Harmine inhibits pulmonary fibrosis through regulating DNA damage repair-related genes and activation of TP53-Gadd45α pathway.

BACKGROUND: Harmine has many pharmacological activities and has been found to significantly inhibit the fibrosis of keloid fibroblasts. DNA damage repair (DDR) is essential to prevent fibrosis. This study aimed to investigate the effects of harmine on pulmonary fibrosis and its underlying mechanisms. METHODS: Bleomycin and TGF-ß1 were used to construct pulmonary fibrosis models in vivo and in vitro, then treated with harmine to explore harmine's effects in treating experimental pulmonary fibrosis and its related mechanisms. Then, RNA sequencing was applied to investigate further the crucial DDR-related genes and drug targets of harmine against pulmonary fibrosis. Finally, the expression levels of DDR-related genes were verified by real-time quantitative PCR (RT-qPCR) and western blot. RESULTS: Our in vivo experiments showed that harmine treatment could improve weight loss and lung function and reduce tissue fibrosis in mice with pulmonary fibrosis. The results confirmed that harmine could inhibit the viability and migration of TGF-ß1-induced MRC-5 cells, induce their apoptosis, and suppress the F-actin expression, suggesting that harmine could suppress the phenotypic transition from lung fibroblasts to lung myoblasts. In addition, RNA sequencing identified 1692 differential expressed genes (DEGs), and 10 DDR-related genes were screened as critical DDR-related genes. RT-qPCR and western blotting showed that harmine could down-regulate the expression of CHEK1, ERCC1, ERCC4, POLD1, RAD51, RPA1, TOP1, and TP53, while up-regulate FEN1, H2AX and GADD45α expression. CONCLUSIONS: Harmine may inhibit pulmonary fibrosis by regulating DDR-related genes and activating the TP53-Gadd45α pathway.

Da-yuan-yin decoction alleviates ulcerative colitis by inhibiting complement activation, LPS-TLR4/NF-κB signaling pathway and NET formation.

ETHNOPHARMACOLOGICAL RELEVANCE: Da-yuan-yin decoction (DYY) is a classical traditional Chinese medicine prescription for ulcerative colitis (UC). AIM OF STUDY: This study explored the protective effects and mechanisms of DYY on UC. MATERIALS AND METHODS: The mice were fed 2.5% dextran sulfate sodium (DSS) for 7 days to establish UC. On the second day, DYY (0.4 g/kg, 0.8 g/kg, 1.6 g/kg) was orally administered daily for 7 consecutive days. The colon tissues and serum were measured by histopathological examination and biochemical analysis. RESULTS: DYY significantly reduced the disease activity index (DAI) and severity of colon shortening and alleviated pathological changes in the colon tissue. DYY restored the protein expression of intestinal tight junction (TJ) protein (ZO-1, occludin and claudin-3). DYY remarkably decreased the level of lipopolysaccharide (LPS), Lactic acid (LA), circulating free DNA (cfDNA), complement (C3, C3a, C3c, C3aR1, C5a and C5aR1) and regulated the levels of inflammatory cytokines in serum. DYY significantly inhibited the expressions of nuclear factor kappa-B p65 (NF-κB p65) and Toll-like receptor 4 (TLR4), citrullinated histone H3 (CitH3) and myeloperoxidase (MPO), reactive oxygen species (ROS) peptidylarginine deiminase 4 (PAD4) and CD 11b, the mRNA levels of PADI4, MPO and ELANE in colon tissues. CONCLUSIONS: DYY significantly attenuated DSS-induced UC, which was related with regulating the inflammatory response by the inhibition of complement activation, the LPS-TLR4/NF-κB signaling pathway and neutrophil extracellular traps (NETs) formation. DYY is a potential therapeutic agent for UC.

Bacterial-fungal interactions and response to heavy metal contamination of soil in agricultural areas.

