Scutellaria polysaccharide mediates the immunity and antioxidant capacity of giant freshwater prawn (Macrobrachium rosenbergii).

The giant freshwater prawn (Macrobrachium rosenbergii) is a commercially valuable freshwater crustacean species that frequently appears a death affected by various diseases, resulting in substantial economic losses. Improving the survival rate of M. rosenbergii is a hot and essential issue for feeding the prawns. Scutellaria polysaccharide (SPS) extracted from Scutellaria baicalensis (a Chinese medicinal herb) is conducive to the survival rate of organisms by enhancing immunity and antioxidant ability. In this study, M. rosenbergii was fed 50, 100, and 150 mg/kg of SPS. The immunity and antioxidant capacity of M. rosenbergii were tested by mRNA levels and enzyme activities of related genes. The mRNA expressions of NF-κB, Toll-R, and proPO (participating in the immune response) in the heart, muscle, and hepatopancreas were decreased after four weeks of SPS feeding (P < 0.05). This indicated that long-term feeding of SPS could regulate the immune responses of M. rosenbergii tissues. The activity levels of antioxidant biomarkers, alkaline phosphatase (AKP), and acid phosphatase (ACP) had significant increases in hemocytes (P < 0.05). Moreover, catalase (CAT) activities in the muscle and hepatopancreas, as well as superoxide dismutase (SOD) activities in all tissues, significantly decreased after four weeks of culture (P < 0.05). The results demonstrated that long-term feeding of SPS could improve the antioxidant capacity of M. rosenbergii. In summary, SPS was conducive to regulating the immune capacity and enhancing the antioxidant capacity of M. rosenbergii. These results provide a theoretical basis for supporting SPS addition to the feed of M. rosenbergii.

Sex Differences in the Relationship between Abdominal Obesity and Cardiovascular Death in Elderly Patients with Permanent Pacemakers Implantation: A Retrospective Cohort Study.

Objectives: This study aims to investigate the association between waist circumference (WC) and cardiovascular death in patients with permanent pacemakers (PPMs). Methods: This is a retrospective cohort study that enrolled patients who underwent PPM implantation in Fuwai Hospital from May 2010 to April 2014, according to the BIOTRONIK Home Monitoring database. The WC was treated as sex-specific quartiles, and patients were divided into three groups according to body mass index (BMI): normal (≤22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (≥25 kg/m2). Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for cardiovascular death according to WC and BMI in patients. Results: 492 patients with PPMs implantation were analyzed (mean age: 71.9 ± 10.8 years; 55.1% men (n = 271)). Data showed that after a mean follow-up 67.2 ± 17.5 months, 24 (4.9%) patients had experienced cardiovascular death and 71 (14.4%) were cases of all-cause mortality. Men in the third quartile of WC had an HR of 10.67 (Model 4, 95% CI: 1.00-115.21, p trend = 0.04) for cardiovascular death. However, the association disappeared in female patients (Model 4, HR = 3.99, 95% CI: 0.37-42.87, p trend = 0.25). There was no association between BMI and cardiovascular death or all-cause mortality in both male and female patients. Conclusions: Abdominal obesity was associated with an increased risk of cardiovascular death in patients with PPMs, and this relationship was only in male patients.

Development of fermented sea buckthorn (Hippophae rhamnoides L.) juice and investigation of its antioxidant and antimicrobial activity.

Sea buckthorn (Hippophae rhamnoides L.) is an edible and medicinal plant species. However, due to its sour taste, it is not readily accepted by consumers. To overcome this, fermentation can be used to change its flavor profile. In this study, we used response surface methodology (RSM) to determine the best process for producing fermented sea buckthorn juice (FSBJ) using probiotics. The biological enzyme activity and total flavonoid content (TFC) of sea buckthorn juice (SBJ) increased after fermentation. When the number of bacteria inoculated was 4.08 × 106 CFU/mL and the inoculation ratio was 30% Z. mobilis, 5% L. casei, 13.75% L. plantarum, 31.25% P. acidilactici, 12.5% L. animalis, and 7.5% P. pentosaceus, the amount of sugar was 2.98% (w/v) after 20 h of fermentation at 37°C, and the superoxide dismutase (SOD) activity reached 725.44 U/mL, and the TFC reached 2.38 mg/mL. FSBJ demonstrated strong antimicrobial activity against Escherichia coli, Staphylococcus aureus and Botrytis cinerea. Then, to investigate the antioxidant capacity of FSBJ, we used H2O2 to induce oxidative stress in C2C12 cells and assessed the protection conferred by FSBJ to damaged cells. It was discovered that after 24 h of treatment with FSBJ, not only was there an increase in the activities of intracellular SOD and glutathione peroxidase (GSH-Px), but also a reduction in reactive oxygen species (ROS) content, catalase (CAT) activity, and malondialdehyde (MDA) content. This research lays the theoretical groundwork and provides reference materials for the improved fermentation of sea buckthorn and demonstrates its resulting antioxidant effect.

