New animal model of chronic gout reproduces pathological features of the disease in humans.

OBJECTIVES: Gout, as the most prevalent form of inflammatory arthritis, necessitates the use of animal models to investigate the molecular mechanisms involved in its development. Therefore, our objective was to develop a novel chronic mouse model of gout that more closely mimics the progression of gout in humans. METHODS: A novel chronic mouse model of gout was established by a simple method, which does not require high technical proficiency, predominantly involves daily intraperitoneal injections of potassium oxonate for approximately 4 months, combined with a high fat-diet and injections of acetic acid into the hind paws to facilitate the formation of monosodium urate (MSU). Arthritis scores and paw oedema were assessed, behavioural tests were conducted, and histopathological and imaging evaluations of the arthritic paw joints were performed. RESULTS: After 4 months of induction, mice in the model group exhibited noticeable increases in arthritis severity, joint and cartilage damage, as well as bone erosion. Gomori's methenamine silver stain revealed the presence of MSU crystal deposition or tophi in the paw joints or ankle joints of up to 37.9% of the model mice (11 out of 29 mice). Moreover, treatment with benzbromarone effectively prevented the further development of gout or tophi formation in model mice. CONCLUSIONS: Our model more accurately replicates the pathological features of gouty arthritis compared with gout induced by MSU crystal injections. Therefore, it is particularly suitable for further investigations into the pathogenesis of gout and also serves as a valuable platform for screening potential antigout agents.

Curcumin promotes functional recovery and inhibits neuronal apoptosis after spinal cord injury through the modulation of autophagy.

Objective: The study was aimed to investigate whether the neuroprotective role of curcumin is associated with regulation of autophagy.Methods: Rat spinal cord injury (SCI) models were established according to Allen's weight-drop trauma method. Curcumin was administered 30 min after the contusion and continued weekly. At 3, 7, 14, 21, and 28 days after SCI, functional recovery was evaluated using the Basso, Beattie and Bresnahan (BBB) scoring and the oblique plate test, following which, spinal cord tissues were obtained. Histological changes and apoptosis were then measured with H&E staining and TUNEL assay. Glia activation, inflammatory infiltration, inflammatory factor release, and myelination were observed through immunohistochemical (IHC) staining and ELISA. Autophagy and Akt activation were detected by western blotting. After autophagy was inhibited by injection of chloroquine, TUNEL, inflammatory factor release, myelin basic protein (MBP) IHC staining and functional recovery evaluation were performed again.Results: Curcumin treatment promoted functional recovery after SCI and reduced neuron apoptosis, improved spinal cord integrity, recovery, and re-myelination, and suppressed the inflammatory response. Autophagy was enhanced and Akt/mTOR pathway was inhibited by curcumin. Autophagy inhibition partially eliminated the protective effect of curcumin on SCI.Conclusion: Curcumin may exert its therapeutic effect on SCI through the enhancement of autophagy, in which, inhibition of the Akt/mTOR signaling pathway may be also involved.

MiR-374a Activates Wnt/ß-Catenin Signaling to Promote Osteosarcoma Cell Migration by Targeting WIF-1.

MiR-374a was proved to take part in the initiation and development of several cancers. However, the molecular mechanism of miR-374a in osteosarcoma (OS) cells remains unclear. The aim of our research was to investigate the role of miR-374a in OS cells migration and clarify the potential mechanisms. Quantitative real-time PCR (qRT-PCR) and western blot analysis were applied to evaluate the expression of miR-374a and Wnt inhibitory factor-1 (WIF-1). Bioinformatical methods and luciferase reporter assay were carried out to predict and confirm the combination of miR-374a and WIF-1. Transwell and wound healing assays were performed to detect the migration capacity of OS cells. Lithium chloride (LiCl) was used to investigate the role of LiCl-activated Wnt/ß-catenin signaling pathway in regulating cell migration. Our studies revealed that miR-374a was up-regulated whereas WIF-1 was down-regulated in OS cells. Besides, WIF-1 was the target of miR-374a by performing luciferase reporter assay. By transfection of miR-374a inhibitor and/or WIF-1 siRNA to OS cells, we found that miR-374a promoted the migration of OS cells. In addition, the inhibition of WIF-1 abolished the miR-374a inhibitor-induced migration suppression of OS cells. LiCl experiment revealed that miR-374a promoted OS cells migration by regulating Wnt/ß-catenin signaling. In conclusion, miR-374a promotes OS cells migration by activating Wnt/ß-catenin signaling pathway via targeting WIF-1.

