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Xiangli Zeng

Publications and source records attributed to Xiangli Zeng.

6 recordsLinked to original sources
PubMed2025

MLL1 downregulation drives hair cell ferroptosis via mitochondrial and endoplasmic reticulum stress mechanisms through PERK-eIF2α-ATF4-Chop and PI3K/Akt-Lrp1 signaling pathway.

BACKGROUND: Sensorineural hearing loss is characterized by irreversible hair cell (HC) degeneration. Ferroptosis, which is marked by the accumulation of reactive oxygen species and elevated levels of lipid peroxidation products, has been shown to contribute to drug-mediated auditory impairment. This study aimed to elucidate the role of mixed-lineage leukemia 1 (MLL1) in HC survival in the auditory system. METHODS: The HEI-OC1 auditory cell line and postnatal cochlear explants were evaluated using MM-102, a specific MLL1 histone methyltransferase inhibitor. Western blotting, quantitative polymerase chain reaction, electron microscopy, and immunofluorescence were used to elucidate the role of MLL1 in regulating ferroptosis in HC injury. RNA sequencing (RNA-seq) was used to analyze the molecular mechanisms of MLL1 intervention in HC injury from an epigenetic perspective. RESULTS: Our findings demonstrated that immunofluorescence staining revealed a crucial role of MM-102 in promoting intracellular accumulation of lipid peroxides and ferrous ions. Subsequent analysis showed MLL1 downregulation-induced mitochondrial dysfunction and endoplasmic reticulum (ER) stress, with transmission electron microscopy imaging confirming ultrastructural alterations in mitochondria and ER. Mechanistic investigations identified the PERK-eIF2α-ATF4-Chop signaling axis as the regulatory pathway, evidenced by Western blotting quantification of phosphorylated PERK (p-PERK), ATF4, and Chop levels. RNA-seq analysis revealed 741 differentially expressed genes (335 upregulated and 406 downregulated). Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis specifically highlighted significant enrichment of the PI3K/Akt-Lrp1 pathway, with corresponding activation patterns of phospho (p)-Akt and Lrp1 confirmed through Western blotting analysis. CONCLUSIONS: MLL1 downregulation initiates ferroptosis in cochlear HCs. This process is intrinsically associated with the activation of mitochondrial dysfunction and ER stress. The study highlights the importance of MLL1 in HC survival, suggesting its potential as a therapeutic target for treating hearing loss.

Endoplasmic Reticulum Stress↗
PubMed2006

[The diagnostic value of TEOAE-glycerine test in patients with vertigo on the first attack].

OBJECTIVE: To investigate the diagnostic value of transiently evoked otoacoustic emissions (TEOAE) combined with glycerine test in patients with vertigo on the first attack. METHOD: PTT and TEOAE-glycerine test were conducted on the 28 patients who suffered the first attack of vertigo without hearing loss, tinnitus or a sensation of fullness in the ear. At the same time, history and clinical manifestation of the patients were not supportive for the non-Meniere's disease. RESULT: Among the 28 cases, four of them had nothing changed on the PTT and TEOAE parameters after glycerol administration, all of the indexes were in the normal range. Among the 20 positive cases in the TEOAE-glycerine test (unilateral ear 16 cases, bilateral ears 4 cases), TEOAE for 2 cases were not evoked before glycerol administration, while it was evocable after glycerol administration. For the positive ears, all of the parameters of TEOAE were lower than those in the normal standard before and after glycerol administration; there were 4 positive cases in the PTT glycerine test, however, both TEOAE were not evoked before and after glycerol administration. CONCLUSION: TEOAE-glycerine test can be used as a routine method for the early diagnosis of Meniere's disease and differentiating diagnosis in the patients who suffer vertigo on the first attack with normal hearing.

Adolescent↗
PubMed2006

[The artifacts and test-retest reliability of multiple auditory steady-state response].

OBJECTIVE: To investigate the characteristics and clinical application of artifacts and the test-retest reliability of multiple auditory steady-state response (MASSR). METHOD: The authors tested a group of healthy young volunteers and a group of patients with sensory hearing loss with the MASSR by analysing the rate of false negative artifacts (FNA) and their distribution. The healthy young volunteers were retested with MASSR several days after the first test to investigated the test retest reliability of MASSR. Furthermore, three cases of healthy young volunteers were retested in the sleeping status to explore the stability of MASSR threshold and the influence of sleep. RESULT: (1) The FNA mainly distributed in low frequencies districts and the intensities were near threshold, no remarkable differences could be seen between the normal ears and the ear with sensory hearing loss. The FNA disappeared when the volunteers were asleep. (2) The test-retest variability was much higher in 0.5 kHz than in other frequencies. The variable range was 0 - 30 dB in 0.5 kHz, and there was test-retest reliability in 1.0-4.0 kHz. (3) The artificial response was present when using strong stimulus for the patients with profound hearing loss. When MASSR was recorded in awake condition, the FNA appeared. When using strong stimulus for the cases with profound hearing loss, the artificial response existed and the test-retest variabilities were large. The whole test duration was often much longer than the auditory brainstem response (ABR) and 40 Hz auditory evoked potential (40 Hz AEP). CONCLUSION: As an objective auditory evaluation method, MASSR scarcely has superior characteristics to ABR and 40 Hz AEP.

