Magnesium sulphate (MgSO₄) has potent anti-inflammatory capacity. It is a natural calcium antagonist and a potent L-type calcium channel inhibitor. We sought to elucidate the possible role of calcium, the L-type calcium channels, or both in mediating the anti-inflammatory effects of MgSO₄. RAW264.7 cells, an immortalized murine macrophage-like cell line, were treated with phosphate buffered saline, MgSO₄, lipopolysaccharide (LPS), LPS plus MgSO₄, LPS plus MgSO₄ plus extra-cellular supplement with calcium chloride (CaCl₂), or LPS plus MgSO₄ plus the L-type calcium channel activator BAY-K8644. After harvesting, the production of inflammatory molecules was evaluated. Because the production of endotoxin-induced inflammatory molecules is regulated by the crucial transcription factor nuclear factor (NF)-κB, we also evaluated the expression of NF-κB. LPS significantly induced the production of inflammatory molecules, including macrophage inflammatory protein-2, tumour necrosis factor-α, interleukin (IL)-1β, IL-6, nitric oxide/inducible nitric oxide synthase, and prostaglandin E₂/cyclo-oxygenase-2. LPS also induced NF-κB activation, as inhibitor-κB degradation, NF-κB nuclear translocation, and NF-κB-DNA binding activity were significantly increased in LPS-treated RAW264.7 cells. MgSO₄, in contrast, significantly inhibited the LPS-induced inflammatory molecules production and NF-κB activation. Moreover, the effects of MgSO₄ on inflammatory molecules and NF-κB were reversed by extra-cellular calcium supplement with CaCl₂ and L-type calcium channel activator BAY-K8644. MgSO₄ significantly inhibited endotoxin-induced up-regulation of inflammatory molecules and NF-κB activation in activated RAW264.7 cells. The effects of MgSO₄ on inflammatory molecules and NF-κB may involve antagonizing calcium, inhibiting the L-type calcium channels, or both.

Background Hepatitis C virus (HCV) infection has been linked to an increased risk of insulin resistance and carotid atherosclerosis. Aim To investigate the association between HCV infection and stroke, and the effect of interferon‐based therapy (IBT) on stroke risk in chronic hepatitis C (CHC) patients. Methods We conducted a retrospective cohort study that followed up 3113 subjects with a newly detected HCV infection and 12 452 age‐ and gender‐matched subjects without HCV infection selected from a random sample of 10⁶ beneficiaries from the Taiwan National Health Insurance Program up to 5 years. Use of IBT was defined as treatment with interferon alpha, pegylated interferon alpha‐2a or pegylated interferon alpha‐2b for at least 3 months. The hazard ratio (HR) for newly detected stroke was calculated for subjects with HCV compared to those without HCV, and for IBT‐treated HCV patients compared to non‐IBT‐treated HCV patients while adjusting for possible confounding factors. Results The overall person‐years of follow‐up were 8624.11 in patients with HCV, 54 533.69 in patients without HCV, 666.65 in IBT‐treated patients, and 7886.49 in nontreated patients. The multivariable‐adjusted hazard ratio (HR) for newly detected stroke was 1.23 for subjects with HCV compared to the age‐ and sex‐matched subjects without HCV (adjusted HR = 1.23, 95% CI = 1.06–1.42, P = 0.008). Moreover, use of IBT significantly reduced the risk of stroke in HCV patients (adjusted HR = 0.39, 95% CI = 0.16–0.95, P = 0.039) after adjusting for known prognostic factors. Conclusions Interferon‐based therapy may reduce the long‐term risk of stroke in patients with chronic HCV infection.

