Leber’s hereditary optic neuropathy (LHON) is a paradigm maternal hereditary eye disease, mainly involving the retinal and macular fibers of the optic disc in the anterior ethmoid plate of the sclera. LHON has the characteristics of sex bias among males and incomplete penetrance. Primary mitochondrial DNA mutations m.11778G>A, m. 14484T>C, m.3460G>A are the molecular basis of LHON. However, other risk factors, such as secondary mitochondrial DNA mutations, mitochondrial haplotypes, nuclear modification genes, estrogen, vitamin B12 and environmental factors, work together to affect its phenotypic expression. The clinical diagnosis of LHON mainly limited to the detection of the primary mutation site of mitochondrial DNA. Therefore, comprehensive analysis of multiple risk factors of LHON will facilitate to construct multi-dimensional model of prevention, diagnosis and treatment system, which provide accurate and individualized medical services for patients. These may alleviate the incidence in LHON families. It also provides new ideas and different angles for the in-depth study of the pathogenesis of LHON.
Purpose To investigate mitochondrial DNA (mt-DNA) mutations in optic neuritis of unknow reason (ONUR) and to assess the pathogenic and differential diagnostic values of screening for mt-DNA mutations in ONUR. Method Thirty patients with ONUR were screened for mt-DNA mutations by using SSCP,mutation-specific primer PCR and sequencing. Results mt-DNA mutations were found in 12 out of the thirty patients.All of the mutations were at 11778 position,but no one at 3460 and 15257. Conclusions Quite a number of patients (12/30,40%) with ONUR were caused actually by mt-DNA mutation．Screening for mt-DNA mutation in these patients has a pathogenic and differential diagnostic significance. (Chin J Ocul Fundus Dis,2000,16:78-79)
ObjectiveTo investigate the expression of circular RNA mitochondrial fusin 2 (circ-MFN2) in pancreatic cancer and analyze its correlation with clinicopathological features and prognosis.MethodsThe expressions of circ-MFN2 miRNA in 55 cases of pancreatic cancer tissues and serum were detected by qRT-PCR, and analyzed the correlation between circ-MFN2 and clinicopathological factors of pancreatic cancer and prognosis. The sensitivity, specificity and accuracy of expression of circ-MFN2 miRNA in the diagnosis of pancreatic cancer were statistically analyzed. ROC curve was used to analyze its efficacy as a biomarker for early diagnosis of pancreatic cancer.ResultsCompared with paracancerous tissues of pancreatic cancer and serum of healthy control group, circ-MFN2 miRNA was highly expressed in pancreatic cancer tissues and serum, and the difference were all statistically significant (all P<0.05). Chi square test showed that the expression of circ-MFN2 miRNA in pancreatic cancer tissues was not related to age, gender, tumor size, pathological type, and tumor site (P>0.05), but was significantly related to CA19-9 level, TNM stage, tumor differentiation and lymph node metastasis (P<0.05). The sensitivity, specificity and accuracy of expression of circ-MFN2 miRNA for pancreatic cancer were 72.7%, 70.9% and 83.6% respectively, which were all higher than that of CA19-9 (54.5%, 50.9% and 52.7%, P<0.05). Kaplan-Meier analysis showed that the median survival time of pancreatic cancer patients with high expression of circ-MFN2 miRNA was significantly shorter than that of patients with low expression (9.1 months vs 22.3 months, P<0.05). The area under ROC curve of circ-MFN2 miRNA as a serum biomarker for the diagnosis of pancreatic cancer was 0.861 [95%CI (0.775, 1.157), P=0.000]. Cox multivariate analysis showed that the expression of cirC-MFN2 miRNA and lymph node metastasis were independent risk factors for the prognosis of pancreatic cancer patients.ConclusionsCirc-MFN2 miRNA is highly expressed in pancreatic cancer tissues, and it is related to the clinical characteristics and prognosis of patients. It is expected to be a new molecular marker to predict the prognosis of pancreatic cancer.