Introduction: Long-term heavy metal contamination of soil affects the structure and function of microbial communities. The aim of our study was to investigate the effect of soil heavy metal contamination on microorganisms and the impact of different heavy metal pollution levels on the microbial interactions. Methods: We collected soil samples and determined soil properties. Microbial diversity was analyzed in two groups of samples using high-throughput sequencing technology. Additionally, we constructed microbial networks to analyze microbial interactions. Results: The pollution load index (PLI) < 1 indicates that the area is not polluted. 1 < PLI < 2 represents moderate pollution. PLI was 1.05 and 0.14 for the heavy metal contaminated area and the uncontaminated area, respectively. Cd, Hg, Pb, Zn, and Cu were identified as the major contaminants in the contaminated area, with the contamination factors were 30.35, 11.26, 5.46, 5.19, and 2.46, respectively. The diversities and compositions of the bacterial community varied significantly between the two groups. Compared to the uncontaminated area, the co-occurrence network between bacterial and fungal species in the contaminated area was more complex. The keystone taxa of the co-occurrence network in the contaminated area were more than those in the uncontaminated area and were completely different from it. Discussion: Heavy metal concentrations played a crucial role in shaping the difference in microbial community compositions. Microorganisms adapt to long-term and moderate levels of heavy metal contamination through enhanced interactions. Bacteria resistant to heavy metal concentrations may play an important role in soils contaminated with moderate levels of heavy metals over long periods of time.

Isolation, structural characterization, and bioactivities of neutral polysaccharides from Zizania latifolia.

The swollen culm (also known as Jiaobai) of Zizania latifolia is formed by the smut Ustilago esculenta invades the Z. latifolia. The new tissue formed due to the symbiotic relationship has entices the attention of researchers to study its polysaccharide structure along with biological evaluation. Five fractions of polysaccharides were obtained owing to hot water extraction, alcoholic precipitation, and chromatographic purification. Bioactivity assays showed that ZLPs have good antioxidant, hypoglycemic activities and protective activity against oxidative damage. The ZLP-1 and ZLP-2 were determined to be neutral polysaccharides with high purity, exhibiting propitious bioactivity, consequently they were subjected to indispensable structural characterization. These results showed that ZLP-1 has molecular weight (Mw) of 103 kDa and glucose (Glc) (76.68 %) as the primary monosaccharide; the ZLP-2 has Mw of 122 kDa and galactose (Gal) (41.04 %) and arabinose (Ara) (27.12 %). Structural elucidation by methylation and nuclear magnetic resonance (NMR) analysis suggested ZLP-1 is a glucan, with →3)-ß-Glcp-(1→3)-ß-Glcp-(1→4)-ß-Glcp-(1→4)-ß-Glcp-(1→3,6)-ß-Galp-(1→3)-ß-Glcp-(1→ as the mainchain and the terminal Araf and Glcp; the ZLP-2 is a Galactoxylan, with →3,4)-ß-xylp-(1→3)-ß-Galp-(1→3,6)-ß-Galp-(1→3,6)-ß-Galp-(1→ as the mainchain and the terminal Araf and Glcp. The structural arrangements provide a chemical basis for understanding the nutritional and pharmacological activities of polysaccharides from Zizania latifolia.

Heavy metal contamination impacts the structure and co-occurrence patterns of bacterial communities in agricultural soils.

Heavy metal (HM) contamination caused by mining and smelting activities can be harmful to soil microbiota, which are highly sensitive to HM stress. Here, we explore the effects of HM contamination on the taxonomic composition, predicted function, and co-occurrence patterns of soil bacterial communities in two agricultural fields with contrasting levels of soil HMs (i.e., contaminated and uncontaminated natural areas). Our results indicate that HM contamination does not significantly influence soil bacterial α diversity but changes the bacterial community composition by enriching the phyla Gemmatimonadetes, Planctomycetes, and Parcubacteria and reducing the relative abundance of Actinobacteria. Our results further demonstrate that HM contamination can strengthen the complexity and modularity of the bacterial co-occurrence network but weaken positive interactions between keystone taxa, leading to the gradual disappearance of some taxa that originally played an important role in healthy soil, thereby possibly reducing the resistance of bacterial communities to HM toxicity. The predicted functions of bacterial communities are related to membrane transport, amino acid metabolism, energy metabolism, and carbohydrate metabolism. Among these, functions related to HM detoxification and antioxidation are enriched in uncontaminated soils, while HM contamination enriches functions related to metal resistance. This study demonstrated that microorganisms adapt to the stress of HM pollution by adjusting their composition and enhancing their network complexity and potential ecological functions.

