canalostomy-as-surgical-approach-to-local-drug-delivery-into-inner

Canalostomy As a Surgical Approach to Local Drug Delivery into the Inner Ears of Adult and Neonatal Mice

Local delivery of therapeutic drugs into the inner ear is a promising therapy for inner ear diseases. Injection through semicircular canals (canalostomy) ...

morphological-functional-evaluation-ribbon-synapses-at-specific

Morphological and Functional Evaluation of Ribbon Synapses at Specific Frequency Regions of the Mouse Cochlea

Cochlear inner hair cells (IHCs) transmit acoustic signals to spiral ganglion neurons (SGNs) through ribbon synapses. Several experimental studies have ...

Capital Medical University

Urine metabolomics have been used to identify biomarkers for clinical diseases. However, inter-individual variations and effect factors need to be further evaluated. In our study, we explored the urine metabolome in a cohort of 203 health adults, 6 patients with benign bladder lesions, and 53 patients with bladder cancer (BCa) using liquid chromatography coupled with high resolution mass spectrometry. Inter-individual analysis of both healthy controls and BCa patients showed that the urine metabolome was relatively stable. Further analysis indicated that sex and age affect inter-individual variations in urine metabolome. Metabolic pathways such as tryptophan metabolism, the citrate cycle, and pantothenate and CoA biosynthesis were found to be related to sex and age. To eliminate age and sex interference, additional BCa urine metabolomic biomarkers were explored using age and sex-matched urine samples (Test group: 44 health adults vs. 33 patients with BCa). Metabolic profiling of urine could significantly differentiate the cases with cancer from the controls and high-grade from low-grade BCa. A metabolite panel consisting of trans-2-dodecenoylcarnitine, serinyl-valine, feruloyl-2-hydroxyputrescine, and 3-hydroxynonanoyl carnitine were discovered to have good predictive ability for BCa with an area under the curve (AUC) of 0.956 (cross validation: AUC = 0.924). A panel of indolylacryloylglycine, N -galacturonyl-L-lysine, and aspartyl-glutamate was used to establish a robust model for high- and low-grade BCa distinction with AUC of 0.937 (cross validation: AUC = 0.891). External sample (26 control vs. 20 BCa) validation verified the acceptable accuracy of these models for BCa detection. Our study showed that urinary metabolomics is a useful strategy for differential analysis and biomarker discovery.

Investigation of the urinary metabolic variations and the application in bladder cancer biomarker discovery.

We established a glioma biobank at Beijing Tiantan Hospital in November, 2010. Specialized residents have been trained to collect, store and manage the biobank in accordance with standard operating procedures.

Establishment and quality evaluation of a glioma biobank in Beijing Tiantan Hospital.

We intend to assess the effectiveness of a novel tinnitus treatment therapy, the Cochleural Alternating Acoustic Beam Therapy (CAABT) using the psychoacoustic measures, the questionnaires and rs-fMRI.

The Cochleural Alternating Acoustic Beam Therapy (CAABT): A pre-clinical trial.

Presbycusis has become a common sensory deficit in humans. Oxidative damage to mitochondrial DNA and mitochondrial dysfunction is strongly associated with the aging of the auditory system. A previous study established a mimetic rat model of aging using D-galactose (D-gal) and first reported that NADPH oxidase-dependent mitochondrial oxidative damage and apoptosis in the ventral cochlear nucleus (VCN) might contribute to D-gal-induced central presbycusis. In this study, we investigated the effects of apocynin, an NADPH oxidase inhibitor, on mitochondrial dysfunction and mitochondria-dependent apoptosis in the VCN of D-gal-induced aging model in rats. Our data showed that apocynin decreased NADPH oxidase activity, HO levels, mitochondrial DNA common deletion, and 8-hydroxy-2-deoxyguanosine (8-OHdG) expression and increased total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activity in the VCN of D-gal-induced aging model in rats. Moreover, apocynin also decreased the protein levels of phospho-p47 (p-p47), tumor necrosis factor alpha (TNFα), and uncoupling protein 2 (UCP2) in the VCN of D-gal-induced aging model in rats. Meanwhile, apocynin alleviated mitochondrial ultrastructure damage and enhanced ATP production and mitochondrial membrane potential (MMP) levels in the VCN of D-gal-induced aging model in rats. Furthermore, apocynin inhibited cytochrome c (Cyt c) translocation from mitochondria to the cytoplasm and suppressed caspase 3-dependent apoptosis in the VCN of D-gal-induced aging model in rats. Consequently, our findings suggest that neuronal survival promoted by an NADPH oxidase inhibitor is a potentially effective method to enhance the resistance of neurons to central presbycusis.

