Preparation of vincristine loaded low density lipoprotein nanoparticles modified by T7 peptide and evaluation of therapeutic effect on glioma / 药学学报

The purpose of this study was to prepare T7 peptide modified vincristine loaded low density lipoprotein (T7-LDL-VCR) nanoparticles to penetrate through blood brain barrier for targeting the brain tumor cells. Firstly, the low density lipoprotein (LDL) nanoparticles were extracted and separated from human serum by density gradient centrifugation method, and then was loaded into the nanoparticle's lipid core by the dry film method, T7 peptide was covalent modified on the surface of the nanoparticles. T7-LDL-VCR was characterized by particle size, entrapment efficiency and peptide attachment efficiency. The fluorescent probe DiR was used to track the brain biodistribution of T7-LDL-VCR in mice bearing intracranial C6 glioma by means of in vivo imaging. The therapeutic effect of nanoparticles was observed with magnetic resonance imaging (MRI). Finally, relative tumor volume and survival curve were determined in mice. The results showed that the mean size of the prepared T7-LDL-VCR nanoparticle was about 30 nm, encapsulation efficiency was 30.1%, and peptide attachment efficiency was 63.88%. As expected, the prepared preparation has good brain targeting and good effect on the treatment of glioma in mice:the relative tumor volumes of T7-VCR-LDL, LDL-VCR and VCR were 30%, 51.50% and 79.25%, respectively; the median survival time (36 days), which was 2, 1.85 and 1.38 fold higher than that of physiological saline, free VCR and LDL-VCR, respectively. This study suggests that dual modified hposomes possessed a better ability penetrating the blood brain barrier to target the brain tumor with significant antitumor activities.

Efficacy of ultrasound-guided lauromacrogol sclerotherapy for benign thyroid cysts and factors affecting the therapeutic effect / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy of ultrasound-guided lauromacrogol sclerotherapy for benign thyroid cysts and analyze the factors affecting the efficacy.</p><p><b>METHODS</b>Ultrasound-guided lauromacrogol sclerotherapy was performed in 97 patients with a total of 99 benign thyroid cysts. The changes in cystic volume and other thyroid parameters were evaluated at 1, 3, 6, and 12 months after sclerotherapy. According to changes in the cystic volume, the efficacy of sclerotherapy was defined as therapeutic failure (with a volume reduction <50%), treatment success (volume reduction ≥50%) and cure (volume reduction ≥90%). The factors of affecting the efficacy of sclerotherapy was analyzed using COX regression.</p><p><b>RESULTS</b>The mean cystic volume at 1, 3, 6 and 12 months after sclerotherapy were reduced from the baseline volume of 12.08∓11.56 cmto 5.63∓8.51 cm, 5.96∓8.42 cm, 3.80∓5.50 cmand 2.85∓3.98 cm, respectively, with an average cystic volume reduction rate of (70.02∓33.72)%. Therapeutic success was achieved 82 of the 99 cysts (82.83%) and cure was achieved 63cysts (63.64%) at 12 months after the procedure. A second sclerotherapy was performed for 13 cysts which did not show a volume reduction at 1-3 months after the initial procedure. A disease course of over 12 months was an independent risk factor for a second sclerotherapy (23.7% [9/38] vs 6.6% [4/61], OR=4.473 [1.238-16.169], P=0.022). The efficacy of sclerotherapy was related to cystic cavity separation, cystic fluid viscosity, cystic/solid ratio and cystic wall thickness. COX regression analysis revealed that cystic cavity separation (HR=2.25, 95%CI: 1.19-4.25) and cystic fluid viscosity (HR=2.02, 95%CI: 1.19-3.43) were the major factors affecting the treatment efficacy.</p><p><b>CONCLUSION</b>Ultrasound-guided lauromacrogol sclerotherapy is effective and safe for treatment of benign thyroid cysts, and the maximal treatment effect can be achieved at 6 months after sclerotherapy and in cases of uncomplicated cysts with non-viscous cystic fluid, no solid cystic cavity separation and a disease course of less than 12 months.</p>

A preliminary study of long-term mitochondrial dysfunction in rat brain caused by lipopolysaccharide-induced sepsis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To preliminarily investigate the long-term structural and functional injuries of mitochondria in rat brain caused by sepsis.</p><p><b>METHODS</b>Wistar rats were randomly assigned into sepsis and control groups. A rat model of sepsis was prepared by an intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS) of gram-negative bacteria, and the survival assay was performed. Eight rats in the sepsis group were sacrificed at 12, 24, 48, or 72 hours after LPS injection, while rats in the control group were sacrificed after an intraperitoneal injection of an equal volume of normal saline. Mitochondria were extracted from rat brain tissue. Mitochondrial membrane potential (MMP) and mitochondrial swelling level were determined by flow cytometry, and the activities of electron transport chain complexes (I-V) were measured using enzyme assay kits. Hematoxylin-eosin (HE) staining and electron microscopy were used to observe morphological changes in brain tissue and mitochondria.</p><p><b>RESULTS</b>The sepsis group had a significantly lower survival rate than the control group (P<0.01). The MMP and activities of electron transport chain complexes (I-V) in the sepsis group, which were significantly lower than those in the control group (P<0.05), were reduced to the lowest levels at 48 hours and partially recovered at 72 hours. The mitochondrial swelling level in the sepsis group, which was significantly higher than that in the control group (P<0.05), increased to the peak level at 48 hours and partially recovered at 72 hours. Hematoxylin and Eosin staining revealed substantial damages in the structure of brain tissue, and electron microscopy showed mitochondrial swelling, and vacuolization in a few mitochondria.</p><p><b>CONCLUSIONS</b>In the rat model of LPS-induced sepsis, both structural and functional injuries are found in cerebral mitochondria, and achieve the peak levels probably at around 48 hours.</p>

