Impact of oseltamivir on the risk of cancer.

Purpose: Mounting evidence has revealed the anti-cancer activity of various anti-viral drugs. Oseltamivir phosphate (OP), namely Tamiflu®, is routinely used to combat influenza infections. Although evidence has indicated the anti-cancer effects of OP in vitro and in vivo, little information is known about the effect of OP use on cancers in humans. Methods: A nationwide population-based cohort study involving 13,977,101 cases with 284,733 receiving OP was performed to examine the association between OP use and cancers using the National Health Insurance Research Database in Taiwan between 2009 and 2018. Results: The cohort study found that OP users showed a significantly lower incidence of lung cancer, colon cancer, liver, and intrahepatic bile duct cancer, oral cancer, pancreas cancer, esophagus cancer, stomach cancer, and prostate cancer. Additionally, OP users exhibited a lower risk of cancer-related mortality (adjusted HR=0.779; 95% confidence interval [CI] 0.743-0.817; p<0.001) and a reduced risk of developing liver cancer (adjusted HR=0.895; 95% CI 0.824-0.972; p=0.008), esophagus cancer (adjusted HR=0.646; 95% CI 0.522-0.799; p<0.001) and oral cancer (adjusted HR=0.587; 95% CI 0.346-0.995; p=0.048). Notably, OP users had a significant reduction in liver cancer occurrence over a 10-year period follow-up and a lower cancer stage at liver cancer diagnosis. Conclusion: These findings first suggest the beneficial effects and therapeutic potential of OP use for certain cancers, especially liver cancer.

Challenges of Large Vessel Vasculitis Stroke Patient with Complicated Endovascular Thrombectomy: A Case Report.

PURPOSE: The causes of acute stroke in patients with SLE are multifactorial. Antiphospholipid-associated hypercoagulability and inflammation-induced platelet activation are major causes of ischemic stroke in SLE patients. As such patients underwent intravenous thrombolysis and endovascular thrombectomy, they may have higher risk of complications and less favorable outcome. CASE REPORT: A 30-year-old woman with underline SLE and Takayasu arteritis who presented with right CCA and MCA occlusion status post rtPA and endovascular thrombectomy. Twelve hours after the procedure, head CT was ordered due to anisocoria with loss of pupillary light reflex. The head CT showed partial obliteration of suprasellar and quadrigeminal cistern due to extensive brain edema, leading to her decompressive craniectomy. Two days later, patient's both pupil became dilated with head CT showing occlusion of the left MCA. Her condition drastically went downhill when complications such as central DI and myocardial stunning occurred. CONCLUSION: Although autoimmune vasculitis is not listed as an absolute contraindication to endovascular thrombectomy, given the antecedent reports, it is prudent to disclose possible complications to both the patient and family while making the decision.

Accuracy of calculating mechanical power of ventilation by one commonly used equation.

Gattinoni's equation, [Formula: see text], now commonly used to calculate the mechanical power (MP) of ventilation. However, it calculates only inspiratory MP. In addition, the inclusion of PEEP in Gattinoni's equation raises debate because PEEP does not produce net displacement or contribute to MP. Measuring the area within the pressure-volume loop accurately reflects the MP received in a whole ventilation cycle and the MP thus obtained is not influenced by PEEP. The MP of 25 invasively ventilated patients were calculated by Gattinoni's equation and measured by integration of the areas within the pressure-volume loops of the ventilation cycles. The MP obtained from both methods were compared. The effects of PEEPs on MP were also evaluated. We found that the MP obtained from both methods were correlated by R2 = 0.75 and 0.66 at PEEP 5 and 10 cmH2O, respectively. The biases of the two methods were 3.13 (2.03 to 4.23) J/min (P < 0.0001) and - 1.23 (- 2.22 to - 0.24) J/min (P = 0.02) at PEEP 5 and 10 cmH2O, respectively. These P values suggested that both methods were significantly incongruent. When the tidal volume used was 6 ml/Kg, the MP by Gattinoni's equation at PEEP 5 and 10 cmH2O were significantly different (4.51 vs 7.21 J/min, P < 0.001), but the MP by PV loop area was not influenced by PEEPs (6.46 vs 6.47 J/min, P = 0.331). Similar results were observed across all tidal volumes. We conclude that the Gattinoni's equation is not accurate in calculating the MP of a whole ventilatory cycle and is significantly influenced by PEEP, which theoretically does not contribute to MP.