Based on 16 S rRNA sequencing and metabonomics to reveal the new mechanism of aluminum potassium sulfate induced inflammation and abnormal lipid metabolism in mice.

More and more discoveries have been made about the chronic toxic effects of aluminum, but the specific mechanism of action remains unclear. In this study, we explored the perturbation of aluminum on intestinal microflora and its effects on host and microbial metabolites through a more realistic nutrient absorption model. The microorganisms Turicibacter, Lactobacillus murinus, Lactobacillus_reuteri and Bifidobacterium pseudolongum may be the main targets of the aluminum affecting microbiota. Lysine, proline, putrescine, serotonin and cholesterol may be important metabolites affected by aluminum ions after the interference of intestinal flora composition, leading to abnormal metabolism pathways of amino acids and lipids in the body, and thus promoting inflammation and lesion. The possible mechanisms of aluminum action on the body: (1) Affecting immune cell response, ROS generation and production of a series of pro-inflammatory factors to promote inflammation; (2) Through the disturbance of intestinal microbiota composition structure, change the abundance of metabolites, and then affect amino acid metabolism, lipid metabolism pathways. The joint analysis of multiple omics showed significant difference in microbiome abundance and metabolomics expression between high dose group and the control group.

Network Pharmacology-Based Dissection of the Anti-diabetic Mechanism of Lobelia chinensis.

Diabetes mellitus (DM) is a chronic inflammatory disease, and the rapidly increasing DM is becoming a major problem of global public health. Traditional Chinese medicine (TCM) has a long history of treating diabetes. It has been developed and utilized because of its good efficacy and no toxic side effects. Lobelia chinensis is a traditional whole grass herbal. With the continuous deepening of pharmacological research on TCM, the active ingredients of L. chinensis are continuously revealed, which contained the alkaloids, flavonoids, flavonoid glycosides and amino acids that have the good effects of anti-inflammatory, anti-viral and anti-diabetic. In order to further explore the targets of active ingredients and its anti-diabetic mechanism, a feasible network pharmacology analysis model based on chemical, pharmacokinetic and pharmacological data was developed by network construction method to clarify the anti-diabetic mechanism of L. chinensis. The present study conducted by gas chromatography-mass spectrometer (GC/MS), which identified 208 metabolites of L. chinensis, of which 23 ingredients may have effective pharmacological effects after absorption, distribution, metabolism, and excretion (ADME) screening. Network pharmacological analysis on the active ingredients revealed that 5-hydroxymethylfurfural in L. chinensis affects the insulin resistance signaling pathway by acting on GSK3B, TNF, and MAPK1, acacetin affects the diabetic pathway by acting on INSR, DPP4, and GSK3B, that regulate type 2 diabetes, non-insulin-dependent DM, and inflammatory diseases. These results successfully indicated the potential anti-diabetic mechanism of the active ingredients of L. chinensis.

Network pharmacology-based analysis on bioactive anti-diabetic compounds in Potentilla discolor bunge.

