Regulation of PPARγ/CPT-1 expression ameliorates cochlear hair cell injury by regulating cellular lipid metabolism and oxidative stress.

This study aimed to investigate the protective effects of PPARγ/CPT-1 regulation on cisplatin-induced cochlear hair cell injury. The viability, apoptosis and mitochondrial membrane potential of cisplatin-induced HEI-OC1 cells were determined by CCK-8 assay, TUNEL and JC-1 staining, respectively. The oxidative stress and lipid metabolism were detected by the assay kits of MDA, ROS, SOD, CAT, TG and FFA. The transfection efficiency of overexpression (OV)-PPARG and OV-CPT1A was examined by RT-qPCR and the expressions of apoptosis- and lipid metabolism-related proteins were detected by western blot. As a result, cisplatin with varying concentrations (5, 10, 30 µM) suppressed the viability, promoted the apoptosis and hindered the mitochondrial function of HEI-OC1 cells, accompanied with up-regulated expressions of Bax and cleaved caspase-3 and down-regulated expression of Bcl-2. The oxidative stress was aggravated and lipid metabolism was inhibited by cisplatin (5, 10, 30 µM) induction, evidenced by the increased levels of MDA, ROS, TG, FFA and the decreased levels of SOD and CAT. Overexpression of PPARG or CPT1A could improve the viability, mitochondrial function, lipid metabolism and suppress the oxidative stress and apoptosis of cisplatin-induced HEI-OC1 cells. In conclusion, up-regulation of PPARG or CPT1A ameliorated cochlear hair cell injury by improving cellular lipid metabolism and inhibiting oxidative stress.

Associations between expression levels of nine core nucleotide excision repair genes in lymphocytes and risk of head and neck squamous cell carcinomas in a Chinese population.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are one of the most common cancers in the world, and nucleotide excision repair (NER) is involved in HNSCCs susceptibility. We investigated whether mRNA expression levels of nine core NER genes were associated with risk of HNSCCs in a Chinese population. METHODS: In this study of 251 HNSCC patients and 232 healthy controls, we quantified NER gene mRNA expression levels in cultured peripheral lymphocytes using a quantitative real-time PCR. RESULTS: Compared with the controls, HNSCC patients had statistically significantly lower expression levels of XPA and XPB (P = 0.029 and 0.001, respectively). After dividing the subjects by the controls' median values of expression levels, we found a dose-dependent association between an increased risk of HNSCCs and low expression levels of XPB (adjusted OR 1.56 and 95% CI 1.07-2.28; Ptrend = 0.001). We also identified a significant multiplicative interaction between smoking status as well as alcohol status and mRNA expression levels of XPB (P = 0.014 and 0.042, respectively). Finally, after integrating demographic variables, we found the addition of smoking status and XPB expression levels to the model significantly improved the sensitivity of the expanded model on HNSCC risk. CONCLUSION: Reduced mRNA expression levels of XPB were associated with an increased risk of HNSCCs in a Chinese population.

[Vestibular Dysfunction in Patients with Sudden Sensorineural Hearing Loss without Vertigo].

OBJECTIVE: To observe the vestibular dysfunction in sudden sensorineural hearing loss (SSHL) patients without vertigo. METHODS: Forty-two cases of unilateral SSHL without vertigo were enrolled in the study from May 2012 to May 2014. All patients underwent air conducted sound elicited oVEMP and cVEMP respectively. Some of them also received caloric test. Sixty-two SSHL patients with vertigo and twenty-five age-and gender-matched normal subjects were recruited as controls to analyze the vestibular dysfunction in SSHL patients without. vertigo. RESULTS: Abnormal oVEMP was observed in 54. 8% affected ears without vertigo (23/42), 64. 5% ears with vertigo (40/62), and 26. 0% normal ears (13/50). Abnormal cVEMP was observed in 52. 4% affected ears without vertigo (22/42), 48. 4% ears with vertigo (30/62), and 14. 0% normal ears (7/50). Caloric test was operated in 21 SSHL patients without vertigo and 29 patients with vertigo. Abnormal caloric test was observed in 52.4% (11/21) SSHL patients without vertigo and 75. 9% (22/29) SSHL patients with vertigo respectively. Statistical significance was found in oVEMP and cVEMP rates between SSHL without vertigo and normal group (P<0. 01). However, no significant statistical difference was found in oVEMP, cVEMP rates and caloric test between SSHL without vertigo and SSHL with vertigo group (P>0. 05). CONCLUSION: Vestibular function could be damaged in SSHL patients without vertigo. The abnormal rates of oVEMP, cVEMP and caloric test in SSHL patients without vertigo were similar to that of SSHL patients with vertigo. The appearance of vertigo might be irrelevant to the range and extent of vestibular dysfunction.

