PDI) score showed the significant difference for patients in different statuses (before vs after massage, and MI vs ME). CONCLUSIONS: Massage not only affects the quiet status, but also affects the MI and ME. Clinical Impact: Massage therapy may affect a bit on the accuracy of MI with trunk left/right bending and it change the topography of MI and ME with trunk left/right bending for the patients with skeletal muscle pain.

LncRNA SNHG5 upregulation induced by YY1 contributes to angiogenesis via miR-26b/CTGF/VEGFA axis in acute myelogenous leukemia.

Acute myelogenous leukemia (AML) is the most common acute leukemia in adults. Despite great progress has been made in this field, the pathogenesis of AML is still not fully understood. We report here the biological role of lncRNA small nucleolar RNA host gene 5 (SNHG5) in the pathogenesis of AML and the underlying mechanisms. The results showed that lncRNA SNHG5 was highly expressed in AML cancer cell lines. In vitro studies displayed that inhibition of SNHG5 with shRNA resulted in suppression of survival, cell cycle progression, migration/invasion of AML and capacity of adhesion and angiogenesis in human umbilical vein endothelial cells. Mechanistic studies revealed a SNHG5/miR-26b/connective tissue growth factor (CTGF)/vascular endothelial growth factor A (VEGFA) axis in the regulation of AML angiogenesis. Finally, Yin Yang 1 (YY1) was found to transactivate and interact with SNHG5 promoter, leading to the upregulation of SNHG5 in AML. Collectively, upregulation of lncRNA SNHG5 mediated by YY1, activates CTGF/VEGFA via targeting miR-26b to regulate angiogenesis of AML. Our work provides new insights into the molecular mechanisms of AML.

Lipid-Lowering Activities of Cucurbitacins Isolated from Trichosanthes cucumeroides and Their Synthetic Derivatives.

In the ongoing efforts to discover natural cholesterol-lowering compounds, dihydrocucurbitacin B, isolated from Trichosanthes cucumeroides roots, was found to promote LDL uptake by upregulating LDLR protein in a PCSK9-dependent process. In this study, an in-depth investigation of T. cucumeroides roots afforded 27 cucurbitacins (1-27), including seven new cucurbitacins (1-7), and their structures were elucidated by spectroscopic data analyses. In order to gain insight into their structure-activity relationship, cucurbitacin derivatives (B1-11 and DB1-11) were synthesized. Evaluation of lipid-lowering activities of these cucurbitacins by an LDL uptake assay in HepG2 cells revealed that most of the compounds improved the LDL uptake rate, among which hexanorisocucurbitacin D (6) and isocucurbitacin D (21) exhibited the highest activities (rates of 2.53 and 2.47, respectively), which were comparable to that of the positive control, nagilactone B (rate of 2.07). According to a mechanistic study by Western blot analysis, compounds 6 and 21 dose-dependently increased LDLR protein levels and reduced PCSK9 protein levels, representing promising new lipid-lowering drug candidates.

Iron accumulation in macrophages promotes the formation of foam cells and development of atherosclerosis.

BACKGROUND: Macrophages that accumulate in atherosclerotic plaques contribute to progression of the lesions to more advanced and complex plaques. Although iron deposition was found in human atherosclerotic plaques, clinical and pre-clinical studies showed controversial results. Several epidemiological studies did not show the positive correlation between a systemic iron status and an incidence of cardiovascular diseases, suggesting that the iron involvement occurs locally, rather than systemically. RESULTS: To determine the direct in vivo effect of iron accumulation in macrophages on the progression of atherosclerosis, we generated Apoe-/- mice with a macrophage-specific ferroportin (Fpn1) deficiency (Apoe-/-Fpn1LysM/LysM). Fpn1 deficiency in macrophages dramatically accelerated the progression of atherosclerosis in mice. Pathophysiological evidence showed elevated levels of reactive oxygen species, aggravated systemic inflammation, and altered plaque-lipid composition. Moreover, Fpn1 deficiency in macrophages significantly inhibited the expression of ABC transporters (ABCA1 and ABCG1) by decreasing the expression of the transcription factor LXRα, which reduced cholesterol efflux and therefore promoted foam cell formation and enhanced plaque formation. Iron chelation relieved the symptoms moderately in vivo, but drastically ex vivo. CONCLUSIONS: Macrophage iron content in plaques is a critical factor in progression of atherosclerosis. The interaction of iron and lipid metabolism takes place in macrophage-rich atherosclerotic plaques. And we also suggest that altering intracellular iron levels in macrophages by systemic iron chelation or dietary iron restriction may be a potential supplementary strategy to limit or even regress the progression of atherosclerosis.