Adolescent↗
PubMed2005

[Alteration of the auditory function and auditory nerve pathology in Guinea pigs with peripheral nerve demyelination].

OBJECTIVE: To study the auditory function and auditory nerve pathological changes of the experimental allergic neuritis (EAN) animal model in Guinea pigs. METHOD: To establish the animal model of EAN, heterologous myelin basic protein (MBP) of peripheral nerve was used to the immunize Guinea pigs. Serum anti-MBP-IgG levels, sciatic nerve conduction velocity (NCV), hearing thresholds and wave latencies, and pathological changes in auditory nerve, sciatic nerve and cochlea were observed. The immune lesions in inner ear were examined with immunohistochemistry. Auditory brainstem response (ABR) and compound action potential (CAP) were assayed weekly before and after immunization for a period of seven weeks. In the control group, antigen was replaced by the 0.9% saline. RESULT: Serum anti-MBP-IgG levels increased significantly in experimental group comparing with the control group (P < 0.01). Seiatic nerve conduction velocity decreased after immunization, as comparing with the control group (P < 0.01). Sciatic nerve and auditory nerve showed the existence of demyelination. There was significant increase of ABR and CAP thresholds and the latencies of wave I, III, V and N1 in experimental group when compared to the controls (P < 0.01), but no significant changes in inter-peak latencies of I-III, III-V were found( P > 0.05). In addition, there were 4 Guinea pigs (8 ears) in which only appeared lengthened wave latencies with normal hearing thresholds. Immunohistochemistry indicated that antibodies to inner ear from the MBP-sensitized animals distributed in cochlear nerve, neurofiber of inner ear and spiral ganglion cells. Cochlear scanning electron microscopy showed the pathology of inner hair cell with stereociliary disorder and cytoplasmic protrusions. CONCLUSION: The results suggest that auditory nerve demyelination are involved in this experimental allergic neuritis animal model and sciatic nerve demyelination as well, and the auditory abnormalities are elicited. This animal model seems to be a promising one of auditory dysfunction due to demyelination disorders.

Action Potentials↗
PubMed2004

[Probe to the bone-conduction phenomenon].

OBJECTIVE: To probe into the rule of bone-conduction measurement by testing a group of health young students with normal hearing and groups of case with different diseased ears, in order to provide some instructions for clinical audiometry. METHOD: Subjects included 20 health young students with normal hearing, 113 cases with different hearing loss. We tested all the subjects Weber Test and bone-conduction threshold by masking. RESULT: Weber Test lateralization dependented on the difference of binanural sensitivity when binaural had no conductive impairment. Different conductive impairment improved bone-conduction response at different frequencies. When monaural had conductive impairment and the other ear normal, there were 3-5 octaves WT lateralizated to the diseased ear. When there were binaural conductive impairments, bone-conduction response dependented on the nature and degree of the impairment, WT lost the rule. CONCLUSION: In order to avoid the negative effects of central masking and overmasking, our observations came to the conclusion that some conditions as follow need no masking: (1) There are no conductive impairment binaural, and the air-conduction pure tone threshold (PTT) gap between binaural higer than 40 dB, when we test bone-conduction PTT of better ear, we need no masking, as for the poor ear, it's bone conduction will come cross to the contralateral ear. (2) When one ear normal and the other is the conductive impairment,need no masking when testing the diseased ear. (3) There are conductive impairments binaural, bone-conduction PTT is normal, and air-conduction PTT is higher than interaural attenuation, we cannt get a true bone-conduction PTT by masking, but can determine the type of hearing loss and estimate the integrity of the sensory-neural system by other audiometry measurements.

Adolescent↗
PubMed2002

[The appearance of contralateral otoacoustic emissions with unilateral cochlear hearing loss].

OBJECTIVE: To investigate the latent influence on the contralateral ear when one ear was involves by different deaf elements. METHOD: TEOAE and DPOAE were recorded from contralateral ears with unilateral cochlear hearing loss, who were divided into 5 groups, group S1, sudden deafness last within two months (9 ears), group S2, sudden deafness last over one year or so(6 ears), Meniere's disease (13 ears M1, M2) cochlear hearing loss of unknown etiology(7 ear, UNK), using ILO-96 analyzer system. RESULT: Response amplitude, wave reproducibility, band reproducibility of TEOAE in S1, M2 were significantly lower than normal values. Amplitude of DPOAE in S1, M2 were significantly lower than normal values. All record were the same with normal in S2, M1. UNK. CONCLUSION: In all sorts of deaf elements, some have an effect on binaural ears, the others have an effect on unilateral ear.

Adolescent↗