Thrombosis inhibited by Corydalis decumbens through regulating PI3K-Akt pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis decumbens (Thunb.) Pers. was used as stasis-eliminating medicine traditionally to treat cardiovascular disease potentially attributed to its antithrombotic effect, but lack of pharmacological research on it. AIM OF THE STUDY: To investigate the antithrombotic effect of C. decumbens and its preliminary mechanism. MATERIALS AND METHODS: A carrageenan-induced mouse thrombus model and adenosine diphosphate stimulated platelet aggregation of rabbits were used to confirm the inhibitory effect of C. decumbens extract and compounds on thrombosis in vivo. Then, H2O2-induced human umbilical vein endothelial cells (HUVECs) injury model was further adopted to verify the effects of bioactive compounds in vitro. Moreover, in silico network pharmacology analyses and molecular docking were performed to predict the underlying mechanisms, targets, and pathways, and which were further confirmed through western blotting assay. RESULTS: The administration of total extract (TE), total alkaloids (TA) and tetrahydropalmatine (TET) resulted in a significant reduction in black tail thrombus and congestion, along with a decreasing in platelet aggregation of rabbits. A superior antithrombotic effect indicated the bioactive fraction, and then the isolated bioactive compounds, TET and protopine (PRO) increased cell survival, and decreased reactive oxygen species (ROS) and lactate dehydrogenase (LDH) release in H2O2-induced HUVECs injury model. Moreover, the two alkaloids targeted 33 major proteins and influenced 153 pathways in network pharmacology prediction. Among these, HSP90AA1, COX-2, NF-κB/p65, MMP1 and HIF-1α were the key proteins and PI3K-Akt emerged as the major signaling pathway. Further western blotting results supported that five key proteins were downregulated by the two bioactive compounds in H2O2-stimulated HUVECs model. CONCLUSION: C. decumbens exerted protective effect on thrombosis through inhibiting PI3K-Akt pathway and related key proteins, which supported the traditional use and presented potential antithrombotic alkaloids for further investigation.

Shengxian decoction protects against chronic heart failure in a rat model via energy regulation mechanisms.

BACKGROUND: Chronic heart failure (CHF) is actually a disease caused by an imbalanced energy metabolism between myocardial energy demand and supply, ultimately resulting in abnormal myocardial cell structure and function. Energy metabolism imbalance plays an important role in the pathological process of chronic heart failure (CHF). Improving myocardial energy metabolism is a new strategy for the treatment of CHF. Shengxian decoction (SXT), a well-known traditional Chinese medicine (TCM) formula, has good therapeutic effects on the cardiovascular system. However, the effects of SXT on the energy metabolism of CHF is unclear. In this study, we probed the regulating effects of SXT on energy metabolism in CHF rats using various research methods. METHODS: High-performance liquid chromatography (HPLC) analysis was used to perform quality control of SXT preparations. Then, SD rats were randomly assigned into 6 groups: sham, model, positive control (trimetazidine) and high-, middle-, and low-dose SXT groups. Specific reagent kits were used to detect the expression levels of ALT and AST in rats' serum. Echocardiography was used to evaluate cardiac function. H&E, Masson and TUNEL staining were performed to examine myocardial structure and myocardial apoptosis. Colorimetry was used to determine myocardial ATP levels in experimental rats. Transmission electron microscopy was used to observe the ultrastructure of myocardial mitochondria. ELISA was used to estimate CK, cTnI, and NT-proBNP levels, and LA、FFA、MDA、SOD levels. Finally, Western blotting was used to examine the protein expression of CPT-1, GLUT4, AMPK, p-AMPK, PGC-1α, NRF1, mtTFA and ATP5D in the myocardium. RESULTS: HPLC showed that our SXT preparation method was feasible. The results of ALT and AST tests indicate that SXT has no side effect on the liver function of rats. Treatment with SXT improved cardiac function and ventricular remodelling and inhibited cardiomyocyte apoptosis and oxidative stress levels induced by CHF. Moreover, CHF caused decrease ATP synthesis, which was accompanied by a reduction in ATP 5D protein levels, damage to mitochondrial structure, abnormal glucose and lipid metabolism, and changes in the expression of PGC-1α related signal pathway proteins, all of which were significantly alleviated by treatment with SXT. CONCLUSION: SXT reverses CHF-induced cardiac dysfunction and maintains the integrity of myocardial structure by regulating energy metabolism. The beneficial effect of SXT on energy metabolism may be related to regulating the expression of the PGC-1α signalling pathway.

Low-intensity, long-wavelength red light slows the progression of myopia in children: an Eastern China-based cohort.