Regulation of Hippo/YAP signaling pathway ameliorates cochlear hair cell injury by regulating ferroptosis.

Cisplatin, which is effective for the treatment of solid tumors, also can induce cochlear hair cell damage. Therefore, this study was intended to explore how Hippo/YAP signaling pathway affects the cochlear hair cell injury by regulating ferroptosis. After cisplatin induction, or LAT1-IN-1 (YAP activator) and verteporfin (YAP inhibitor) treatment or transfection, the viability of HEI-OC1 cells was detected by cell counting kit-8 (CCK-8) assay. The iron level and the levels of oxidative stress markers (ROS, MDA and 4-HNE) were analyzed by iron assay kit, reactive oxygen species (ROS), malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) assay kits, respectively. The expression of ferritin light chain (FTL) in HEI-OC1 cells was detected by immunofluorescence and protein expressions of yes associated protein (YAP,) phosphorylated YAP (p-YAP), transferrin receptor (TFRC), glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) in HEI-OC1 cells were detected by western blot. The transcription of FTL and TFRC by YAP1 was verified by dual-luciferase reporter assay. The transfection efficiency of small interfering RNA (si-RNA) specific to FTL (siRNA-FTL) and TFRC (siRNA-TFRC) was confirmed by reverse transcription­quantitative polymerase chain reaction (RT­qPCR). As a result, cisplatin inhibited the viability of HEI-OC1 cells by increasing free Fe2+ level and decreasing FTL level. LAT1-IN-1 promoted the viability of cisplatin-induced HEI-OC1 cells by suppressing oxidative stress level, free Fe2+ level, ferroptosis and increasing FTL level, while the effect of verteporfin was the opposite. YAP1 transcriptionally regulated the expression of FTL and TFRC. Inhibition of FTL suppressed the viability of cisplatin-induced HEI-OC1 cells by increasing oxidative stress level, free Fe2+ level, ferroptosis and decreasing FTL level, while the effect of TFRC inhibition was the opposite. In conclusion, YAP1 ameliorated cochlear hair cell injury by upregulating FTL and TFRC to suppress ferroptosis.

Circular RNA hsa_circ_0003892 promotes the development of papillary thyroid carcinoma by regulating the miR-326/LASP1 axis.

BACKGROUND: Thyroid cancer is the most common malignancy of the endocrine system. Circular RNA (circRNA) is recognized as a key regulator of tumorigenesis in papillary thyroid carcinoma (PTC). Here this work focused on the mechanism of circRNA_0003892 (circ_0003892) in PTC progression. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine circ_0003892, microRNA-326 (miR-326) and LIM and SH3 protein 1 (LASP1) mRNA expression levels in PTC tissues and cell lines. Besides, cell counting kit-8 (CCK-8), EdU and transwell assays were conducted to detect the proliferative, migrative and invasive abilities of PTC cells, respectively. B The targeting relationships between miR-326 and circ_0003892 or LASP1 3'-UTR were verified by dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. RESULTS: Circ_0003892 expression was raised in PTC tissues and cells, which was significantly interrelated with larger tumor size and extrathyroidal extension in PTC sufferers. Overexpression of circ_0003892 significantly promoted the malignant biological behaviors of PTC cells. Additionally, miR-326 was a downstream target of circ_0003892, and miR-326 overexpression weakened the promoting effect of circ_0003892 overexpression on the malignant progression of PTC. MiR-326 specifically inhibited LASP1. Circ_0003892 positively regulated LASP1 expression by targeting miR-326. CONCLUSION: Circ_0003892 up-regulates LASP1 expression and facilitates PTC progression via competitively binding to miR-326.

Diagnostic techniques for critical respiratory infections: Update on current methods.

