The SIRT1 activator SRT2104 promotes BMP9-induced osteogenic and angiogenic differentiation in mesenchymal stem cells.

Bone defects resulting from trauma, bone tumors, infections and skeletal abnormalities are a common osteoporotic condition with respect to clinical treatment. Of the known bone morphogenetic proteins (BMPs), BMP9 has the strongest osteogenic differentiation potential, which could be beneficial in the construction of tissue-engineered bone. Silent mating type information regulator 2 homolog-1 (SIRT1) is a highly conserved nicotinamide adenine dinucleotide-dependent deacetylase that deacetylates and modulates histone or non-histone substrates. However, the role of SIRT1 in BMP9-induced osteogenic differentiation of stem cells has not been studied. Furthermore, it is unclear whether SIRT1 interacts with the BMP/Smad and BMP/MAPK pathways in stem cells. We found that SIRT1 expression decreased gradually in a time-dependent manner during BMP9-induced osteogenic differentiation of MSCs. Interactions between SIRT1 and Smad7 promoted degradation of Smad7 and increased Smad1/5/8 phosphorylation. SRT2104, an activator of SIRT, enhanced the expression of osteogenic- and angiogenic-related proteins in BMP9-induced MSCs. In addition, we found that activation of the BMP/MAPK pathway led to osteogenic and angiogenic differentiation of MSCs. Our study demonstrated that SIRT1 expression decreased during BMP9-induced differentiation. The SIRT1 activator SRT2104 promoted BMP9-induced osteogenic and angiogenic differentiation of MSCs through the BMP/Smad and BMP/MAPK signaling pathways.

Pathological study of otitis media with effusion after treatment with intranasal pulmonary surfactant.

OBJECTIVES/HYPOTHESIS: To evaluate the histopathological effect of intranasal pulmonary surfactant (PS) on the eustachian tube (ET) in guinea pigs with otitis media with effusion (OME). STUDY DESIGN: Randomized control trial. METHODS: Nonviable heat-killed Hemophilus influenzae solution was injected into the tympanum of guinea pigs by a trans-eardrum approach to establish OME. Guinea pigs were divided into four groups: normal controls (group A), untreated OME (group B), saline-treated (group C), PS-treated (group D). The response threshold of the guinea pigs was measured by auditory brainstem response (ABR), and data were analyzed by one-way analysis of variance. The histopathological changes in the osseous, cartilaginous, and muscular portions of the ET were observed systematically by light microscopy. RESULTS: The ABR threshold in OME group B was raised significantly compared with normal group (A). The response in saline-treated group C was not statistically significantly different compared with OME group B. Seven days after intranasal dripping of pulmonary surfactant in PS-treated group D, the response threshold showed at statistically significant decrease compared with OME B and saline-treated C groups. In OME group B and saline-treated group C, mucosa showed swelling with goblet cell hyperplasia, and cilia were irregularly arranged. In PS-treated group D, there was slight mucosal swelling with fewer goblet cells, and cilia were regularly arranged, similar to the normal group A. CONCLUSIONS: The findings of the study indicate that intranasal pulmonary surfactant drops have protective and hyposecretory effects on the mucociliary system of the ET in guinea pigs suffering from OME.

[Surgical treatment of trigeminal neuralgia with microvascular decompression sensory root of trigeminal nerve combing].

OBJECTIVE: To evaluate the short-term and long-term curative effect of microvascular decompression sensory root of trigeminal nerve combing (MVD + SRTNC) by post-sigmoid approach as well as the complications in these operations. METHODS: The data from 138 idiopathic trigeminal neuralgia (TN) patients treated with MVD + STRNC that followed up 33 months to 58 months was analyzed. RESULTS: Immediate relief from pain occurred in 136 patients (98.6%). On Kaplan-Meier analysis, cumulative proportion effectiveness at the end of 25 months decreased to 91.4%, and 85.8% from 49 months to 58 months. There were cases of 63.83% and 19.15% with slight and midrange hypoesthesia after surgery but majority recovered at the end of 3-58 months (P < 0.01). No serious hypoesthesia occurred. The complications including leakage of cerebrospinal fluid, herpes and headache caused by high intracranial pressure, were observed in 4 cases (2.90%), 36 cases (26.09%) and 3 cases (2.17%), respectively. Two cases (1.43%) died of cerebral hemorrhage. CONCLUSIONS: The proposed surgical strategy of standard MVD plus sensory root of trigeminal nerve combing was a good strategy option for TN, but It was important for surgeons to think highly of the risks of the surgery.

[Histo-morphological changes of eustachian tube of guinea pigs with effusion after being treated by pulmonary surfactant].

OBJECTIVE: To study the effect of pulmonary surfactant on otitis media with effusion in guinea pigs to find a new way to manage otitis media with effusion. METHODS: Nonviable heat-killed pneumococci (HKP) solution was inoculated into the middle ear cavity in guinea pigs via a transeardrum approach to set up a model of otitis media with effusion in guinea pigs. Seven days after being injected with pulmonary surfactant (PS) by transeardrum approach, ABR threshold and histomorphological changes of eustachian tube mucosa of guinea pigs were examined by light microscopy and scanning microscopy. RESULTS: Five days following inoculation of HKB serous effusion were present in the middle ear cavity of guinea pigs, but disappearance of light cone. Response (mean +/- s) threshold raised from (14.0 +/- 3.1) dB to (45.0 +/- 5.7) dB. The eustachian tube mucosa was thickened and lined eosin-stained structureless matter over mucosa, while cilia of eustachian tube mucosa irregularly arranged. Seven days after being treated by PS, serous effusion of tympanum was reduced or disappeared, and response threshold decreased from (45.0 +/- 5.7) dB to (23.5 +/- 6.3) dB. There was significantly difference between them (P < 0.001). Eustachian tube mucosa was thinned, Cilia of eustachian tube mucosa regularly arranged to the nasopharynx. CONCLUSION: Pulmonary surfactant plays a important role in otitis media with effusion of guinea pigs.