Objective To investigate the major types and clinical manifestations of mitochondrial DNA (mtDNA)mutations in Chinese patients with Leber′s hereditary optic neuropathy(LHON). Methods A total of 119 patients with bilateral optic neuropathy from 117 pedigrees, including 37 with determinate diagnosis of LHON(group A) and 82 with suspected LHON(group B),were tested for mtDNA mutations by using single-strand conformational polymorphism, mutation-specific primer polymerase chain reaction and sequencing. Pertinent clinical data and history of the patients with the 11778 mutation were collected. Results Nucleotide positions(np)11778 mutation and np 14484 mutation was found in 33 (89.2%) and 3 (8.1%) patients respectively in group A, while np 11778 mutation was obtained in 26（31.7%）in group B. No 3460 mutation was found in group A or B. The clinical manifestations of 59 patients with np 11778 mutation were as follows: acute or chronic visual loss，no ophthalmalgia, the age of onset of 10-25, and either a central or paracentral scotoma in perimetry. The visual recovery rate was 8.6%～11.6%. Conclusion Chinese patients with LHON have a very high incidence of np 11778 mutation and the clinical manifestations of the patients with np 11778 mutation are similar to those of Caucasian patients. (Chin J Ocul Fundus Dis，2004，20：78-80)
Leber hereditary optic neuropathy (LHON) is a matrilineal hereditary optic neuropathy in which mitochondrial DNA mutations lead to retinal ganglion cell degeneration. At present, the treatment for LHON is limited. Early symptomatic treatment and medical treatment may improve the vision of patients. In recent years, rapid progress has been made in gene therapy. Many clinical studies have confirmed its safety and efficacy. Monocular gene therapy is helpful to improve the visual function of LHON patients, and it can also improve the visual acuity of uninjected eyes. Patients do not have serious eye or systemic adverse events during the treatment period, showing good safety and tolerance. Studies with larger sample size and longer follow-up time are needed to further verify the efficacy and safety of gene therapy in the future. Gene therapy is expected to become a safe and effective treatment, bringing hope to LHON patients.
The present study was to investigate the effects of infusing remifentanil-poly-caprolactone (REM-PCL) through the abdominal aorta on spinal cord ischemia reperfusion injury (SCIRI). The model of SCIRI was created by clamping the infrarenal aortic in thirty-six New Zealand white rabbits, which were randomly divided into sham group (group S), control group (group C), and REM-PCL group (group R) with 12 rabbits in each one. The spinal cord microcirculatory blood flow (SCMBF) and blood flow rate (BFR) were monitored before ischemia, 15 min, 30 min, 60 min and 120 min after reperfusion, respectively. Neurologic Function was evaluated before ischemia, 6h, 12h and 24h after reperfusion. The concentration of serum neuron-specific enolase (NSE), interleukin-lβ (IL-lβ) and interleukin-8 (IL-8) were monitored before ischemia, 45 min after ischemia, 30 min, 60 min, 6 h, 12 h and 24 h after reperfusion. The abnormal rate of motor neuron of spinal cord tissues and the level of superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), total anti-oxidation capacity (T-AOC) and mitochondrial swelling degree (MSD) in neural mitochondria were determined before ischemia, 45 min after clamping, 60 min and 120 min after reperfusion. As a result, the neural mitochondrial SOD, GSH-PX and T-AOC decreased while ROS, MDA, MSD, IL-lβ, IL-8 and NSE distinctly increased after clamping of the abdominal aorta as compared to the value before ischemia in group C (P < 0.01). Neurologic function scores recovered more rapidly in group R than those in group C during reperfusion (P < 0.01). The neural mitochondrial SOD, GSH-PX and T-AOC were distinctly higher while ROS, MDA, MSD, IL-lβ, IL-8 and NSE were distinctly lower in group R than those in group C (P < 0.01). The abnormal rate of motor neuron was significantly higher in group C during reperfusion than that in group R (P < 0.01). It has been shown that the intra-aortic REM-PCL infusion can alleviate SCIRI by inhibiting inflammatory response and improving mitochondrial anti-oxidation capacity.
