The Anti-atherosclerosis Mechanism of Ziziphora clinopodioides Lam. Based On Network Pharmacology.

We investigated the mechanisms underlying the effects of Ziziphora clinopodioides Lam. (ZCL) on atherosclerosis (AS) using network pharmacology and in vitro validation.We collected the active components of ZCL and predicted their targets in AS. We constructed the protein-protein interaction, compound-target, and target-compound-pathway networks, and performed GO and KEGG analyses. Molecular docking of the active components and key targets was constructed with Autodock and Pymol software. Validation was performed with qRT-PCR, ELISA, and Western blot.We obtained 80 components of ZCL. The network analysis identified that 14 components and 37 genes were involved in AS. Then, 10 key nodes in the PPI network were identified as the key targets of ZCL because of their importance in network topology. The binding energy of 8 components (Cynaroside, α-Spinasterol, Linarin, Kaempferide, Acacetin, Genkwanin, Chrysin, and Apiin) to 4 targets (MMP9, TP53, AKT1, SRC) was strong and <-1 kJ/mol. In addition, 13 of the 14 components were flavonoids and thus total flavonoids of Ziziphora clinopodioides Lam. (ZCF) were used for in vitro validation. We found that ZCF reduced eNOS, P22phox, gp91phox, and PCSK9 at mRNA and protein levels, as well as the levels of IL-1ß, TNF-α, and IL-6 proteins in vitro (P < 0.05).We successfully predicted the active components, targets, and mechanisms of ZCL in treating AS using network pharmacology. We confirmed that ZCF may play a role in AS by modulating oxidative stress, lipid metabolism, and inflammatory response via Cynaroside, Linarin, Kaempferide, Acacetin, Genkwanin, Chrysin, and Apiin.

Dietary Bacillus velezensis R-71003 and sodium gluconate improve antioxidant capacity, immune response and resistance against Aeromonas hydrophila in common carp.

This study aimed to evaluate the effects of dietary supplementation with Bacillus velezensis R-71003 combined with sodium gluconate on antioxidant capacity, immune response and resistance against Aeromonas hydrophila in common carp. In addition, the biocontrol potential of the secondary metabolites of B. velezensis R-71003 was also evaluated to analyze the possible mechanism of B. velezensis R-71003 against A. hydrophila. The results indicated that the antibacterial crude extract of B. velezensis R-71003 can destroy the cell wall of A. hydrophila. Moreover, the results showed that dietary B. velezensis R-71003 could promote antioxidant capacity, which significantly increased the activities of CAT and SOD and decreased the content of MDA. Additionally, B. velezensis R-71003 supplementation significantly enhanced the immunity of common carp, as measured by the mRNA expression levels of cytokine-related genes (TNF-α, TGF-ß, IL-1ß and IL-10). In addition, dietary B. velezensis R-71003 exhibited an upregulation of IL-10 and a downregulation of IL-1ß, coupled with higher survival rates when challenged with A. hydrophila compared to the positive group. Furthermore, compared to prechallenge, the mRNA expression levels of TLR-4, MyD88, IRAK1, TRAF6, TRIF and NF-κB in the head kidney of common carp were significantly increased after challenge. The fish fed the B. velezensis R-71003 diet showed lower expression of TLR-4, MyD88, IRAK1, TRAF6, TRIF and NF-κB after the challenge than those fed the control diet. Thus, this study revealed that B. velezensis R-71003 can improve the resistance of common carp to pathogenic bacteria by destroying bacterial cell walls and improving fish immunity by activating the TLR4 signaling pathway. Importantly, this study indicated that sodium gluconate has a positive effect on B. velezensis R-71003 in enhancing the anti-infection ability of common carp. The results of this study will lay the foundation for the application of B. velezensis R-71003 in combination with sodium gluconate as an alternative to antibiotics in aquaculture.

Intracellular and extracellular enzymatic responsive micelle for intelligent therapy of cancer.

