Loss of Fascin2 increases susceptibility to cisplatin-induced hearing impairment and cochlear cell apoptosis in mice.

Objectives: Deletion of gene in mice has been linked to progressive hearing loss and degeneration of cochlear cells. Cisplatin, an antitumor drug, can cause various side effects, including ototoxicity. The aim of this study was to investigate the effects of on cisplatin-induced hearing impairment in mice and to explore the possible mechanism.

Inhibition of the ILK-AKT pathway by upregulation of PARVB contributes to the cochlear cell death in Fascin2 gene knockout mice.

The Fscn2 (Fascin2) gene encodes an actin cross-linking protein that is involved in the formation of hair cell stereocilia and retina structure. Mutations in Fscn2 gene have been linked to hearing impairment and retinal degeneration in humans and mice. To understand the function of the Fscn2 gene, we generated the Fscn2 knockout mice, which showed progressive loss of hearing and hair cells.

Construction and evaluation of hourly average indoor PM concentration prediction models based on multiple types of places.

Background: People usually spend most of their time indoors, so indoor fine particulate matter (PM) concentrations are crucial for refining individual PM exposure evaluation. The development of indoor PM concentration prediction models is essential for the health risk assessment of PM in epidemiological studies involving large populations.

Methods: In this study, based on the monitoring data of multiple types of places, the classical multiple linear regression (MLR) method and random forest regression (RFR) algorithm of machine learning were used to develop hourly average indoor PM concentration prediction models.

Effect of downregulated citrate synthase on oxidative phosphorylation signaling pathway in HEI-OC1 cells.

Background: Citrate Synthase (Cs) gene mutation (locus ahL4) has been found to play an important role in progressive hearing loss of A/J mice. HEI-OC1 cells have been widely used as an in vitro system to study cellular and molecular mechanisms related to hearing lose. We previously reported the increased apoptosis and the accumulation of reactive oxygen species in shRNACs-1429 cells, a Cs low-expressed cell model from HEI-OCI.

Thyroid-disrupting effects caused by exposure to alternative flame retardants from groundwater contamination in rural central China.

Accumulating evidence reveals that exposure to alternative flame retardants (AFRs) results in defective thyroid functions. AFRs are detectable in various environmental media in developed cities in China. However, few studies have reported the contamination levels of AFR in groundwater in rural areas, indicating an urgent need to investigate exposure of AFRs and perform health risk assessment for populations that use groundwater as the main source of drinking water.

H55 N variation in citrate synthase leads to decrement in the enzyme activity and transport rate to mitochondria in HEI-OC1 cells.

A/J mouse is a typical animal model of age-related deafness. Previous studies have shown that the mice suffer from progressive hearing loss and degeneration of cochlear cells, and a variation of H55 N in citrate synthase (CS) causes about 40% the hearing loss. CS is a key enzyme in the tricarboxylic acid cycle, which is transported from cytoplasm to mitochondria after synthesis, sorted by the mitochondrial targeting sequence (MTS).

A newly identified mutation (c.2029 C > T) in SLC26A4 gene is associated with enlarged vestibular aqueducts in a Chinese family.

Background: The enlarged vestibular aqueduct (EVA), associated with mutations in the SLC26A4 gene, characterized by non-syndromic hearing loss, is an autosomal recessive disorder. Here, we intended to investigate genetic causes of hearing loss in a Han Chinese man.

Method: First, whole-exome sequencing was performed to identify the gene mutations responsible for hearing loss in the proband.

Role of TGF-β1-mediated epithelial-mesenchymal transition in the pathogenesis of tympanosclerosis.

The present study aimed to explore the role of TGF-β1-mediated epithelial-mesenchymal transition (EMT) in the pathogenesis of tympanosclerosis. Sprague Dawley rats were injected with inactivated suspension to establish a rat model of tympanosclerosis. The rats were sacrificed 8 weeks after the model was established.

A novel mutation in TRIOBP gene leading to congenital deafness in a Chinese family.

Background: The autosomal recessive non-syndromic deafness DFNB28 is characterized by prelingual sensorineural hearing loss. The disease is related with mutations in TRIOBP (Trio- and F-actin-Binding Protein) gene, which has three transcripts referred to as TRIOBP-5, TRIOBP - 4 and TRIOBP-1. Among them, TRIOBP-5/- 4 are expressed in the inner ears and crucial for maintaining the structure and function of the stereocilia.