Effect of UCP2-siRNA on inflammatory response of cardiomyocytes induced by septic serum / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effect of uncoupling protein 2 (UCP2)-siRNA on the inflammatory response of rat cardiomyocytes (H9C2) induced by septic serum and to investigate the possible role of UCP2 in the development of septic cardiomyopathy.</p><p><b>METHODS</b>Serum samples were separately collected from normal rats and septic rats. Cultured rat cardiac cells (H9C2) were randomly divided into blank control, normal serum, 10% septic serum, UCP2-siRNA+10% septic serum and negative siRNA+10% septic serum groups. Stimulation with 10% septic serum was performed for 12 hours in relevant groups. The mRNA expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) was measured by RT-PCR. The expression of phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and nuclear factor-kappa B (NF-κB) was measured by Western blot.</p><p><b>RESULTS</b>The expression levels of p-p38 and NF-κB in the UCP2-siRNA+10% septic serum group were significantly higher than in the 10% septic serum group (P<0.05). The UCP2-siRNA+10% septic serum group had a significantly higher TNF-α mRNA expression than the 10% septic serum group (P<0.01), but IL-1β mRNA expression showed no significant difference between the two groups.</p><p><b>CONCLUSIONS</b>UCP2 plays a regulatory role in the activation of p38 MAPK and NF-κB and the expression of downstream inflammatory mediators in H9C2 cells stimulated with septic serum.</p>

Research progress of microRNA in mitochondrial dysfunction of children with sepsis / 中华实用儿科临床杂志

Sepsis is the systemic inflammatory respond syndrome and autoimmunity injury caused by pathogenic microorganism or any other immunogenicity.Mitochondria,an important organelle,which has an essential role in cellular growth,metabolism,occurrence and development of disease by generating ATP following the oxidative phosphorylation from glycolysis.There had been some progresses on the research of sepsis in several decades.A number of studies had shown that the degree of mitochondrial dysfunction was related to the eventual outcome of sepsis.microRNA are endogenous small noncoding RNAs that post-transcriptionally regulate gene and bio-protein expression,and then adjust mitochondrial oxidative stress,has important influence on the process of sepsis and prognosis.Here,a current review of how microRNA impinge on mitochondrial dysfunction in sepsis was performed.

The expression of neuronal nitric oxide synthase in caudal medulla of two-kidney one clip Goldblatt hypertension rat / 生理学报

Experiments were performed in male Sprague-Dawley rats (150-200 g). A silver clip (0.2 mm internal diameter) was placed on the left renal artery of rats. After operation the rats were divided into 4 groups sham group, 2K1C (two-kidney one clip) group, 2K1C+Arg (2K1C and L-Arg 150 mg/kg x d(-1) by drinking) group, and 2K1C+NAME (2K1C and L-NAME 10 mg/kg x d(-1) i.p.) group. The animals were studied at two time points (4 and 7 weeks after operation) corresponding to phases I and II of Goldblatt hypertension. The animals were deeply anesthetized with pentobarbital and perfused by the cardiac route with saline (100 ml) and freshly prepared 4% paraformaldehyde in phosphate buffer (300 ml). The caudal medulla was removed, then placed in 25% sucrose in PB for 12 h in a 4 degrees C fridge. The 40 microm coronal slices of brainstems were cut with cryostat, collected in PBS for nNOS study by immunohistochemistry. The results showed that (1) only a few neuronal nitric oxide synthase (nNOS) positive neurones were found in caudal medulla, including the depressor area of the ventral surface of medulla oblongata (VSMd) and the caudal pressor area (CPA) of the sham operated animals. The number of nNOS positive neurons in caudal medulla was significantly increased in 2K1C Goldblatt hypertension rats at 4 and 7 weeks. (2) The number of nNOS positive neurons in VSMd and CPA were 2K1C+Arg > 2K1C >2K1C +NAME > sham. (3) L-Arg enhanced the expression of nNOS whereas L-NAME inhibited the expression of nNOS in caudal medulla. (4) The character of nNOS expression was similar in Goldblatt hypertension rats at 4 weeks with that of the rats at 7 weeks.