ETHNOPHARMACOLOGICAL RELEVANCE: Potentilla discolor Bunge (PDB) is a commonly used herbal for alleviating diabetes mellitus and its complications. Although accumulating evidences show the anti-diabetic efficacy of PDB, the vital anti-diabetic compounds and their functional targets remain elusive. AIM OF THE STUDY: To investigate the anti-diabetic ingredients and their functional mechanisms in PDB, gas chromatograph-mass spectrometry analysis was performed on PDB extract and 21 were testified as anti-diabetic compounds. MATERIALS AND METHODS: Subsequently their potential protein targets were also identified. The bioinformatics analysis was implemented by network pharmacology-based approaches. STRING analysis was performed to reveal enrichment of these target proteins, protein-protein interactions, pathways and related diseases. Cytoscape was used to determine the potential protein targets for these components in PDB, indicating that 21 anti-diabetic compounds in PDB regulate 33 diabetes-related proteins in 28 signal pathways and involve 21 kinds of diabetes-related diseases. Among the 21 potential anti-diabetic components predicted by network analysis, tricetin was firstly experimentally validated at the molecular and cellular level. RESULTS: Results indicated that this active small-molecule compound may have beneficial effects on improving glucose uptake. CONCLUSIONS: We envisage that network analysis will be useful in screening bioactive compounds of medicinal plants.

Glutamine starvation inhibits snakehead vesiculovirus replication via inducing autophagy associated with the disturbance of endogenous glutathione pool.

Autophagy is a degradation cellular process which also plays an important role in virus infection. Glutamine is an essential substrate for the synthesis of glutathione which is the most abundant thiol-containing compound within the cells and plays a key role in the antioxidant defense and intracellular signaling. There is an endogenous cellular glutathione pool which consists of two forms of glutathione, i.e. the reduced form (GSH) and the oxidized form (GSSG). GSH serves as an intracellular antioxidant to maintain cellular redox homeostasis by scavenging free radicals and other reactive oxygen species (ROS) which can lead to autophagy. Under physiological conditions, the concentration of GSSG is only about 1% of total glutathione, while stress condition can result in a transient increase of GSSG. In our previous report, we showed that the replication of snakehead fish vesiculovirus (SHVV) was significant inhibited in SSN-1 cells cultured in the glutamine-starvation medium, however the underlying mechanism remains enigmatic. Here, we revealed that the addition of L-Buthionine-sulfoximine (BSO), a specific inhibitor of the GSH synthesis, could decrease the γ-glutamate-cysteine ligase (GCL) activity and GSH levels, resulting in autophagy and significantly inhibition of the replication of SHVV in SSN-1 cells cultured in the complete medium. On the other hand, the replication of SHVV was rescued and the autophagy was inhibited in the SSN-1 cells cultured in the glutamine-starvation medium supplemented with additional GSH. Furthermore, the inhibition of the synthesis of GSH had not significantly affected the generation of reactive oxygen species (ROS). However, it significantly decreased level of GSH and enhanced the level of GSSG, resulting in the decrease of the value of GSH/GSSG, indicating that it promoted the cellular oxidative stress. Overall, the present study demonstrated that glutamine starvation impaired the replication of SHVV in SSN-1 cells via inducing autophagy associated with the disturbance of the endogenous glutathione pool.

Analysis of mulberry leaf components in the treatment of diabetes using network pharmacology.

Mulberry leaves are one of the most commonly used medicinal and herbaceous traditional Chinese medicines that are currently considered for the treatment of diabetes mellitus and its complications. The alkaloids, flavonoids, and polysaccharides in mulberry leaves impart regulatory effects on blood sugar levels. To identify the hypoglycemia-related active components in mulberry leaves and their targets, the present study conducted gas chromatography-mass spectrometer (GC/MS), which identified 202 components of mulberry leaf, of which 22 components may have significant curative effects on diabetes mellitus and its complications and chronic inflammation. The network-based pharmacological analysis platform was used to identify target proteins related to diabetes. Finally, the interaction networks of these target proteins were identified using STRING and Cytoscape. The results showed that mulberry leaf powder contains tricetin, gallic acid, chlorogenic acid, and other drug components that can regulate tumor necrosis factor (TNF), peroxisome proliferator-activated receptor gamma (PPARG), glycogen synthase kinase-3 beta (GSK3B), insulin receptor substrate 1 (IRS1), interleukin 6 (IL-6) and other proteins, which are related to the insulin and inflammatory signaling pathways, glucose metabolism and other related pathways, chronic inflammatory diseases, obesity, diabetic nephropathy, non-insulin-dependent diabetes mellitus and other diseases.