Respiratory infections, whether chronic or acute, are frequent in both children and adults and result in an economic burden in health care systems. In particular, for an immunocompromised patient, respiratory infection leads to acute hypoxemic respiratory failure, a leading cause of intensive care unit (ICU) admission. Most respiratory infections are caused by bacteria, viruses, parasites, smoking, or air pollution. Over the last two decades, considerable improvements have been made in understanding and identifying respiratory infections. Various biosensing techniques have been developed with a range of targets to identify the infection at earlier stages. Recently, nanomaterials have been effectively applied to improve biosensors and their analytical performances. This review discusses recent biosensor developments for identifying respiratory infections caused by viruses and bacteria assisted by different types of nanomaterials and target molecules.

[A family-based association study of the EGR3 gene polymorphisms and schizophrenia].

Previous studies showed that EGR3 gene located in chromosome 8p21.3 was involved in the etiology of schizophrenia. However, the finding failed to be replicated in several case-control studies. To investigate the genetic role of the EGR3 gene in Chinese psychiatric patients, we genotyped five single nucleotide polymorphisms (SNPs) in EGR3 gene locus using 93 nuclear families in Han Chinese, and performed transmission disequilibrium test (TDT). In this study, two SNPs (rs1996147 and rs3750192) showed significant association with schizophrenia (c2>4.40, P<0.05). In the linkage disequilibrium analysis, the significant association was also found in two- (rs3750192-rs35201266), three- (rs1877670- rs3750192-rs7009708) and four-SNP (rs1996147-rs1877670-rs3750192-rs7009708) tests of haplotype analyses (c2>7.10, global P<0.05). Overall, the results suggested that EGR3 gene may play an important role in schizophrenia susceptibility in the Han Chinese population, and further functional exploration of the EGR3 gene will contribute to the underlying molecular mechanism for schizophrenia pathogenesis.

Bilateral Dysfunction of Otolith Pathway in Patients With Unilateral Idiopathic BPPV Detected by ACS-VEMPs.

Objective: To observe the functional status of the otolith pathway in patients with unilateral idiopathic benign paroxysmal positional vertigo (BPPV) by combining air-conducted sound elicited cervical vestibular-evoked myogenic potential (ACS-cVEMP) and ocular vestibular-evoked myogenic potential (ACS-oVEMP). Methods: One hundred and eighty patients with BPPV were recruited for conventional cVEMP and oVEMP tests. The abnormal rates of VEMPs were compared between BPPV patients and control participants. Results: The abnormal rates of cVEMP and oVEMP in BPPV patients were 46.7% (84/180) and 57.2% (103/180) in affected ears, respectively, and 45.0% (81/180) and 56.7% (102/180) in unaffected ears, respectively; both were significantly higher than the abnormal rates of cVEMP and oVEMP in normal control ears. Compared with normal subjects, the cVEMP response rate was lower in affected and unaffected ears in BPPV patients. The abnormal rates of cVEMP and oVEMP were 48.1% (76/158) and 57.6% (91/158) in patients with posterior semicircular canal BPPV, and 36.4% (8/22) and 54.5% (12/22) in lateral semicircular canal BPPV. There was no significant difference in VEMP abnormalities between posterior semicircular canal BPPV and lateral semicircular canal BPPV. Conclusion: The prevalence of abnormal cVEMPs and oVEMPs in both affected and unaffected ears of patients with BPPV was significantly higher than that observed in the control group. The pathological mechanism of unilateral idiopathic BPPV may be associated with bilateral degeneration of otolith pathways.

Long non-coding RNA AGAP2-AS1 promotes cell proliferation and invasion through regulating miR-193a-3p/LOXL4 axis in laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is an aggressive malignancy with highly mortality rate. Long non-coding RNA (lncRNA) AGAP2-AS1 is an identified oncogene in several types of cancers. However, the role of AGAP2-AS1 in LSCC remains unclear. The expression levels of AGAP2-AS1 in LSCC tissues and cell lines were measured using qRT-PCR. AGAP2-AS1 was knocked down in LSCC cells through transfection with siRNA-AGAP2-AS1. Cell proliferation and invasion were detected using MTT and transwell assays. Dual-luciferase reporter gene assay was performed to confirm the interaction with AGAP2-AS1 and downstream genes. Our results showed that AGAP2-AS1 expression was remarkably increased in human LSCC tissues and cell lines. Knockdown of AGAP2-AS1 significantly inhibited the proliferation and invasion of LSCC cells. In addition, AGAP2-AS1 sponged miR-193a-3p and regulated its expression in LSCC cells. Inhibition of miR-193a-3p reversed the effects of AGAP2-AS1 knockdown on LSCC cells. Furthermore, Lysyl oxidase-like 4 (LOXL4) was a target gene of miR-193a-3p and the role of miR-193a-3p was mediated by LOXL4. In conclusion, these findings suggest that knockdown of AGAP2-AS1 inhibited the proliferation and invasion of LSCC cells through regulating the miR-193a-3p/LOXL4 axis.

