Saponins from Allium macrostemon Bulbs Attenuate Endothelial Inflammation and Acute Lung Injury via the NF-κB/VCAM-1 Pathway.

Endothelial inflammation is a multifaceted physiological process that plays a pivotal role in the pathogenesis and progression of diverse diseases, encompassing but not limited to acute lung infections like COVID-19, coronary artery disease, stroke, sepsis, metabolic syndrome, certain malignancies, and even psychiatric disorders such as depression. This inflammatory response is characterized by augmented expression of adhesion molecules and secretion of pro-inflammatory cytokines. In this study, we discovered that saponins from Allium macrostemon bulbs (SAMB) effectively inhibited inflammation in human umbilical vein endothelial cells induced by the exogenous inflammatory mediator lipopolysaccharide or the endogenous inflammatory mediator tumor necrosis factor-α, as evidenced by a significant reduction in the expression of pro-inflammatory factors and vascular cell adhesion molecule-1 (VCAM-1) with decreased monocyte adhesion. By employing the NF-κB inhibitor BAY-117082, we demonstrated that the inhibitory effect of SAMB on VCAM-1 expression may be attributed to the NF-κB pathway's inactivation, as characterized by the suppressed IκBα degradation and NF-κB p65 phosphorylation. Subsequently, we employed a murine model of lipopolysaccharide-induced septic acute lung injury to substantiate the potential of SAMB in ameliorating endothelial inflammation and acute lung injury in vivo. These findings provide novel insight into potential preventive and therapeutic strategies for the clinical management of diseases associated with endothelial inflammation.

U-shaped association between 25-hydroxyvitamin D concentration and the prevalence of asthma in the overweight and obese U.S. population.

INTRODUCTION: Vitamin D supplementation has shown promise in averting asthma. However, the association between 25(OH)D levels and asthma prevention in various demographic groups remains inconclusive. Here, we explore this relationship in the context of overweight and obese individuals in the United States. METHODS: We scrutinized cross-sectional data derived from the National Health and Nutrition Examination Survey conducted between 2007 and 2018. This dataset encompasses comprehensive information about asthma patients with a body mass index greater than 25 kg/m2, in addition to data regarding 25(OH)D concentration and other pertinent variables. Among the 3889 participants, 16.2% (631/3889) reported a history of asthma, constituting 1765 (45.4%) males and 2124 (54.6%) females. The median age was 56.0 years, with a standard deviation of 16.0 years. We conducted restricted cubic spline (RCS) regression analysis to assess the correlation between 25(OH)D levels and asthma. RESULTS: After adjusting for confounders, compared to individuals with lower 25-hydroxyvitamin D concentration (group1 ≤ 46.6 nmol/L), the adjusted odds ratios (OR) for asthma in group2 (46.7-62 nmol/L), group3 (62.1-78.2 nmol/L), and group4 (≥78.3 nmol/L) were 0.68 (95% CI: 0.49-0.94, p < 0.021), 0.65 (95% CI: 0.47-0.88, p < 0.006), and 0.83 (95% CI: 0.61-1.12, p < 0.22), respectively. Restricted cubic spline (RCS) regression analysis revealed a nonlinear U-shaped curve (p = 0.017) with an inflection point at approximately 84.95 nmol/L. CONCLUSIONS: High levels of 25(OH)D are correlated with a diminished prevalence of asthma among overweight and obese individuals in the United States.

Vitamin D supplementation may reduce the incidence of asthma in the overweight and obese individuals.A u-shaped association was observed between 25-hydroxyvitamin D levels and asthma, with an inflection point of 84.95 nmol/L.Presenting supportive evidence for vitamin D supplementation in the overweight and obese individuals.

A Modified Method for Transient Transformation via Pollen Magnetofection in Lilium Germplasm.

