Age-related macular degeneration is one of the major causes of blindness in the elderly. As an important pathway of cell metabolism, autophagy maintains intracellular homeostasis through the degradation and recycle of damaged organelles and macromolecules. Understanding its mechanism may promote discoveries to delay aging process, reduce the incidence of age-related diseases. In mammals, silent information regulator protein 6 (SIRT6) plays its deacetylase and ribonucleotransferase activity in multiple signaling pathways, including inhibition of cellular senescence, tumorigenesis, metabolic diseases, regulating cellular lifespan. It has a significant impact on the structure and function of tissues and organs. SIRT6 regulates intracellular autophagy mainly through the insulin-like growth factor-protein kinase B-mammalian target of rapamycin, reducing the accumulation of toxic metabolites and cellular senescence. The function of SIRT6 in age-related macular degeneration need to be combined with the genetic background, pathogenesis, clinical manifestations and other aspects of the disease, and it is expected to be further studied in subsequent studies.
Neonatal broncho-pulmonary dysplasia (BPD) is a common chronic lung disease in premature infants, with a complex pathogenesis and limited treatment options, severely affecting health. In recent years, targeted autophagy and mesenchymal stem cell (MSC) have received attention as potential therapeutic approaches. Autophagy is crucial in the development of BPD, as it can improve pathological processes such as alveolarization disorders, abnormal pulmonary vascular development, and inflammatory responses through targeted regulation, and enhance the pulmonary microenvironment. Meanwhile, MSC is considered to have promising applications in promoting lung development and repair due to immune regulatory properties and paracrine functions. This article reviews the mechanisms and synergistic effects of targeted autophagy and MSC therapy for BPD, providing a theoretical basis for optimizing clinical treatment strategies for BPD and improving the quality of life of premature infants.
Objective To analyze the hotspots and development trends in the research field of tumor cell apoptosis and autophagy. Methods Relevant literature on tumor apoptosis and autophagy published between January 2012 and December 2021 were searched through the Web of Science core collection database, and CiteSpace 5.8.R3 software and VOSviewer version 1.6.10 software were used to analyze the country/region, institution, keywords and citation node information of the literature. Results A total of 6716 foreign-language articles were included in the study after searching and screening, and the number of papers showed a linear upward trend year by year. China published the largest number of articles and cooperated closely with other research institutions, but there were not many high-quality and influential articles. The two journals Autophagy and Cell were more authoritative in the field of tumor apoptosis and autophagy research. The signaling pathways and related proteins of apoptosis and autophagy, and the study of tumor suppressor mechanisms based on apoptosis/autophagy were current research hot topics. The migration, apoptosis and epithelial mesenchymal transformation of cancer cells would be the research focus and direction in the future. Conclusions In the past 10 years, the research on tumor apoptosis and autophagy has continued to develop. With the in-depth research on the molecular level, the study of its mechanism is expected to further reveal the mystery of tumor apoptosis and autophagy.
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.
ObjectiveTo investigate the role of p22phox and NOX5 in autophagy and apoptosis of osteoblasts induced by hypoxia.MethodsThe skull tissue of newborn rats was cut into small pieces, and the osteoblasts were separated and purified by the tissue block adherent method and the differential adherent method. The first generation cells were harvested and identified by HE staining, Alizarin red staining, alkaline phosphatase (ALP) staining, and flow cytometry. A three-gas incubator was used to prepare a hypoxia model of osteoblasts. At 0, 3, 6, 12, and 24 hours of hypoxia, the expressions of p22phox, NOX5, and LC3Ⅱ/Ⅰ were detected by Western blot, and the level of reactive oxygen species (ROS) and cell apoptosis rate were detected by flow cytometry. And the time point of the highest level of ROS was selected as the hypoxia time point for subsequent experiments. The first generation osteoblasts were divided into normal group, si-p22phox hypoxia group, and si-NOX5 hypoxia group and subjected to corresponding transfection and hypoxia treatment. The inhibition efficiency of si-p22phox and si-NOX5 were detected by RT-PCR. Then the osteoblasts were divided into normal group, si-NC hypoxia group, si-p22phox hypoxia group, and si-NOX5 hypoxia group. After transfection and hypoxia treatment, Western blot was used to detect the expressions of p22phox, NOX5, autophagy-related proteins (LC3Ⅱ/Ⅰ, Beclin), and apoptosis-related proteins (Bcl-2, Bax), and flow cytometry was used to detect the cell apoptosis rate and level of ROS. The first generation osteoblasts were divided into a hypoxia group for 12 hours (hypoxia group) and a group that simultaneously inhibited si-p22phox and si-NOX5 and hypoxia for 12 hours (inhibition+hypoxia group). The expressions of Beclin and Bax were observed by immunofluorescence staining after the corresponding treatment.ResultsAfter identification, the isolated cells were osteoblasts. After hypoxia treatment, the relative expressions of p22phox, NOX5, and LC3Ⅱ/Ⅰ proteins and the apoptosis rate of osteoblasts gradually increased (P<0.05), and the level of ROS also significantly increased (P<0.05) and reached the peak value at 12 hours. The 12-hour hypoxia model was selected for subsequent experiments. Silencing the p22phox gene did not affect the expression of NOX5, and silencing the NOX5 gene did not affect the expression of p22phox. Compared with hypoxia treatment, the relative expressions of LC3Ⅱ/Ⅰ, Beclin, and Bax proteins after inhibiting the expression of p22phox or NOX5 gene significantly decreased (P<0.05), the relative expression of Bcl-2 protein significantly increased (P<0.05), the cell apoptosis rate and level of ROS also significantly decreased (P<0.05). After silencing the expressions of p22phox and NOX5 genes at the same time, the immunofluorescence staining showed that the fluorescence of Beclin and Bax were weak.ConclusionInhibiting the expressions of p22phox and NOX5 genes can reduce the level of ROS in osteoblasts under hypoxia-induced conditions, and at the same time reduce autophagy and apoptosis, especially attenuate the excessive apoptosis of cells in the early to late stages, and strengthen the hypoxic osteoblasts proliferation.