Downregulation of Sepina3n Aggravated Blood-Brain Barrier Disruption after Traumatic Brain Injury by Activating Neutrophil Elastase in Mice.

Traumatic brain injury (TBI) is the leading cause of death in young adults and the main cause of mortality and disability across all ages worldwide. We previously analyzed the expression profile data of TBI models obtained from the Gene Expression Omnibus (GEO) database and found that the seripina3n mRNA was markedly upregulated in the acute phase of TBI in four mRNA expression profile data sets, indicating that serpina3n may be involved in the pathophysiological process of TBI. Therefore, we further investigated the biological role and molecular mechanism of serpina3n in traumatic brain injury in this study. As a result, the endogenous level of sepina3n was markedly elevated in the cortex around the contusion sit in mice at day 1 and day 3 after TBI. Inhibiting the expression of serpina3n caused aggravation of neutrophil elastase (NE) expression, BBB disruption, and neurological deficit. With the inactivation of NE, even if serpina3n was silenced, the disruption of the BBB was not further aggravated. In vitro experiments further proved that recombinant serpina3n dose-dependently inhibited the activity of recombinant NE. Based on the above, this study demonstrated that the endogenous level of sepina3n was significantly elevated in the cortex around the contusion sit after TBI in mice, which reduced the secondary blood-brain barrier disruption by inhibiting the activity of neutrophil elastase.

[A family-based association study of FXYD6 gene polymorphisms and schizophrenia].

OBJECTIVE: To study the association between the single nucleotide polymorphisms (SNPs) in FXYD6 gene and schizophrenia in a family-trios population. METHODS: Six SNPs (rs10790212, rs11544201, rs555577, rs1815774, rs4938446 and rs497768) in the FXYD6 gene were genotyped by allele-specific PCR method in 101 nuclear families, and transmission disequilibrium test (TDT) was performed. RESULTS: SNPs rs10790212 and rs11544201 showed significant association with schizophrenia (P<0.05). Furthermore, significant association of schizophrenia with the haplotype rs10790212-rs11544201 was found (P<0.05). CONCLUSION: FXYD6 gene might play an important role in schizophrenia susceptibility and functional analysis of FXYD6 are needed.

Sudden onset of static equilibrium dysfunction in patients receiving a cochlear implant.

BACKGROUND: We investigated the sudden onset of static equilibrium dysfunction caused by cochlear implantation (CI) in congenital hearing loss patients. METHOD: Twenty-five patients were selected from a cohort of unilateral CI recipients to form the CI group. Static posturography was performed 1 to 3 days before and 3 to 5 days after CI. Each patient underwent the test with eyes open (EO) and eyes closed (EC) for 30 seconds, separately. Another group of age- and sex-matched patients with no history of hearing impairment undergoing unrelated surgeries formed the control group, and were examined with the same tests pre- and post-surgery. A third group of patients undergoing middle ear surgery formed the otitis media (OM) group. Postural sway parameters including sway velocity (SV) in the X-axis, SV in the Y-axis, length of sway locus length (LNG), and environmental area (ENV) were measured and recorded. RESULTS: Comparison of pre-surgery posturographical parameters between the CI and control groups revealed no significant differences. Significant differences were found in most parameters in pre- and post-surgery comparisons in the CI group. Mean SV values in the X-axis pre- and post-surgery were 8.48 and 11.52 mm/s, respectively, in the EO condition (P < .05), and 14.94 and 20.16 mm/s, respectively, in the EC condition (P < .05). In the Y-axis, mean SV values were 15.36 and 20.24 mm/s pre- and post-surgery, respectively, in the EC condition (P < .05). The LNG values in the CI group pre- and post-surgery were 319.60 and 469.88 mm in the EO condition (P < .05), and 571.40 and 764.12 mm in the EC condition (P < .05). No significant functional equilibrium change was observed in the control group between pre- and post-surgery (P > .05) except SV in the X-axis and LNG in the EO condition (P < .05). No significant pre- and post-surgery differences were found in the OM group. CONCLUSION: CI appeared to influence static equilibrium function within 1 week post-surgery. This influence was greater when eyes were closed.