Lily (Lilium spp.) is a popular ornamental plant. Traditional genetic transformation methods have low efficiency in lily, thus development of a high-efficiency genetic transformation system is important. In this study, a novel transient transformation method involving pollen magnetofection was established and optimized pollen viability, and exogenous gene expression in magnetofected pollen and that of different germplasm were assessed. The highest germination percentage of Lilium regale pollen was 85.73% in medium containing 100 g/L sucrose, 61.5 mg/L H3BO3, and 91.5 mg/L CaCl2. A 1:4 ratio of nanomagnetic beads to DNA plasmid and transformation time of 0.5 h realized the highest transformation efficiency (88.32%). The GFP activity in transformed pollen averaged 69.66%, while that of the control pollen was 0.00%. In contrast to the control, transgenic seedlings obtained by pollination with magnetofected pollen showed strong positive GUS activity with 56.34% transformation efficiency. Among the lily germplasm tested, 'Sweet Surrender' and L. leucanthum had the highest transformation efficiency (85.80% and 54.47%), whereas L. davidii var. willmottiae was not successfully transformed. Transformation efficiency was positively correlated with pollen equatorial diameter and negatively correlated with polar axis/equatorial diameter ratio. The results suggest that pollen magnetofection-mediated transformation can be applied in Lilium but might have species or cultivar specificity.

Rapid identification of chemical compositions of three species of Schisandra chinensis by ultra-high-performance liquid chromatography quadrupole-orbitrap-mass spectrometry.

Schisandra chinensis is a traditional Chinese medicine, which has played an important role in the field of medicine and food. In this study, ultra-high-performance liquid chromatography quadrupole-orbitrap-mass spectrometry was used to rapidly classify and identify the chemical compositions. Note that 32, 28, and 30 kinds of compounds were successfully identified from northern Schisandra chinensis, vinegar-processed Schisandra chinensis, and wine-processed Schisandra chinensis, respectively. The cleavage patterns of various components including lignans, organic acids, flavonoids, and terpenoids were summarized, and the effects of different processing methods on Schisandra chinensis were analyzed through chemical composition. This method realized the rapid classification and identification of raw Schisandra chinensis and two different processed products, and provided references for improving the traditional processing methods, strengthening quality control, and ensuring safe clinical application.

Scientific Evidence of Acupuncture for Post-Stroke Cognitive Impairment: An Overview of Systematic Reviews and Meta-Analyses.

Background: Acupuncture may be effective to treat post-stroke cognitive impairment (PSCI). We aimed to evaluate the reliability of the systematic reviews/meta-analyses (SRs/MAs) evidence regarding acupuncture treatment of PSCI. Methods: The methodological quality was appraised with Methodological Quality of Systematic Reviews 2 (AMSTAR-2). We evaluated reporting quality with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and evidence quality with Grade of Recommendation, Assessment, Development and Evaluation (GRADE) system. Results: The inclusion criteria were met by fifteen reviews. All studies assessed by AMSTAR-2 had critically poor methodological quality due to the limitations on the lack of the provision of the list of excluded trails, screening of duplicate study, and protocol registration. For reporting quality, response rate of "yes" was less than 50% in Q5 (protocol and registration topic), Q8 (Search) and Q23 (Additional analysis). Evidence quality of outcome measures was low or worse with GRADE because when the data was qualitatively synthesized, low quality and small sample size trials provided the data. Conclusion: Acupuncture may be beneficial for PSCI. Because of limitations and inconsistent conclusions, further research is needed to provide higher evidence for acupuncture on PSCI.

Comprehensive Screening for EPA/DHA-Structured Phospholipids in Aquatic Products by a Specific Precursor Ion Scanning-Based HILIC-MS/MS Method.

