Background: Ceftriaxone is a β-lactam antibiotic used to treat central nervous system infections. Whether the neuroprotective effects of ceftriaxone after TBI are mediated by attenuating neuroinflammation but not its antibacterial actions is not well established. Methods: Anesthetized male Sprague–Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + ceftriaxone groups. Ceftriaxone was intraperitoneally injected at 0, 24, and 48 h with 50 or 250 mg/kg/day after TBI. During the first 120 min after TBI, we continuously measured heart rate, arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure. The infarct volume was measured by TTC staining. Motor function was measured using the inclined plane. Glutamate transporter 1 (GLT-1), neuronal apoptosis and TNF-α expression in the perilesioned cortex were investigated using an immunofluorescence assay. Bacterial evaluation was performed by Brown and Brenn’s Gram staining. These parameters above were measured at 72 h after TBI. Results: Compared with the TBI + vehicle group, the TBI + ceftriaxone 250 mg/kg group showed significantly lower ICP, improved motor dysfunction, reduced body weight loss, decreased infarct volume and neuronal apoptosis, decreased TBI-induced microglial activation and TNF-α expression in microglia, and increased GLT-1 expression in neurons and microglia. However, the grades of histopathological changes of antibacterial effects are zero. Conclusions: The intraperitoneal injection of ceftriaxone with 250 mg/kg/day for three days may attenuate TBI by increasing GLT-1 expression and reducing neuroinflammation and neuronal apoptosis, thereby resulting in an improvement in functional outcomes, and this neuroprotective effect is not related to its antibacterial effects.

Vitamin D has been identified as an innate anti-hepatitis C virus (HCV) agent but the possible mechanisms for this issue remain unclear. Here, we clarified the mechanisms of calcitriol-mediated inhibition of HCV infection. Calcitriol partially inhibited HCV infection, nitric oxide (NO) release and lipid accumulation in Huh7.5 human hepatoma cells via the activation of vitamin D receptor (VDR). When cells were pretreated with the activators of peroxisome proliferator-activated receptor (PPAR)-α (Wy14643) and -γ (Ly171883), the calcitriol-mediated HCV suppression was reversed. Otherwise, three individual stimulators of PPAR-α/β/γ blocked the activation of VDR. PPAR-β (linoleic acid) reversed the inhibition of NO release, whereas PPAR-γ (Ly171883) reversed the inhibitions of NO release and lipid accumulation in the presence of calcitriol. The calcitriol-mediated viral suppression, inhibition of NO release and activation of VDR were partially blocked by an inhibitor of endoplasmic reticulum-associated degradation (ERAD), kifunensine. Furthermore, calcitriol blocked the HCV-induced expressions of apolipoprotein J and 78 kDa glucose-regulated protein, which was restored by pretreatment of kifunensine. These results indicated that the calcitriol-mediated HCV suppression was associated with the activation of VDR, interference with ERAD process, as well as blockades of PPAR, lipid accumulation and nitrative stress.

Purpose: The aim of this study was to use a network meta-analysis to evaluate the relative efficacy of various agents at preventing invasive fungal infections (IFIs). In this way, suitable prophylactic regimens may be selected for patients with hematopoietic stem cell transplantation (HSCT). Methods: We conducted a systematic review of randomized controlled trials comparing the prophylactic effects of two antifungal agents or an antifungal agent and a placebo administered to patients with HSCT. Relevant studies were found in the PubMed and Cochrane databases. Unpublished studies were collected from the ClinicalTrials.gov registry. Results: Sixteen two-arm studies were identified. Compared with placebo, all six antifungal agents (amphotericin B, fluconazole, itraconazole, micafungin, posaconazole, and voriconazole) presented with greater efficacy at controlling proven IFIs. OR ranged from 0.08 to 0.29. Voriconazole (surface under the cumulative ranking curve [SUCRA]=71.6%), posaconazole (SUCRA=68.9%), and itraconazole (SUCRA=64.7%) were the three top-ranking drugs for preventing proven IFIs. Itraconazole ranked highest (SUCRA=83.1%) and had the greatest efficacy at preventing invasive candidiasis. Posaconazole and micafungin were the two top-ranking drugs (SUCRA=81.3% and 78.4%, respectively) at preventing invasive aspergillosis. Micafungin and voriconazole were the drugs of choice because they lowered mortality more than the other agents (SUCRA=74.6% and 61.1%, respectively). Conclusion: This study is the first network meta-analysis to explore the prophylactic effects of antifungal agents in patients with HSCT. Voriconazole was the best choice for the prevention of proven IFIs in HSCT patients.