Potential of antiviral drug oseltamivir for the treatment of liver cancer.

Liver cancer is a leading cause of cancer­related mortality globally. Since hepatitis virus infections have been strongly associated with the incidence of liver cancer, studies concerning the effects of antiviral drugs on liver cancer have attracted great attention in recent years. The present study investigated the effects of two anti­hepatitis virus drugs, lamivudine and ribavirin, and one anti­influenza virus drug, oseltamivir, on liver cancer cells to assess alternative methods for treating liver cancer. MTT assays, wound healing assays, Τranswell assays, flow cytometry, immunoblotting, ELISA, immunofluorescence staining and a xenograft animal model were adopted to verify the effects of lamivudine, ribavirin and oseltamivir on liver cancer cells. Treatment with ribavirin and oseltamivir for 24 and 48 h significantly decreased the viability of both Huh-7 and HepG2 cells compared with that of THLE­3 cells in a dose­dependent manner. The subsequent investigations focused on oseltamivir, considering the more serious clinical adverse effects of ribavirin than those of oseltamivir. Significantly decreased migration and invasion were observed in both Huh-7 and HepG2 cells that were treated with oseltamivir for 24 and 48 h. In addition, oseltamivir significantly increased autophagy in Huh­7 cells, as revealed by the significantly higher ratios of LC3­II/LC3­I, increased expression of Beclin­1, and decreased expression of p62, whereas no significant increases in the expression of apoptosis­related proteins, including Apaf­1, cleaved caspase­3, and cleaved PARP­1, were detected. Notably, apoptosis and autophagy were significantly increased in HepG2 cells in the presence of oseltamivir, as revealed by the significant increases in the expression of Apaf­1, cleaved caspase­3, and cleaved PARP­1, the higher ratios of LC3­II/LC3­I, the increased expression of Beclin­1, and the decreased expression of p62. Additionally, significant inhibitory effects of oseltamivir on xenografted Huh­7 cells in athymic nude mice were observed. The present study, for the first time to the best of our knowledge, reported the differential effects of oseltamivir on inducing liver cancer cell death both in vitro and in vivo and may provide an alternative approach for treating liver cancer.

Effects of antibodies against human parvovirus B19 on angiogenic signaling.

Human parvovirus B19 (B19V) infection has symptoms similar to those of anti­phospholipid syndrome (APS). Antibodies against B19V­VP1 unique region (VP1u) exhibit activity similar to that of anti­phospholipid antibodies (aPLs) by inducing vascular endothelial cell adhesion factors and APS­like syndrome. Previous studies have identified an effect of aPLs on angiogenesis. However, little is understood regarding the effect of anti­B19V­VP1u antibodies on angiogenesis. The present study investigated the effects of anti­B19V­VP1u antibodies on the expression of adhesion molecules and angiogenic signaling using an aPL­induced human umbilical vein endothelial cell (HUVEC) model, and trypan blue staining and western blotting. The effect of B19V­VP1u antibodies on vascular endothelial growth factor (VEGF) expression in A549 cells, another well­known model used to study angiogenesis, was also examined. Significantly higher intracellular adhesion molecule 1 expression was observed following treatments with 10% fetal calf serum (FCS), aPL immunoglobulin G (IgG), B19V­VP1u IgG or B19V­NS1 IgG, compared with in the normal human (NH) IgG­treated cells. Conversely, significantly higher vascular cellular adhesion molecule 1 was only detected in HUVECs treated with B19V­VP1u IgG. Significantly increased integrin ß1 was detected in HUVECs treated with aPL IgG or B19V­VP1u IgG, whereas no difference in integrin ß1 was observed in those treated with 10% FCS, NH IgG or B19V­NS1 IgG. No difference in AKT­mTOR­S6 ribosomal protein (S6RP) signaling was observed in HUVECs treated with B19­VP1u IgG or B19V­NS1 IgG, compared with NH IgG­treated cells. Significantly higher human inducible factor­1α was detected in HUVECs treated with 10% FCS, aPL IgG, B19V­VP1u IgG or B19V­NS1 IgG, compared with in NH IgG­treated cells. However, there was no difference in the level of VEGF observed among HUVECs treated with NH IgG, B19V­VP1u IgG or B19V­NS1 IgG. Notably, no difference in VEGF level was observed in A549 cells treated with NH IgG, aPL IgG, B19V­VP1u IgG or B19V­NS1 IgG. These findings suggest that anti­B19V­VP1u antibodies may serve a role in activating adhesion molecules, but not in AKT­mTOR­S6RP signaling.

