Yinhuapinggan granule ameliorates lung injury caused by multidrug-resistant Acinetobacter baumannii via inhibiting NF-κB/NLRP3 pathway.

Yinhuapinggan granule (YHPG) is a traditional Chinese medicine prescription with rich clinical experience for the treatment of colds and coughs. The aim of this study is to investigate the protective effect of YHPG on multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infection in vivo and its potential anti-inflammatory mechanism. BALB/c mice were intranasally inoculated with MDR A. baumannii strain to establish the pneumonia infection model, and received intraperitoneally cyclophosphamide to form immunosuppression before attack. YHPG (6, 12 and 18 g/kg) was administered by gavage once a day for 3 consecutive days after infection. The protective effect of YHPG was evaluated by lung index, spleen index, thymus index, pathological changes of lung tissue and inflammatory factors (IL-1ß, IL-6 and TNF-α) in serum. The expression of key targets of NF-κB/NLRP3 signaling pathway in vivo was analyzed by immunohistochemistry, immunofluorescence, reverse transcription quantitative PCR (RT-qPCR) and Western blot. The results showed that YHPG improved the lung index and its inhibition rate, immune organ indexes and lung pathological changes in infected mice, and significantly reduced IL-1ß, IL-6 and TNF-α levels in serum. In addition, YHPG significantly down-regulated the mRNA and protein expression of NF-κB p65, NLRP3, ASC, Caspase-1, TNF-α, IL-6 and IL-1ß in mice lung tissue. The results of the current study demonstrated that YHPG has significant protective effects on mice infected with MDR A.baumannii, which may be related to the regulation of inflammatory factors and NF-κB/NLRP3 signaling pathway, indicating that YHPG has a wide range of clinical application value and provides a theoretical basis for its treatment of MDR A.baumannii infection.

Calycosin alleviates cerebral ischemia/reperfusion injury by repressing autophagy via STAT3/FOXO3a signaling pathway.

BACKGROUND: As a common cerebrovascular disease (CVD) of the elderly, ischemic stroke (IS) is characterized by high disability and mortality. Excessive autophagy induced by IS is implicated in neuronal death, therefore, the inhibition of immoderate autophagy is viewed as a potential therapeutic avenue to treat IS. Calysoin (CA) is a bioactive component of Radix Astragali, which has been widely used to treat CVDs. However, the mechanism of the treatment of IS by CA is still problematic. PURPOSE: Based on the result of network pharmacology, whether CA inhibited autophagy by regulating the STAT3/FOXO3a pathway to alleviate cerebral ischemia-reperfusion injury (CIRI) was investigated in vivo and in vitro for the first time. STUDY DESIGN: Integrate computational prediction and experimental validation based on network pharmacology. METHODS: In current study, network pharmacology was applied to predict the mechanism of the treatment of IS by CA, and it was shown that CA alleviated CIRI by inhibiting autophagy via STAT3/FOXO3a signaling pathway. One hundred and twenty adult male specific pathogen-free Sprague-Dawley rats in vivo and PC12 cells in vitro were used to verify the above prediction results. The rat middle cerebral artery occlusion/reperfusion (MCAO/R) model was established by suture method, and oxygen glucose deprivation/re-oxygenation (OGD/R) model was used to simulate cerebral ischemia in vivo. The content of MDA, TNF-α, ROS and TGF-ß1 in rat serum were detected by ELISA kits. The mRNA and protein expressions in brain tissue were detected by RT-PCR and Western Blotting. The expressions of LC3 in brain were detected immunofluorescent staining. RESULTS: The experimental results demonstrated that administration of CA dosage-dependently improved rat CIRI as evidenced by the reduction in the cerebral infarct volume, amelioration of the neurological deficits. HE staining and transmission electron microscopy results revealed that CA ameliorated cerebral histopathological damage, abnormal mitochondrial morphology, and damaged mitochondrial cristae structure in MCAO/R rats. CA treatment exerted protective effects in CIRI by inhibiting inflammation response, oxidative stress injury, and cell apoptosis in rat and PC12 cells. CA relieved excessive autophagy induced by MCAO/R or OGD/R through downregulating the LC3Ⅱ/LC3Ⅰ ratio and upregulating the SQSTM1 expression. CA treatment also decreased p-STAT3/STAT3 and p-FOXO3a/FOXO3a ratio in the cytoplasm and modulated the autophagy-related gene expression both in vivo and in vitro. CONCLUSION: Treatment with CA attenuated CIRI by reducing excessive autophagy via STAT3/FOXO3a signal pathway in rat and PC12 cells.

