Suppression of the RAC1/MLK3/p38 Signaling Pathway by β-Elemene Alleviates Sepsis-Associated Encephalopathy in Mice

It is still difficult to treat sepsis-associated encephalopathy (SAE) which is a diffuse brain dysfunction caused by sepsis, with excessive activation of microglia as one of the main mechanisms. Ras-related C3 botulinum toxin substrate 1 (RAC1) is proven to be a key molecule in the inflammatory signaling network. By using microglial cell line BV-2 and a mouse model of cecal ligation puncture (CLP), we herein evaluated the effects of β-elemene, an extract of Curcuma zedoaria Rosc., on RAC1 signaling in microglia. β-Elemene decreased the expressions of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6] and attenuated translocation of nuclear factor-κB (NF-κB) p65 from the cytosol to the nucleus in BV-2 cells after lipopolysaccharide (LPS) treatment. It also inhibited the activation of RAC1, mixed-lineage protein kinase 3 (MLK3) and p38 mitogen-activated protein kinase (MAPK). The phosphorylation of the RAC1 Ser71 site was increased by β-elemene. Moreover, the learning and memory abilities of CLP mice in the water maze test and fear conditioning test were improved after β-elemene treatment. It reduced the expression of the microglial marker IBA1, significantly increased RAC1 Ser71 phosphorylation, and suppressed the RAC1/MLK3/p38 signaling activation and inflammatory response in the hippocampus. In conclusion, β-elemene effectively alleviated SAE in mice and inhibited the RAC1/MLK3/p38 signaling pathway in microglia, and might be an eligible potential candidate for SAE treatment

Analysis of 30 patients with acupuncture-induced primary inoculation tuberculosis.

Primary inoculation tuberculosis is a skin condition that develops at the site of inoculation of Mycobacterium tuberculosis in tuberculosis-free individuals. This report describes the diagnosis, treatment and >1 year follow-up of 30 patients presenting with acupuncture-induced primary inoculation tuberculosis. Our data provide a deeper insight into this rare route of infection of tuberculosis. We also review effective treatment options

Additional file 1: of Procyanidins attenuate neuropathic pain by suppressing matrix metalloproteinase-9/2

Figure S1. PC significantly inhibited CCI-induced phosphorylation of JNK, p38, and ERK and decreased p65 expression in nuclear in vivo. (A) Single administration of PC (90 mg/kg, p.o.) significantly decreased the expression of p-JNK, p-p38, and p-ERK (Cell Signaling Technology, MA, USA) in the spinal cord of CCI mice. (B) Single administration of PC (90 mg/kg, p.o.) significantly decreased the expression of p65 (Cell Signaling Technology, MA, USA) in nuclear in vivo. (C) Single administration of PC (90 mg/kg, p.o.) significantly decreased MDA level induced by CCI injury in the spinal cord. PC (90 mg/kg, p.o.) was administered at day 14 after CCI operation. The lumbar spines (L1–L6) were collected and analyzed 120 min after the last drug administration. Representative bands and a data summary (n = 4) was shown. (*P < 0.05, **P < 0.01 vs. control; #P < 0.05, ##P < 0.01 vs. CCI group; Bonferroni post hoc tests). (DOCX 262 kb

Hyperplasia of the knee joint synovium, grey and dark in color, with a soft texture, complicated by necrotic tissues.

<p>Some knee joint synovium underwent caseous changes, and articular cartilage necrosis and desquamation were observed. Subchondral bone was exposed, and vermiform bone destruction was observed on the condyle of femur and the margin of the tibial plateau.</p

Enhanced MRI scan shows tuberculous, ring-shaped, signal-intensified lesions in bilateral frontal and parietal lobes, centrum semiovale, peri-lateral ventricular region, basal ganglia regions, thalamus, brainstem and cerebellum.

<p>Enhanced MRI scan shows tuberculous, ring-shaped, signal-intensified lesions in bilateral frontal and parietal lobes, centrum semiovale, peri-lateral ventricular region, basal ganglia regions, thalamus, brainstem and cerebellum.</p

A fresh lesion on the right side of the neck.

<p>The ulcer was oval, with the largest diameter of about 5</p

Information on clinical features and treatments in 30 patients.

+<p>: positive;</p>-<p>: negative;</p><p>*: severe case,</p>K<p>: knee TB,</p>D<p>: type 2 diabetes,</p>S<p>: symptoms commonly associated with tuberculosis, including low-grade fever, night sweats, anorexia and marasmus.</p><p>Good efficacy of drug treatment in nine suspected patients named group I; moderate efficacy of drug treatment in four confirmed and ten suspected patients named group II; poor efficacy of drug treatment in three confirmed and four suspected patients named group III.</p