Recently, the incidence of cancer keeps increasing, seriously endangers human health, and has evolved into the main culprit of human death. Conventional chemotherapeutic drugs, such as paclitaxel and doxorubicin (DOX), have some disadvantages, including low therapeutic effect, poor water solubility, high toxic side effects, short blood circulation time in the body, and so on. To improve the anti-tumor effect of the drug in vivo and reduce its side effects on the body, researchers have designed and developed a variety of responsive nanocarriers. In this work, we synthesized D-α-tocopherol polyethylene glycol 3350 succinate (TPGS3350)-Gly-Pro-Leu-Gly-Val-Arg (GPLGVR)-DOX (TPD) prodrugs in response to extracellular enzymes of matrix metalloproteinase (MMP-9) in the tumor microenvironment and FA-Asp-Glu-Val-Asp (DEVD)-DOX (FPD) prodrugs responsive to intracellular enzymes of caspase-3. Then, intracellular and extracellular enzyme-responsive TPD&FPD micelles with DOX (TPD&FPD&D) were successfully prepared through dialysis method. The outer layer of TPGS3350 can prolong the blood circulation time of micelles in vivo, followed by accumulation of micelles at tumor tissue through enhanced permeability and retention (EPR) effect. The peptide of GPLGVR can be cleaved by MMP-9 enzymes to remove the outer layer of TPGS3350, exposing the targeting molecule of folate, and then the micelles are engulfed by tumor cells through folate receptor-mediated endocytosis. After entering the tumor cells, the free DOX loaded in the micelles is released, which induces tumor cell apoptosis to activate caspase-3 in the cells, cutting the peptide DEVD to accelerate the intracellular release of the DOX, which further enhances cytotoxicity to improve antitumor effect. Electronic Supplementary Material: Supplementary material () is available in the online version of this article at 10.1007/s12274-022-4967-1.

Network pharmacology study on the potential effect mechanism of Chuanzhi Tongluo Capsule in the treatment of cerebral infarction.

BACKGROUND: Chuanxiong Tongluo capsules have been widely used to treat recovered stroke and cerebral infarction, but their specific therapeutic mechanism is not well understood. METHODS: This study aims to investigate the mechanism of action for Chuanzhi Tongluo capsule on cerebral infarction based on a network pharmacology approach. The TCMSP platform collected the chemical composition of Chuanzhi Tongluo capsules. Its potential targets were predicted by Swiss target prediction and standardized using the Uniprot database for gene normalization. Meanwhile, the OMIM, Genecards, and TTD databases were used to obtain the targets related to cerebral infarction. The standard targets of Chuanzhi Tongluo capsule and cerebral infarction were uploaded to the STRING database to construct protein-protein interaction networks. Topological methods analyzed the key targets and components in the drug-component-disease-target network. Gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the shared targets were performed using the DAVID database. RESULTS: A total of 105 active ingredients and 427 targets were associated with Chuanzhi Tongluo capsule, and there were 3055 targets related to cerebral infarction disease and 240 common targets between the two keywords. The key targets included INS, ALB, IL-6, VEGFA, TNF, and TP53. The conduction pathways involved include the calcium signaling pathway, cAMP signaling pathway, cGMP-PKG signaling pathway, and TNF signaling pathway. CONCLUSION: The active ingredients in Chuanzhi Tongluo capsule may participate in the therapeutic process of cerebral infarction by regulating the calcium, cAMP, cGMP-PKG, and TNF signaling pathway through critical targets such as INS, ALB, IL-6, VEGFA, TNF, and TP53.

Skeletal muscle mass, meat quality and antioxidant status in growing lambs supplemented with guanidinoacetic acid.

Guanidinoacetic acid (GAA) exists naturally as a precursor of creatine, which possesses several biological functions. In the present study, the effects of dietary GAA supplementation on skeletal muscle mass and meat quality of lambs were investigated. The GAA supplementation increased final body weight, promoted muscle mass and changed the distribution of myofiber size. Meanwhile, elevated ultimate pH and water holding capacity (WHC) of resulting meat were observed in GAA fed lambs. Moreover, the total antioxidative capacity was elevated. Dietary GAA accelerated myofibril protein synthesis through regulation with IGF-1/Akt/mTOR signaling pathway and minimized protein breakdown via regulating abundances of myostatin and phosphorylated FoxO1. In vitro, GAA treatment inhibited sheep primary myoblasts proliferation, and enhanced its myogenic potential. Collectively, these results suggested that GAA might be a feed additive for use by the lamb meat industry as it has potential to improve growth performance, antioxidant status and WHC of resulting meat.

Clinical Efficacy of Tuomin Zhiti Decoction in Allergic Rhinitis.