Corrigendum: Clinical efficacy protocol of yinhuapinggan granules: A randomized, double-blind, parallel, and controlled clinical trial program for the intervention of community-acquired drug-resistant bacterial pneumonia as a complementary therapy.

[This corrects the article DOI: 10.3389/fphar.2022.852604.].

Clinical Efficacy Protocol of Yinhuapinggan Granules: A Randomized, Double-Blind, Parallel, and Controlled Clinical Trial Program for the Intervention of Community-Acquired Drug-Resistant Bacterial Pneumonia as a Complementary Therapy.

Background: Community-acquired bacterial pneumonia (CABP) is an important health care concern in the worldwide, and is associated with significant morbidity, mortality, and health care expenditure. Streptococcus pneumoniae is the most frequent causative pathogen of CABP. Common treatment for hospitalized patients with CABP is empiric antibiotic therapy using ß-lactams in combination with macrolides, respiratory fluoroquinolones, or tetracyclines. However, overuse of antibiotics has led to an increased incidence of drug-resistant S. pneumoniae, exacerbating the development of community-acquired drug-resistant bacterial pneumonia (CDBP) and providing a challenge for physicians to choose empirical antimicrobial therapy. Methods: Traditional Chinese medicine (TCM) is widely used as a complementary treatment for CDBP. Yinhuapinggan granules (YHPG) is widely used in the adjuvant treatment of CDBP. Experimental studies and small sample clinical trials have shown that YHPG can effectively reduce the symptoms of CDBP. However, there is a lack of high-quality clinical evidence for the role of YHPG as a complementary drug in the treatment of CDBP. Here, we designed a randomized, double-blind, placebo-controlled clinical trial to explore the efficacy and safety of YHPG. A total of 240 participants will be randomly assigned to the YHPG or placebo group in a 1:1 ratio. YHPG and placebo will be added to standard treatment for 10 days, followed by 56 days of follow-up. The primary outcome is the cure rate of pneumonia, and the secondary outcomes includes conversion rate of severe pneumonia, lower respiratory tract bacterial clearance, lactic acid (LC) clearance rate, temperature, C-reactive protein (CRP), criticality score (SMART-COP score), acute physiological and chronic health assessment system (APACHEII score) and clinical endpoint events. Adverse events will be monitored throughout the trial. Data will be analyzed according to a pre-defined statistical analysis plan. This research will disclose the efficacy of YHPG in acquired drug-resistant pneumonia. Clinical Trial Registration: https://clinicaltrials.gov, identifier ChiCTR2100047501.

Screening of Antiviral Components of Yinhuapinggan Granule and Protective Effects of Yinhuapinggan Granule on MDCK Cells with Influenza A/H1N1 Virus.

BACKGROUND: Traditional Chinese medicine Yinhuapinggan granule (YHPG) has been used for treating upper respiratory tract infection like influenza, cough, and viral pneumonia. However, its active ingredients that really exert the main efficacy have not been well elucidated. This study is aimed at screening its antiviral components and investigating the potential therapeutic mechanisms of YHPG against the influenza A/PR8/34 (H1N1) virus in Madin Darby canine kidney (MDCK). METHODS: MDCK cells were infected with the influenza virus and then treated with ribavirin, YHPG, and main active ingredients in YHPG. Based on the maximum nontoxic concentration (TC0), half-maximal toxic concentration (TC50), half-maximal inhibitory concentration (IC50), and therapeutic index (TI), interferon-ß (IFN-ß) and interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the gene expression of TLR7, MyD88, tumor necrosis factor receptor-associated factor 6 (TRAF6), c-Jun amino terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK), and p65 nuclear transcription factor-kappa B (p65 NF-κB) was quantified using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The results indicated that the components of YHPG, such as ephedrine hydrochloride, pseudoephedrine hydrochloride, chlorogenic acid, and emodin, had significant antiviral effects. High and medium doses of YHPG effectively reduced the cytopathic effect (CPE) and significantly decreased IFN-ß and IL-6 levels in the supernatant. Simultaneously, the transcript levels of TLR7, MyD88, TRAF6, JNK, p38 MAPK, and p65 NF-κB decreased in infected MDCK cells. Moreover, a certain dose-dependent relationship among different groups of YHPG was observed. CONCLUSIONS: These results indicated that YHPG and the components of YHPG had a significant inhibitory function on the proliferation of the H1N1 virus. The mechanism might be associated with suppressing the activation of the TLR7/MyD88 signaling pathway, a decrease in the mRNA expression of key target genes, and inhibition of IFN-ß and IL-6 secretion.

Effectiveness and safety of selected traditional Chinese medicine injections in patients with combined diabetes mellitus and coronary heart disease: A systematic review and network meta-analysis of randomized clinical trials.