Grouping attributes zero-shot learning for tongue constitution recognition.

Traditional Chinese Medicine (TCM) considers that the personal constitution determines the occurrence trend and therapeutic effects of certain diseases, which can be recognized by machine learning through tongue images. However, current machine learning methods are confronted with two challenges. First, there are not some larger tongue image databases available. Second, they do not use the domain knowledge of TCM, so that the imbalance of constitution categories cannot be solved. Therefore, this paper proposes a new constitution recognition method based on the zero-shot learning with the knowledge of TCM. To further improve the performance, a new zero-shot learning method is proposed by grouping attributes and learning discriminant latent features, which can better solve the imbalance problem of constitution categories. Experimental results on our constructed databases validate the proposed methods.

PPARα ligand, AVE8134, and cyclooxygenase inhibitor therapy synergistically suppress lung cancer growth and metastasis.

BACKGROUND: Lung cancer (LC) is one of the leading causes of death worldwide, which highlights the urgent need for better therapies. Peroxisome proliferator-activated nuclear receptor alpha (PPARα), known as a key nuclear transcription factor involved in glucose and lipid metabolism, has been also implicated in endothelial proliferation and angiogenesis. However, the effects and potential mechanisms of the novel PPARα ligand, AVE8134, on LC growth and progression remain unclear. METHODS: A subcutaneous tumour was established in mice by injecting TC-1 lung tumour cells (~ 1 × 106 cells) into their shaved left flank. These mice were treated with three different PPARα ligands: AVE8134 (0.025% in drinking water), Wyeth-14,643 (0.025%), or Bezafibrate (0.3%). Tumour sizes and metastasis between treated and untreated mice were then compared by morphology and histology, and the metabolites of arachidonic acid (AA) were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Inhibition of either Cyp2c44 expression by genetic disruption or cyclooxygenase (COX) activity by indomethacin was used to test the mechanisms by which AVE8134 affects tumour growth. RESULTS: The pharmacodynamics effects of AVE8134, Wyeth-14,643, and Bezafibrate on lipids control were similar. However, their effects on tumour suppression were different. Eicosanoid profile analysis showed that all PPARα ligands reduced the production of AA-derived epoxyeicosatrienoic acids (EETs) and increased the hydroxyl product, 11-hydroxyeicosatetraenoic acids (11-HETE). Moreover, increased 11-HETE promoted endothelial proliferation, angiogenesis, and subsequent tumour deterioration in a dose-dependent manner possibly via activating the AKT/extracellular signal-regulated kinase (ERK) pathway. The increased 11-HETE partly neutralized the benefits provided by the Cyp2c44-EETs system inhibited by PPARα ligands in tumour-bearing mice. AVE8134 treatment worsened the tumour phenotype in Cyp2c44 knockout mice, indicating that AVE8134 has contradictory effects on tumour growth. The COX inhibitor indomethacin strengthened the inhibitory actions of AVE8134 on tumour growth and metastasis by inhibiting the 11-HETE production in vivo and in vitro. CONCLUSION: In this study, we found that the degrees of inhibition on LC growth and metastasis by PPARα ligands depended on their bidirectional regulation on EETs and 11-HETE. Considering their safety and efficacy, the novel PPARα ligand, AVE8134, is a potentially ideal anti-angiogenesis drug for cancer treatment when jointly applied with the COX inhibitor indomethacin.