PURPOSE: To determine the effect of low-intensity, long-wavelength red light therapy (LLRT) on the inhibition of myopia progression in children. METHODS: A retrospective study was conducted. One hundred and five myopic children (spherical equivalent refractive error [SER] -3.09 ± 1.74 dioptres [D]; mean age, 9.19 ± 2.40 years) who underwent LLRT treatment (power 0.4 mW, wavelength 635 nm) twice per day for 3 min each session, with at least a 4-h interval between sessions, and a control group of 56 myopic children (SER -3.04 ± 1.66 D; mean age, 8.62 ± 2.45 years) were evaluated. Both groups wore single-vision distance spectacles. Each child returned for a follow-up examination every 3 months after the initial measurements for a total of 9 months. RESULTS: At 9 months, the mean SER in the LLRT group was -2.87 ± 1.89 D, significantly greater than that of the control group (-3.57 ± 1.49 D, p < 0.001). Axial length (AL) changes were -0.06 ± 0.19 mm and 0.26 ± 0.15 mm in the LLRT group and control group (p < 0.001), respectively. The subfoveal choroidal thickness changed by 45.32 ± 30.88 µm for children treated with LLRT at the 9-month examination (p < 0.001). Specifically, a substantial hyperopic shift (0.31 ± 0.24 D and 0.20 ± 0.14 D, respectively, p = 0.02) was found in the 8-14 year olds compared with 4-7 year old children. The decrease in AL in subjects with baseline AL >24 mm was -0.08 ± 0.19 mm, significantly greater than those with a baseline AL ≤24 mm (-0.04 ± 0.18 mm, p = 0.03). CONCLUSIONS: Repetitive exposure to LLRT therapy was associated with slower myopia progression and reduced axial growth after short durations of treatment. These results require further validation in randomised controlled trials.

Investigation of the metabolites of five major constituents from Berberis amurensis in normal and pseudo germ-free rats.

Berberis amurensis (Berberidaceae) is a traditional Chinese medicine, which is often used to treat hypertension, inflammation, dysentery and enteritis. It contains alkaloids, mainly including berberine, berbamine, magnoflorine, jatrorrhizine and palmatine. Berberis amurensis extracts (BAEs) is often orally taken. Oral herbs might be metabolized by intestinal bacteria in the small intestine. However, the interaction between the herb and the gut microbiota is still unknown. In the current study, UPLC/Q-TOF-MS/MS combined with Metabolitepilot and Peakview software was used to identify the metabolites of BAEs in anti-biotic cocktail induced pseudo germ-free rats and normal rats. As a result, a total of 46 metabolites in normal rats were detected and its main metabolic pathways include demethylation, dehydrogenation, methylation, hydroxylation, sulfation and glucuronidation. Only 29 metabolites existed in pseudo germ-free rats. Dehydrogenated metabolites (M29, M30, M34 and M36), methylated metabolites (M33, M41 and M46) and other metabolites were not detected in pseudo germ-free rats. The result implied that the intestinal bacteria have an influence on the metabolism of BAEs. Furthermore, this investigation might contribute to the understanding of the metabolism of BAEs, and further promote its clinical application.

Modified citrus pectin prevents isoproterenol-induced cardiac hypertrophy associated with p38 signalling and TLR4/JAK/STAT3 pathway.

Modified citrus pectin (MCP) is a specific inhibitor of galectin-3 (Gal-3) that is regarded as a new biomarker of cardiac hypertrophy, but its effect is unclear. The aim of this study is to investigate the role and mechanism of MCP in isoproterenol (ISO)-induced cardiac hypertrophy. Rats were injected with ISO to induce cardiac hypertrophy and treated with MCP. Cardiac function was detected by ECG and echocardiography. Pathomorphological changes were evaluated by the haematoxylin eosin (H&E) and wheat germ agglutinin (WGA) staining. The hypertrophy-related genes for atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and ß-myosin heavy chain (ß-MHC), and the associated signal molecules were analysed by qRT-PCR and western blotting. The results show that MCP prevented cardiac hypertrophy and ameliorated cardiac dysfunction and structural disorder. MCP also decreased the levels of ANP, BNP, and ß-MHC and inhibited the expression of Gal-3 and Toll-like receptor 4 (TLR4). Additionally, MCP blocked the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), but it promoted the phosphorylation of p38. Thus, MCP prevented ISO-induced cardiac hypertrophy by activating p38 signalling and inhibiting the Gal-3/TLR4/JAK2/STAT3 pathway.