Comprehensive screening for functional substances from natural resources is always a hot research topic. Eicosapentaenoic acid- (EPA) and docosahexaenoic acid (DHA)-structured phospholipids (PLEPA/DHA) have versatile cardiovascular benefits as well as superior bioavailability. Herein, the abundance of PLEPA/DHA in 16 aquatic products was specifically and selectively screened using a recently developed precursor ion scan-driven hydrophilic interaction chromatography-mass spectrometry (PreIS-HILIC/MS) method with the fatty acyl moieties of EPA (m/z 301.6) and DHA (m/z 327.6) locked. The aim focused on the characteristics and differences in the varieties and contents of EPA/DHA-structured phosphatidylcholine (PCEPA/DHA) and EPA/DHA-structured phosphatidylethanolamine (PEEPA/DHA) molecular species. A total of 80 PLEPA/DHA molecules were identified in these natural sources, including 47 PCEPA/DHA and 33 PEEPA/DHA. After analysis, PC 16:0/20:5 and PC 16:0/22:6 are present in all aquatic products and at high levels. Antarctic krill was found to be the best resource of PLEPA/DHA in total (2574.69 µg·g-1), followed by mackerel (2330.11 µg·g-1), salmon (2109.91 µg·g-1), and Farrer's scallop (1883.59 µg·g-1), while abalone contained the lowest level of PLEPA/DHA (310.44 µg·g-1). Besides, sea cucumber and sea bass contained the highest contents of EPA-structured and DHA-structured ether phospholipids, respectively, which could be highly recommended as dietary sources of special functional phospholipids. Finally, the multiple discrepancies between the 16 aquatic products were revealed by multivariate statistical analysis. These findings improve the awareness of the composition and content of PLEPA/DHA contained in aquatic products, providing a reference for their integrated development.

Stepwise changes in flavonoids in spores/pollen contributed to terrestrial adaptation of plants.

Protecting haploid pollen and spores against UV-B light and high temperature, 2 major stresses inherent to the terrestrial environment, is critical for plant reproduction and dispersal. Here, we show flavonoids play an indispensable role in this process. First, we identified the flavanone naringenin, which serves to defend against UV-B damage, in the sporopollenin wall of all vascular plants tested. Second, we found that flavonols are present in the spore/pollen protoplasm of all euphyllophyte plants tested and that these flavonols scavenge reactive oxygen species to protect against environmental stresses, particularly heat. Genetic and biochemical analyses showed that these flavonoids are sequentially synthesized in both the tapetum and microspores during pollen ontogeny in Arabidopsis (Arabidopsis thaliana). We show that stepwise increases in the complexity of flavonoids in spores/pollen during plant evolution mirror their progressive adaptation to terrestrial environments. The close relationship between flavonoid complexity and phylogeny and its strong association with pollen survival phenotypes suggest that flavonoids played a central role in the progression of plants from aquatic environments into progressively dry land habitats.

Baicalin can enhance odonto/osteogenic differentiation of inflammatory dental pulp stem cells by inhibiting the NF-κB and ß-catenin/Wnt signaling pathways.

BACKGROUND: Scutellaria baicalensis Georgi is a famous traditional Chinese medicine, which is widely used in treating fever, upper respiratory tract infection and other diseases. Pharmacology study showed it can exhibit anti-bacterial, anti-inflammation and analgesic effects. In this study, we investigated the effect of baicalin on the odonto/osteogenic differentiation of inflammatory dental pulp stem cells (iDPSCs). METHODS AND RESULTS: iDPSCs were isolated from the inflamed pulps collected from pulpitis. The proliferation of iDPSCs was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2,5-tetrazolium bromide (MTT) assay and flow cytometry. Alkaline phosphatase (ALP) activity assay, alizarin red staining, Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay were conducted to examine the differentiation potency along with the involvement of nuclear factor kappa B(NF-κB) and ß-catenin/Wnt signaling pathway. MTT assay and cell-cycle analysis demonstrated that baicalin had no influence on the proliferation of iDPSCs. ALP activity assay and alizarin red staining demonstrated that baicalin could obviously enhance ALP activity and calcified nodules formed in iDPSCs. RT-PCR and Western blot showed that the odonto/osteogenic markers were upregulated in baicalin-treated iDPSCs. Moreover, expression of cytoplastic phosphor-P65, nuclear P65, and ß-catenin in iDPSCs was significantly increased compared with DPSCs, but the expression in baicalin-treated iDPSCs was inhibited. In addition, 20 µM Baicalin could accelerate odonto/osteogenic differentiation of iDPSCs via inhibition of NF-κB and ß-catenin/Wnt signaling pathways. CONCLUSION: Baicalin can promote odonto/osteogenic differentiation of iDPSCs through inhibition of NF-κB and ß-catenin/Wnt pathways, thus providing direct evidence that baicalin may be effective in repairing pulp with early irreversible pulpitis.