This study compared the odds ratio (OR) of surgical site infection (SSI) within 30 days after operation with general anaesthesia (GA) or neuraxial anaesthesia (NA) in Taiwanese women undergoing Caesarean delivery (CD). An epidemiologic design was used. The study population was based on the records of all deliveries in hospitals or obstetric clinics between January 2002 and December 2006 in Taiwan. Anonymized claim data from the Taiwan National Health Insurance Research Database (NHIRD) were analysed. Women who received CD were identified from the NHIRD by Diagnosis-Related Group codes. The mode of anaesthesia was defined by order codes. Multivariate logistic regression was used to estimate the OR and associated 95% confidence interval (CI) of post-CD SSIs for GA when compared with NA. The outcome was whether a woman had been diagnosed as having an SSI during the hospitalization or was re-hospitalized within 30 days after CD for the treatment of SSIs using five or 81 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Among the 303 834 Taiwanese women who underwent CD during the 5 yr observation period, the 30 day post-CD SSI rate was 0.3% or 0.9% based on five or 81 ICD-9-CM codes. The multivariate-adjusted OR of having post-CD SSIs in the GA group was 3.73 (95% CI, 3.07–4.53) compared with the NA group (P<0.001) using five ICD-9-CM codes for the definition of SSI. GA for CD was associated with a higher risk of SSI when compared with neuraxial anaesthesia.

Inflammation is a major root of several diseases such as allergy, cancer, Alzheimer’s, and several others, and the present state of existing drugs provoked researchers to search for new treatment strategies. Plants are regarded to be unique sources of active compounds holding pharmacological properties, and they offer novel designs in the development of therapeutic agents. Therefore, this study aimed to explore the anti-inflammatory mechanism of esculetin in lipoteichoic acid (LTA)-induced macrophage cells (RAW 264.7). The relative expression of inducible nitric oxide synthase (iNOS), nitric oxide (NO) production and COX-2 expression were intensified in LTA-induced RAW cells. The phosphorylation status of mitogen-activated protein kinases (extracellular signal-regulated kinase (ERK)1/2, p38 MAPK, and c-Jun N-terminal kinase (JNK)) and nuclear factor kappa B (NF-κB) p65 were detected by using Western blot assay. The nuclear translocation of p65 was assessed by confocal microscopic image analysis. Esculetin significantly and concentration-dependently inhibited LTA-induced NO production and iNOS expression, but not COX-2 expression, in RAW cells. Esculetin was not effective in LTA-induced MAPK molecules (ERK, p38 and JNK). However, esculetin recovered LTA-induced IκBα degradation and NF-κB p65 phosphorylation. Moreover, esculetin at a higher concentration of 20 µM evidently inhibited the nuclear translocation of NF-κB p65. At the same high concentration, esculetin augmented Nrf2 expression and decreased DPPH radical generation in RAW 264.7 cells. This study exhibits the value of esculetin for the treatment of LTA-induced inflammation by targeting NF-κB signaling pathways via its antioxidant properties.

The role of activated platelets in acute and chronic cardiovascular diseases (CVDs) is well established. Therefore, antiplatelet drugs significantly reduce the risk of severe CVDs. Evodia rutaecarpa (Wu-Chu-Yu) is a well-known Chinese medicine, and rutaecarpine (Rut) is a main bioactive component with substantial beneficial properties including vasodilation. To address a research gap, we investigated the inhibitory mechanisms of Rut in washed human platelets and experimental mice. At low concentrations (1–5 μM), Rut strongly inhibited collagen-induced platelet aggregation, whereas it exerted only a slight or no effect on platelets stimulated with other agonists (e.g., thrombin). Rut markedly inhibited P-selectin expression; adenosine triphosphate release; [Ca²⁺]i mobilization; hydroxyl radical formation; and phospholipase C (PLC)γ2/protein kinase C (PKC), mitogen-activated protein kinase, and phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK3β) phosphorylation stimulated by collagen. SQ22536 (an adenylate cyclase inhibitor) or ODQ (a guanylate cyclase inhibitor) did not reverse Rut-mediated antiplatelet aggregation. Rut was not directly responding to vasodilator-stimulated phosphoprotein phosphorylation. Rut significantly increased the occlusion time of fluorescence irradiated thrombotic platelet plug formation. The findings demonstrated that Rut exerts a strong effect against platelet activation through the PLCγ2/PKC and PI3K/Akt/GSK3β pathways. Thus, Rut can be a potential therapeutic agent for thromboembolic disorders.