Fe2+/H2O2-Strengite method with the enhanced settlement for phosphorus removal and recovery from pharmaceutical effluents.

Phosphorus excessively discharged into the water body is a primary cause of eutrophication, but phosphorus resource is limited and non-renewable. If phosphorus could be recovered from wastewaters, it can not only prevent phosphorus pollution but also achieve the recycling of phosphorus resources. This work proposed a novel strategy, Fe2+/H2O2-strengite method with the enhanced settlement, for phosphorus removal and recovery from pharmaceutical wastewater containing organic phosphorus (OP). In this scheme, OP could be converted into inorganic phosphorus (IP) in the Fe2+/H2O2 oxidation system, and then IP was recovered in the strengite system. This approach possessed the advantages of simple operation, high efficiency and valuable recovery products, besides, reducing the consumption of reagents, and hardly resulting in secondary pollution. Sixty cycles of phosphorus removal and recovery experiments were conducted, in which pH value was 4 and the initial molar ratio of Fe/P was 1.5. This process achieved a satisfactory and steady phosphorus removal performance, with soluble phosphate and total phosphorus removal efficiencies of 95.3% ± 1.7% and 91.4% ± 2.5%, respectively, and phosphorus was recovered. Possible mechanisms involved: the formation of amorphous strengite (FePO4·2H2O) analogue, the adsorption of hydrous ferric oxide (HFO) to phosphorus, and the flocculation of ferric salts. Besides, the presence of quartz as carriers could enhance the settling efficiency of products. Also, via various characterizations, products included amorphous strengite analogue and goethite mixed with phosphorus. This work provided an effective method to reduce OP pollution and recover phosphorus, and supplied thoughts for the treatment of refractory pollutants and the recycling of limited resources.

Investigation of the metabolites of five major constituents from Berberis amurensis in normal and pseudo germ-free rats / 中国天然药物

Berberis amurensis (Berberidaceae) is a traditional Chinese medicine, which is often used to treat hypertension, inflammation, dysentery and enteritis. It contains alkaloids, mainly including berberine, berbamine, magnoflorine, jatrorrhizine and palmatine. Berberis amurensis extracts (BAEs) is often orally taken. Oral herbs might be metabolized by intestinal bacteria in the small intestine. However, the interaction between the herb and the gut microbiota is still unknown. In the current study, UPLC/Q-TOF-MS/MS combined with Metabolitepilot and Peakview software was used to identify the metabolites of BAEs in anti-biotic cocktail induced pseudo germ-free rats and normal rats. As a result, a total of 46 metabolites in normal rats were detected and its main metabolic pathways include demethylation, dehydrogenation, methylation, hydroxylation, sulfation and glucuronidation. Only 29 metabolites existed in pseudo germ-free rats. Dehydrogenated metabolites (M29, M30, M34 and M36), methylated metabolites (M33, M41 and M46) and other metabolites were not detected in pseudo germ-free rats. The result implied that the intestinal bacteria have an influence on the metabolism of BAEs. Furthermore, this investigation might contribute to the understanding of the metabolism of BAEs, and further promote its clinical application.

Chemical intervention of influenza virus mRNA nuclear export.

Influenza A viruses are human pathogens with limited therapeutic options. Therefore, it is crucial to devise strategies for the identification of new classes of antiviral medications. The influenza A virus genome is constituted of 8 RNA segments. Two of these viral RNAs are transcribed into mRNAs that are alternatively spliced. The M1 mRNA encodes the M1 protein but is also alternatively spliced to yield the M2 mRNA during infection. M1 to M2 mRNA splicing occurs at nuclear speckles, and M1 and M2 mRNAs are exported to the cytoplasm for translation. M1 and M2 proteins are critical for viral trafficking, assembly, and budding. Here we show that gene knockout of the cellular protein NS1-BP, a constituent of the M mRNA speckle-export pathway and a binding partner of the virulence factor NS1 protein, inhibits M mRNA nuclear export without altering bulk cellular mRNA export, providing an avenue to preferentially target influenza virus. We performed a high-content, image-based chemical screen using single-molecule RNA-FISH to label viral M mRNAs followed by multistep quantitative approaches to assess cellular mRNA and cell toxicity. We identified inhibitors of viral mRNA biogenesis and nuclear export that exhibited no significant activity towards bulk cellular mRNA at non-cytotoxic concentrations. Among the hits is a small molecule that preferentially inhibits nuclear export of a subset of viral and cellular mRNAs without altering bulk cellular mRNA export. These findings underscore specific nuclear export requirements for viral mRNAs and phenocopy down-regulation of the mRNA export factor UAP56. This RNA export inhibitor impaired replication of diverse influenza A virus strains at non-toxic concentrations. Thus, this screening strategy yielded compounds that alone or in combination may serve as leads to new ways of treating influenza virus infection and are novel tools for studying viral RNA trafficking in the nucleus.