Exogenous γ-aminobutyric acid (GABA) alleviates nitrogen deficiency by mediating nitrate uptake and assimilation in Andrographis paniculata seedlings.

γ-Aminobutyric acid (GABA) plays significant metabolic and signaling roles in plant stress responses. Recent studies have proposed that GABA alleviates plant nitrogen (N) deficient stress; however, the mechanism by which GABA mediates plant N deficiency adaptation remains not yet well understood. Herein we found in a medicinal plant Andrographis paniculata that 5 mmol L-1 exogenous GABA promoted plant growth under N deficient (1 mmol L-1 NO3-) condition, with remarkably increments in total N and NO3- concentrations in plants. GABA increased N assimilation and protein synthesis by up-regulating the activities and expression of N metabolic enzymes. GABA also increased the accumulation of α-ketoglutarate and malate, which could facilitate the assimilation of NO3-. Inhibition of NR by Na2WO4 counteracted the promoting effects of GABA on plant growth, and the effects of GABA were not affected by L-DABA and 3-MP, the inhibitors of GABA transaminase (GABA-T) and glutamate decarboxylase (GAD), respectively. These results suggested that the nutritional role of GABA was excluded in promoting plant growth under low N condition. The results of 15N isotopic tracing and NRTs transcription indicated that exogenous GABA could up-regulate NRT2.4 and NRT3.2 to increase plant NO3- uptake under N deficient condition. Interestingly, primidone, an inhibitor of GABA receptor, impeded the effects of GABA on plant growth and N accumulation. Thus, our results revealed that exogenous GABA acted as a signal to up-regulate NRTs via its receptor to increase NO3- uptake, and subsequently promoted NO3- assimilation to alleviate N deficiency in A. paniculata.

Assessment of integrated patterns of human-animal-environment health: a holistic and stratified analysis.

BACKGROUND: Data-driven research is a very important component of One Health. As the core part of the global One Health index (GOHI), the global One Health Intrinsic Drivers index (IDI) is a framework for evaluating the baseline conditions of human-animal-environment health. This study aims to assess the global performance in terms of GOH-IDI, compare it across different World Bank regions, and analyze the relationships between GOH-IDI and national economic levels. METHODS: The raw data among 146 countries were collected from authoritative databases and official reports in November 2021. Descriptive statistical analysis, data visualization and manipulation, Shapiro normality test and ridge maps were used to evaluate and identify the spatial and classificatory distribution of GOH-IDI. This paper uses the World Bank regional classification and the World Bank income groups to analyse the relationship between GOH-IDI and regional economic levels, and completes the case studies of representative countries. RESULTS: The performance of One Health Intrinsic Driver in 146 countries was evaluated. The mean (standard deviation, SD) score of GOH-IDI is 54.05 (4.95). The values (mean SD) of different regions are North America (60.44, 2.36), Europe and Central Asia (57.73, 3.29), Middle East and North Africa (57.02, 2.56), East Asia and Pacific (53.87, 5.22), Latin America and the Caribbean (53.75, 2.20), South Asia (52.45, 2.61) and sub-Saharan Africa (48.27, 2.48). Gross national income per capita was moderately correlated with GOH-IDI (R2 = 0.651, Deviance explained = 66.6%, P < 0.005). Low income countries have the best performance in some secondary indicators, including Non-communicable Diseases and Mental Health and Health risks. Five indicators are not statistically different at each economic level, including Animal Epidemic Disease, Animal Biodiversity, Air Quality and Climate Change, Land Resources and Environmental Biodiversity. CONCLUSIONS: The GOH-IDI is a crucial tool to evaluate the situation of One Health. There are inter-regional differences in GOH-IDI significantly at the worldwide level. The best performing region for GOH-IDI was North America and the worst was sub-Saharan Africa. There is a positive correlation between the GOH-IDI and country economic status, with high-income countries performing well in most indicators. GOH-IDI facilitates researchers' understanding of the multidimensional situation in each country and invests more attention in scientific questions that need to be addressed urgently.