The Beneficial Effects of Raffinee in Permanent Occulted Stroke Mice.

Ischemic stroke is a major cause of disability and mortality globally. Although thrombolytic therapy is routinely adopted in cases of ischemic stroke, various alternative natural neuroprotectants are also used as effective adjuvant therapies to recover neurofunction following ischemic stroke. Raffinee, a natural fermented product with strong antioxidant and neuroprotective activities, has antiatherogenic effects in animals and has exhibited neuroprotective effects in a clinical trial by recovering motor and sensory function following spinal cord lesion. This study reveals the advantageous effects of Raffinee on PC12 cells by decreasing hypoxia-induced apoptosis in mice with permanent middle cerebral artery occlusion (pMCAO) by increasing the levels of neurotrophic factors such as S100ß, reducing serum inflammatory factors such as matrix metalloproteinases (MMP)-9/MMP-2 ratio, tumor necrosis factor-α, and interleukin (IL)-6 level, and increasing IL-10 levels. Significantly reduced brain infarct volume along with a favorable survival ratio was observed for pMCAO mice that received Raffinee, suggesting a neuroprotective potential of Raffinee in cases of acute ischemic stroke by suppressing apoptosis.

Excessive Sodium Bicarbonate Infusion May Result in Osmotic Demyelination Syndrome During Treatment of Diabetic Ketoacidosis: A Case Report.

INTRODUCTION: We present a case wherein diabetic ketoacidosis (DKA) was treated with a large amount of sodium bicarbonate and potassium chloride, resulting in the development of osmotic demyelination syndrome (ODS). CASE PRESENTATION: Our patient was a 29-year-old male with a history of post-surgical repair for ventricular septal defect. Upon arrival, the patient's Glasgow Coma Scale (GCS) score was E2M4V3. Laboratory examinations revealed leukocytosis, severe metabolic acidosis, hypokalemia, and hyperglycemia. His consciousness status and hemodynamics improved after resuscitation (GCS: E3M6Ve). However, they declined at the 40th hour of admission and dropped to GCS E2M2Ve. Magnetic resonance imaging revealed multifocal abnormal signal intensity changes in the whole brain stem. The diagnosis of type 1 diabetes mellitus was made during the hospitalization period. The patient exhibited improved consciousness status after 17-day medical care at the ICU. CONCLUSIONS: We recommend that in the case of DKA, the correction of hypokalemia should be prioritized during treatment. Sodium bicarbonate infusion should be reserved for pH < 6.9. In addition, close monitoring of the serum sodium level and prompt actions to lower it if it exceeds the threshold may be necessary.

Selective activation of inflammation factors by human parvovirus B19 and human bocavirus VP1 unique region on H9c2 cardiomyocyte.

