The mitophagy pathway and its implications in human diseases.

Mitochondria are dynamic organelles with multiple functions. They participate in necrotic cell death and programmed apoptotic, and are crucial for cell metabolism and survival. Mitophagy serves as a cytoprotective mechanism to remove superfluous or dysfunctional mitochondria and maintain mitochondrial fine-tuning numbers to balance intracellular homeostasis. Growing evidences show that mitophagy, as an acute tissue stress response, plays an important role in maintaining the health of the mitochondrial network. Since the timely removal of abnormal mitochondria is essential for cell survival, cells have evolved a variety of mitophagy pathways to ensure that mitophagy can be activated in time under various environments. A better understanding of the mechanism of mitophagy in various diseases is crucial for the treatment of diseases and therapeutic target design. In this review, we summarize the molecular mechanisms of mitophagy-mediated mitochondrial elimination, how mitophagy maintains mitochondrial homeostasis at the system levels and organ, and what alterations in mitophagy are related to the development of diseases, including neurological, cardiovascular, pulmonary, hepatic, renal disease, etc., in recent advances. Finally, we summarize the potential clinical applications and outline the conditions for mitophagy regulators to enter clinical trials. Research advances in signaling transduction of mitophagy will have an important role in developing new therapeutic strategies for precision medicine.

[miR-30e-3p in natural killer cell-derived exosomes inhibits the proliferation and invasion of human esophageal squamous carcinoma cells].

Objective To investigate the effects of natural killer (NK)-cell-derived miR-30e-3p-containing exosomes (Exo) on esophageal squamous cell carcinoma (ESCC) cell proliferation, apoptosis and invasion. Methods NK cells were isolated and amplified from the peripheral blood of healthy donors, and NK cell-derived Exo was isolated and identified, which were further co-cultured with NEC cells and were randomly grouped into Exo1 and Exo2 groups. Transmission electron microscopy (TEM) was used to observe the morphology and size of exosomes. Western blot analysis was used to detect the expression levels of exosome markers apoptosis related gene 2- interacting protein X(ALIX), tumor susceptibility gene 101(TSG101), CD81 and calnexin. The NC plasmids, mimics and inhibitors of miR030e-3p were respectively delivered into the NK cells, and the corresponding NK cells-derived Exo were co-cultured with NEC cells, which were divided into NC, Exo, mimic and inhibitor groups. CCK-8 assay was used to evaluate cell proliferation, flow cytometry was conducted to determine cell cycle, annexin V-FITC/PI double staining was employed to detect cell apoptosis, and TranswellTM assay was performed to detect cell invasion abilities. Real-time quantitative PCR was used to detect the expression of miR-23b, miR-422a, miR-133b, miR-124, miR-30e-3p and miR-99a in NCE cells and exosomes. Results The percentages of CD56+CD3+ cells and CD56+CD16+ cells in NK cells were (0.071±0.008)% and (90.6±10.6)%, respectively. Exosome isolated from NK cells ranged from 30 nm to 150 nm, and was positive for ALIX, TSG101 and CD81, while negative for calnexin. NK cell-derived Exos inhibited the proliferation, reduced the proportion of S-phase cells and the number of invaded cells of NEC cells, and promoted the apoptosis and the proportion of G1 phase cells. Overexpression of miR-30E-3p in NK cell-derived exosome inhibited the proliferation and invasion of NEC cells, and blocked cell cycle and promoted apoptosis, while knockdown miR-30e-3p in NK cell-derived exosomes did the opposite. Conclusion miR-30e-3p in NK cell-derived exosomes can inhibit the proliferation and invasion of ESCC cells, block their cell cycle and induce their apoptosis.

[Clinical and sleep EEG monitoring characteristics and long-term follow-up study on narcolepsy].

OBJECTIVE: Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucination and sleep paralysis, with abnormal characteristics of shorter rapid eye movement (REM) sleep latency. The management of the patients is very important. The present study focused on the clinical characteristics, diagnostic methods and long-term prognosis of this particular syndrome. METHODS: The clinical data of 39 narcoleptic children were analyzed. Sleep EEG monitoring was performed in all patients. Among the 39 cases, 23 were followed up. RESULTS: All the patients manifested with excessive daytime sleepiness, with disrupted nocturnal sleep occurring in 35 cases. Cataplexy appeared in 36 cases, and sleep paralysis in 9, hypnagogic hallucination in 19, and automatic behavior in 6 cases, respectively. Sleep EEG monitoring demonstrated a short mean sleep latency (< 5 minutes) and two or more sleep onset REM periods (SOREMPs) in 38 cases. Twenty-three of the 39 cases were followed-up. Seventeen cases were followed-up for over one year. The longest follow-up duration was 14 years. Methylphenidate was administered in 10 cases. The excessive daytime sleepiness had been improved in 7 cases (70%). No obvious adverse effects were found. Psychosocial and academic problems appeared in most cases. CONCLUSION: Narcolepsy is a chronic neurological disorder. A definite diagnosis is established when the symptoms of cataplexy and excessive daytime sleepiness occur in association with the characteristic findings on sleep EEG monitoring. Appropriate drug therapy and psychosocial management are of help for such patients. Stimulant medication is an important component of the overall treatment program. A comprehensive approach is necessary to meet the needs of children with narcolepsy. Family education and emotional support are key elements in the management plan. The overall goal for managing childhood narcolepsy is to assist the child and family in achieving optimal quality of life.

[Clinical observation and long-term follow-up of benign infantile epilepsy].

OBJECTIVE: To investigate clinical characteristics, EEG changes and therapeutic response of benign infantile epilepsy and to study the early diagnostic methods. METHODS: Clinical observation and Video-EEG monitoring were carried out in babies with convulsions at 3 - 24 months of age. In these children, febrile convulsion, symptomatic epilepsies and developmental abnormalities were excluded, and the therapeutic effect and long-term outcome were followed up. RESULTS: Forty-two babies were diagnosed to have benign infantile epilepsy by two-year follow-up. Three of them had familial history of benign infantile convulsions. Nineteen percent had mild diarrhea during the onset of convulsions, cluster seizures occurred during a short period in 67% of cases and no status epilepticus occurred. Video-EEG monitoring confirmed seizures originating from temporal, occipital or multifocal areas separately in 3 patients with partial seizures. Interictal EEG background was normal and there were Rolandic small spikes during sleep in 24% of patients. Thirty-nine patients were treated with single antiepileptic drugs and the mean treatment course was 9 months. Three cases did not take medicine. All the patients were seizure free within a year. CONCLUSION: Benign infantile epilepsy should be considered when the following characteristics occur in early stage of the disease: (1) convulsions occurring between 3 to 12 month of age and not later than 24 months of age with or without familial history of benign infantile convulsion; (2) normal psychomotor development before and after convulsion occurs; (3) no evoked factors or only mild diarrhea; (4) majority of cases have partial seizures, or secondary generalized seizures. There are often cluster convulsions during the onset stage, but no status epilepticus; (5) normal EEG background and there may be Rolandic small spikes during sleep; (6) normal neuroimaging.