Kazinol B protects H9c2 cardiomyocytes from hypoxia/reoxygenation-induced cardiac injury by modulating the AKT/AMPK/Nrf2 signalling pathway.

CONTEXT: Kazinol B (KB), an isoprenylated flavan derived from Broussonetia kazinoki Sieb. (Moraceae) root, has long been used in folk medicine. OBJECTIVE: This study examines the protective effects of KB and its underlying mechanisms in hypoxia and reoxygenation (H/R)-induced cardiac injury in H9c2 rat cardiac myoblasts. MATERIALS AND METHODS: H9c2 cells were incubated with various concentrations of KB (0, 0.3, 1, 3, 10 and 30 µM) for 2 h and then subjected to H/R insults. The protective effects of KB and its underlying mechanisms were explored. RESULTS: KB significantly elevated cell viability (1 µM, 1.21-fold; 3 µM, 1.36-fold, and 10 µM, 1.47-fold) and suppressed LDH release (1 µM, 0.77-fold; 3 µM, 0.68-fold, and 10 µM, 0.59-fold) in H/R-induced H9c2 cells. Further, 10 µM KB blocked apoptotic cascades, as shown by the Annexin-V/PI (0.41-fold), DNA fragmentation (0.51-fold), caspase-3 (0.52-fold), PARP activation (0.27-fold) and Bax/Bcl-2 expression (0.28-fold) assays. KB (10 µM) downregulated reactive oxygen species production (0.51-fold) and lipid peroxidation (0.48-fold); it upregulated the activities of GSH-Px (2.08-fold) and SOD (1.72-fold). KB (10 µM) induced Nrf2 nuclear accumulation (1.94-fold) and increased ARE promoter activity (2.15-fold), HO-1 expression (3.07-fold), AKT (3.07-fold) and AMPK (3.07-fold) phosphorylation. Nrf2 knockdown via using Nrf2 siRNA abrogated KB-mediated protective effects against H/R insults. Moreover, pharmacological inhibitors of AKT and AMPK also abrogated KB-induced Nrf2 activation and its protective function. DISCUSSION AND CONCLUSIONS: KB prevented H/R-induced cardiomyocyte injury via modulating the AKT and AMPK-mediated Nrf2 induction. KB might be a promising drug candidate for managing ischemic cardiac disorders.

Total alkaloids from the seed embryo of Nelumbo nucifera Gaertn. improve cognitive impairment in APP/PS1 mice and protect Aß-damaged PC12 cells.

The seed embryo of Nelumbo nucifera Gaertn. is a famous traditional Chinese medicine and food which is considered conducive to the prevention of Alzheimer's disease (AD). In this study, the effect and mechanism of TASENN (total alkaloids from the seed embryo of Nelumbo nucifera Gaertn.) on AD mice and amyloid-ß (Aß) injured PC12 cells were evaluated. HPLC-UV analysis showed that the extracted TASENN (purity = 95.6%) mainly contains Liensinine, Isoliensinine, and Neferine (purity was 23.01, 28.02, and 44.57%, respectively). In vivo, oral treatment with TASENN (50 mg/kg/day for 28 days) improved the learning and memory functions of APP/PS1 transgenic mice, ameliorated the histopathological changes of cortical and hippocampal neurons, and inhibited neuronal apoptosis. We found that TASENN reduced the phosphorylation of Tau and the formation of neurofibrillary tangles (NFTs) in APP/PS1 mouse brain. Moreover, TASENN down-regulated the expression of APP and BACE1, ameliorated Aß deposition, and inhibited microglial proliferation and aggregation. The elevated protein expression of CaM and p-CaMKII in APP/PS1 mouse brain was also reduced by TASENN. In vitro, TASENN inhibited the apoptosis of PC12 cells injured by Aß25-35 and increased the cell viability. Aß25-35-induced increase of cytosolic free Ca2+ level and high expression of CaM, p-CaMKII, and p-Tau were decreased by TASENN. Our findings indicate that TASENN has a potential therapeutic effect on AD mice and a protective effect on PC12 cells. The anti-AD activity of TASENN may be closely related to its negative regulation of the CaM pathway.