Allergic rhinitis (AR) is a noninfectious inflammatory disease seriously affecting the quality of life. This study aimed to assess the efficacy of the Tuomin Zhiti decoction in allergic rhinitis and to provide a reference for clinical treatment. One hundred patients with AR treated in the Department of Otolaryngology of our hospital from January 2019 to December 2020 were recruited and assigned via a random number table method (1 : 1) to receive either oral loratadine and mometasone nasal spray (control group) or the Tuomin Zhiti decoction plus oral loratadine and mometasone nasal spray (study group). The total clinical efficacy was 86% (43/50) in the study group, which was significantly higher than that of 64% (32/50) in the control group. After treatment, the Total Nasal Symptoms Scores (TNSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores between the two groups were similar, but 12 weeks after treatment, the study group had significantly lower TNSS and RQLQ scores than the control group. After treatment, the study group obtained lower levels of interleukin (IL)-4 and higher levels of interferon-γ (IFN-γ) than the control group. Significantly lower post-treatment peripheral blood eosinophil count (EOS) and eosinophil cationic protein (ECP) levels were observed in the study group in contrast to those of the control group. The Tuomin Zhiti decoction for the treatment of AR patients alleviates their clinical symptoms, reduces the inflammatory responses, enhances the immune function of patients by regulating IL-4 and IFN-γ, and lowers the long-term recurrence rate.

Effect of Dietary Inclusion of Riboflavin on Growth, Nutrient Digestibility and Ruminal Fermentation in Hu Lambs.

The study evaluated the influences of riboflavin (RF) supply on the growth performance, nutrient digestibility and ruminal fermentation in lambs. Forty-eight Hu lambs were randomly assigned into four groups receiving RF of 0, 15, 30 and 45 mg/kg dry mater (DM), respectively. Increasing RF supply did not affect the DM intake, but quadratically increased the average daily gain and linearly decreased feed conversion ratio. Total-tract DM, neutral detergent fibre, acid detergent fibre and crude protein digestibility increased quadratically. Rumen pH and propionate molar percentage decreased linearly, total volatile fatty acids concentration, acetate proportion and the ratio of acetate to propionate increased linearly, but ammonia nitrogen concentration was unchanged with increasing RF supply. Linear increases were observed on the activities of carboxymethyl-cellulase, xylanase, pectinase and protease, and the populations of bacteria, fungi, protozoa, dominant cellulolytic bacteria, Ruminobacter amylophilus and Prevotella ruminicola. Methanogens population was not affected by RF supplementation. The microbial protein amount and urinary total purine derivatives excretion increased quadratically. The results indicated that 30 mg/kg DM RF supply improved growth performance, rumen fermentation and nutrient digestion in lambs.

Effects of an exopolysaccharide from Lactococcus lactis Z-2 on innate immune response, antioxidant activity, and disease resistance against Aeromonas hydrophila in Cyprinus carpio L.

Microbial exopolysaccharides (EPS) from Lactococcus have been found to have an important role in the probiotic activity of this bacterium; however, the immunomodulatory and antioxidant activities have not been fully explored in aquaculture. In the present study, we investigated EPS-2 from Lactococcus lactis Z-2, isolated from healthy common carp, for its immunomodulatory and antioxidant effects and disease resistance against Aeromonas hydrophila in Cyprinus carpio L. We found that the molecular weight of EPS-2 was 18.65 KDa. The monosaccharide composition of this polymer was rhamnose, xylose, mannose, glucose, and galactose at a molar percentage of 13.3%, 14.1%, 18.5%, 27.4%, and 26.7%, respectively. EPS-2 treatment could modulate the immune responses in vitro and in vivo. In vitro tests showed that EPS-2 could significantly enhance the proliferation and phagocytosis activities (P < 0.05) as well as induce the production of nitic oxide (NO), pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6), and anti-inflammatory cytokines (IL-10, TGF-ß) (P < 0.05) in head kidney cells. When the fish were gavaged with three different concentrations of EPS-2 (250, 500, 1000 µg/mL) for 7 days and infected with A. hydrophila, different expression patterns of the NO, cytokines, lysozyme (LZM), and alkaline phosphatase (AKP) in the serum and of antioxidants (T-AOC, SOD, CAT, GSH, GSH-Px and MDA) in hepatopancreas were observed. Before infection with A. hydrophila, EPS-2 supplementation significantly up-regulated the NO production, protein levels of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6), LZM and AKP activities, and levels of antioxidant molecules compared to those in the negative (G1) group (P < 0.05), whereas levels of NO and pro-inflammatory cytokines and LZM and AKP activities were significantly lower than those in the positive (G2) group after infection (P < 0.05). However, whether infected or not, the expression levels of anti-inflammatory cytokines (IL-10, TGF-ß) were significantly increased in the EPS-2 treatment groups (P < 0.05). These results indicate that EPS-2 has immunomodulatory and antioxidant effects on common carp, both in vitro and/or in vivo, and can be applied as a common carp feed supplement to enhance fish immunity and disease resistance against A. hydrophila.