Enzymatic synthesis of Vaccinium blue using vaccinoside as a bifunctional precursor.

Since Tang dynasty in China, the fresh leaves of Vaccinium bracteatum (VBL) have been applied as natural pigment to produce black rice. However, detailed information on its biosynthetic mechanism still remained unclear. Following rice dyeing capacity assay, vaccinoside, one of iridoid glycosides, was identified as the key active compound. Increased methodical research demonstrated vaccinoside as a distinct bifunctional precursor, which could be catalyzed by polyphenol oxidase or ß-glucosidase independently, followed by reaction with 15 amino acids to give blue pigments (VBPs; λmax 581-590 nm) of different hues. Two synthetic pathways of VBPs were proposed, using multiple techniques such as HPLC, HPSEC, UV-Vis spectrum and colorimeter as analysis tools. Black rice was interpreted to be prepared by cooking, using vaccinoside, intrinsic enzymes from fresh VBL and rice protein in combination. These findings promote the understanding of VBP formation mechanisms and provide an efficient method of producing novel Vaccinium blue pigments.

Ecological and health risk assessment of heavy metals in agricultural soils from northern China.

Soil pollution by heavy metals can cause continuing damage to ecosystems and the human body. In this study, we collected nine fresh topsoil samples and 18 maize samples (including nine leaf samples and nine corn samples) from agricultural soils in the Baiyin mining areas. The results showed that the order of heavy metal concentrations (mg/kg) in agricultural soils was as follows: Zn (377.40) > Pb (125.06) > Cu (75.06) > Ni (28.29) > Cd (5.46) > Hg (0.37). Cd, Cu, Zn, and Pb exceeded the Chinese risk limit for agricultural soil pollution. The average the pollution load index (4.39) was greater than 3, indicating a heavy contamination level. The element that contributed the most to contamination and high ecological risk in soil was Cd. Principal component analysis (PCA) and Pearson's correlation analysis indicated that the sources of Ni, Cd, Cu, and Zn in the soil were primarily mixed, involving both industrial and agricultural activities, whereas the sources of Hg and Pb included both industrial and transportation activities. Adults and children are not likely to experience non-carcinogenic impacts from the soil in this region. Nonetheless, it was important to be aware of the elevated cancer risk presented by Cd, Pb, and especially Ni. The exceedance rates of Cd and Pb in corn were 66.67% and 33.3%, respectively. The results of this research provide data to improve soil protection, human health monitoring, and crop management in the Baiyin district.

Effects of long-term metal exposure on the structure and co-occurrence patterns of the oral microbiota of residents around a mining area.

Objectives: The aim of our study was to investigate the impact of long-term exposure to heavy metals on the microbiome of the buccal mucosa, to unveil the link between environmental contamination and the oral microbial ecosystem, and to comprehend its potential health implications. Methods: Subjects were divided into two groups: the exposure group and the control group. We collected samples of buccal mucosa, soil, and blood, and conducted microbial diversity analysis on both groups of oral samples using 16S rRNA gene sequencing. The concentrations of heavy metals in blood and soil samples were also determined. Additionally, microbial networks were constructed for the purpose of topological analysis. Results: Due to long-term exposure to heavy metals, the relative abundance of Rhodococcus, Delftia, Fusobacterium, and Peptostreptococcus increased, while the abundance of Streptococcus, Gemella, Prevotella, Granulicatella, and Porphyromonas decreased. The concentrations of heavy metals in the blood (Pb, Cd, Hg, and Mo) were associated with the growth of Rhodococcus, Delftia, Porphyromonas, and Gemella. In addition, the relative abundances of some pathogenic bacteria, such as Streptococcus anginosus, S. gordonii, and S. mutans, were found to be enriched in the exposure group. Compared to the exposure group network, the control group network had a greater number of nodes, modules, interactive species, and keystone taxa. Module hubs and connectors in the control group converted into peripherals in the exposure group, indicating that keystone taxa changed. Metals in the blood (Pb, Cd, Hg, and Mo) were drivers of the microbial network of the buccal mucosa, which can have adverse effects on the network, thus providing conditions for the occurrence of certain diseases. Conclusion: Long-term exposure to multiple metals perturbs normal bacterial communities in the buccal mucosa of residents in contaminated areas. This exposure reduces the complexity and stability of the microbial network and increases the risk of developing various diseases.

