Maternally inherited non-syndromic hearing loss is linked with a novel mitochondrial ND6 gene mutation.

BACKGROUND: Maternally inherited non-syndromic hearing loss is linked with mitochondrial DNA mutations. AIM: This investigation demonstrates the features of a Chinese pedigree suffering from maternally inherited non-syndromic hearing loss. METHODS: Biochemical characterizations included the measurements ofprotein synthesis levels, membrane potential, and the synthesis of reactive oxygen species (ROS) and adenosine triphosphate (ATP) using cybrid cell lines derived from an affected matrilineal subject and control subject. RESULTS: Non-congenital early or late-onset/development hearing impairment has been observed in 4 of 9 in a family (matrilineal), with different degrees of hearing impairment, ranging from normal to severe. A pedigree's whole mitochondrial genome sequence analysis revealed the homoplasmic m.14502 T > C (I58V) mutation at ND6's isoleucine location-58, and specific mitocchondrial DNA polymorphisms set haplogroups M10 were highly conserved. In vitro models indicated that m.14502 T > C mutation-derived respiratory deficiency decreases ND6 protein synthesis, mitochondrial membrane potential, and ATP synthesis. These mitochondrial dysregulations enhance the generation of ROS in the mutant cells. Identifying nuclear modifiers is essential for elucidating hearing loss's pathogenesis and furnishing novel therapeutic interventions. CONCLUSIONS: The m.14502 T > C mutation should be considered an inherited risk factor that can help diagnose. The data of this investigation help counsel families of individuals with hearing loss.

Self-assembling porphyrin conjugate-carboplatin(IV) prodrug nanoparticles for enhancing high efficacy nasopharyngeal cancer and low systemic toxicity.

Nanomedicine has developed as a potential technique for successful cancer therapy. A simple supramolecular self-assembly process is a helpful strategy for generating carrier-free nanodrugs. Mixing photodynamic treatment with chemotherapy has been sought to obtain a high therapeutic impact. In this study, we effectively construct a nanocarrier (CD-Por-PEG: Ada-CPT-Pt(IV)) combined with Carboplatin prodrug (Ada-CPT-Pt(IV)) and photosensitizer porphyrin (CD-Por-PEG) by host-guest interactions to accomplish stimuli-response combination treatment. Supported by greater spatial control of the binding ratio among host-guest molecules, Carboplatin and porphyrin were independently altered with ß-cyclodextrin and adamantane to produce the amphiphilic host-guest combination for sequential self-assembly into therapeutic nanoparticles. The colloidal stability of the produced CD-Por-PEG: Ada-CPT-Pt(IV)-NPs was excellent, with an average hydrodynamic diameter of ∼170 nm. The microscopy images showed that CD-Por-PEG: Ada-CPT-Pt(IV) could aggregate cells and generate ROS after light irradiation (630 nm). Monotherapy had a cytotoxicity three times greater than the CD-Por-PEG: Ada-CPT-Pt(IV) nanoparticles. Studies in mice carrying SUNE1 nasopharyngeal tumours showed that nanoparticles effectively suppressed tumour development without causing systemic damage in this examination. The current self-assembly nanosystem makes precise control over the photosensitizer and drug loading possible ratio. It reduces the systemic adverse toxicity issues of drugs carrier, making this system ideal for nasopharyngeal cancer treatment.

Suppressed "Warburg Effect" in Nasopharyngeal Carcinoma Via the Inhibition of Pyruvate Kinase Type M2-Mediated Energy Generation Pathway.

Warburg effect describes the abnormal energy metabolism in cancer cells and pyruvate kinase type M2 is involved in the regulation of this effect. In the current study, the role of pyruvate kinase type M2 in the initiation of Warburg effect in nasopharyngeal carcinoma cells was explored. The expression status of pyruvate kinase type M2 was detected in nasopharyngeal carcinoma samples and analyzed by different clinicopathological characteristics. Then the level of pyruvate kinase type M2 was suppressed in 2 nasopharyngeal carcinoma cell lines. The effects of pyruvate kinase type M2 inhibition on cell viability, apoptosis, invasion, glucose uptake, ATP generation, and glycolysis metabolism were determined. The data showed that the high expression of pyruvate kinase type M2 in nasopharyngeal carcinoma tissues was associated with the larger tumor size and advanced metastasis in the patients. The inhibition of pyruvate kinase type M2 resulted in the repressed proliferation and invasion in nasopharyngeal carcinoma cells, along with the increased apoptotic rate. The lack of pyruvate kinase type M2 function inhibited glucose uptake, while increased ATP generation in nasopharyngeal carcinoma cells. Moreover, the production of glycolysis metabolites, including pyruvic acid, lactate, citrate, and malate, was also suppressed by pyruvate kinase type M2 inhibition. At molecular level, the expressions of glucose transporter and hexokinase 2 were downregulated by pyruvate kinase type M2 inhibition, confirming the changes in glucose metabolism. Collectively, the current study demonstrated that the function of pyruvate kinase type M2 was important to maintain the proliferation and invasion of nasopharyngeal carcinoma cells, and the inhibition of the factor would antagonize nasopharyngeal carcinoma by blocking Warburg effect.

[Comparative analysis of 226 Hz and 1 000 Hz probe tone tympanometry in infants].

OBJECTIVE: To analyze the judgement standard and evaluate the diagnostic value of the low frequency and high frequency tympanometry in infants with otitis media. METHOD: Tympanograms for admittance with 226 Hz and 1 000 Hz probe tones and resonant frequency were obtained from normal infants (195 cases, 321 ears) and infants with otitis media(122 cases, 171 ears). The mean, standard deviation, median, 5% quantile, 95% quantile and 95% confidence interval of peak admittance, gradient and resonant frequency were measured and calculated in different age groups. The significant differences of 1000 Hz peak admittance, 226 Hz peak admittance and gradient between normal infants and infants with otitis median were analyzed using SPSS 11.0. The false positive rate and the false negative rate of different age groups in infants with otitis media were evaluated according to such judgement standards as 1000 Hz peak admittance, 226Hz peak admittance or gradient. RESULT: The false positive rate and the false negative rate of the 1000 Hz probe tone tympanometry in infants with otitis media unter one year of age were 3.07% and 1.84% as the normal range of positive peak was more than 0.2 mmho. The false positive rate and the false negative rate of the 1000 Hz probe tone tympanometry in infants with otitis media aged 1-2 years and aged 2-3 years were 3.26%, 5.26% and 1.52%, 0.00% respectively,as the normal range of positive peak was more than 0.3 mmho. These was no significant difference in the gradient with 226 Hz probe tone between normal infants and infants with otitis median under one year of age. The false positive rate and the false negative rate of the 226 Hz probe tone tympanometry in infants with otitis media aged 1-2 years and aged 2-3 years were 44.57%, 31.58% and 16.67%, 6.67% respectively, as the gradient with 226 Hz probe tone was a judgement standard. CONCLUSION: (1) The diagnostic accuracy of tympanometry with 1000 Hz probe tone for otitis media in infants younger than 3 years of age exceeded 226 Hz probe tone tympanometry, the 1000 Hz probe tone tympanometry is suggested to the evaluation of middle ear function in infants before 3 years. (2) It is reasonable that the normal range of positive peak is more than 0.2 mmho in infants unter one year of age and the normal range of positive peak is more than 0.3 mmho in infants aged 1-3 years.