Background: In view of the high morbidity and mortality of Diabetes mellitus-Coronary heart disease (DM-CHD) in diabetics, the combination therapy of traditional Chinese medicine injections (TCMIs) and conventional therapy (CT) is receiving extensive attention. Therefore, the effectiveness and security of conventional therapy with traditional Chinese medicine injections in the therapy of diabetes mellitus-coronary heart disease were compared by systematical review and network meta-analysis. Methods: According to the preset inclusion criteria and exclusion criteria, we searched seven electronic literature databases from their inception to JAN 5,2022, to obtain the relevant RCT literature on the therapy of diabetes mellitus-coronary heart disease with traditional Chinese medicine injections. Two researchers independently reviewed the papers, two other researchers worked in extracting data and quality assessment of the included literature. The primary outcomes were total effective rate. The secondary outcomes included electrocardiogram (EGG)effective rate, the effective rate of angina pectoris, fasting blood glucose (FBG), 2-h postprandial blood glucose (PBG), hemoglobinA1c (HbA1c), total cholesterol (TC) and triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), frequency of angina pectoris, and duration of angina pectoris. We adopted stata16.0 software for the systematic review and network meta-analysis. Results: A total of 53 trials involved 4,619 patients and one of the following 16 traditional Chinese medicine injections: Danhong, Danshen, Gualoupi, Gegen, Chuanxiongqin, Danshenchuanxiongqin, Shenmai, Shenqi, Xixin, Xuesaitong, Shuxuetong, Guanxinning, Kudiezi, Ciwujia, Xingding, Shuxuening. The meta-analysis revealed that Chuanxiongqin injection was superior to all other therapies in improving the total effective rate, [vs. conventional therapy odds ratio (OR): 14.52, 95% confidence interval (CI): 4.13-51.02], vs. Xuesaitong injection (odds ratio: 7.61, confidence interval: 1.25-46.40), and vs. Danshenchuanxiongqin injection (odds ratio: 3.98, confidence interval: 1.03-15.28)]. Xixin injection + conventional therapy was superior to conventional therapy only for electrocardiogram effective rate (odds ratio: 5.44, confidence interval: 1.55-19.18). Shenmai injection + conventional therapy was superior to conventional therapy in effective rate of angina (odds ratio: 11.05, confidence interval: 2.76-44.28). There was not different significantly in the comparisons of frequency of angina pectoris and duration of angina pectoris, we considered that this may be due to the lack of sufficient data. As most of the included RCTs did not monitor Adverse Events, the safety of those traditional Chinese medicine injections remains to be further explored. Conclusion: Basing on our study, traditional Chinese medicine injections combined with conventional therapy takes important role in the treatment of diabetes mellitus-coronary heart disease, and its curative effect is better than conventional therapy. Nevertheless, properly designed RCTs are required to validate our conclusions in the future. Systematic Review Registration: [https://inplasy.com/inplasy-2021-12-0125/], identifier [INPLASY2021120125].

Danhong injection enhances the therapeutic effect of mannitol on hemispheric ischemic stroke by ameliorating blood-brain barrier disruption.

Mannitol, a representative of hyperosmolar therapy, is indispensable for the treatment of malignant cerebral infarction, but its therapeutic effect is limited by its exacerbation of blood-brain barrier (BBB) disruption. This study was to explore whether Danhong injection (DHI), a standardized product extracted from Salvia miltiorrhiza Bunge and Carthamus tinctorius L., inhibits the destructive effect of mannitol on BBB and thus enhancing the treatment of hemispheric ischemic stroke. SD rats were subjected to pMCAO followed by intravenous bolus injections of mannitol with/without DHI intervention. Neurological deficit score, brain edema, infarct volume at 24 h after MCAO and histopathology, microvascular ultrastructure, immunohistochemistry and immunofluorescence staining of endothelial cell junctions, energy metabolism in the ischemic penumbra were assessed. Intravenous mannitol after MCAO resulted in a decrease in 24 h mortality and cerebral edema, whereas no significant benefit on neurological deficits, infarct volume and microvascular ultrastructure. Moreover, mannitol led to the loss of endothelial integrity, manifested by the decreased expression of occludin, junctional adhesion molecule-1 (JAM-1) and zonula occluden-1 (ZO-1) and the discontinuity of occludin staining around the periphery of endothelial cells. Meanwhile, after mannitol treatment, energy-dependent vimentin and F-actin, ATP content, and ATP5D expression were down-regulated, while MMP2 and MMP9 expression increased in the ischemic penumbra. All the insults after mannitol treatment were attenuated by addition of intravenous DHI. The results suggest DHI as a potential remedy to attenuate mannitol-related BBB disruption, and the potential of DHI to upregulate energy metabolism and inhibit the activity of MMPs is likely attributable to its effects observed.