Silkworm: A Promising Model Organism in Life Science.

As an important economic insect, silkworm Bombyx mori (L.) (Lepidoptera: Bombycidae) has numerous advantages in life science, such as low breeding cost, large progeny size, short generation time, and clear genetic background. Additionally, there are rich genetic resources associated with silkworms. The completion of the silkworm genome has further accelerated it to be a modern model organism in life science. Genomic studies showed that some silkworm genes are highly homologous to certain genes related to human hereditary disease and, therefore, are a candidate model for studying human disease. In this article, we provided a review of silkworm as an important model in various research areas, including human disease, screening of antimicrobial agents, environmental safety monitoring, and antitumor studies. In addition, the application potentiality of silkworm model in life sciences was discussed.

Treatment of Diabetes Mellitus Using iPS Cells and Spice Polyphenols.

Diabetes mellitus is a chronic disease that threatens human health. The disease is caused by a metabolic disorder of the endocrine system, and long-term illness can lead to tissue and organ damage to the cardiovascular, endocrine, nervous, and urinary systems. Currently, the disease prevalence is 11.4%, the treatment rate is 48.2%, and the mortality rate is 2.7% worldwide. Comprehensive and effective control of diabetes, as well as the use of insulin, requires further study to develop additional treatment options. Here, we reviewed the current reprogramming of somatic cells using specific factors to induced pluripotent stem (iPS) cells capable of repairing islet ß cell damage in diabetes patients to treat patients with type 1 diabetes mellitus. We also discuss the shortcomings associated with clinical use of iPS cells. Additionally, certain polyphenols found in spices might improve glucose homeostasis and insulin resistance in diabetes patients, thereby constituting promising options for the treatment of type 2 diabetes.

Virosome, a hybrid vehicle for efficient and safe drug delivery and its emerging application in cancer treatment.

A virosome is an innovative hybrid drug delivery system with advantages of both viral and non-viral vectors. Studies have shown that a virosome can carry various biologically active molecules, such as nucleic acids, peptides, proteins and small organic molecules. Targeted drug delivery using virosome-based systems can be achieved through surface modifications of virosomes. A number of virosome-based prophylactic and therapeutic products with high safety profiles are currently available in the market. Cancer treatment is a big battlefield for virosome-based drug delivery systems. This review provides an overview of the general concept, preparation procedures, working mechanisms, preclinical studies and clinical applications of virosomes in cancer treatment.

Anti-HBV agents derived from botanical origin.

There are 350,000 hepatitis B virus (HBV) carriers all over the world. Chronic HBV infection is at a high risk of developing liver cirrhosis and hepatocelluar carcinoma (HCC), and heavily threatened people's health. Two kinds of drugs approved by FDA for anti-HBV therapy are immunomodulators (interferon α, pegylated-interferon α) and nucleos(t)ide analogues (lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate). These drugs have been proved to be far from being satisfactory due to their low specificity, side effects, and high rate of drug resistance. There is an urgent need to discover and develop novel effective anti-HBV drugs. With vast resources, various structures, diverse biological activities and action mechanisms, as well as abundant clinical experiences, botanical agents become a promising source of finding new anti-HBV drugs. This review summarizes the recent research and development of anti-HBV agents derived from botanical origin on their sources and active components, inhibitory effects and possible toxicities, as well as action targets and mechanisms, and also addresses the advantages and the existing shortcomings in the development of botanical inhibitors. This information may not only broaden the knowledge of anti-HBV therapy, and offer possible alternative or substitutive drugs for CHB patients, but also provides considerable information for developing new safe and effective anti-HBV drugs.

[Clinical characteristics and outcome of 32 patients with long-QT syndrome accompanied with torsade de pointes].