Differences of airborne and mural microorganisms in a 1,500-year-old Xu Xianxiu's Tomb, Taiyuan, China.

Background: Microbial colonization represents one of the main threats to the conservation of subterranean cultural heritage sites. Recently, the microbial colonization on murals in tombs has gradually attracted attention. Methods: In this study, a total of 33 samples, including 27 aerosol samples and 6 mural painting samples, were collected from different sites of Xu Xianxiu's Tomb and analyzed using culture-dependent methods. We compared the diversities of culturable bacteria and fungi isolated from the air and murals and explored the potential impacts of microorganisms on the biodeterioration of the murals. Results: Phylogenetic analyses revealed that the culturable bacteria belonged to Bacillus, Microbacterium, Lysobacter and Arthrobacter. And the most of fungal belonged to the Penicillium, Cladosporium and Aspergillus genera. The composition and structure of airborne bacteria and fungi outside the tomb were both significantly different from that inside the tomb. The variation trends of airborne bacterial and fungal concentrations at different sampling sites were remarkably similar. Bacillus frigoritolerans, Bacillus halotolerans, Bacillus safensis, Exiguobacterium mexicanum, Microbacterium trichothecenolyticum, and Micrococcus yunnanensis were bacterial species commonly isolated from both the mural and air environments. Fungal species commonly isolated from aerosol samples and mural painting samples were Alternaria alternata, Cladosporium cladosporioides, Penicillium brevicompactum, and Peyronellaea glomerata. The prediction of the ecological functions of the bacteria revealed that chemoheterotrophy or aerobic_chemoheterotrophy accounted for substantial relative proportions in all sample types. Conclusion: These results suggest that the aerosol circulation between the inside and outside environments of the tomb was weak and that the outside environment had yet to have an impact on the air microbial community inside the tomb. Selective colonization of microorganisms, which is mediated by interaction between microorganisms and special microenvironmental factors, is an important reason for the biodeterioration of murals.

Metatranscriptomic Sequencing Reveals Host Species as an Important Factor Shaping the Mosquito Virome.

Mosquitoes are important vector hosts for numerous viral pathogens and harbor a large number of mosquito-specific viruses as well as human-infecting viruses. Previous studies have mainly focused on the discovery of mosquito viruses, and our understanding of major ecological factors associated with virome structure in mosquitoes remains limited. We utilized metatranscriptomic sequencing to characterize the viromes of five mosquito species sampled across eight locations in Yunnan Province, China. This revealed the presence of 52 viral species, of which 19 were novel, belonging to 15 viral families/clades. Of particular note was Culex hepacivirus 1, clustering within the avian clade of hepaciviruses. Notably, both the viromic diversity and abundance of Aedes genus mosquitoes were significantly higher than those of the Culex genus, while Aedes albopictus mosquitoes harbored a higher diversity than Aedes aegypti mosquitoes. Our findings thus point to discernible differences in viromic structure between mosquito genera and even between mosquito species within the same genus. Importantly, such differences were not attributable to differences in sampling between geographical location. Our study also revealed the ubiquitous presence of the endosymbiont bacterium Wolbachia, with the genetic diversity and abundance also varying between mosquito species. In conclusion, our results suggested that the mosquito host species play an important role in shaping the virome's structure. IMPORTANCE This study revealed the huge capability of mosquitoes in harboring a rich diversity of RNA viruses, although relevant studies have characterized the intensively unparalleled diversity of RNA viruses previously. Furthermore, our findings showed discernible differences not only in viromic structure between mosquito genera and even between mosquito species within the same genus but also in the genetic diversity and abundance of Wolbachia between different mosquito populations. These findings emphasize the importance of host genetic background in shaping the virome composition of mosquitoes.