Danhong injection alleviates cerebral ischemia/reperfusion injury by improving intracellular energy metabolism coupling in the ischemic penumbra.

Danhong injection (DHI) is a compound Chinese medicine widely used in China for treatment of ischemic cardio-cerebrovascular diseases. However, limited data are available regarding the protective effect of DHI on the ischemic penumbra in ischemic stroke. This study aimed to investigate the effect of intravenous DHI on neuronal injure in the ischemic penumbra after cerebral ischemia/reperfusion (CI/R), focusing especially on the involvement of intracellular energy metabolism coupling. Male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion for 60 min followed by reperfusion with or without intravenous DHI (0.5, 1.0, or 2.0 mL/kg) once daily for 7 days. Post-treatment with DHI ameliorated neurological defects, diminished cerebral infarction, alleviated cerebral edema, improved microcirculatory perfusion after 7days of reperfusion, and inhibited apoptosis and enhanced neuronal survival in the ischemic penumbra. In addition, DHI significantly ameliorated oxidative stress, reduced DNA damage, and inhibited the activation of PARP1/AIF pathway, thereby restoring cytoplasmic glycolytic activity. Furthermore, this drug increased PDH activity by inhibiting the HIF1α/PDK1 signaling pathway, thus eliminating the inhibitory effect of CI/R on mitochondrial metabolism. The results of this study suggest that DHI can alleviate cerebral edema after CI/R and rescue the ischemic penumbra, and these protective effects are due to the regulation of intracellular energy metabolic coupling.

Danhong Injection Attenuates Cerebral Ischemia-Reperfusion Injury in Rats Through the Suppression of the Neuroinflammation.

Neuroinflammation is one of the major causes of damage of the central nervous system (CNS) and plays a vital role in the pathogenesis of cerebral ischemia, which can result in long-term disability and neuronal death. Danhong injection (DHI), a traditional Chinese medicine injection, has been applied to the clinical treatment of cerebral stoke for many years. In this study, we investigated the protective effects of DHI on cerebral ischemia-reperfusion injury (CIRI) in rats and explored its potential anti-neuroinflammatory properties. CIRI in adult male SD rats was induced by middle cerebral artery occlusion (MCAO) for 1 h and reperfusion for 24 h. Results showed that DHI (0.5, 1, and 2 ml/kg) dose-dependently improved the neurological deficits and alleviated cerebral infarct volume and histopathological damage of the cerebral cortex caused by CIRI. Moreover, DHI (0.5, 1, and 2 ml/kg) inhibited the mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), intercellular cell adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in ischemic brains, downregulated TNF-α, IL-1ß, and monocyte chemotactic protein-1 (MCP-1) levels in serum, and reduced the neutrophil infiltration (myeloperoxidase, MPO) in ischemic brains, in a dose-dependent manner. Immunohistochemical staining results also revealed that DHI dose-dependently diminished the protein expressions of ICAM-1 and COX-2, and suppressed the activation of microglia (ionized calcium-binding adapter molecule 1, Iba-1) and astrocyte (glial fibrillary acidic protein, GFAP) in the cerebral cortex. Western blot analysis showed that DHI significantly downregulated the phosphorylation levels of the proteins in nuclear factor κB (NF-κB) and mitogen-activated protein kinas (MAPK) signaling pathways in ischemic brains. These results indicate that DHI exerts anti-neuroinflammatory effects against CIRI, which contribute to the amelioration of CNS damage.