Soy Products Ameliorate Obesity-Related Anthropometric Indicators in Overweight or Obese Asian and Non-Menopausal Women: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The effect of soy products on the weight of overweight or obese people is controversial, so we aimed to conduct a systematic review and a meta-analysis of published randomized controlled trials to analyze whether supplementation with soy products can help them to lose weight. METHODS: The relevant data before January 2019 in PubMed, Embase and Cochrane Library were searched. A random-effect model was adopted to calculate the weighted average difference of net changes of body weight, body mass index (BMI), body fat percentage, fat mass, waist circumference, etc. Results: A total of 22 trials (870 overweight or obese participants) were reflected in the present meta-analysis. Analysis showed that soy products significantly reduced body weight, BMI, body fat percent and waist circumference in overweight or obese Asian populations (-0.37 kg, P = 0.010; -0.27 kg/m2, P = 0.042; -0.36%, P = 0.032; -0.35 cm, P = 0.049) and more significant effects were observed in non-menopausal women reduced body weight (-0.59 kg, P = 0.041), BMI (-0.59, P = 0.041) and waist circumference (-0.59 cm, P = 0.041) in overweight or obese populations. CONCLUSION: This meta-analysis showed that soy products have weight loss effects, mainly due to soy protein, isoflavone and soy fiber.

Safety and Efficacy of Tianfoshen Oral Liquid in Non-Small Cell Lung Cancer Patients as an Adjuvant Therapy.

ETHNOPHARMACOLOGICAL RELEVANCE: As an important Chinese herb injection, Tianfoshen (TFS) oral liquid is widely used in Chinese non-small cell lung cancer (NSCLC) patients. AIM OF THE STUDY: To evaluate the efficacy and safety of Tianfoshen (TFS) oral liquid plus chemotherapy in Chinese NSCLC patients with Qi and Yin deficiency syndrome, an observational study was conducted in Beijing Friendship Hospital between August 2012 and July 2016. Patients, enrolled in this study, were diagnosed with NSCLC and were treated with Cisplatin in combination with Paclitaxel/Navelbine/Gemcitabine/Docetaxel as a first-line treatment, or Pemetrexed for recurrent patients. The primary endpoint was the improvement of traditional Chinese medicine syndrome and objective response rate in patients. The secondary endpoint was the occurrence of drug-related adverse events. RESULTS: A total of 108 patients were included in this study and underwent the safety and efficacy assessments. Compared to the baseline, the total scores of traditional Chinese medicine (TCM) syndrome after 3 or 8/9 weeks of TFS treatment were statistically significant (P<0.0001), and the clinical efficiency rate was 36.11% and 50.93%, respectively. The objective response rate (ORR) and disease control rate (DCR) of TFS group were slightly higher than those of without-TFS group, although the comparison was not statistically significant. The incidence of common adverse events related to TFS was 7.41% whereas the incidence of serious adverse events was 0.93%. CONCLUSIONS: As an adjuvant therapy of chemotherapy, TFS showed an acceptable tolerability profile in the clinical practice of Chinese NSCLC patients with Qi and Yin deficiency syndrome, but it seems to have no effect on the ORR and DCR.

Genomic Prediction using Existing Historical Data Contributing to Selection in Biparental Populations: A Study of Kernel Oil in Maize.

Maize ( L.) kernel oil provides high-quality nutrition for animal feed and human health. A certain number of maize breeding programs seek to enhance oil concentration and composition. Genomic selection (GS), which entails selection based on genomic estimated breeding values (GEBVs), has proven to be efficient in breeding programs. Here, we estimate the robustness of predictions for the oil traits of maize kernels in biparental recombination inbred lines (RILs) using a GS model built based on an association population. Most statistical models, including ridge regression-best linear unbiased prediction (RR-BLUP), showed high prediction accuracy in the training population through a cross validation procedure. The training population size was more important than marker density and a statistical model for prediction performance. Using the optimized GS model, prediction of the biparental RIL population showed medium-high prediction accuracy (0.68) compared with prediction using only oil associated markers ( = 0.43). The potential to apply the GS model to another RIL population that is genetically less related to the training population was also examined, showing promising prediction accuracy in the top selected lines. Our results proved that genomic prediction using existing data is robust for the prediction of polygenic traits with moderate to high heritability.