Low-level laser therapy 810-nm up-regulates macrophage secretion of neurotrophic factors via PKA-CREB and promotes neuronal axon regeneration in vitro.

Macrophages play key roles in the secondary injury stage of spinal cord injury (SCI). M1 macrophages occupy the lesion area and secrete high levels of inflammatory factors that hinder lesion repair, and M2 macrophages can secrete neurotrophic factors and promote axonal regeneration. The regulation of macrophage secretion after SCI is critical for injury repair. Low-level laser therapy (810-nm) (LLLT) can boost functional rehabilitation in rats after SCI; however, the mechanisms remain unclear. To explore this issue, we established an in vitro model of low-level laser irradiation of M1 macrophages, and the effects of LLLT on M1 macrophage polarization and neurotrophic factor secretion and the related mechanisms were investigated. The results showed that LLLT irradiation decreased the expression of M1 macrophage-specific markers, and increased the expression of M2 macrophage-specific markers. Through forward and reverse experiments, we verified that LLLT can promote the secretion of various neurotrophic factors by activating the PKA-CREB pathway in macrophages and finally promote the regeneration of axons. Accordingly, LLLT may be an effective therapeutic approach for SCI with clinical application prospects.

Effects of Astragalus membranaceus roots supplementation on growth performance, serum antioxidant and immune response in finishing lambs.

OBJECTIVE: Astragalus membranaceus root is a well-known traditional Chinese herbal medicine with many biological active constituents. This study was conducted to examine the effects of Astragalus membranaceus root powder (AMP) on growth performance, serum antioxidant and immune response in finishing lambs. METHODS: A total of thirty-six Guangling fat-tailed ram lambs (body weight = 19±2 kg, mean ±standard deviation) were randomly assigned to one of six treatments for a 40 d feeding period, with the first 10 d for adaptation. Treatments consisted of the lambs' basal diets with addition of 0, 5, 10, 15, 20, and 30 g/kg of diet of AMP. RESULTS: Response to supplementation level of AMP was quadratic (p≤0.032) for final weight and ADG with the greatest at 10 g/kg of diet, but dry matter intake was not affected (p≥0.227) by treatments. The increase of AMP supplementation resulted in a quadratic response in contents of triglyceride and creatinine (p<0.05), with the lowest values for 10 and 20 g/kg of diet, respectively. A linear and quadratic decrease was observed in activity of alkaline phosphatase in serum of lambs. As the AMP supplementation increased, the activities of total superoxide dismutase and total antioxidant capacity increased linearly (p≤0.018) and hydroxyl radical (OH-) decreased linearly (p = 0.002). For catalase (CAT) and malondialdehyde (MDA), quadratic (p≤0.001) effects were observed among treatments, with the greatest CAT and lowest MDA values at 10 g/kg AMP. Additionally, supplementing AMP up to a level of 10 or 15 g/kg of diet quadratically increased immunoglobulin and interleukin contents in the serum. CONCLUSION: The results indicated that AMP can be used as natural feed additive in the ration of lambs to improve ADG, antioxidant status, and immune functions, and the optimal dose was 10 g/kg of diet under the condition of this experiment.

Photobiomodulation Therapy Inhibit the Activation and Secretory of Astrocytes by Altering Macrophage Polarization.

Spinal cord injury (SCI) stimulates reactive astrogliosis and the infiltration of macrophages, which interact with each other at the injured area. We previously found Photobiomodulation (PBM) significantly decreases the number of M1 macrophages at the injured area of SCI. But the exact nature of the astrocyte response following PBM and relationship with the macrophage have not been explored in detail. In this study, a BALB/c mice model with standardized bilateral spinal cord compression and a macrophage-astrocyte co-culture model were applied to study effects of PBM on astrocytes. Results showed that PBM inhibit the expression of the astrocyte markers glial fibrillary acidic protein (GFAP) and the secretion of chondroitin sulfate proteoglycans (CSPG) in the para-epicenter area, decrease the number of M1 macrophage in vivo. The in vitro experiments indicated M1 macrophages promote the cell viability of astrocytes and the expression of CSPG. However, PBM significantly inhibited the expression of GFAP, decreased activation of astrocyte, and downregulated the expression of CSPG by regulating M1 macrophages. These results demonstrate that PBM may regulate the interaction between macrophages and astrocytes after spinal cord injury, which inhibited the formation of glial scar.

