MicroRNAs (miRNAs) may be important mediators of the profound molecular and cellular changes that occur after traumatic brain injury (TBI). However, the changes and possible roles of miRNAs induced by voluntary exercise prior to TBI are still not known. In this report, the microarray method was used to demonstrate alterations in miRNA expression levels in the cerebral cortex of TBI mice that were pretrained on a running wheel (RW). Voluntary RW exercise prior to TBI: i) significantly decreased the mortality rate and improved the recovery of the righting reflex in TBI mice, and ii) differentially changed the levels of several miRNAs, upregulating some and downregulating others. Furthermore, we revealed global upregulation of miR-21, miR-92a, and miR-874 and downregulation of miR-138, let-7c, and miR-124 expression among the sham-non-runner, TBI-non-runner, and TBI-runner groups. Quantitative reverse transcription polymerase chain reaction data (RT-qPCR) indicated good consistency with the microarray results. Our microarray-based analysis of miRNA expression in mice cerebral cortex after TBI revealed that some miRNAs such as miR-21, miR-92a, miR-874, miR-138, let-7c, and miR-124 could be involved in the prevention and protection afforded by voluntary exercise in a TBI model.

The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells. The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT. The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondria-related pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells. The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases.

Searching for effective Smad3 gene-based gene therapies for hepatic fibrosis, we constructed siRNA expression plasmids targeting the rat Smad3 gene and then delivered these plasmids into hepatic stellate cells (HSCs). The effect of siRNAs on the mRNA levels of Smad2, Smad3, Smad4, and collagens I-α1, III-α1 and IV-α1 (Colα1, Col3α1, Col4α1, respectively) was determined by RT-PCR. Eighty adult male Sprague-Dawley rats were randomly divided into three groups. Twice a week for 8 weeks, the untreated hepatic fibrosis model (N = 30) and the treated group (N = 20) were injected subcutaneously with 40% (v/v) carbon tetrachloride (CCl4)-olive oil (3 mL/kg), and the normal control group (N = 30) was injected with olive oil (3 mL/kg). In the 4th week, the treated rats were injected subcutaneously with liposome-encapsulated plasmids (150 µg/kg) into the right liver lobe under general anesthesia once every 2 weeks, and the untreated rats were injected with the same volume of buffer. At the end of the 6th and 8th weeks, liver tissue and sera were collected. Pathological changes were assessed by a semi-quantitative scoring system (SSS), and a radioimmunoassay was used to establish a serum liver fibrosis index (type III procollagen, type IV collagen, laminin, and hyaluronic acid). The mRNA expression levels of the above cited genes were reduced in the HSCs transfected with the siRNA expression plasmids. Moreover, in the treated group, fibrosis evaluated by the SSS was significantly reduced (P < 0.05) and the serum indices were greatly improved (P < 0.01). These results suggest that Smad3 siRNA expression plasmids have an anti-fibrotic effect.

OBJECTIVE: To test the efficacy of locally produced Vi vaccine over a time period of longer than one year. METHODS: A double-blinded, randomized field trial was performed in Guangxi Zhuang Autonomous Region in south-western China, using 30 mg doses of locally produced Vi. Enrolled subjects were 3-50 years of age, although the majority (92%) were school-aged children, who have the highest rate of typhoid fever in this setting. A total of 131 271 people were systematically allocated a single dose of 30 mg of Vi polysaccharide or saline placebo. The study population was followed for 19 months, with passive surveillance conducted in the Ministry of Health and the Regional Health and Anti-epidemic Centre (HAEC). Clinically suspected cases of typhoid fever were confirmed by blood culture, or by serological reaction with O-antigen (Widal tests). FINDINGS: After 19 months, there were 23 culture-confirmed cases of typhoid fever in the placebo group versus 7 cases in the Vi group (Protective efficacy (PE) = 69%; 95% CI = 28%, 87%). Most of the isolates were from school-aged children: 22 cases in the placebo group versus 6 in the Vi group (PE = 72%; 95% CI = 32%, 82%). No serious post-injection reactions were observed. The locally produced Vi polysaccharide vaccine showed levels of protective efficacy similar to those for Vi vaccine produced in industrial countries. CONCLUSION: The slightly higher dose of vaccine did not seem to alter efficacy significantly in China.