A black phosphorus nanosheet-based siRNA delivery system for synergistic photothermal and gene therapy.

Gene therapy with small interfering RNA (siRNA) has been proved to be a promising technology to treat various diseases by hampering the production of target proteins. However, developing a delivery system that has high efficiency in transporting siRNA without obvious side effects remains a challenge. Herein, we designed a new survivin siRNA delivery system based on polyethyleneimine functionalized black phosphorus (BP) nanosheets which could suppress tumor growth by silencing survivin expression. Combined with the photothermal properties of the BP nanosheets, the presented delivery system shows excellent therapy efficiency for tumors. Therefore, the BP-based delivery system would be a promising tool for future clinical applications.

Low serum 25-hydroxyvitamin D level and risk of urinary tract infection in infants.

The aim of the study is to determine whether serum 25-hydroxyvitamin D (25(OH)D) deficiency in infants increased odds of urinary tract infection (UTI). A total of 238 infants including 132 patients experiencing a first episode of UTI and 106 controls, aged from 1 to 12 months, were enrolled. Serum 25(OH)D levels were tested through blood sampling. The serum 25(OH)D levels were significantly lower in cases with UTI than controls. The mean serum 25(OH)D levels were 29.09 ±â€Š9.56 ng/mL in UTIs and 38.59 ±â€Š12.41 ng/mL in controls (P < 0.001). Infants with acute pyelonephritis (APN) had lower serum 25(OH)D than those with lower UTI. The multivariate logistic regression analyses showed that serum 25(OH)D < 20 ng/mL (OR 5.619, 95% CI 1.469-21.484, P = 0.012) was positively related to an increased odds of UTI. Vitamin D supplementation (OR 0.298, 95% CI 0.150-0.591; P = 0.001) was associated with a decreased likelihood of UTI. Vitamin D deficiency in infants was associated with an increased odds of UTI. Interventional studies evaluating the role of vitamin D supplementation to reduce the burden of UTI are warranted.

Polygonumnolides C1-C4; minor dianthrone glycosides from the roots of Polygonum multiflorum Thunb.

Four new dianthrone glycosides, named polygonumnolides C1-C4 (1-4), were isolated from the dried roots of Polygonum multiflorum Thunb, together with two known emodin dianthrones (5-6). Their hepatotoxicities were evaluated against L-02 cell lines. Compounds 1-4 showed weak hepatotoxicity against L-02 cell lines with IC50 values of 313.05, 205.20, 294.20, and 207.35 µM, respectively.

Vitamin D supplementation for the prevention of childhood acute respiratory infections: a systematic review of randomised controlled trials.

Results from recent trials assessing the effect of vitamin D supplementation on the prevention of childhood acute respiratory infections (ARI) have been inconsistent. In the present study, we determined whether vitamin D supplementation prevents ARI in healthy children and repeated infections in children with previous ARI. We conducted a systematic literature search using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The search included only randomised controlled clinical trials (RCT) comparing vitamin D supplementation with either placebo or no intervention in children younger than 18 years of age. We identified seven RCT and found that the summary estimates were not statistically significantly associated with a reduction in the risk of ARI (relative risk (RR) 0·79, 95% CI 0·55, 1·13), all-cause mortality (RR 1·18, 95% CI 0·71, 1·94), or the rate of hospital admission due to respiratory infection in healthy children (RR 0·95, 95% CI 0·72, 1·26). However, in children previously diagnosed with asthma, vitamin D supplementation resulted in a 74% reduction in the risk of asthma exacerbation (RR 0·26, 95% CI 0·11, 0·59; test of heterogeneity, I 2= 0·0%). Our findings indicate a lack of evidence supporting the routine use of vitamin D supplementation for the prevention of ARI in healthy children; however, they suggest that such supplementation may benefit children previously diagnosed with asthma. Due to the heterogeneity of the included studies and possible publication biases related to this field, these results should be interpreted with caution.

[Experimental study on preventive effect of Yougui drink on femoral head necrosis in rats under micro CT].