Characterization of a polysaccharide HP-02 from Honeysuckle flowers and its immunoregulatory and anti-Aeromonas hydrophila effects in Cyprinus carpio L.

Aquaculture systems are known to be major reservoirs of Aeromonas hydrophila. The use of Chinese medicinal polysaccharides has become a successful strategy to prevent bacterial diseases in aquaculture. A water-soluble polysaccharide, HP-02, was purified from honeysuckle flowers, and the present study was aimed to examine its immunomodulatory and anti-A. hydrophila effects in Cyprinus carpio L. The results showed that the molecular weight of HP-02 was estimated to be 38 kDa. Monosaccharide composition was determined to be arabinose, rhamnose, mannose, glucose, and galactose in a molar ratio of 2.5: 1.8: 3.6: 3.7: 1.9. HP-02 not only distinctly improved the proliferation and phagocytosis of head kidney cells, but also exerted significant immunoregulation activity by increasing the secretion of the pro-inflammatory cytokines TNF-α, IL-1ß, IL-6, and IL-12 and the anti-inflammatory cytokines IL-10 and TGF-ß at the protein level in head kidney cells and serum. Moreover, during pathogen infection in vivo, HP-02 significantly reduced the expression of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines. These results indicated that HP-02 had immunomodulatory effects on common carp both in vitro and in vivo, and HP-02 can be applied as a common carp feed supplement to enhance fish immunity and disease resistance against A. hydrophila.

Study on the nutritional value and ruminal degradation characteristics of fermented waste vinegar residue by N. sitophila.

Chemical composition and rumen degradability of waste vinegar residue (WVR) as roughage feed used for mutton sheep were evaluated in this work. Compared with the unfermented WVR, the WVR fermented by N. sitophila had more (P < 0.01) ash, crude protein (CP), and true protein (TP), less (P < 0.01) ether extract (EE), and significantly more carotenoid by about 27 times. But the contents of dry matter (DM), crude fiber (CF), neutral detergent fiber (NDF), and acid detergent fiber (ADF) had no obvious differences (P > 0.05) between unfermented and fermented WVR. The results suggested that the nutritional value of fermented WVR was higher for mutton sheep as roughage feed than that of unfermented WVR. The effective degradability (ED) of DM was higher (P < 0.05) in sheep with fermented WVR-based diet. The ED of CP and NDF of fermented WVR was reduced (P < 0.01) compared with the unfermented WVR. The results further suggested that the fermentation improved the degradability of WVR, and the rumen degradability of protein by ruminal flora decreased in fermented WVR, saving more protein for the sheep post-ruminal digestion and absorption. Furthermore, the results presented here clearly indicated the potential of fermented WVR by N. sitophila as an unconventional and functional feedstuff with rich carotenoid for ruminants, which could reduce WVR discharge in vinegar brewing industry and improve ruminant production. This work laid a foundation for the development of ruminant carotenoid functional feed.

Astragalus Polysaccharide Improves Insulin Sensitivity via AMPK Activation in 3T3-L1 Adipocytes.

Astragalus polysaccharide (APS) is an important bioactive component of Astragalus membranaceus which is used as an anti-diabetes herb in traditional Chinese medicine. The objective of this study was to investigate the effects and mechanisms of APS on insulin-sensitizing of adipocytes. Mouse 3T3-L1 preadipocytes were used as a model. The results showed that APS increased preadipocytes proliferation in a dose dependent manner, and 0.1 µg/mL APS sufficiently increased Proliferating Cell Nuclear Antigen (PCNA) content (p < 0.01). Moreover, APS enhanced intracellular lipid accumulation and mRNA expression of proliferator-activated receptor γ (PPARγ, p < 0.01), CCAAT/enhancer binding protein α (C/EBPα, p < 0.01) and fatty acid binding protein (aP2, p < 0.01). As expected, corresponding protein contents were elevated. Importantly, APS increased 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2-NBDG) uptake (p < 0.01). Meanwhile, both mRNA and protein content of glucose transporter 4 (Glut4) were elevated by APS (p < 0.01). The APS treatment enhanced tyrosine phosphorylation of insulin receptor substrate 1 (IRS1, p < 0.05) and phosphor-Akt content (p < 0.01). Besides, phosphorylated AMP-activated protein kinase (AMPK) content was increased in the APS treated cells (p < 0.01). Taken together, APS improved insulin sensitivity by enhancing glucose uptake, possibly through AMPK activation. These results suggested that APS might be a therapeutic candidate for insulin resistance.