OBJETIVO: Determinar la eficacia de la vacuna de Vi producida localmente a lo largo de un periodo superior a un año. MÉTODOS: Se llevó a cabo un ensayo sobre el terreno aleatorizado y en doble ciego en la región autónoma (provincia) de Guangxi Zhuang, en el suroeste de China, usando dosis de 30 mg de la vacuna Vi producida localmente. El intervalo de edades de las personas participantes era de 3-50 años, si bien la mayoría de ellas (92%) eran niños en edad escolar, los más afectados por la fiebre tifoidea en ese lugar. Se asignó de forma sistemática a un total de 131 271 personas para que recibieran ya fuera una dosis única de 30 mg de polisacárido Vi o bien un placebo constituido por suero fisiológico. La población estudiada fue objeto de seguimiento durante 19 meses, y la vigilancia pasiva corrió a cargo del Ministerio de Salud y del Centro Regional de Salud y Lucha contra las Epidemias (HAEC). Los casos con manifestaciones clínicas sugestivas de fiebre tifoidea fueron confirmados mediante cultivo sanguíneo o mediante la reacción serológica con el antígeno O (pruebas de Widal). RESULTADOS: Al cabo de 19 meses se habían confirmado mediante cultivo 23 casos de fiebre tifoidea en el grupo placebo, frente a 7 casos en el grupo tratado con la vacuna Vi (eficacia protectora (EP) = 69%; IC95% = 28-87%). La mayoría de los aislados correspondían a niños en edad escolar: 22 casos en el grupo placebo, frente a 6 en el grupo tratado con Vi (EP = 72%; IC95% = 32-82%). No se observó ninguna reacción grave postinyección. La vacuna basada en el polisacárido Vi producida localmente demostró tener una eficacia protectora similar a la de la vacuna Vi producida en los países industrializados. CONCLUSIÓN: El ligero aumento de la dosis de vacuna no parece haber influido de forma significativa en su eficacia en China.

OBJECTIF:Tester l’efficacité du vaccin antityphoïdique polyosidique Vi de production locale sur une période de plus d’un an. MÉTHODS: Un essai de terrain randomisé en double aveugle a été réalisé dans la région autonome (province) de Guanxi Zhuang dans le sud-ouest de la Chine, au moyen de doses de 30 mg de polyoside Vi de production locale. Les sujets recrutés dans l’étude étaient âgés de 3 à 50 ans, mais étaient pour la plupart (92 %) des enfants d’âge scolaire, groupe qui présente le taux le plus élevé de fièvre typhoïde dans cette région. Au total, 131 271 personnes ont reçu systématiquement une dose unique de 30 mg de polyoside Vi ou un placebo (soluté physiologique). La population d’étude a été suivie pendant 19 mois dans le cadre d’une surveillance passive exercée par le Ministère de la Santé et le Centre régional de la santé et de la lutte contre les épidémies (HAEC). Les suspicions cliniques de fièvre typhoïde ont été confirmées par hémoculture ou par réaction sérologique en présence d’antigène O (test de Widal). RÉSULTATS: Au bout de 19 mois, on a dénombré 23 cas de fièvre typhoïde confirmés par culture dans le groupe placebo contre 7 cas dans le groupe Vi (efficacité protectrice (EP) = 69% ; intervalle de confiance à 95% (IC 95 %) : 28-87 %). La plupart des isolements ont été réalisés chez les enfants d’âge scolaire, avec 22 cas dans le groupe placebo contre 6 cas dans le groupe Vi (EP = 72%; IC 95%: 32-82 %). Aucune réaction grave n’a été observée après l’injection. Le vaccin polyosidique Vi de production locale a montré des taux d’efficacité protectrice similaires à ceux des vaccins produits dans les pays industrialisés. CONCLUSION: La dose légèrement plus forte de vaccin n’a pas semblé modifier l’efficacité de fac¸on significative en Chine.