ASPS Exhibits Anti-Rheumatic Effects by Reprogramming Gut Microbiota and Increasing Serum γ-Glutamylcysteine Level.

Rheumatoid arthritis (RA) is an essential cause of labor loss and disability for people worldwide. Acanthopanax senticosus polysaccharide (ASPS) is one of the most important active components from A. senticosus, which exhibits various pharmacological activities such as antioxidation and immunomodulation. However, no studies have reported the application of ASPS in treating RA. This study aims to investigate the therapeutic effect of ASPS on RA and reveal its underlying mechanism. The potential therapeutic effect of ASPS against RA is initially verified in this study using the collagen-induced arthritis model. Moreover, the protective benefits of ASPS are transmitted through the fecal microbiota and blocked by simultaneous antibiotic cocktail treatment, indicating that gut microbiota may be correlated with ASPS. The 16S rRNA sequencing using feces samples and untargeted UPLC-MS metabolomics using serum samples further reveal that ASPS reprograms the arthritic progression triggered dysbiosis, enhances the expression of γ-glutamylcysteine (GGC) synthetase, and enriches the serum concentration of GGC. Furthermore, metabolites GGC is found to be able to effectively interrupt NLRP3 inflammasome activation via inhibiting ASC nucleation and therefore attenuate inflammatory arthritis. Taken together, this work highlights ASPS's therapeutic potential against RA, which mainly exhibits its effects via modulating gut microbiota and regulating GGC production.

Microwave-assisted enzymatic extraction brings a notably high yield of polysaccharides from mountain Zizania latifolia.

Mountain Zizania latifolia is produced at scale in China, and the edible swollen culm is exported to many countries, but little attention has been paid to its functional components. In this work, microwave-assisted enzymatic extraction (MAEE) is used for the first time to extract polysaccharides from mountain Z. latifolia swollen culm (PMZL). MAEE conditions optimized by Box-Behnken design-response surface methodology were as follows: 2.4% cellulase, microwaving for 6.0 min at 607 W, with a liquid-to-solid ratio of 63:1 ml g-1 . Under these conditions, a notably high yield of 60.43% ± 1.12% for PMZL was achieved, which was significantly higher (p < 0.01) than from plain-grown varieties. PMZL are naturally occurring sulfated polysaccharide-protein complexes containing 8.46% ± 0.18% proteins and 7.86% ± 0.73% sulfates. PMZL comprises mannose, glucosamine, rhamnose, glucose, galactose, and arabinose at molar ratios of 3.80:2.68:1.00:17.41:5.12:2.91, with a weight-average molecular weight of 1569,219 Da and a number-average molecular weight of 364,088 Da. The surface morphology of PMZL is composed of tightly packed oval particles, and this kind of promising polysaccharides preferentially scavenges reactive nitrogen species. PRACTICAL APPLICATION: Due to global warming, the land available for planting vegetables is likely to expand to higher areas, so greater attention should now be paid to mountain-grown vegetables. This study provides an efficient way to obtain novel polysaccharides from mountain Zizania latifolia using microwave-assisted enzymatic extraction with a remarkably high yield of 60.4%. This promising source of natural carbohydrates has potential uses in pharmaceutical, nutraceutical, functional foods, cosmetics, and functional materials industries.

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.

Effect of hypoproteinemia on the mortality of sepsis patients in the ICU: a retrospective cohort study.