Effects of Danhong injection on dyslipidemia and cholesterol metabolism in high-fat diets fed rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI) is a Chinese medical injection applied to the clinical treatment of cardiovascular diseases that has anti-inflammatory, antiplatelet aggregation and antithrombotic effects. This study aimed to explore the effects of DHI on dyslipidemia and cholesterol metabolism in high-fat diet-fed rats. METHODS: Sprague Dawley (SD) rats were randomly divided into six groups: normal group (Normal); hyperlipidemia model group (Model); DHI-treated groups at doses of 1.0 mL/kg, 2.0 mL/kg, 4.0 mL/kg; and simvastatin positive control group (2.0 mg/kg). The hypolipidemic effects of DHI were evaluated by measuring serum lipid levels, hepatic function and oxidative stress, respectively. And pathological changes in liver tissues were determined using hematoxylin-eosin (H&E) and oil red O staining. Moreover, the mRNA and protein expression levels of cholesterol metabolism related genes were detected by real-time PCR (RT-PCR) and Western blot. RESULTS: Compared with the Model group, DHI treatment markedly decreased the liver index and improved the pathological morphology of liver tissues. DHI treatment dose-dependently decreased the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA), and free fatty acids (FFA) in serum or liver tissues (P < 0.01 or P < 0.05), and increased the high-density lipoprotein cholesterol (HDL-C) and tripeptide glutathione (GSH) (P < 0.01 or P < 0.05). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased in the DHI-treated groups (P < 0.01 or P < 0.05), while the alanine transaminase (ALT) and aspartate transaminase (AST) were decreased (P < 0.01 or P < 0.05). Furthermore, the expression levels of LDL receptor (LDLR), cholesterol 7-α-hydroxylase (CYP7A1), liver X receptor α (LXRα), and peroxisome proliferator-activated receptor α (PPARα) were dose-dependently upregulated in the DHI-treated groups, whereas the expression of sterol regulatory element-binding protein-2 (SREBP-2) was downregulated. CONCLUSIONS: Our study demonstrated that DHI markedly ameliorated hyperlipidemia rats by regulating serum lipid levels, inhibiting hepatic lipid accumulation and steatosis, improving hepatic dysfunction, and reducing oxidative stress. The potential mechanism was also tentatively investigated and may be related to the promotion of bile acid synthesis via activation of the PPARα-LXRα-CYP7A1 pathway. Therefore, DHI could be regarded as a potential hypolipidemic drug for the treatment of hyperlipidemia.

Dissolved organic matter and bacterial population changes during the treatment of solid potato waste in a microbial fuel cell.

This study investigated the effect of mixed feeding of anaerobically cultured waste activated sludge (WAS) on the performance of microbial fuel cells (MFCs) in the treatment of solid potato waste. The maximum current densities of the four MFCs was estimated as 36, 5, 10 and 150 mA/m2, with the columbic efficiencies of 6.1, 0.3, 0.9 and 31.1%, respectively. Composition changes of dissolved organic matter (DOM) coupled with its interrelation with electricity generation and total and viable bacterial population at the end of the operation were investigated. The experimental results demonstrated that mixing WAS into solid potato enhanced the presence of the tyrosine-like aromatic amino acids and aromatic protein-like substances from the beginning of the operation and promoted hydrolysis and humification of the solid potato. In the final solution of the anodic chamber, more viable bacteria were detected for the reactors treating solid potato alone and the mixed feedstock with the smaller amount of sludge, where distinct electricity generation was observed.

Preliminary study of Yinhuapinggan granule against H1N1 influenza virus infection in mice through inhibition of apoptosis.

CONTEXT: Yinhuapinggan granule (YHPG) is frequently used for treating fever, cough, and viral pneumonia in traditional Chinese medicine. OBJECTIVE: This study investigated the antiviral effects of YHPG in H1N1 influenza virus (IFV)-infected mice and its possible mechanism. MATERIALS AND METHODS: ICR mice were intranasally infected with 10 LD50 viral dose of IFV and then oral administration of YHPG (6, 12, and 18 g/kg) or oseltamivir (positive control) once a day for 2 or 4 consecutive days, six mice in each group. The lung, spleen and thymus indexes of IFV-infected mice, the expression of viral loads and pathological changes in lung tissues were performed to evaluate the antiviral effects of YHPG. Real-time PCR, immunohistochemistry and western blot assays were used to determine the expression of Bax, Bcl-2 and caspase-3. RESULTS: LD50 in mice was 10-3.5/0.02 mL. YHPG (6, 12, and 18 g/kg) dose-dependently decreased the lung index and viral load; the inhibition ratio of lung index was 5.31, 18.22, and 34.06%, respectively. Further detection revealed that YHPG (12 and 18 g/kg) significantly attenuated lung pathological changes, and increased the spleen and thymus indexes. Moreover, YHPG significantly down-regulated the mRNA and protein expression of Bax and caspase-3 in lung tissues of mice infected with IFV, and up-regulated the expression of Bcl-2. CONCLUSIONS: YHPG has significant antiviral effects in IFV-infected mice, partially by inhibiting influenza virus replication and regulating the occurrence of apoptosis induced by influenza virus infection, suggesting that YHPG may be a promising antiviral agent with potential clinical application prospects.

Kangtaizhi Granule Alleviated Nonalcoholic Fatty Liver Disease in High-Fat Diet-Fed Rats and HepG2 Cells via AMPK/mTOR Signaling Pathway.