OBJECTIVE: To summarize the clinical characteristics and outcome of patients with long-QT syndrome (LQTs) accompanied with torsade de pointes. METHODS: Thirty-two eligible patients were included in this study. Clinical and electrocardiographic data were analyzed and telephone or out-patient follow-up were made in all patients. RESULTS: There were 15 patients with inherited LQTs (h-LQTs) and 17 patients with acquired LQTs (a-LQTs). There are more women (n = 24) than men (n = 8). ß blockers, potassium and magnesium supplement were the basic therapy for h-LQTs patients, bivent pacemaker was implanted in 2 patients and implantable cardioverter defibrillator was implanted in 5 patients. Ventricular tachyarrhythmias and syncope occurred in 4 patients during (39.4 ± 25.1) months follow-up. In 17 a-LQTs patients, one patient with dilated cardiomyopathy died suddenly and another patient with implanted cardioverter defibrillator experienced one ventricular tachycardia during (30.9 ± 13.3) months follow-up. CONCLUSIONS: The prognosis in h-LQTs and a-LQTs patients with structure heart disease is poor. ICD or CRT-D therapy is suggestive for a-LQTs patients with structure heart disease.

Breviscapine, a traditional Chinese medicine, alleviates myocardial ischaemia reperfusion injury in diabetic rats.

OBJECTIVE: The aim of this study was to explore the effects of breviscapine on the expressions of intercellular adhesion molecule-I (ICAM-I), ATPase activities and oxidative stress in ischaemia-reperfused (I/R) myocardium of diabetic rats. METHODS: Sprague Dawley rats were randomly divided into two groups (a diabetic group and a non-diabetic group), and each group divided into two subgroups including a control group and a breviscapine group. Reperfusion surgery was carried out in all rats.The contents of malonaldehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-P(x)) in serum and myocardial tissues were measured. The activities of Na(+)-K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase in myocardial mitochondria were measured. The ICAM-I protein expressions in myocardium were determined with the immunohistochemical method. RESULTS: The activities of Na(+)-K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase were significantly increased in diabetic rats in the breviscapine group compared with the control group. Compared with the non-diabetic control group, the contents of MDA in serum and myocardium were significantly increased in the diabetic control group. Breviscapine led to a reduction of the contents of MDA in the diabetic and non-diabetic group. Compared with the non-diabetic control group, the activities of SOD and GSH-P(x) in the myocardium were significantly decreased in the diabetic control group.The activities of SOD and GSH-P(x) in serum and myocardium were increased in the diabetic and non-diabetic group after breviscapine treatment. Compared with the non-diabetic control group, the ICAM- I protein expressions were increased significantly in the diabetic control group. Breviscapine decreased the ICAM-I protein expression in the diabetic and the non-diabetic group. CONCLUSION: Breviscapine may have protective effects on myocardial ischaemia reperfusion injury of diabetic rats by scavenging oxygen free radicals, decreasing the expressions of ICAM-I protein in myocardium and increasing the activities of Na(+)-K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase in myocardial mitochondria.

Radiofrequency ablation of the ventricular tachycardia with arrhythmogenic right ventricular cardiomyopathy using non-contact mapping.

BACKGROUND: Intracardiac non-contact mapping provides a rapid and accurate isopotential mapping that facilitates catheter ablation of the ventricular tachyarrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS: Thirty-two consecutive patients (26 men and 6 women, mean 37.2 +/- 13.8 years) were treated with ablation. Fourteen patients had a history of syncope/pre-syncope. Two patients had an implantable cardiac defibrillator (ICD) previously implanted. RESULTS: There were 67 ventricular tachycardias (VTs) induced in the 32 patients. The average VT rate was 210 +/- 32.2 (130-310) bpm. There were 42 episodes of VT that had a heart rate > or =200 bpm and 24 of the 32 patients (75%) had > or =2 morphologies of VT. Regional ablation was applied by targeting the earliest VT activation sites under the guidance of non-contact mapping. Acute success was achieved in 84.4% (27/32) patients, and significant improvement was seen in 15.6% (5/32) patients as evidenced by a slower rate of VT. None of the patients experienced syncope/pre-syncope or sudden death during the 28.6 +/- 16 (9-72) month follow-up. There were no complications of the procedure. At the end of follow-up, 81.3% of the patients were free of VT without medication while the rest of the patients achieved a modified success. CONCLUSIONS: The rapid ventricular tachyarrhythmias in ARVC patients can be abolished or improved significantly by regional RF catheter ablation under the guidance of non-contact mapping. There was no sudden cardiac arrest or death in those patients without ICD implantation. Delayed efficacy may occur in some patients after ablation.