Nano selenium-enriched probiotic Lactobacillus enhances alum adjuvanticity and promotes antigen-specific systemic and mucosal immunity.

Nano selenium-enriched probiotics have been identified to improve immune responses, such as alleviating inflammation, antioxidant function, treatment of tumors, anticancer activity, and regulating intestinal flora. However, so far, there is little information on improving the immune effect of the vaccine. Here, we prepared nano selenium-enriched Levilactobacillus brevis 23017 (SeL) and heat-inactivated nano selenium-enriched L. brevis 23017 (HiSeL) and evaluated their immune enhancing functions on the alum-adjuvanted, inactivated Clostridium perfringens type A vaccine in mouse and rabbit models, respectively. We found that SeL enhanced immune responses of the vaccine by inducing a more rapid antibody production, eliciting higher immunoglobulin G (IgG) antibody titers, improving secretory immunoglobulin A (SIgA) antibody level and cellular immune response, and regulating Th1/Th2 immune response, thus helping to induce better protective efficacy after challenge. Moreover, we confirmed that the immunoenhancement effects are related to regulating oxidative stress, cytokine secretion, and selenoprotein expression. Meanwhile, similar effects were observed in HiSeL. In addition, they show enhanced humoral immune response at 1/2 and 1/4 standard vaccine doses, which confirms their prominent immune enhancement effect. Finally, the effect of improving vaccine immune responses was further confirmed in rabbits, which shows that SeL stimulates the production of IgG antibodies, generates α toxin-neutralizing antibodies rapidly, and reduces the pathological damage to intestine tissue. Our study demonstrates that nano selenium-enriched probiotics improve the immune effect of the alum adjuvants vaccine and highlight its potential usage in remedying the disadvantages of alum adjuvants.

NBP Relieves Cardiac Injury and Reduce Oxidative Stress and Cell Apoptosis in Heart Failure Mice by Activating Nrf2/HO-1/Ca2+-SERCA2a Axis.

Although heart failure (HF) has become one of the most fatal diseases in the whole world, there are fewer drugs for its treatment. Therefore, we focused on the protective effect of Dl-3-n-butylphthalide (NBP) on myocardial injury and oxidative stress in heart failure mice and further investigated the relationship with the Nrf2/HO-1/Ca2+-SERCA2a axis. Methods. C57BL/6J mice were divided into the sham group (Sham), heart Failure model group (HF), HF + NBP group (HN), HN + Nrf2 inhibitor (HNM), HN + Calmodulin-dependent protein kinase II (CaMKII) antagonist, KN93 (HNK). The HF mice model was prepared using abdominal aorta ligation. Mice's heart function was accessed by echocardiography. Hematoxylin-eosin staining and MASSON staining were used to identify myocardial injury; the cell apoptosis was determined by the TUNEL staining assay. The expression of oxidative stress-related proteins was detected by the ELISA assay. The reactive oxygen species and Nrf2 expression in heart tissue were observed with the immunofluorescence assay. SERCA2a, calmodulin, endoplasmic reticulum stress regulatory proteins, and Nrf2/HO-1 in mice' heart tissues were measured using Western blotting. Results. Moreover, NBP could significantly promote heart failure mice's heart function, relieve the injury and inhibit cell apoptosis. Meanwhile, it could reduce ERS injury of heart failure mice through increasing SERCA2a level and reducing Ca2+ influx. NBP was demonstrated to minimize CaMKII phosphorylation level and decrease cAMP-response element-binding protein phosphorylation level, suggesting NBP could also activate the Nrf2/HO-1 signaling pathway. Conclusions. We demonstrated that NPBs treatment promotes the cardiomyocyte's ERS and alleviates myocardial injury in heart failure mice, related to stimulating the Nrf2/HO-1 signaling pathway, regulating Ca2+-SERCA2a, and reducing Ca2+ influx.

A rare endocrine cause of ventricular tachycardia: a case series of two patients and a literature review.

Sheehan's syndrome is a type of hypopituitarism caused by massive uterine bleeding and hypovolaemic shock after or during delivery. Heart involvement has been documented sporadically among the various clinical manifestations of Sheehan's syndrome but life-threatening arrhythmias are infrequent. Here, we report on two rare cases of ventricular tachycardia caused by Sheehan's syndrome. Both female patients were diagnosed with Sheehan's syndrome 30 years previously, due to massive postpartum bleeding. Both of them terminated hormone replacement therapy recently. Both patients presented with torsade de pointes. The electrocardiogram showed prolonged QT interval. In addition to potassium supplementation and anti-arrhythmia therapy, steroids and thyroid hormone replacement therapy were employed, QT-interval prolongation and T-wave inversion were normalised, and implantable cardioverter defibrillator implantation was avoided. One of the patients was recovering well at the one-year follow up and the other patient was in a coma at the time of this report. We also review the literature for cases of Sheehan's syndrome presenting with ventricular tachycardia.