Kangtaizhi granule (KTZG) is a Chinese medicine compound prescription and has been proven to be effective in nonalcoholic fatty liver disease (NAFLD) treatment clinically. However, the underlying mechanisms under this efficacy are rather elusive. In the present study, network pharmacology and HPLC analysis were performed to identify the chemicals of KTZG and related target pathways for NAFLD treatment. Network pharmacology screened 42 compounds and 79 related targets related to NAFLD; HPLC analysis also confirmed six compounds in KTZG. Further experiments were also performed. In an in vivo study, SD rats were randomly divided into five groups: control (rats fed with normal diet), NAFLD (rats fed with high-fat diet), and KTZG 0.75, 1.5, and 3 groups (NAFLD rats treated with KTZG 0.75, 1.5, and 3 g/kg, respectively). Serum lipids were biochemically determined; hepatic steatosis and lipid accumulation were evaluated with HE and oil red O staining. In an in vitro study, HepG2 cells were incubated with 1 mM FFA to induce lipid accumulation with or without KTZG treatment. MTT assay, intracellular TG level, oil red O staining, and glucose uptake in cells were detected. Western blotting and immunohistochemical and immunofluorescence staining were also performed to determine the expression of lipid-related genes PPAR-γ, SREBP-1, p-AKT, FAS, and SIRT1 and genes in the AMPK/mTOR signaling pathway. In high-fat diet-fed rats, KTZG treatment significantly improved liver organ index and serum lipid contents of TG, TC, LDL-C, HDL-C, ALT, and AST significantly; HE and oil red O staining also showed that KTZG alleviated hepatic steatosis and liver lipid accumulation. In FFA-treated HepG2 cells, KTZG treatment decreased the intracellular TG levels, lipid accumulation, and attenuated glucose uptake significantly. More importantly, lipid-related genes PPAR-γ, SREBP-1, p-AKT, FAS, and SIRT1 expressions were ameliorated with KTZG treatment in high-fat diet-fed rats and FFA-induced HepG2 cells. The p-AMPK and p-mTOR expressions in the AMPK/mTOR signaling pathway were also modified with KTZG treatment in high-fat diet-fed rats and HepG2 cells. These results indicated that KTZG effectively ameliorated lipid accumulation and hepatic steatosis to prevent NAFLD in high-fat diet-fed rats and FFA-induced HepG2 cells, and this effect was associated with the AMPK/mTOR signaling pathway. Our results suggested that KTZG might be a potential therapeutic agent for the prevention of NAFLD.

[Lipid-lowering effect and mechanism of Danhong Injection on hyperlipidemia rats based on lipid metabolism disorder].

The animal model of hyperlipidemia in rats was established to investigate the lipid-lowering effect and mechanism of Danhong Injection on hyperlipidemic rats. SD rats were selected as the research object. The rats in normal group were fed with basic diet, and the rats in other groups were fed with high-fat diet to establish hyperlipidemia model. The successfully modeled rats were randomly divided into model group, Danhong Injection low, medium, high dose(1.0, 2.0, 4.0 mL·kg~(-1)) groups, and simvastatin(2.0 mg·kg~(-1)) group. Danhong Injection groups received intraperitoneal administration, and simvastatin group received intragastrical administration, once a day for 4 weeks. At the first, second, third, and fourth weekends after administration, blood was collected from the orbital vein to detect the levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), and high-density lipoprotein cholesterol(HDL-C), and then the atherosclerosis index(AI) was calculated. After 4 weeks of administration, the animals were sacrificed, and their heart, liver, spleen, lung, kidney and adipose tissue were extracted and weighed respectively to calculate the organ index of each group. The expressions of acyl-coaoxidase 1(Acox1), adenosine 5'-monophosphate(AMP)-activated protein kinase alpha(AMPK-α), bile salt export pump(BSEP), peroxisome proliferator-activated receptor gamma(PPAR-γ), catalase(CAT) and superoxide dismutase(SOD) mRNA in liver tissues were detected by fluorescence quantitative PCR; the content of cholesteryl ester transfer protein(CETP) and lecithin cholesterol acyltransferase(LCAT) in serum was detected by ELISA. The results showed that as compared with the normal group, the levels of serum TC, TG and LDL-C in the model group were significantly increased, and the level of HDL-C was significantly decreased, indicating that the hyperlipidemia rat model was successfully constructed. As compared with the model group, Danhong Injection could decrease the contents of TC, TG, LDL-C and increase the content of HDL-C in hyperlipidemia rats; reduce the body weight of hyperlipidemia rats, and reduce the liver weight, liver index, fat weight and fat index; it had no significant effect on the main organ indexes such as heart, spleen, lung and kidney; but it could increase the expressions of Acox1, AMPK-α, BSEP, PPAR-γ, CAT and SOD mRNA in liver tissues of rats; it could also reduce the level of CETP and increase the level of LCAT in serum; and the regulatory effect of Danhong Injection groups all showed a dose-dependent effect. It can be concluded that Danhong Injection can regulate the blood lipid contents, reduce the blood lipid levels and alleviate the accumulation of body fat in rats with hyperlipidemia. The mechanism may be related to inhibiting lipid metabolism disorder and oxidative stress induced by high-fat diet feeding, and improving the imbalance of lipid transport system.