Human parvovirus B19 (B19) and human bocavirus 1 (HBoV) are the only known pathogenic parvoviruses, and are responsible for a variety of diseases in human beings. Mounting evidence indicates a strong association between B19 infection and cardiac disorders including myocarditis, dilated cardiomyopathy and heart failure. However, very limited information about the role of HBoV in cardiac disorders is known. To elucidate the effects of B19 and HBoV on cardiac disorders, we expressed EGFP­conjugate constructs of B19­VP1 unique region (VP1u) and HBoV­VP1u, along with the mutants EGFP­B19­VP1uD175A and EGFP­HBoV­VP1uV12A, in H9c2 cells by stable transfection. The protein expression levels of EGFP, EGFP­B19­VP1u, EGFP­B19­VP1uD175A, EGFP­HBoV­VP1u and EGFP­HBoV­VP1uV12A in H9c2 cells were observed under a fluorescence microscope and confirmed by western blotting. Secreted phospholipase A2 (sPLA2) activity was detected in B19­VP1u and HBoV­VP1u but not B19­VP1uD175A and HBoV­VP1uV12A recombinant proteins. Significantly higher expression levels of MCP2 and IP­10 mRNA were detected in H9c2 cells that were transfected with pEGFP­B19­VP1u, compared with in those cells transfected with pEGFP­HBoV­VP1u, pEGFP­B19­VP1uD175A or pEGFP­HBoV­VP1uV12A. Significantly higher protein levels of IL­1ß and IL­6 were detected in H9c2 cells transfected with pEGFP­B19­VP1u or pEGFP­HBoV­VP1u, compared with in those cells transfected with pEGFP­B19­VP1uD175A or pEGFP­HBoV­VP1uV12A. Notably, significantly higher expression of both TNF­α and NF­κB was observed only in H9c2 cells transfected with pEGFP­B19­VP1u, but not in those cells transfected with pEGFP­HBoV­VP1u, pEGFP­B19­VP1uD175A or pEGFP­HBoV­VP1uV12A. These findings, to our knowledge for the first time, reveal the difference between B19­VP1u and HBoV­VP1u in H9c2 cells and provide insight into the roles of B19­VP1u and HBoV­VP1u in the pathogenesis of cardiac inflammation.

Effects of taurine on striatal dopamine transporter expression and dopamine uptake in SHR rats.

Dopaminergic deficits in the prefrontal cortex and striatum have been attributed to the pathogenesis of attention-deficit hyperactivity disorder (ADHD). Our recent study revealed that high-dose taurine improves hyperactive behavior and brain-functional signals in SHR rats. This study investigates the effect of taurine on the SHR striatum by detecting the spontaneous alternation, DA transporter (DAT) level, dopamine uptake and brain-derived neurotrophic factor (BDNF) expression. A significant increase in the total arm entries was detected in both WKY and SHR rats fed with low-dose taurine but not in those fed with high-dose taurine. Notably, significantly increased spontaneous alternation was observed in SHR rats fed with high-dose taurine. Significantly higher striatal DAT level was detected in WKY rats fed with low-dose taurine but not in SHR rats, whereas significantly reduced striatal DAT level was detected in SHR rats fed with high-dose taurine but not in WKY rats. Significantly increased dopamine uptake was detected in the striatal synaptosomes of both WKY and SHR rats fed with low-dose taurine. Conversely, significantly reduced dopamine uptake was detected in the striatal synaptosomes of SHR rats fed with high-dose taurine. Accordingly, a negative correlation was detected between striatal dopamine uptake and spontaneous alternation in SHR rats fed with low or high-dose taurine. Significantly increased BDNF was detected in the striatum of both WKY and SHR rats fed with low or high-dose taurine. These findings indicate that different dosages of taurine have opposite effects on striatal DAT expression and dopamine uptake, suggesting high-dose taurine as a possible candidate for ADHD treatment.

Antigenicity analysis of human parvovirus B19-VP1u protein in the induction of anti-phospholipid syndrome.

Mounting evidence suggests a connection between human parvovirus B19 (B19) and autoimmune diseases, and especially an association between the B19-VP1 unique region (VP1u) and anti-phospholipid syndrome (APS). However, little is known about the antigenicity of B19-VP1u in the induction of APS-like syndrome. To elucidate the antigenicity of B19-VP1u in the induction of APS, N-terminal truncated B19-VP1u (tVP1u) proteins were prepared to immunize Balb/c mice to generate antibodies against B19-tVP1u proteins. The secreted phospholipase A2 (sPLA2) activities and binding specificity of mice anti-B19-tVP1u antibodies with cardiolipin (CL) and beta-2-glycoprotein I (ß2GPI) were evaluated by performing immunoblot, ELISA and absorption experiments. A mice model of passively induced APS was adopted. Although sPLA2 activities were identified in all B19-tVP1u proteins, only amino acid residues 61-227 B19-tVP1u exhibited a higher sPLA2 activity. Autoantibodies against CL and ß2GPI exhibited binding activities with all B19-tVP1u proteins. IgG that was purified from mice that had been immunized with amino acid residues 21-227 to 121-227 B19-tVP1u proteins exhibited significantly higher binding activity with CL. IgG that was purified from mice that had been immunized with amino acid residues 21-227, 31-227, 82-227 and 91-227 B19-tVP1u proteins exhibited significantly higher binding activity with ß2GPI. Accordingly, significantly higher binding inhibition of CL was detected in the presence of amino acid residues 61-227 and 101-227 B19-tVP1u. Significantly higher binding inhibition of ß2GPI was detected in the presence of amino acid residues 21-227, 31-227, 82-227 and 91-227 B19-tVP1u. The mice that received amino acid residues 31-227 or 61-227 anti-tB19-VP1u IgG revealed significant thrombocytopenia and those that received amino acid residues 21-227, 31-227, 61-227, 71-227, 82-227, 91-227, 101-227 or 114-227 anti-tB19-VP1u IgG exhibited significantly prolonged aPTT. These findings provide further information concerning the role of B19-VP1u antigenicity in APS-like autoimmunity.