Dabigatran as an alternative for atrial thrombosis resistant to rivaroxaban: A case report.

RATIONALE: Anti-thrombosis therapy for atrial fibrillation (AF) management and stroke prevention is an important aspect of disease management. Novel oral anticoagulants (NOACs) are recommended by guidelines for AF management. However, if one can switch one NOAC to another when the former showed a poor effect has not been fully determined. PATIENT CONCERNS: A 52-year-old man was admitted to our center for heart failure and AF with a thrombus in the left atrium. DIAGNOSES: Cardiomyopathy was diagnosed by cardiac magnetic resonance (CMR) and echocardiography. INTERVENTIONS: He was prescribed rivaroxaban (20 mg daily) as treatment, and dabigatran (150 mg twice daily) was used when the thrombus was found to be non-response to rivaroxaban. OUTCOMES: The rivaroxaban did not diminish the atrial thrombus, and dabigatran was given instead which finally eliminated the thrombus. LESSONS: Individualized responsiveness to NOACs should be considered and paid more attention to during clinical practice.

Antitussive effect of naringin on experimentally induced cough in Guinea pigs.

The mechanism of action of naringin has been investigated in different models of experimentally induced cough in guinea pigs. In contrast to codeine phosphate (6 mg/kg, intravenous administration [i. v.]), naringin (15, 30, and 60 mg/kg, i. v.) had no central antitussive effect on cough elicited by electrical stimulation of the superior laryngeal nerve. Naringin (0.5, 1.0, and 2.0 µmol) could not prevent the cough reflex induced by stimulation of the trachea after intracerebroventricular injection (i. c. v.), while codeine phosphate (0.5 µmol) was highly effective. Further characterizing the peripheral mechanism of naringin, we found that its effect (50 mg/kg, i. v.) was not affected by the depletion of sensory neuropeptides, whereas levodropropizine (10 mg/kg, i. v.) lost its capacity to prevent cough in the capsaicin-desensitized guinea pig. Furthermore, pretreatment with glibenclamide (10 mg/kg, intraperitoneal [i. p.]) significantly reduced the antitussive effect of pinacidil (5 mg/kg, subcutaneous [s. c.]), but could not antagonize the antitussive effect of naringin (30 mg/kg, s. c.). Our present results suggest that naringin is not a central antitussive drug. And naringin does not exert its peripheral antitussive effect through either the sensory neuropeptides system or the modulation of ATP-sensitive K (+) channels.

Growth inhibition and induction of apoptosis and differentiation of tanshinone IIA in human glioma cells.

Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen, a widely used Chinese herbal medicine. It has antioxidant properties, cytotoxic activities against multiple human cancer cells, inducing apoptosis and differentiation of some human cancer cells. The purpose of this study is to confirm its anticancer activity on human glioma cells, and to elucidate mechanism of its activity. Human glioma cells were tested in vitro for cytotoxicity, colony formation inhibition, BrdU incorporation after treatment with tanshinone IIA. Its effect of apoptosis induction was detected through EB/AO staining, cell cycle analysis and the expressions of ADPRTL1 and CYP1A1 genes, the differentiation induction effect was investigated through morphology, mRNA and protein expressions of GFAP and nestin genes by RT-PCR and immunocytochemistry. Tanshinone IIA demonstrated a dose- and time-dependent inhibitory effect on cell growth, IC(50) was 100 ng/ml, and it significantly inhibited colony formation and BrdU incorporation of human glioma cells. After treatment with 25-100 ng/ml of tanshinone IIA, the apoptotic cells increased significantly (P < 0.01), the cells in G(0)/G(1) phase increased (P < 0.01), and decreased in S phase, ADPRTL1 and CYP1A1 mRNA expression increased 1-2 folds. The cells treated with 100 ng/ml tanshinone IIA demonstrated astrocytes or neuron-like morphology, GFAP mRNA and protein expressions increased, nestin mRNA and protein expressions decreased significantly. The findings in this study suggested that tanshinone IIA exhibited strong effects on growth inhibition and induction of apoptosis and differentiation in human glioma cells. It might serve as a novel promising differentiation-inducing and/or therapeutic agent for human gliomas, and need to be investigated further.