The objective of the study was to evaluate the effect of hypoproteinemia on the prognosis of sepsis patients and the effectiveness of exogenous albumin supplementation. A retrospective cohort study was conducted in adult ICUs. The subjects were 1055 sepsis patients in MIMIC III database from June 2001 to October 2012. There were no interventions. A total of 1055 sepsis patients were enrolled and allocated into two groups based on the lowest in-hospital albumin level: 924 patients were in the hypoproteinemia group (the lowest in-hospital albumin ≤ 3.1 g/dL) and 131 patients were in the normal group (the lowest in-hospital albumin > 3.1 g/dL). A total of 378 patients [331 (35.8%) were in the hypoproteinemia group, and 47 (35.9%) were in the normal group] died at 28 days, and no statistically significant difference was found between the two groups (P = 0.99). The survival analysis of the 28-day mortality rate was performed using the Cox proportional risk model and it was found that the lowest in-hospital albumin level showed no significant effect on the 28-day mortality rate (P = 0.18, 95%CI). Patients in the hypoproteinemia group exhibited a longer length of stay in ICU and hospital and more complications with AKI than those in the normal group. However, multivariate regression analysis found that there was no statistical significance between the two groups. In addition, multivariate regression analysis showed that patients in the hypoproteinemia group had a shorter time without vasoactive drugs and time without mechanical ventilation than those in the normal group (P < 0.01). In the subgroup analysis, univariate analysis and multivariate regression analysis showed that there was no significant difference in the 28-day mortality rate (39.6% vs 37.5%, P = 0.80), the proportion of mechanical ventilation time (P = 0.57), and vasoactive drug time (P = 0.89) between patients with and without albumin supplementation. However, patients in the albumin supplementation group had a longer length of ICU stay and hospital stay than those in the non-supplementation group (P < 0.01). Albumin level may be an indicator of sepsis severity, but hypoproteinemia has no significant effect on the mortality of sepsis patients. Despite various physiological effects of albumin, the benefits of albumin supplementation in sepsis patients need to be evaluated with caution.

Systematic Study on a Quantitative Analysis of Multicomponents by Single Marker (QAMS) Method for Simultaneous Determination of Eight Constituents in Pneumonia Mixture by UPLC-MS/MS.

Pneumonia mixture was formulated and is available to treat children acute pneumonia and acute bronchitis in our hospital for nearly forty years, but there are few studies of its quality evaluation or control. In this paper, a new strategy for quality evaluation of pneumonia mixture was explored and verified through qualitative and quantitative analyses of multicomponents by single marker (QAMS) by UPLC-MS/MS. Baicalein was selected as an internal reference, and the relative correction factors (RCFs) and the relative retention time (RRT) of (R, S)-goitrin, amygdalin, chlorogenic acid, pseudoephedrine hydrochloride, ephedrine hydrochloride, ammonium glycyrrhizinate, and baicalin were established. The robustness and durability of the QAMS method were investigated. RCF values calculated by the average (AVG) method and linear regression (LRG) method had good repeatability and were acceptable for quantitative analysis, and the RTT combined with the exact masses of precursor and fragment ions and their abundance could be adopted for accurately positioning the chromatographic peak of the eight constituents. The consistency and feasibility of the QAMS method were verified by comparing the contents of the seven components calculated by a classic and validated external standard method (ESM) with those of the QAMS method, which reduces analytical cost and time of detection and avoids the problem of the diversity and large quantity of reference standards. The results demonstrated that the QAMS method developed in this paper could provide a new, alternative, and promising method to comprehensively and effectively determine multicomponents and control the quality of pneumonia mixture or even a group of similar medicines.

The safety and effectiveness of early anti-platelet therapy after alteplase for acute ischemic stroke: A meta-analysis.