A study of affecting the recovery of Chinese patients with Bell palsy.

We explored the risk factors for preventing recovery of Bell palsy (BP) in Chinese inpatients. Five hundred thirteen patients were included. The two end-points of assessment were the discharge and final follow-up results. Relationship between discharge and baseline: long patients delay (unhealed 4.03 ±â€Š1.16 d vs improved 2.24 ±â€Š1.0 d, P < .001), combined diseases (yes 77.06% vs no 86.71%, P = .01), and early use of acupuncture (yes 47.46% vs no 97.62%, P < .001) were bad factors. Therapeutic factors and discharge: only use of steroids was a positive factor (yes 92.54% vs no 57.30%, P < .001). Binary logistic regression found that early use of steroids was a favorable factor (P = .001), while early use of acupuncture (P < .001) and long patient delay (P < .001) were adverse factors. Subgroups analysis showed early use of steroids plus antivirals (steroids + antivirals vs antivirals + mecobalamin, P < .001) and early use of steroids plus mecobalamin were good choices (steroids + antivirals vs steroids + mecobalamin, P = .745), while early use of antivirals plus mecobalamin was a bad choice (vs other 2 groups, P < .001). Effect of drug dose and treatment course on discharge: long time use of steroids didn't mean good efficacy (unhealed 10.80 ±â€Š1.53 d vs improved 10.38 ±â€Š1.21 d, P = .026). Final follow-up results: improved patients were better than that of unhealed at discharge (P < .001). Risk factors of discharge included long patient delay, combined diseases, and early use of acupuncture. Steroids plus antivirals or steroids plus mecobalamin were good choices for treatment. Long time use of steroids didn't mean good effect. Improved patients at discharge had better results finally.

Enhancing microbial fuel cell (MFC) performance in treatment of solid potato waste by mixed feeding of boiled potato and waste activated sludge.

The effects of mixed feeding of boiled potato and waste activated sludge (WAS) on the performance of a microbial fuel cell (MFC) in treating solid potato waste were investigated. The coulombic efficiency (CE) of four MFCs fed with potato cubes containing 0, 48.7, 67.3 and 85.6% of boiled potato was 53.5, 70.5, 92.7 and 71.1%, respectively, indicating enhanced electricity generation and the existence of an optimum mixing ratio. The hydrolysis rate estimated using a first-order sequential hydrolysis model increased from 0.061 to 0.191 day-1, leading to shortening of the startup time for current density reaching its maximum from 25 to 5 days. The final chemical oxygen demand (COD) removal reached 85%. The CE of seven MFCs, fed with raw potato alone, sterilized/unsterilized WAS alone, and four mixed samples of raw potato with sterilized WAS at ratios of 2:1 and 4:1 and unsterilized WAS at 2:1 and 4:1, was found to be 6.1, 43.6, 0.3, 31.0, 16.5, 0.9 and 31.1%, respectively. The hydrolysis rate increased from 0.056 to 0.089 day-1, and the final COD removal changed from 39.5 to 89.6% following the order: potato alone > mixture of potato & WAS > sterilized WAS alone > unsterilized WAS alone.

[Immunologic mechanisms of Yinhua Pinggan granule and San-ao decoction against influenza virus in vivo].

This paper aimed to investigate the effect of Yinhua Pinggan granule and San-ao decoction on the immunologic mechanisms of influenza viral pneumonia mice in vivo, in order to study the activity of the combined administration of different formulas on influenza A/H1N1 virus. The model of pneumonia was established in mice through nasal dropping influenza virus, and then divided randomly into five groups: normal control group, influenza virus model group, oseltamivir control group, Yinhua Pinggan granule group, and San-ao decoction group. The animals were put to death at the 5th day after gavage administration with the corresponding drugs. The contents in mice serum of TNF-α, IL-6 and IFN-γ were respectively measured by ELISA. The mRNA expressions of TLR3/7, MyD88, JNK, p38MAPK and NF-κB p65 in lung tissues were respectively detected by RT-PCR. The protein expressions of JNK, p38MAPK and NF-κB p65 in lung tissues were determined by immunohistochemical analysis, respectively. According to the results, Yinhua Pinggan granule and San-ao decoction could significantly decrease the levels of TNF-α and IL-6, increase the level of IFN-γ in mice serum of lung tissues, significantly reduce the gene expressions of TLR3/7, MyD88, JNK, p38MAPK and NF-κB p65 in influenza virus-infected mice lung tissues, and significantly reduce the protein expressions of JNK, p38MAPK and NF-κB p65 in lung tissues. Furthermore, the regulatory effect of Yinhua Pinggan granule was superior to that of San-ao decoction. In conclusion, Yinhua Pingan granule and San-ao decoction have the therapeutic effect on pneumonia mice infected by H1N1 virus in vivo. The anti-influenza mechanisms of Yinhua Pinggan granule and San-ao decoction may be the results of interactions by regulating the immunologic function of influenza virus-infected mice and TLR3/7 signaling pathway with multiple links of the gene and protein expressions. Moreover, the combined administration of warm-natured and cold-natured Yinhua Pinggan granule with the effects of detoxification and exhalation has a better effect than the single administration of warm-natured San-ao decoction.