Dietary supplementation with Rehmannia glutinosa affects the composition of intestinal microorganisms in common carp.

A feeding experiment was conducted to investigate the effects of Rehmannia glutinosa (RG) on the bacterial, archaeal, and fungal community composition in the gut of common carp (Cyprinus carpio L.). Common carp were given a control diet and an RG-supplemented diet (basal diet plus 4% prepared Rehmannia root powder) over a period of 80 days. Our results indicated that the bacteria Fusobacteria, Proteobacteria, and Bacteroidetes; the archaea Crenarchaeota and Euryarchaeota; and the fungi Basidiomycota are the most abundant microbial taxa in the gut of common carp. Compared with the common carp fed a control diet, the common carp fed an RG-supplemented diet contained a higher content of Akkermansia sp., and a lower proportion of Aeromonas sp. These results indicate that the consumption of a diet containing RG can lead to the accumulation of more beneficial microorganisms while inhibiting the growth of potential pathogens. Moreover, Crenarchaeota, the methanogenic, and Basidiomycota were detected in this study, these populations may be of high physiological relevance in carp because they have been implicated in human health and disease. Our results suggest that an RG-supplemented diet changes the intestinal microbial composition of common carp, which could have positive effects on the immune response of carp.

[Effects of hydrogen sulfide on mitochondria of lung in rats with ALI induced by lipopolysaccharide].

OBJECTIVE: To observe the effects of hydrogen sulfide (H2S) on structure and function of mitochondria of lung in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: Forty healthy male Sprague-Dawley (SD) rats were randomly divided into control group, LPS injury group, and low-, middle-, and high-dose NaHS groups, with 8 rats in each group. The rats in LPS injury group were given LPS 5 mg/kg via sublingual vein, and those in low-, middle-, and high-dose NaHS groups were challenged by LPS for 3 hours followed by intraperitoneally injection of 0.78, 1.56 and 3.12 mg/kg NaHS respectively in a volume of 2 mL/kg. The rats in control group were given 2 mL/kg normal saline via sublingual vein. The rats were sacrificed at 6 hours after model reproduction, and the lung tissues were harvested on time. The mitochondria in lung tissues were isolated with differential centrifugation. The lung mitochondria ultra structures were observed with electron microscope. The content of malondialdehyde (MDA) in mitochondria was determined with thiobarbituric acid method, and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and adenosine triphosphatase (ATPase) were determined with xanthine oxidase method. The mitochondrial activity and swelling were determined by multiskan spectrum. RESULTS: It was shown by transmission electron microscope that the mitochondrial structure in the control group was normal. The mitochondria in rat lung cells was swollen with disrupted or disintegrated cristae, the osmiophilic lamellar bodies had fused or disappeared, and rough endoplasmic reticulum degranulation phenomenon was obvious in LPS injury group. The mitochondrial damage was slightly mitigated in the low-dose NaHS group, and it was significantly mitigated in the middle-dose and high-dose NaHS groups. Compared with control group, the MDA content in lung mitochondria in LPS injury group was significantly increased (nmol/mg: 26.30±1.45 vs. 11.16±1.20), and SOD, GSH-Px, and ATPase activities were significantly decreased [SOD (U/mg): 18.78±1.13 vs. 27.44±1.97, GSH-Px (U/mg): 63.91±1.99 vs. 128.15±3.47, ATPase (U/mg): 4.83±0.25 vs. 9.92±0.65]; as well as the activity of the mitochondria was significantly decreased (A value: 0.164±0.025 vs. 0.319±0.045), and the swelling of the mitochondria was significantly increased (A value: 0.182±0.012 vs. 0.273±0.023), all with significantly statistical differences (all P < 0.01). Compared with LPS injury group, the MDA contents in low-, middle-, and high-dose NaHS groups were significantly decreased (nmol/mg: 21.89±1.23, 17.63±1.56, 12.19±1.30 vs. 26.30±1.45), and the SOD, GSH-PX, and ATPase activities were significantly increased [SOD (U/mg): 20.13±0.85, 21.38±1.22, 24.05±1.56 vs. 18.78±1.13; GSH-Px (U/mg): 82.06±1.65, 101.45±2.14, 117.80±2.12 vs. 63.91±1.99; ATPase (U/mg): 5.34±0.23, 7.06±0.37, 8.78±0.44 vs. 4.83±0.25]; as well as the activity of the mitochondria was markedly increased (A value: 0.194±0.018, 0.230±0.032, 0.297±0.038 vs. 0.164±0.025), and the swelling of mitochondria was markedly decreased (A value: 0.195±0.008, 0.219±0.017, 0.249±0.018 vs. 0.182±0.012), all with significantly statistical differences (all P < 0.05). Moreover, the protective effect of NaHS showed a dose-dependent manner. CONCLUSIONS: It could be concluded that LPS induce mitochondrial structural damage and functional impairment in rats with ALI induced by LPS, and H2S have a beneficial effect against ALI induced by LPS with decreasing the mitochondrial lipid peroxidation level and protecting the cell structure and function, and the effect is correlated with the dosage.