NADPH oxidase inhibitor apocynin decreases mitochondrial dysfunction and apoptosis in the ventral cochlear nucleus of D-galactose-induced aging model in rats.

Porphyromonas gingivalis is one of the most commonly detected pathogens in periodontal disease and root canal infections. Its viability and pathogenicity are greatly increased in plaque biofilms. Some caseinolytic proteases (Clp) reportedly regulate biofilm formation by various pathogenic bacteria, including P. gingivalis. However, the specific influence of ClpP and its mechanism of regulating biofilm formation by P. gingivalis remains unclear. Hence, in this study, a clpP deletion strain and complemented strain were constructed by homologous recombination, and an in vitro biofilm model was established. Biofilm architecture was observed by scanning electron microscopy. Bacterial cells within the biofilms were examined using confocal scanning laser microscopy. Crystal violet staining was used to determine the amount of formed biofilm. mRNA levels of related regulatory genes were assessed using real-time PCR. The clpP deletion and complemented strains of P. gingivalis were successfully constructed. The biofilm formation ability of the deletion strain was significantly reduced compared with that of the wild-type strain, while that of the complemented strain did not differ from that of the wild-type strain. The expression of fimA, mfa1, and luxS in the deletion strain was lower than in the wild-type and complemented strains at each timepoint. It can be concluded that ClpP increases the biofilm formation of P. gingivalis by regulating the expression levels of fimA, mfa1, and luxS.

The regulation of Porphyromonas gingivalis biofilm formation by ClpP.

Conductive hearing loss is a prevalent condition globally. It remains unclear whether conductive hearing loss that occurs during early development disrupts auditory peripheral systems. In this study, a mouse model of conductive auditory deprivation (CAD) was achieved using external auditory canal closure on postnatal day 12, which marks the onset of external ear canal opening. Short-term (2 weeks) and long-term (6 weeks) deprivations involving external ear canal closure were conducted. Mice were examined immediately, 4 weeks, and 8 weeks after deprivation. Short-term deprivation induced reversible auditory brainstem response (ABR) threshold and latencies of ABR wave I, whereas long-term deprivation caused irreversible ABR thresholds and latencies of ABR wave I. Complete recovery of ribbon synapses and latencies of ABR wave I was observed in the short-term group. In contrast, we observed irreversible ABR thresholds, latencies of ABR wave I, and quantity of ribbon synapses in the long-term deprivation group. Positive 8-hydroxy-2'-deoxyguanosine signals were noted in cochlear hair cells in the long-term group, suggesting that long-term auditory deprivation could disrupt auditory maturation via mitochondrial damage in cochlear hair cells. Conversely, no significant changes in cellular morphology were observed in cochlear hair cells and spiral ganglion cells in either short- or long-term groups. Collectively, our findings suggest that long-term conductive hearing deprivation during early stages of auditory development can cause significant and irreversible disruption that persists into adulthood.

ArticleTotal : 2	Year
Publication title Cited by 43	2018
Publication title Cited by 3	2019

Article	Year
Investigation of the urinary metabolic variations and the application in bladder cancer biomarker discovery. International journal of cancer\| PubMed ID: 29451296	2018
Establishment and quality evaluation of a glioma biobank in Beijing Tiantan Hospital. PeerJ\| PubMed ID: 29576945	2018
The Cochleural Alternating Acoustic Beam Therapy (CAABT): A pre-clinical trial. American journal of otolaryngology\| PubMed ID: 29655489	2018
NADPH oxidase inhibitor apocynin decreases mitochondrial dysfunction and apoptosis in the ventral cochlear nucleus of D-galactose-induced aging model in rats. Neurochemistry international\| PubMed ID: 30578839	2019
The regulation of Porphyromonas gingivalis biofilm formation by ClpP. Biochemical and biophysical research communications\| PubMed ID: 30579592	2019
Long-Term Conductive Auditory Deprivation During Early Development Causes Irreversible Hearing Impairment and Cochlear Synaptic Disruption. Neuroscience\| PubMed ID: 30742960	2019

Lu He

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