Endovascular treatment of a ruptured thoracic aortic pseudoaneurysm secondary to Pott disease during a spine surgery: A case report and a literature review.

RATIONALE: The coexistence of a tuberculous aortic pseudoaneurysm and Pott disease in patients with a history of tuberculosis (TB) is relatively rare, and the treatment strategies remain still controversial. PATIENT CONCERNS: A 57-year-old female patient with a history of primary pulmonary TB presented with symptoms of breathlessness, chest pain, weight loss, and fever. Magnetic resonance imaging (MRI) and computed tomography (CT) showed a thoracic aortic pseudoaneurysm secondary to Pott disease at T11/12 level. DIAGNOSES: Tuberculous pseudoaneurysm at the descending thoracic aorta associated with tuberculous vertebral osteomyelitis. INTERVENTIONS: We originally planned a combined surgery consisting of posterior spine stabilization, anterior excision of the infected field, and aortic reconstruction. When we surgically stabilized the posterior spine, unexpectedly, the pseudoaneurysm ruptured. Immediately, we terminated the surgery and appropriately placed an endovascular stent graft, which successfully rescued the patient. OUTCOMES: When the patient's conditions were stable, we anteriorly debrided all infected tissues and then performed a spinal fusion by grafting autologous iliac bone. After the debridement and spinal fusion, we arranged a 1-year anti-tuberculous chemotherapy for this patient and performed a 24-month follow-up. This patient had no signs of recurrent infection during the follow-up. LESSONS: For the patients with tuberculous aortic aneurysm(s) complicated with vertebral osteomyelitis, the endovascular repair of an aneurysm(s) should be considered a conventional therapy before the spine surgery, lowering the risk of aortic aneurysm rupture. Meanwhile, minimally invasive endovascular stent graft combined with anti-tuberculosis drugs may be considered one of the therapeutic regimens for the patients whose conditions are not suitable for open surgery, such as age, weakness, or severe organ failure.

Lipopolysaccharide-induced preconditioning protects against traumatic spinal cord injury by upregulating Nrf2 expression in rats.

AIMS: Lipopolysaccharide (LPS)-induced preconditioning protects neurons against traumatic spinal cord injury (TSCI) in rats. This study sought to test whether Nrf2, a transcription factor, mediated LPS-induced preconditioning. MAIN METHODS: The TSCI model was established using a standardized NYU impactor on adult female rats. Rats were pretreated with LPS (0.2mg/kg, IP; 72h before injury). Nrf2 was silenced by injecting a lentivirus encoding RNAi against Nrf2 into injured spinal cords. Neurologic function was assessed by Basso, Beattie and Bresnahan (BBB) scores 6h, 12h, 24h, 48h, 72h, 7d and 14d after TSCI. Neuronal apoptosis was measured by a TUNEL staining. Ultrastructure was observed using transmission electron microscope (TEM). The protein expression of HO-1, NQO1 and GCLC was examined using immunohistochemistry and immunoblotting. KEY FINDINGS: The injection of a lentivirus effectively transfected GFP into injured spinal cords. The expression of Nrf2 was significantly decreased in spinal cords receiving a lentivirus encoding RNAi against Nrf2. BBB scores showed that TSCI markedly impaired nervous function, which was markedly preserved by LPS pretreatment. Nrf2 knockdown significantly suppressed LPS pretreatment-induced protection of nervous function. TEM images and TUNEL staining showed an increase in apoptotic cells when Nrf2 was silenced. Moreover, immunohistochemistry and immunoblotting analysis exhibited that LPS pretreatment significantly upregulated the expression of anti-oxidative proteins including HO-1, NQO1 and GCLC, which was suppressed when Nrf2 expression was silenced in injured spinal cords. SIGNIFICANCE: LPS preconditioning effectively alleviates TSCI-induced impairment and preserves nervous function in a Nrf2-dependent manner.