Magnesium lithospermate B protects the endothelium from inflammation-induced dysfunction through activation of Nrf2 pathway.

Magnesium lithospermate B (MLB) is an active component of Salvia miltiorrhiza Radix, a traditional Chinese herb used in treating cardiovascular diseases. In this study, we investigated the protective effects of MLB against inflammation-induced endothelial dysfunction in vitro and in vivo, and the underlying mechanisms. Endothelial dysfunction was induced in human dermal microvascular endothelial cells (HMEC-1) in vitro by lipopolysaccharide (LPS, 1 µg/mL). We showed that pretreatment with MLB (10-100 µM) dose-dependently inhibited LPS-induced upregulation of inflammatory cytokines ICAM1, VCAM1, and TNFα, which contributed to reduced leukocytes adhesion and attenuation of endothelial hyperpermeability in HMEC-1 cells. SD rats were injected with LPS (10 mg/kg, ip) to induce endothelial dysfunction in vivo. We showed that pretreatment with MLB (25-100 mg/kg, ip) dose-dependently restored LPS-impaired endothelial-dependent vasodilation in superior mesenteric artery (SMA), attenuated leukocyte adhesion in mesenteric venules and decreased vascular leakage in the lungs. We further elucidated the mechanisms underlying the protective effects of MLB, and revealed that MLB pretreatment inhibited NF-κB activation through inhibition of IκBα degradation and subsequent phosphorylation of NF-κB p65 in vitro and in vivo. In HMEC-1 cells, MLB pretreatment activated the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. Knockdown of Nrf2 with siRNA abolished the inhibitory effects of MLB on IκBα degradation and ICAM1 up-regulation, which were mimicked by PKC inhibition (Gö6983) or PI3K/Akt inhibition (LY294002). In summary, our results demonstrate that MLB inhibits NF-κB activation through PKC- and PI3K/Akt-mediated Nrf2 activation in HMEC-1 cells and protects against LPS-induced endothelial dysfunction in murine model of acute inflammation.

Indole alkaloid from Nauclea latifolia promotes LDL uptake in HepG2 cells by inhibiting PCSK9.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been found to play a major role in atherosclerotic cardiovascular disease (ASCVD) by promoting hyperlipidemia. Its inhibition has therefore emerged as a viable drug target for improving the outcome of ASCVD. However, current monoclonal antibody PCSK9 inhibitors are considered cost ineffective and there is the need to discover new effective and cheaper small molecule alternatives. PURPOSE: The methanolic and ethanolic crude extracts of Nauclea latifolia have been shown to possess anti-hyperlipidemic activity, but the chemical component(s) responsible for this activity and the mechanism of action have remained unknown. The objective of this study was therefore to identify N. latifolia constituents with anti-hyperlipidemic activity and to investigate the inhibition of PCSK9 as a probable mechanism of action. METHOD: In the present study, compounds were isolated from the ethanolic extract of the stem of N. latifolia. The alkaloids were evaluated for their DiI-LDL uptake promoting activity in HepG2 cell. The most active compound was further assessed for its effect on low density lipoprotein receptor (LDLR) and PCSK9 protein expressions by western blot. RESULTS: 3R-3,14-dihydroangustoline (5), showed a relatively good activity in promoting LDL uptake (1.26-fold). It further increased LDLR protein expression and decreased the protein expression of PCSK9 in a dose dependent manner (1-50  µM). CONCLUSION: Alkaloids from N. latifolia may serve as a source of new PCSK9 inhibitors.