Prednisone lowers serum uric acid levels in patients with decompensated heart failure by increasing renal uric acid clearance.

Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA. The reduction in SUA in high-dose prednisone groups was associated with a significant increase in renal uric acid clearance. In conclusion, prednisone can reduce SUA levels by increasing renal uric acid clearance in patients with decompensated HF.

Diterpene alkaloids and diterpenes from Spiraea japonica and their anti-tobacco mosaic virus activity.

Five new naturally occurring natural products, including two atisine-type diterpene alkaloids (1 and 2), two atisane-type diterpenes (3 and 4), and a new natural product spiramine C2 (5), along with nine known ones (6-14), were isolated from the ethanolic extracts of the whole plant of Spiraea japonica var. acuminata Franch. Their structures were elucidated by extensive spectroscopic analysis. The anti-tobacco mosaic virus (TMV) activities of all the compounds were evaluated by the conventional half-leaf method. Six compounds (2, 3, 6, 7, 11, and 12) exhibited moderate activities at 100 µg/mL with inhibition rates in the range of 69.4-92.9%, which were higher than that of the positive control, ningnanmycin. Their preliminary structure-activity relationships were also discussed.

Limonoids from Munronia henryi and their anti-tobacco mosaic virus activity.

Five new compounds (1-5), including three limonoids, one diterpenoid, and one phytosterol, along with four known limonoids (6-9), were isolated from the ethanolic extracts of whole plants of Munronia henryi. Their structures were elucidated by extensive spectroscopic analysis. In addition, the anti-tobacco mosaic virus (TMV) activities of all the isolated compounds were evaluated by the conventional half-leaf and leaf-disk methods along with Western blot analysis. Most of the tested compounds showed strong antiviral activities, with IC50 values in the range of 14.8-34.0µg/mL, compared with ningnanmycin as a positive control (IC50=44.6µg/mL), and their preliminary structure-activity relationships were also discussed.

[Study on chemical constituents of Inula cappa].

Column chromatographies over silica gel, Sephadex LH-20, reverse phase C18, and MCI, and semi-preparative HPLC were used for separation and purification of constituents from Inula cappa. The 22 compounds were obtained and their strutures were determined by NMR and MS spectra data as nine flavonoids: luteolin (1), apigenin (2), chrysoeriol (3), artemetin (4), 2', 5-di- hydroxy-3, 6, 7, 4', 5'-pentamethoxyflavone (5), chrysosplenol C (6), apigenin-5-0-ß-D-glucopyranoside (7), luteolin-3-methyl, luteolin-3-methylether-4'-0-ß-D-glucopyranoside (8), luteolin-4'-0-ß-D-glucopyranoside (9); four triterpenes: darma-20, 24-dien- 3ß-0-acetate (10), darma-20, 24-dien-3ß-ol (11), epirfiedelanol (12), friedelin (13); three coumarins: scopoletin (14) , isosco- poletin (15) , scopolin(16) , and other types of compounds stigmasta-5, 22-dien-3ß-0-7-one (17), stigmasterol (18), palmitic acid (19), linoleic acid (20), linoleic acid methyl ester (21), (E) -9, 12, 13-trihydroxyoetadee-10-enoie acid (22). Compound 5 is a new natural product. Compounds 3-9, 15, 17, 21, and 22 were isolated from this genus for the first time.