Objective To investigate the spectrum of mitochondrial DNA (mtDNA) mutations in Chinese patients with Leber′s hereditary optic neuropathy (LHON). Methods The primary mtDNA mutations (G3460A、G11778A and T14484 C) of 140 patients with LHON were detected by mutation-specific priming polymerase chain reaction (MSP-PCR), heteroduplex-single strand conformation polymorphism polymerase chain reaction (HA-SSCP), restriction fragment length polymorphisms (RFLP) and measurement of DNA sequence. The transmissibility of the patients′ stirps was analyzed.Results In the 140 patients with LHON, G11778A mtDNA primary mutation was found in 130 (92.9%), including 113 males and 17 females; G3460A mutation was found in 2 (1.4%) including 1 male and 1 female; G14484A mutation was found in 8 (5.7% ) including 6 males and 2 females.Conclusion In Chinese patients with LHON, the incidence of G11778A mtDNA mutation is higher than that of G3460A and T14484C. (Chin J Ocul Fundus Dis，2003，19：269-332)
Objective To review the research progress of mitochondrial dynamics mediated by optic atrophy 1 (OPA1) in skeletal system diseases. MethodsThe literatures about OPA1-mediated mitochondrial dynamics in recent years were reviewed, and the bioactive ingredients and drugs for the treatment of skeletal system diseases were summarized, which provided a new idea for the treatment of osteoarthritis. Results OPA1 is a key factor involved in mitochondrial dynamics and energetics and in maintaining the stability of the mitochondrial genome. Accumulating evidence indicates that OPA1-mediated mitochondrial dynamics plays an important role in the regulation of skeletal system diseases such as osteoarthritis, osteoporosis, and osteosarcoma. Conclusion OPA1-mediated mitochondrial dynamics provides an important theoretical basis for the prevention and treatment of skeletal system diseases.
Optic atrophy,hereditary／diagnosis; Polymerase chain reaction; DNA,mitochondrial; Point mutation; Sequence analysis
ObjectiveTo summarize the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis (OA) and analyze its application prospects. Methods The recent literature at home and abroad was reviewed to summarize the mechanism of mitochondrial homeostasis imbalance, the relationship between mitochondrial homeostasis imbalance and the pathogenesis of OA, and the application prospect in the treatment of OA. Results Recent studies have shown that mitochondrial homeostasis imbalance, which is caused by abnormal mitochondrial biogenesis, the imbalance of mitochondrial redox, the imbalance of mitochondrial dynamics, and damaged mitochondrial autophagy of chondrocytes, plays an important role in the pathogenesis of OA. Abnormal mitochondrial biogenesis can accelerate the catabolic reaction of OA chondrocytes and aggravate cartilage damage. The imbalance of mitochondrial redox can lead to the accumulation of reactive oxygen species (ROS), inhibit the synthesis of extracellular matrix, induce ferroptosis and eventually leads to cartilage degradation. The imbalance of mitochondrial dynamics can lead to mitochondrial DNA mutation, decreased adenosine triphosphate production, ROS accumulation, and accelerated apoptosis of chondrocytes. When mitochondrial autophagy is damaged, dysfunctional mitochondria cannot be cleared in time, leading to ROS accumulation, which leads to chondrocyte apoptosis. It has been found that substances such as puerarin, safflower yellow, and astaxanthin can inhibit the development of OA by regulating mitochondrial homeostasis, which proves the potential to be used in the treatment of OA. Conclusion The mitochondrial homeostasis imbalance in chondrocytes is one of the most important pathogeneses of OA, and further exploration of the mechanisms of mitochondrial homeostasis imbalance is of great significance for the prevention and treatment of OA.