ALA protects against ERS-mediated apoptosis in a cochlear cell model with low citrate synthase expression.

A/J mouse is a model of age-related hearing loss (AHL). Mutation in the citrate synthase (Cs) gene of the mouse plays an important role in the hearing loss and degeneration of cochlear cells. To investigate the pathogenesis of cochlear cell damage in A/J mice resulted from Cs mutation, we downregulated the expression level of CS in HEI-OC1, a cell line of mouse cochlea, by shRNA.

Otoprotective Effects of α-lipoic Acid on A/J Mice With Age-related Hearing Loss.

Objective: A/J mice are a mouse model of age-related hearing loss (AHL) with progressive degeneration of outer hair cells (OHCs), spiral ganglion neurons (SGNs), and stria vascularis. This study was carried out to observe the otoprotective effects of α-lipoic acid on A/J mice.

Methods: A/J mouse pups at postnatal day 7 were randomly distributed into the untreated group, the dimethyl sulfoxide (DMSO) group, and the α-lipoic acid + DMSO group.

Precise exposure assessment revealed the cancer risk and disease burden caused by trihalomethanes and haloacetic acids in Shanghai indoor swimming pool water.

Swimming pool disinfection byproducts (DBPs) are becoming increasingly common worldwide. Precise exposure and health risk assessment for DBPs in swimming pool water with optimized parameters for local and specific population is more urgently needed. This study aimed to determine the levels of trihalomethanes (THMs) and haloacetic acids (HAAs) in 16 public indoor swimming pools in Shanghai, China.

Solid-phase extraction of seventeen alternative flame retardants in water as determined by ultra-high-performance liquid chromatography-tandem mass spectrometry.

Flame retardants have evoked public concerns owing to their extensive usage in consumer products and potential adverse effects on human health. In this study, a rapid and sensitive solid-phase extraction-ultra-high-performance liquid chromatography-tandem mass spectrometry (SPE-UPLC-MS/MS) method was developed to determine hexabromocyclododecane (HBCD), tetrabromobisphenol-A (TBBPA), six bromophenols (BPs), and nine organophosphate flame retardants (OPFRs) in water. Because of the differences in elution conditions and ionization modes for group 1 (HBCD, TBBPA, and the BPs) and group 2 (OPFRs), we had to run them twice under the different conditions to analyse group 1 and group 2 using UPLC-MS/MS.

Characterization of the early pathology of cochlear stereocilia in four inbred mouse strains with progressive hearing loss.

Objective: Inbred strains of mice offer promising models for understanding the genetic basis of age-related hearing loss (AHL). NOD/LtJ, A/J, DBA/2J and C57BL/6J mice are classical models of age-related hearing loss and exhibit early onset of pathology of AHL. This study was carried out to characterize the early pathology of cochlear stereocilia in the four mouse strains with age-related hearing loss.

Null Mutation of the Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice.

Fascin2 (FSCN2) is an actin cross-linking protein that is mainly localized in retinas and in the stereocilia of hair cells. Earlier studies showed that a deletion mutation in human () gene could cause autosomal dominant retinitis pigmentosa. Recent studies have indicated that a missense mutation in mouse gene (R109H) can contribute to the early onset of hearing loss in DBA/2J mice.

Combination of stromal vascular fraction and gene therapy improves long-term therapeutic efficacy for diabetes-induced erectile dysfunction.

Men with diabetic erectile dysfunction (ED) respond poorly to the currently available oral phosphodiesterase-5 inhibitors. Therefore, functional therapies for diabetic ED are needed. Stromal vascular fraction (SVF) and the adenovirus-mediated cartilage oligomeric matrix angiopoietin-1 (Ad-COMP-Ang1) gene are known to play critical roles in penile erection.

Recombinant protein of the first two ectodomains of cadherin 23 from erl mice shows impairment in Ca-dependent proteolysis protection.

The erl mouse is a mouse model of nonsyndromic autosomal recessive deafness (DFNB12) on the C57BL/6J background. This project was carried out to express the first two ectodomains of cadherin 23 (CDH23 EC1+2) of erl mice in Escherichia coli and identify the Ca-binding ability of the recombinant protein. DNA sequences of CDH23 EC1+2 from wild type and erl mice were synthesized and cloned into pBV220 plasmids.