Six New Constituents from the Fruit of Hypericum patulum and Their Anti-Inflammatory Activity.

Four new xanthone glucosides, 3-hydroxy-2-methoxyxanthone-4-O-ß-D-glucopyranoside (1), 4,8-dihydroxy-2-methoxyxanthone-3-O-ß-D-glucopyranoside (2), 2-methoxyxanthone-5-O-ß-D-glucopyranoside (3), 4-hydroxy-2-methoxyxanthone-3-O-ß-D-glucopyranoside (4), a new phenolic acid, 4,4'-dihydroxy-3,3'-imino-di-benzoic acid monomethyl ester (5), and a new isoquinoline, methyl 6-hydroxy-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate (6) were isolated from the fruit of Hypericum patulum. The structural elucidation of the isolated compounds was primarily based on HR-ESI-MS, UV, IR, 1D and 2D NMR. All compounds were evaluated for their inhibitory effect against LPS-induced NO production in RAW 264.7 cells. Compound 2, 3 exhibited moderate inhibitory activity against NO production.

Effects of Soundscape Complexity on Urban Noise Annoyance Ratings: A Large-Scale Online Listening Experiment.

Noise annoyance has been often reported as one of the main adverse effects of noise exposure on human health, and there is consensus that it relates to several factors going beyond the mere energy content of the signal. Research has historically focused on a limited set of sound sources (e.g., transport and industrial noise); only more recently is attention being given to more holistic aspects of urban acoustic environments and the role they play in the noise annoyance perceptual construct. This is the main approach promoted in soundscape studies, looking at both wanted and unwanted sounds. In this study, three specific aspects were investigated, namely: (1) the effect of different sound sources combinations, (2) the number of sound sources present in the soundscape, and (3) the presence of individual sound source, on noise annoyance perception. For this purpose, a large-scale online experiment was carried out with 1.2k+ participants, using 2.8k+ audio recordings of complex urban acoustic environments to investigate how they would influence the perceived noise annoyance. Results showed that: (1) the combinations of different sound sources were not important, compared, instead, to the number of sound sources identified in the soundscape recording (regardless of sound sources type); (2) the annoyance ratings expressed a minimum when any two clearly distinguishable sound sources were present in a given urban soundscape; and (3) the presence (either in isolation or combination) of traffic-related sound sources increases noise annoyance, while the presence (either in isolation or combination) of nature-related sound sources decreases noise annoyance.

Interleukin-37 protects against acinar cell pyroptosis in acute pancreatitis.

Acute pancreatitis (AP) is a local and/or systemic inflammatory disease that starts with acinar cell injury and necrosis; it has no effective medical treatment and thus remains a life-threatening condition. Interleukin-37 (IL-37), a natural immunomodulator, has demonstrated an antiinflammatory effect; however, the role of IL-37 in AP remains unknown. The serum IL-37 levels of 39 healthy controls and 94 patients with AP were measured. Cholecystokinin was applied to induce pancreatic acinar cell injury in vitro. Classical experimental AP models, such as caerulein, l-arginine, and taurolithocholic acid 3-sulfate disodium salt, were included in the in vivo study. A transgenic mouse model with the IL-37 gene and administration of recombinant IL-37 were used to further investigate the function of IL-37 in AP. Pancreas-specific gasdermin D-knockout (GSDMD-knockout) mice were used to explore the protective mechanism of IL-37. Our results showed that serum IL-37 levels in humans were negatively correlated with the severity of AP. Furthermore, IL-37-transgenic mice and supplementation with recombinant IL-37 could both protect against AP. Mechanistically, IL-37 was able to suppress pyroptosis of injured acinar cells, and specific depletion of GSDMD in the pancreas counteracted the protective effect of IL-37. Our study demonstrates that IL-37 protects against acinar cell pyroptosis in AP.