The Root Extract of Gentiana macrophylla Pall. Alleviates B19-NS1-Exacerbated Liver Injuries in NZB/W F1 Mice.

The nonstructural protein NS1 of human parvovirus B19 (B19) is known to exacerbate disease activity in systemic lupus erythematosus (SLE). However, no specific medicine for B19 infection is available. The roots of Gentiana macrophylla Pall. (GM), the traditional Chinese medicine "Qinjiao," have been used for centuries to treat rheumatic disease, including SLE. Herein, we aimed to investigate the effects of GM root extract (100 and 300 mg/kg body weight) on B19-NS1-exacerbated liver injury in NZB/W F1 mice; liver tissues were assessed by hematoxylin-eosin staining and immunoblotting. The GM root extract significantly decreased B19-NS1-exacerbated liver inflammation by suppressing the expressions of hepatic inducible nitric oxide synthase, cyclooxygenase type 2 (COX-2), interleukin (IL)-1ß proteins, values of serum asparate transaminase (AST) and alanine transaminase (ALT), and lymphocyte infiltration (P < .05). It also significantly reduced the B19-NS1-exacerbated hepatic matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA) expressions by downregulating tumor necrosis factor (TNF)-α/NF-κB (p65) signaling. These findings suggest a therapeutic potential of GM root extract against B19-NS1-exacerbated liver inflammation in SLE.

Images Diagnosis and Emergent Endovascular Treatment of Acute Hemorrhagic Basilar Artery Dissection: A Case Report.

PURPOSE: Basilar artery dissection (BAD) is a rare but possibly fatal disease with specific neuroimage findings. The management of BAD varies. This report describes a case with hemorrhagic BAD treated by endovascular stent-assisted coil embolization. CASE REPORT: We report an 82-year-old case of acute mid basilar artery dissection complicated with acute subarachnoid hemorrhage (SAH), intraventricular hemorrhage (IVH) and hydrocephalus, which was diagnosed by complete neuroimage surveys including computed tomography angiography (CTA), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA). She was then successfully treated by endovascular stent-assisted coil embolization. CONCLUSION: By modern sophisticated neuroimages, BAD could be diagnosed. Endovascular treatment with stent-assisted coil embolization can be a safe and efficacious choice for relatively poor surgical indicated patients with hemorrhagic BAD.

Lactoferrin Increases Antioxidant Activities and Ameliorates Hepatic Fibrosis in Lupus-Prone Mice Fed with a High-Cholesterol Diet.

Lactoferrin (LF) has beneficial effects against various diseases. However, the effects of LF on liver fibrosis in systematic lupus erythematosus (SLE) are unknown. In this study, NZB/W F1 mice were utilized to investigate the effects of LF on SLE. Experiments reveal that LF significantly increases glutathione and 1,1-diphenyl-2-picryl-hydrazyl levels and significantly decreased malondialdehyde levels in both serum and liver in NZB/W F1 mice. LF also lowered matrix metalloproteinase-9 activity and liver inflammatory indices, such as aminotransferase and alanine aminotransferase. Notably, significantly decreased expression of fibrotic related molecules, including transforming growth factor (TGF)-ß1, tumor necrosis factor-α, interleukin-1ß, and TGF-ß1 receptor, were observed in the livers of NZB/W F1 mice that had been treated with LF. Significantly, suppressed Smad2/3 signaling, α-smooth muscle actin, and collagen deposition were also detected. These findings reveal that LF has beneficial effects on SLE by increasing antioxidant activities and ameliorating liver inflammation and fibrosis, suggesting the therapeutic effectiveness of LF against SLE.