Epilepsy is a heterogeneous disease with a very complex etiological mechanism, characterized by recurrent and unpredictable abnormal neuronal discharge. Epilepsy patients mainly rely on oral antiseizure medication (ASMs) the for treatment and control of disease progression. However, about 30% patients are resistance to ASMs, leading to the inability to alleviate and cure seizures, which gradually evolve into refractory epilepsy. The most common type of intractable epilepsy is temporal lobe epilepsy. Therefore, in-depth exploration of the causes and molecular mechanisms of seizures is the key to find new methods for treating refractory epilepsy. Mitochondria are important organelles within cells, providing abundant energy to neurons and continuously driving their activity. Neurons rely on mitochondria for complex neurotransmitter transmission, synaptic plasticity processes, and the establishment of membrane excitability. The process by which the autophagy system degrades and metabolizes damaged mitochondria through lysosomes is called mitophagy. Mitophagy is a specific autophagic pathway that maintains cellular structure and function. Mitochondrial dysfunction can produce harmful reactive oxygen species, damage cell proteins and DNA, or trigger programmed cell death. Mitophagy helps maintain mitochondrial quality control and quantity regulation in various cell types, and is closely related to the occurrence and development of epilepsy. The imbalance of mitophagy regulation is one of the causes of abnormal neuronal discharge and epileptic seizures. Understanding its related mechanisms is crucial for the treatment and control of the progression of epilepsy in patients.
ObjectiveTo evaluate the effects of icariin on autophagy induced by low-concentration of glucocorticoid and exosome production in bone microvascular endothelial cells (BMECs).MethodsBMECs were isolated from femoral heads resected in total hip arthroplasty and then intervened with hydrocortisone of low concentration (0, 0.03, 0.06, 0.10 mg/mL), which were set as groups A, B, C, and D, respectively. On the basis of hydrocortisone intervention, 5×10−5 mol/L of icariin was added to each group (set as groups A1, B1, C1 and D1, respectively). Western blot was used to detect the expressions of microtubule-associated protein 1 light chain 3B (LC3B) and dead bone slice 1 (p62) after 24 hours. Exosomes were extracted from BMECs treated with icariin (intervention group) and without icariin (non-intervention group), and the diameter and concentration of exosomes were evaluated by nanoparticle tracking analysis technique. The total protein content of exosomes was detected by BCA method, and the expressions of proteins carried by exosomes including CD9, CD81, transforming growth factor β1 (TGF-β1), and vascular endothelial growth factor A (VEGFA) were assessed by Western blot. The BMECs were further divided into three groups: BMECs in the experimental group and the control group were co-cultured with exosomes secreted by BMECs treated with or without icariin, respectively; the blank control group was BMECs without exosome intervention. The three groups were treated with hydrocortisone and Western blot was used to detect the expressions of LC3B and p62. The scratching assay was used to detect cell migration ability; angiogenic ability of BMECs was also assessed.ResultsWith the increase of hydrocortisone concentration, the protein expression of LC3B-Ⅱ increased gradually, and the protein expression of p62 decreased gradually (P<0.01). Compared with group with same concentration of hydrocortisone, the protein expression of LC3B-Ⅱ decreased and the protein expression of p62 increased after the administration of icariin (P<0.01). The concentration of exosomes in the intervention group was significantly higher than that in the non-intervention group (t=−10.191, P=0.001); and there was no significant difference in exosome diameter and total protein content between the two groups (P>0.05). CD9 and CD81 proteins were highly expressed in the non-intervention group and the intervention group, and the relative expression ratios of VEGFA/CD9 and TGF-β1/CD9 proteins in the intervention group were significantly higher than those in the non-intervention group (P<0.01). After co-culture of exosomes, the protein expression of p62 increased in blank control group, control group, and experimental group, while the protein expression of LC3B-Ⅱ decreased. There were significant differences among groups (P<0.05). When treated with hydrocortisone for 12 and 24 hours, the scratch closure rate of the control group and experimental group was significantly higher than that of the blank control group (P<0.05), and the scratch closure rate of the experimental group was significantly higher than that of the control group (P<0.05). When treated with hydrocortisone for 4 and 8 hours, the number of lumens, number of sprouting vessels, and length of tubule branches in the experimental group and the control group were significantly greater than those in the blank control group (P<0.05); the length of tubule branches and the number of lumens in the experimental group were significantly greater than those in the control group (P<0.05).ConclusionIcariin and BMECs-derived exosomes can improve the autophagy of BMECs induced by low concentration of glucocorticoid.