The relationship between hearing loss and vestibular dysfunction in patients with sudden sensorineural hearing loss.

OBJECTIVE: To investigate the relationship between hearing loss and vestibular dysfunction in patients with sudden sensorineural hearing loss (SSHL). METHODS: Clinical data including the symptom of vertigo of 149 SSHL patients were investigated retrospectively. Pure tone audiometry, ocular vestibular-evoked myogenic potential (oVEMP) and cervical vestibular-evoked myogenic potential (cVEMP) evoked by air-conducted sound (ACS), and caloric test were employed for cochlear and vestibular function assessment. The relationship between hearing level and vestibular dysfunction was analyzed. RESULTS: The pure tone averages (PTAs) (mean ± SD) of SSHL patients with and without vertigo were 88.81 ± 21.74 dB HL and 72.49 ± 21.88 dB HL (Z = -4.411, p = 0.000), respectively. The PTAs of SSHL patients with abnormal and normal caloric test were 84.71 ± 22.54 dB HL and 70.41 ± 24.07 dB HL (t = -2.665, p = 0.009), respectively. Conversely, vertigo and abnormal caloric results also happened more frequently in patients with profound hearing loss. However, no consistent tendency could be found among vestibular evoked myogenic potentials (VEMPs) responses or hearing loss. CONCLUSIONS: SSHL patients with vertigo or abnormal caloric test displayed worse hearing loss; and vice versa, vertigo and abnormal caloric results happened more frequently in SSHL patients with profound hearing loss.

[The significance of vestibular function assessment in sudden deafness].

Hearing loss caused by cochlear damage is the main symptom of sudden deafness (SD). Some patients also suffer from vestibular symptoms. In recent years, more attention has been paid to the vestibular dysfunction in patients with SD. The lesions could involve the whole inner ear in SD patients with and without vertigo. Comprehensive evaluation of vestibular function may help us understand the extent of lesions in sudden deafness and analyze the pathogenesis of disease. A less involvement of inner ear lesion may indicate a better hearing recovery.

[Effects of aging on air-conducted sound elicited ocular vestibular- evoked myogenic potential and cervical vestibular-evoked myogenic potential].

OBJECTIVE: To identify the aging effects on air-conducted sound (ACS) elicited ocular vestibular-evoked myogenic potential (oVEMP) and cervical vestibular-evoked myogenic potential (cVEMP) in normal Chinese population. METHODS: Nighty-seven normal subjects (194 ears) were recruited for conventional ACS-oVEMP and ACS-cVEMP examinations. The candidates'age were 4-83 years old (Ave. ± SD, 45.7 ± 19.3), 41 male and 56 female, divided into 5 groups according to age. 500 Hz short tone burst was employed for examinations. Thresholds were identified and the parameters of the responses to 100dB nHL were calculated and compared among groups. SPSS 13.0 software was used to analyze the date. RESULTS: As the age growing, the response rate for oVEMP decreased. It was recorded 100% in both ≤ 10-year-old and 11-30-year-old groups, 84.00% in the 31-50-year-old group, 48.15% in the 51-70-year-old group and 15.00% in the > 70-year-old group; while that for cVEMP were 100% in both ≤ 10-year-old group and 11-30-year-old group, 82.00% in the 31-50-year-old group, 77.78% in the 51-70-year-old group and 45.00% in the > 70-year-old group. The thresholds elevated and the amplitudes decreased in both examinations with the age growing. However, latencies and latency-intervals of both oVEMP and cVEMP examinations displayed minor difference among groups except that nI latency of oVEMP prolonged with age growing. CONCLUSIONS: With the age growing, the otolithic end organ input pathways degenerate in normal subjects, as shown that ACS elicited oVEMP and cVEMP responsed less with higher threshold and smaller amplitude. The extremely low response rates of both VEMPs in the > 70-year-old group in this study indicates that VEMPs can only provide limited diagnostic information among very old people in clinical practice.