New-onset Atrial Fibrillation is Associated With Polycystic Kidney Disease: A Nationwide Population-based Cohort Study.

Cardiovascular complications remain the major problems contributing to morbidity and mortality in patients with polycystic kidney disease (PKD). Therefore, the authors hypothesized that atrial fibrillation (AF) is closely associated with PKD. The authors conducted a nationwide population-based cohort study to investigate the risk of AF in patients with PKD. Using data from inpatient claims, the authors enrolled 7203 patients aged over 20 years who were diagnosed with PKD from 1998 to 2010 with no history of AF as the PKD cohort. They randomly selected 28,739 people without PKD as controls and frequency matched them with patients with PKD according to their age, sex, and baseline comorbidity. In total, 247 PKD patients were diagnosed with AF, representing an incidence of 7.08 per 1000 person-years, whereas 807 cases of AF occurred in the comparison cohort, yielding an incidence of 4.98 per 1000 person-y, with an adjusted HR (aHR) of 1.31 (95% CI = 1.14-1.51). The risk of AF increased from an aHR of 1.59 (95% CI = 1.15-2.21) to 3.64 (95% CI = 1.93-6.85) when the number of risk factors increased from 1 to more than 5 in comparison with patients without risk factors. A remarkably high incidence rate and risk was observed in patients with PKD when multiple risk factors were combined. A high index of suspicion should be maintained when examining PKD patients with irregular betas. Early prophylactic therapy is warranted in these patients.

Human parvovirus B19 VP1u Protein as inflammatory mediators induces liver injury in naïve mice.

Human parvovirus B19 (B19V) is a human pathogen known to be associated with many non-erythroid diseases, including hepatitis. Although B19V VP1-unique region (B19-VP1u) has crucial roles in the pathogenesis of B19V infection, the influence of B19-VP1u proteins on hepatic injury is still obscure. This study investigated the effect and possible inflammatory signaling of B19-VP1u in livers from BALB/c mice that were subcutaneously inoculated with VP1u-expressing COS-7 cells. The in vivo effects of B19-VP1u were analyzed by using live animal imaging system (IVIS), Haematoxylin-Eosin staining, gel zymography, and immunoblotting after inoculation. Markedly hepatocyte disarray and lymphocyte infiltration, enhanced matrix metalloproteinase (MMP)-9 activity and increased phosphorylation of p38, ERK, IKK-α, IκB and NF-κB (p-p65) proteins were observed in livers from BALB/c mice receiving COS-7 cells expressing B19-VP1u as well as the significantly increased CRP, IL-1ß and IL-6. Notably, IFN-γ and phosphorylated STAT1, but not STAT3, were also significantly increased in the livers of BALB/c mice that were subcutaneously inoculated with VP1u-expressing COS-7 cells. These findings revealed the effects of B19-VP1u on liver injury and suggested that B19-VP1u may have a role as mediators of inflammation in B19V infection.

Taurine Attenuates Hepatic Inflammation in Chronic Alcohol-Fed Rats Through Inhibition of TLR4/MyD88 Signaling.

Accumulating evidence indicates that overconsumption of ethanol contributes in many ways to the pathogenesis of hepatic injury. Although studies indicate that taurine decreases lipogenesis, oxidative stress, and inflammatory cytokines, the protective effect of taurine against alcohol-induced liver injury is still unclear. To clarify the precise signaling involved in the beneficial effect of taurine on alcohol-induced liver injury, rats were randomly divided into four treatment groups: (1) control (Ctl), (2) alcohol (Alc), (3) Alc+taurine (Tau), and (4) Alc+silymarin (Sil). The Tau and Sil groups had lower lymphocyte infiltration and significantly lower TLR-4/MyD88 and IκB/NFκB compared to the Alc group. The inducible nitric oxide synthase (iNOS), C-reactive protein (CRP), tumor necrosis factors (TNF)-α, interleukin (IL)-6, and IL-1ß were also significantly lower in the Tau and Sil groups than in the Alc group. The experimental results indicated that hepatoprotection against alcohol-induced inflammation may be mediated by decreased TLR-4/MyD88 signaling.

Attenuated Effects of Deep-Sea Water on Hepatic Apoptosis in STZ-Induced Diabetic Rats.