[Isoquinoline alkaloids from two species of Thalictrum genus plants].

The chemical constituents from the roots of Thalictrum cultratum and T. baicalense were investigated. By various isolation methods, such as silica gel, aluminium oxide, ODS, and Sephadex LH-20 column chromatographies, and semi-preparative HPLC, 11 simple isoquinoline alkaloids were isolated from the ethanol extract of the roots of these two plants, including a new compound, named dehydrothalflavine(1), and ten known ones(2-11): N-methylcorydaline(2), N-methylthalidaldine(3), thaliflavine(4), oxyhydrastinine(5), noroxyhydrastinine(6), dimethoxyisoquinolone(7), thalactamine(8), dehydronoroxyhydrastinine(9), 6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline(10), and isopicnarrhine(11). Their structures were elucidated on the basis of HR-ESI-MS and 1 D and 2 D NMR techniques. Compound 1 was a new isoquinoline alkaloid. Compound 11 was obtained from Tha-lictrum plant for the first time. All compounds did not show cytotoxic activities against HL-60, U937, HCT116, Caco-2, and HepG2 cancer cell lines.

[Effects of Angong Niuhuang Pills against heart failure based on cross-scale polypharmacological study].

Angong Niuhuang Pills(AGNHP) are effective in clearing heat, removing the toxin, and eliminating phlegm for resuscitation. Clinically, it is widely used to treat various diseases such as febrile convulsion due to heat attacking pericardium, but its therapeutic effects on heart failure(HF) have not been well recognized. In this study, the profiles of differential metabolites regulated by AGNHP were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of AGNHP against HF was illustrated based on the integrated analysis of pharmacological data and metabolic molecular network. The HF model was induced by isoproterenol in mice. After oral administration of AGNHP for one week, cardiac functions in HF mice were evaluated by echocardiography, and serum samples of mice were collected for metabolomics analysis. Eight differential metabolites of AGNHP against HF were screened out through partial least square discriminant analysis(PLS-DA) and input into MetaboAnalyst for the analysis of metabolic pathways. Moreover, the critical metabolic pathways regulated by AGNHP were enriched according to the potential targets of major compounds in AGNHP. After AGNHP treatment, the recovered index of relative content of some metabolites underwent cross-scale fusion analysis with therapeutic efficacy data, followed by "compound-reaction-enzyme-gene" network analysis. It is inferred that the anti-HF effects of AGNHP may be attributed to the metabolism of arachidonic acid, amino acid, glycerophospholipid, and linoleic acid. The cross-scale polypharmacological analysis method developed in this study provides a new method to interpret scientific principles of AGNHP against HF with modern technologies.

Towards a global One Health index: a potential assessment tool for One Health performance.

BACKGROUND: A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed. METHODS: We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators. RESULTS: The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8-65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible. CONCLUSIONS: GOHI-subject to rigorous validation-would represent the world's first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge.