BACKGROUND: For acute ischemic stroke patients, there is a risk of reocclusion after intravenous thrombolysis. In theory, early anti-platelet therapy can reduce the risk of vessel reocclusion. Although current guidelines do not recommend routine anti-platelet therapy within 24 h of intravenous thrombolytic therapy, many studies disagreed with it, especially after the emergence of new anti-platelet drugs. It is necessary to conduct a meta-analysis based on high-quality randomized controlled studies to re-evaluate this treatment strategy. METHODS: Literature retrieval was systematically conducted in PubMed, Embase, Cochrane, Web of sicence, clinical trials, CNKI and Wanfang Data, for searching randomized controlled trials (published between January 1, 2000 and April 30, 2020 with no language restrictions) comparing early (within 24 h) with routine (after 24 h) anti-platelet-aggregation therapy after rt-PA intravenous thrombolysis. The primary safety endpoint and primary efficacy indicator are the incidence of symptomatic intracranial hemorrhage and a good prognosis at 90-day (modified Rankin Scale (mRS) score of 0-1 or return to baseline mRS), respectively. We assessed pooled data by use of a random-effects model. FINDINGS: Of the 378 identified studies, only 3 were eligible and included in our analysis (N = 1008 participants). Compared with routine treatment, early anti-platelet-aggregation therapy after rt-PA intravenous thrombolysis in acute ischemic stroke patients did not affect the 90-day efficacy (95% CI 0.97 - 1.32). In terms of safety assessment, the early use of anti-platelet-aggregation drugs after thrombolysis has a neutral effect on the risk of intracranial hemorrhage, symptomatic intracranial hemorrhage, and bleeding from other systemic sites. CONCLUSION: Early anti-platelet therapy after alteplase did not benefit the acute ischemic stroke patients based on the current evidence. However, more clinical trials and statistical evidence are still needed.

The interaction between gut microbiota and flavonoid extract from Smilax glabra Roxb. and its potent alleviation of fatty liver.

Fatty liver is associated with intestinal microbiota dysbiosis and low-grade chronic inflammation. Herein we report the interaction of the flavonoid extract from Smilax glabra Roxb. (FSGR) with gut microbiota. Then, FSGR's function of modulating microbiota in a rat model of high-fat diet (HFD) induced fatty liver has been explored. These investigations indicated that the main compound in FSGR, such as astilbin and its isomers, could be metabolized to aglycone, while further splitting resulted in some phenolic acid compounds through a redox reaction. The data obtained clearly showed that FSGR not only alleviated the steatosis degree of liver cells and modulated the contents of short chain fatty acids (SCFAs) in the intestinal tract, but also reversed gut dysbiosis induced by HFD as prognosticated by the decreased ratio of Firmicutes/Bacteroidetes (F/B) and altered gene expression. The results demonstrated that FSGR probably could be used as a prebiotic agent to impede gut dysbiosis and fatty liver-related metabolic disorders.

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].

A 90-Day Oral Toxicity Study of the Ethanol Extract from Eupatorium japonicum Thunb and Foeniculum vulgare in Rats.

Eupatorium japonicum Thunb and Foeniculum vulgare are two of the most widely used folk herbs and constituents in many traditional Chinese herbal formulas. Nonetheless, little toxicological and safety information associated with following daily repeated exposure is obtained according to previous research. The present study was performed to assess the toxicity of ethanol extract from Eupatorium japonicum Thunb and Foeniculum vulgare (EFE) in male rats administered by dietary oral gavage at target doses of 0.39, 0.78, and 1.56 g/kg body weight/day for 90 days. There were no significant adverse effects on clinical signs, body weight, food conversion efficiency, and vital hematological indices. However, some hematology and biochemical indices such as WCV, MCH, MCHC, LY, MPV, T-CHO, as well as TG revealed significant changes in Sprague-Dawley rats and organ weights in lung and spleen showed diminished in male rats. Necropsy and histopathology findings suggested that no significant differences in absolute weights were found in all organs except lung and spleen, and no treatment-related alteration was identified in any organs. All results obtained in the present study indicated that the proper use of EFE in traditional medicine at oral dosages up to 1.56 g/kg/day body weight may harbor no prolonged toxicity to rats. However, further studies of EFE are still necessary to assess its oral safety in patients.