Diabetes mellitus (DM) is a metabolic disorder and increasing evidences have indicated a connection between DM and hepatic abnormality. Deep-sea water (DSW) has been applied in many fields, especially in medicine; herein, we investigated the influence of DSW on hepatic apoptosis in streptozocin (STZ)-induced diabetes rats. Our experimental results firstly demonstrated the beneficial effects of 1×DSW, 2×DSW and 3×DSW in alleviating hepatic apoptosis in STZ-induced diabetic rats. We demonstrated that 1×DSW, 2×DSW and 3×DSW significantly suppressed the caspase-3 activity and TUNEL-positive cells in livers of STZ-induced diabetic rats. Significant reductions of both Fas-dependent and mitochondrial-dependent apoptotic molecules were also detected in livers of STZ-induced diabetic rats receiving DSW. Additionally, apoptotic signaling molecules such as phosphorylated IκB-α and NF-κB were significantly reduced in livers of DSW-treated STZ-induced diabetic rats. These findings indicate hepatic protective effects of DSW on DM and suggest DSW as a possible ingredient for health food.

Effects of human Parvovirus B19 and Bocavirus VP1 unique region on tight junction of human airway epithelial A549 cells.

As is widely recognized, human parvovirus B19 (B19) and human bocavirus (HBoV) are important human pathogens. Obviously, both VP1 unique region (VP1u) of B19 and HBoV exhibit the secreted phospholipase A2 (sPLA2)-like enzymatic activity and are recognized to participate in the pathogenesis of lower respiratory tract illnesses. However, exactly how, both VP1u from B19 and HBoV affect tight junction has seldom been addressed. Therefore, this study investigates how B19-VP1u and HBoV-VP1u may affect the tight junction of the airway epithelial A549 cells by examining phospholipase A2 activity and transepithelial electrical resistance (TEER) as well as performing immunoblotting analyses. Experimental results indicate that TEER is more significantly decreased in A549 cells by treatment with TNF-α (10 ng), two dosages of B19-VP1u and BoV-VP1u (400 ng and 4000 ng) or bee venom PLA2 (10 ng) than that of the control. Accordingly, more significantly increased claudin-1 and decreased occludin are detected in A549 cells by treatment with TNF-α or both dosages of HBoV-VP1u than that of the control. Additionally, more significantly decreased Na+/K+ ATPase is observed in A549 cells by treatment with TNF-α, high dosage of B19-VP1u or both dosages of BoV-VP1u than that of the control. Above findings suggest that HBoV-VP1u rather than B19 VP1u likely plays more important roles in the disruption of tight junction in the airway tract. Meanwhile, this discrepancy appears not to be associated with the secreted phospholipase A2 (sPLA2)-like enzymatic activity.

Effects of cystamine on antioxidant activities and regulatory T cells in lupus-prone mice.

Attenuated antioxidant activities, irregular cytokines expressions and reduced regulatory T cells, are strongly associated with the pathogenesis of systemic lupus erythematosus (SLE). Despite the well-established beneficial effects of cystamine on lupus-prone mice, the extent to which cystamine contributes to antioxidant activity and the reduction of regulatory T cells has seldom been investigated. Therefore, this study elucidates how cystamine affects anti-oxidant activities in NZB/W F1 mice by performing assays of Glutathione (GSH), 1,1-diphenyl-2- picryl-hydrazyl (DPPH) and malondialdehyde thiobarbituric acid (MDA). In addition, investigations of the effects of cystamine on CD4(+) /CD25(+) regulatory T cells and interleukin-6 (IL6)/STAT-3 signalling were performed with flow cytometry and immunoblots. Experimental results reveal more significantly reduced MDA and increased GSH and DPPH in NZB/W F1 mice receiving cystamine than in those mice receiving PBS. Meanwhile, CD4(+) /CD25(+) regulatory T cells more significantly increase in NZB/W F1 mice receiving cystamine than in those mice receiving PBS, accompanied by significantly reduced IL-6/phosphorylated STAT-3 expression. The above findings suggest the beneficial effects of cystamine in terms of increasing antioxidant activities and CD4(+) /CD25(+) regulatory T cells in lupus-prone mice by suppressing IL-6/STAT3 signalling.