Bushen Jianpi Formula Combined with Entecavir for the Treatment of HBeAg-Negative Chronic Hepatitis B: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Bushen Jianpi formula (BSJPF, also known as Lingmao formula) is a traditional Chinese medicine for chronic hepatitis B (CHB). The previous study has suggested that the treatment combination of BSJPF and entecavir (ETV) can achieve a significant loss of hepatitis B e antigen (HBeAg) and a significant decrease in serum level of hepatitis B virus (HBV) DNA in HBeAg-positive CHB patients with mildly elevated alanine aminotransferase. Objective: This study aimed to evaluate the efficacy and safety of BSJPF combined with ETV for treating HBeAg-negative CHB patients. Methods: A total of 640 patients were assigned randomly to the treatment group (receiving BSJPF combined with ETV for 96 weeks) or the control group (receiving a placebo combined with ETV for 96 weeks) in a 1 : 1 ratio. The primary endpoints are the rate of loss of hepatitis B surface antigen (HBsAg). The secondary outcomes included the rate of decrease in the HBsAg concentration to ≥1 lg·IU/mL, the HBV DNA suppression, the decline of the level of covalently closed circular DNA (cccDNA) in the liver, histological improvements, and the rate of ALT normalization. Results: The rate of HBsAg loss in the treatment group was significantly higher than that of the control group (5.5% versus 1.8%, P=0.031). There were 11.1% of patients in the treatment group who recorded a reduction in HBsAg ≥1 lg·IU/mL, which is better than 5.9% of patients in the control group (P=0.043). There was no significant difference between the two groups with regard to the rate of HBV DNA clearance, the reduction in intrahepatic cccDNA, and the rate of ALT normalization (P > 0.05). The rate of liver fibrosis improvement in the treatment group was better than that of the control group (35.5% versus 11.8%, P=0.031), but there was no difference in necroinflammatory improvement (P > 0.05). The adverse events (AEs) were similar between the two groups, except for the abnormal kidney function, with 2.2% in the control group and 0.0% in the treatment group (P=0.028). Conclusion: The combination of BSJPF and ETV can increase the rate of HBsAg loss and the rate of histological fibrosis improvement without serious adverse events in CHB patients. Trial Registration. This trial is registered with ChiCTR-IOR-16009880 on November 16, 2016-retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=16836.

Efficacy and safety of AnluoHuaxian pills on chronic hepatitis B with normal or minimally elevated alanine transaminase and early liver fibrosis: A randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: The AnluoHuaxian pill (AHP) is a widely used patented medicine for chronic hepatitis B (CHB) patients with advanced fibrosis or cirrhosis that has been used in China for more than 15 years. However, data are lacking on whether monotherapy with AHP can be effective in CHB patients with alanine aminotransferase (ALT) levels less than 2 times the upper limit of normal (ALT<2ULN) and early liver fibrosis (F ≤ 2). AIM OF THE STUDY: We aimed to investigate whether monotherapy with AHP improves liver histology in these patients. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 270 CHB patients with ALT<2ULN and F ≤ 2 were treated in 12 hospitals in China. The patients were randomly assigned to an intervention (AHP) group and a placebo group at a ratio of 2:1. Of these 270 enrolled patients, 147 had paired liver biopsies. The primary end point was histological change after 48 weeks of treatment. RESULTS: Per-protocol analysis revealed that the rate of histologic improvement in liver fibrosis patients in the AHP group was significantly higher than that in the placebo group (37.7% vs. 19.5%, P = 0.035) after 48 weeks of treatment, which was consistent with results from intention-to-treat and sensitivity analyses. Moreover, after adjusting for baseline characteristics, AHP was superior to placebo with respect to improving liver fibrosis (odds ratio [OR] = 2.58, 95% confidence interval [CI]: (1.01, 6.63),P = 0.049) and liver histology (OR = 3.62, 95% CI: (1.42, 9.20),P = 0.007). In noninvasive measurement of liver fibrosis (FibroScan®), the level of liver stiffness measurement (LSM) had decreased significantly at 48 weeks (5.1 kPa) compared with that at baseline (5.7 kPa) (P = 0.008) in the AHP group, whereas it did not decrease significantly in the placebo group. Cirrhosis developed in one patient in the placebo group but in no patients in the AHP group. No serious side effects occurred in the AHP-treated patients. CONCLUSIONS: Treatment of CHB patients who had ALT<2ULN and F ≤ 2 with the traditional Chinese medicine AHP for 48 weeks improves liver fibrosis. However, due to the short duration of treatment and the limited sample size of liver pathology, the long-term benefits of AHP in reducing fibrosis and the risk of cirrhosis and hepatocellular carcinoma in these patients need to be further studied in the future.