ObjectiveTo systematically evaluate relationship between expression of autophagy-related protein Beclin-1 in gastric cancer and its clinicopathologic features and its clinical significances.MethodsThe researches on the expression and significance of Beclin-1 protein in the gastric tumor tissues published from the database establishment to June 1, 2018 in the Cochrane Library, Springer Link, Web of Science, Embase, PubMed, CNKI, Wanfang, VIP, and other databases were searched. Two researchers independently screened and evaluated the literatures, extracted the relevant data, and conducted the meta-analysis using the Review Manager 5.3 and Stata 15.0 software.ResultsFinally, 10 articles were included, and there were 1 402 patients with gastric cancer. The meta-analysis showed that the positive rate of Beclin1 protein expression in the gastric cancer tissues was significantly lower than that in the non-gastric cancer tissues [OR=0.30, 95% CI (0.13, 0.72), P=0.007], which in the patients with TNM stage Ⅲ/Ⅳ and distant metastatic gastric cancer were significantly lower than those in the patients with stage Ⅰ/Ⅱ [OR=1.82, 95% CI (1.03, 3.20), P=0.04] and without distant metastasis [OR=0.36, 95% CI (0.20, 0.63), P=0.000 4], which were not associated with the gender, age, tumor size, lymph node metastasis, serosa invasion, and tumor differentiation degree of gastric cancer patients (P>0.05). For the studies of existed heterogeneity, further the subgroup analysis showed that the positive expression rate of Beclin-1 protein in the gastric cancer tissues was significantly lower than that in the non-gastric cancer tissues [OR=0.19, 95% CI (0.13, 0.29), P<0.000 01], which in the patients with lymph node metastasis, invasion of serosa, and poorly differentiated gastric cancer were significantly lower than those in the non-lymph node metastasis [OR=0.35, 95% CI (0.22, 0.57), P<0.000 1], non-invasion of serosa [OR=0.56, 95% CI (0.33, 0.94), P=0.03], and moderately/highly differentiated gastric cancer tissues [OR=0.29, 95% CI (0.20, 0.43), P<0.000 01].ConclusionsLow expression of Beclin-1 in gastric cancer tissues is related to stage and distant metastasis of gastric cancer. It is suggested that it might not only be an important cause of gastric cancer, but also play a regulatory role in progress of gastric cancer.
Diabetes retinopathy (DR) is a blinding ocular complication of diabetes, and its pathological mechanism is complex. The damage to the retinal neurovascular unit (NVU) and the imbalance of its coupling mechanism are important pathological foundations. Autophagy plays an important role in the progression of DR. Oxidative stress, endoplasmic reticulum stress, hypoxia, and competitive endogenous RNA regulatory networks can affect the occurrence of autophagy, and autophagy induced cell death is crucial in NVU dysfunction. Retinal neurocyte are non- renewable cells, and adaptive autophagy targeting neuronal cells may provide a new direction for early vision rescue in patients with DR. It is necessary that exploring the possible autophagy interrelationships between ganglion cells, glial cells, and vascular constituent cells, searching for targeted specific cell autophagy inhibitors or activators, and exploring the impact of autophagy on the NVU complex more comprehensively at the overall level. Adopting different autophagy intervention methods at different stages of DR may be one promising research directions for future DR.