OBJECTIVE: To explore the preventive effect of Yougui drink on femoral head necrosis in rats under micro CT. METHODS: Twenty-five SD rats were divided into steroid hormone group (group A, 10 rats ), Yougui drink group (group B,10 rats) and normal group (group C,5 rats)with random number table. Endotoxin were injected into abdominal cavity of rats in group A and B for 2 days, methylprednisolone sodium succinate were injected by gluteus for twice a week continued for 6 weeks; group B were gavaged by Yougui drink (veryday for 8 weeks; group C did not do any processing. All rats were killed on the 10th weeks,m icro CT were used to scan femoral head in vitro and preventive effect of Yougui drink (n femoral head necrosis in rats. RESULTS: There was statistical significance in BMD, BV/TV, Tb.N, Tb, Th, Thb, Sp, BS/TV and DA but no significance in SMI between group A and B. Comparison between A and C, there was significant meaning in BMD, BV/TV, Tb.N, Tb, Th, Tb, Sp, BS/TV, DA and SMI. CONCLUSION: Yougui drink on femoral head necrosis in rats under micro CT has preventive effect from BMD BV/TV, Tb.N, Tb, Th, Tb, Sp, BS/TV and DA.

Experimental study on preventive effect of Yougui drink on femoral head necrosis in rats under micro CT / 中国骨伤

<p><b>OBJECTIVE</b>To explore the preventive effect of Yougui drink on femoral head necrosis in rats under micro CT.</p><p><b>METHODS</b>Twenty-five SD rats were divided into steroid hormone group (group A, 10 rats ), Yougui drink group (group B,10 rats) and normal group (group C,5 rats)with random number table. Endotoxin were injected into abdominal cavity of rats in group A and B for 2 days, methylprednisolone sodium succinate were injected by gluteus for twice a week continued for 6 weeks; group B were gavaged by Yougui drink (veryday for 8 weeks; group C did not do any processing. All rats were killed on the 10th weeks,m icro CT were used to scan femoral head in vitro and preventive effect of Yougui drink (n femoral head necrosis in rats.</p><p><b>RESULTS</b>There was statistical significance in BMD, BV/TV, Tb.N, Tb, Th, Thb, Sp, BS/TV and DA but no significance in SMI between group A and B. Comparison between A and C, there was significant meaning in BMD, BV/TV, Tb.N, Tb, Th, Tb, Sp, BS/TV, DA and SMI.</p><p><b>CONCLUSION</b>Yougui drink on femoral head necrosis in rats under micro CT has preventive effect from BMD BV/TV, Tb.N, Tb, Th, Tb, Sp, BS/TV and DA.</p>

Effect of chitosan film incorporated with tea polyphenol on quality and shelf life of pork meat patties.

The objective of this study was to investigate the effect of chitosan (CH) film incorporated with tea polyphenol (TP) on quality and shelf life of pork meat patties stored at 4±1 °C for 12 days. The microbiological, physicochemical (pH, thiobarbituric acid-reactive substances (TBARS) values, and metmyoglobin (MetMb)), and sensory qualities were measured on all the samples. A microbiological shelf-life extension of 6 days was achieved for CH and CH-TP treatment groups when compared to the control group. Wrapping with CH-TP composite film tended to retard the increases in TBARS values and MetMb content. CH-TP composite film maintained acceptable sensory quality of pork meat patties throughout the storage. The results indicated that CH-TP composite film could be a promising material as a packaging film for extending the shelf life of pork meat patties.

Corn oil as a vehicle in drug development exerts a dose-dependent effect on gene expression profiles in rat thymus.

The purpose of this study was to investigate the effects of corn oil (CO), which is widely used as a vehicle for water-insoluble agents in drug development, on the gene expression profiles in rat thymus with microarray technique. Female Wistar rats were administered daily with normal saline (NS) and CO 2, 5 and 10 ml kg⁻¹ per day for 14 days, respectively. Then, the thymus samples of rats were collected for microarray test and histopathology examination. CD4⁺ and CD8⁺ lymphocytes in peripheral blood were also numerated to assess the effects on lymphocyte subpopulations. The microarray data showed that the numbers of differentially expressed genes in the 2, 5 and 10 ml kg⁻¹ CO groups were 0, 40 and 458, respectively, compared with the NS control group. The altered genes were mainly associated with immune response, cellular response to organic cyclic substance and regulation of fatty acid ß-oxidation. However, no abnormal changes in thymus weight, CD4⁺ and CD8⁺ lymphocytes counts and histopathological examination were observed in the three CO groups. These data showed that 10 ml kg⁻¹ CO, the usually recommended dosing volume as a vehicle in drug safety assessment, caused obvious dysregulated genes in rat thymus. Our study suggests that the appropriate dosing volume of CO gavage as a vehicle for water-insoluble agents in drug development should be 2 ml kg⁻¹ per day, if agent effects on thymus will be assessed in gene levels.