Ribonucleic acid interference knockdown of IL-6 enhances the efficacy of cisplatin in laryngeal cancer stem cells by down-regulating the IL-6/STAT3/HIF1 pathway.

Background: Cisplatin has been used in the treatment of many cancers, including laryngeal cancer; however, its efficacy can be reduced due to the development of drug resistance. This study aimed to investigate whether interleukin-6 (IL-6) knockdown may enhance the efficacy of cisplatin in laryngeal cancer stem cells (CSC) and the potential involvement of the signal transducer and activator of transcription 3 (STAT3) and hypoxia-inducible factor 1 (HIF1) in this effect.

Methods: The ALDH+ and CD44+ CSC in Hep2 human laryngeal squamous cancer cells were identified by the fluorescence-activated cell sorting technique.

Hearing Improvement in A/J Mice via the Mouse Nerve Growth Factor.

Objectives: To investigate the otoprotective effects of mouse nerve growth factor (mNGF) in A/J mice.

Methods: The mice at postnatal day 7 (P7) were randomly separated into a mNGF treated group (mNGF group) and a distilled water (for injection) treated group (control group). The mNGF dissolved in distilled water or distilled water alone was given to the mice once every other day from P7 by intramuscular injection in the hips.

Reduced expression of citrate synthase leads to excessive superoxide formation and cell apoptosis.

A/J mice are a mouse model of age-related hearing loss. It has been demonstrated that a mutation in gene of citrate synthase (CS) contributes to the early onset of hearing loss occurring at about one month of age. To understand the effects of a decreased CS activity that results from the mutation in Cs gene on hearing loss in A/J mice, human kidney cell line (293T) was transiently transfected with short hairpin RNA for Cs (shRNA-Cs) to reduce expression of CS.

Plexin-B1 indirectly affects glioma invasiveness and angiogenesis by regulating the RhoA/αvβ3 signaling pathway and SRPK1.

Gliomas are one of the most common primary brain tumors in adults. They display aggressive invasiveness, are highly vascular, and have a poor prognosis. Plexin-B1 is involved in numerous cellular processes, especially cellular migration and angiogenesis.

Anti-apoptotic treatment in mouse models of age-related hearing loss.

Age-related hearing loss (AHL), or presbycusis, is the most common neurodegenerative disorder and top communication deficit of the aged population. Genetic predisposition is one of the major factors in the development of AHL. Generally, AHL is associated with an age-dependent loss of sensory hair cells, spiral ganglion neurons and stria vascularis cells in the inner ear.

Attenuation of hearing loss in DBA/2J mice by anti-apoptotic treatment.

DBA/2J mice are characterized by early onset hearing loss at about 3-4 weeks of age. Mutations in cadherin 23 (Cdh23) and fascin-2 (Fscn2) are responsible for the phenotypes, but the underlying mechanism is unknown. In the present study, DBA/2J mice displayed progressive hair cell loss and degeneration of spiral ganglion neurons (SGNs) after 2 weeks of age; however, the mRNA level of Caspase-3 in the inner ears was much higher at 2 weeks of age than that at 4 or 8 weeks of age.

The influence of SRPK1 on glioma apoptosis, metastasis, and angiogenesis through the PI3K/Akt signaling pathway under normoxia.

Gliomas, the most common primary brain tumors, have low survival rates and poorly defined molecular mechanisms to target for treatment. Serine/arginine SR protein kinases 1 (SRPK1) can highly and specifically phosphorylate the SR protein found in many tumors, which can influence cell proliferation and angiogenesis. However, the roles and regulatory mechanisms of SRPK1 in gliomas are not understood.

Caspase-mediated apoptosis in the cochleae contributes to the early onset of hearing loss in A/J mice.

A/J and C57BL/6 J (B6) mice share a mutation in Cdh23 (ahl allele) and are characterized by age-related hearing loss. However, hearing loss occurs much earlier in A/J mice at about four weeks of age. Recent study has revealed that a mutation in citrate synthase (Cs) is one of the main contributors, but the mechanism is largely unknown.