Antiviral effects and mechanisms of Yinhuapinggan granule against H1N1 influenza virus infection in RAW264.7 cells.

Yinhuapinggan granule (YHPG), a modified prescription based on Ma-Huang-Tang (MHT), is used in traditional Chinese medicine (TCM) to treat influenza, cough, and viral pneumonia. In this study, we investigated the antiviral effects of YHPG by means of pre-, post-, and co-treatment, and its underlying mechanisms on regulating the levels of inflammatory-related cytokines, modulating the mRNA expressions of interferon-stimulated genes in influenza virus-infected murine macrophage cells (RAW264.7), and evaluating the protein expressions of key effectors in the Type I IFN and pattern recognition receptor (PRRs) signaling pathways. The results showed that YHPG markedly inhibited influenza virus (IFV) replication in pre-, post- and co-treatment assay, especially in post-treatment assay. Antiviral mechanisms studies revealed that YHPG (500 and 250 µg/mL) significantly up-regulated levels of IFN-ß, IFN-stimulated genes (Mx-1, ISG-15 and ISG-56) compared with the IFV control group, while the levels of IL-6 and TNF-α were significantly down-regulated. Furthermore, western blot analysis results revealed that the protein expressions of the phosphorylated forms of TBK1, IRF3, ERK1/2, P38 MAPK and NF-κB p65 were significantly down-regulated in RAW264.7 cells with the YHPG (500 and 250 µg/mL) treatment, while the expression of the phosphorylated form of STAT1 was significantly enhanced. Based on these results, YHPG had antiviral effects in IFV-infected RAW264.7 cells, which might be associated with regulation of the inflammatory cytokines production, evaluation of the levels of IFN-stimulated genes, and modulation of the protein expressions of key effectors in the Type I IFN and PRRs signaling pathways.

Effects of varying the ratio of cooked to uncooked potato on the microbial fuel cell treatment of common potato waste.

The effect of varying the ratio of cooked to uncooked potato in the performance of microbial fuel cell (MFC) treating common potato waste was investigated. Four MFCs were fed with a ratio of cooked (boiled) to uncooked (i.e. waste) potato of 0, 48.7, 67.3 and 85.6%. Respectively, the columbic efficiency was estimated as 53.5, 70.5, 92.7 and 71.1%, indicating significantly enhanced electricity generation and waste degradation at an initial feedstock mixing ratio of 2/3 cooked to 1/3 uncooked potato. The hydrolysis rate parameter (estimated using a first-order sequential hydrolysis and degradation model) increased from 0.061 to 0.191day(-1) as cooked potato was added which increased electricity generation efficiency from 24.6 to 278.9mA/m(2)/d and shortened the startup time for maximum current density from 25 to 5days. The potato slurries' chemical oxygen demand (COD) decreased by 86.6, 83.9, 84.1 and 86.3%, respectively, indicating no relationship exists between the fraction of boiled potato and the amount of COD reduction.

Size effects of potato waste on its treatment by microbial fuel cell.

The performance of microbial fuel cell (MFC) in treating potato cubes with different sizes (the edge size of 3, 5 and 7 mm) was investigated. Current density was found lower as the size of potato cubes increased, even if the differences in their removal were less apparent. At the end of MFC operation for 81 days, both total and soluble chemical oxygen demand reached nearly identical values, irrespective of the potato sizes; and citrate and isobutyrate were two major organic acids remaining in the solutions. Bacterial community analysis using polymerase chain reaction, denaturing gradient gel electrophoresis and sequencing indicated that bacterial species on the anode and in the anodic solution were similar and did not change obviously with potato sizes, and that, in similarity with previous studies on potato-processing wastewater treatment, Proteobacteria and Firmicutes were two dominating phyla. Geobacter was found richer on the anode than in the anodic solutions.