Objective To investigate the role of mitochondrial autophagy mediated by PINK1 (homologous phosphatase tensin induced kinase 1) /Parkin (Parkinson’s protein) signaling pathway in severe pneumonia of rats. Methods Twenty rats were randomly divided into control group and model group (severe pneumonia model), with 10 rats in each group, to explore the effects of severe pneumonia on lung function and pathology in rats. Then, 30 rats were randomly divided into control group, model group and mdivi-1 (mitochondrial autophagy inhibitor) group, with 10 rats in each group, to further explore the effects of severe pneumonia on mitochondrial autophagy indicators of rats. ResultsCompared with the control group, the resting ventilation volume [(3.44±0.22) vs. (1.58±0.18) mL/min] and airway resistance ratio (77.48±3.84 vs. 47.76±5.54) in the model group were decreased (P<0.05). In the model group, the lung tissue was injured and a large number of inflammatory cells were infiltrated. The protein and mRNA expression levels of Parkin, PINK1 and microtubule-associated protein1 light chain 3 in lung tissues of model group were increased (P<0.05). Compared with model group, the ratio of resting ventilator-to-airway resistance in mdivi-1 group increased (P<0.05). The injury and inflammatory infiltration of lung tissue were improved in mdivi-1 group. The expression levels of Parkin, PINK1 and microtubule-associated protein1 light chain 3 protein and mRNA in lung tissues of mdivi-1 group were decreased (P<0.05). Conclusion Mdivi-1 can improve the abnormal lung function structure in rats with severe pneumonia, and the mechanism may be related to mitochondrial autophagy mediated by PINK1/Parkin signaling pathway.
Epilepsy is one of the most common neurological disorders, and status epilepticus (SE) can lead to permanent neuronal brain damage in the central nervous system, but the mechanism is not clear. Solving this problem will help to find more SE therapeutic targets, benefiting tens of millions of epilepsy patients. The pathway of SE leading to neuronal damage in the brain has made new progress in neuroinflammation, autophagy, apoptosis and pyroptosis, glial cell hyperplasia and category transformation, and changes in neurotransmitters in the brain, which will be beneficial to the discovery of new targets for the treatment of SE, thus laying a foundation for the development of new anti-epileptic drugs.
ObjectiveTo summarize the recent advances in the relationship between long non-coding RNA (LncRNA) and tumor autophagy, autophagy and drug resistance regulation.MethodsReviewed the relevant literatures at home and abroad, and reviewed the recent research progress of LncRNA regulation of autophagy to affect tumor resistance.ResultsDrug resistance was a common problem in the process of anti-tumor therapy. Autophagy played an important role in the process of tumor resistance as an important mechanism to maintain cell homeostasis. Abnormal regulation of LncRNA could contribute to the occurrence and development of tumors, and could also mediate the resistance of tumor cells to anti-tumor drugs by promoting or inhibiting autophagy.ConclusionsLncRNA can mediate tumor autophagy in a positive or negative direction, and autophagy is a " double-edged sword” for tumor resistance. LncRNA may improve tumor resistance to drugs by regulating autophagy.
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.
Objective To explore the relationship between Beclin-1 and the development of pancreatic ductal adenocarcinoma (PDAC). Methods ① Twenty-five PDAC specimens and 20 matched adjacent normal pancreatic tissues were obtained after radical surgery between April 2009 and November 2009 in West China Hospital of Sichuan University. Beclin-1 mRNA and protein expressions were examined by using real-time PCR and immunohistochemistry, respectively. Correlations between expressions of Beclin-1 protein with clinical data of PDAC patients were evaluated. ② PDAC cells were divided into 2 groups, cells of transfection group were transfected with PLenO-WPI-Beclin-1 vector, and cells of non-transfection group didn’t transfected with PLenO-WPI-Beclin-1 vector. Expressions levels of Beclin-1 mRNA in the 2 groups were detected by real-time PCR at 24 hours and 48 hours after transfection. ③ PDAC cells were divided into 3 groups, cells of transfection group were transfected with PLenO-WPI-Beclin-1 vector, cells of empty vector group transfected with PLenO-WPI, cells of blank control group didn’t accepted any vector. OD value was detected by MTT once a day during 1–7 days after transfection. Results ① Expression levels of Beclin-1 mRNA and its protein were significantly lower in PDAC tissue than those of adjacent normal pancreatic tissues (P<0.05). Increased Beclin-1 expression was associated with early TNM stage of Ⅰ and Ⅱ(P<0.05) and negative distant metastasis (P=0.011). ② At the same time point of 24 hours and 48 hours after transfection, the expression levels of Beclin-1 mRNA were higher in transfection group than those of non-transfection group (P<0.05). ③ MTT assay showed that PANC-1 cell proliferation ability was lower in the transfection group compared to the blank control group and empty vector groups in vitro on day 4–7 after transfection (P<0.05), but there was no significant in the cell proliferation ability among the 3 groups on day 1, 2, and 3 (P>0.05). Conclusions Down regulation of Beclin-1 and autophagy inhibition play an important role in the tumorigenesis and development of PDAC. Activating autophagy via overexpression of Beclin-1 may be a potential treatment for some PDACs and warrants further investigation.
Immunoglobulin A nephropathy (IgAN) is an immune-mediated chronic inflammatory disease with a complex pathogenesis and diverse clinical manifestations. Currently, there is no specific treatment plan. Programmed cell death is an active and orderly way of cell death controlled by genes in the body, which maintains the homeostasis of the body and the development of organs and tissues by participating in various molecular signaling pathways. In recent years, programmed cell death has played an important regulatory role in the occurrence and development of IgAN, involving complex signaling pathways. Under pathological conditions, it may relieve kidney damage through various pathways such as reducing oxidative stress, inhibiting inflammation, and improving energy metabolism. This article provides a review of the research progress of IgAN in apoptosis, autophagy, pyroptosis, ferroptosis,and cuproptosis in order to provide new therapeutic targets for IgAN.
Objective To investigate the effect of epigallocatechin gallate (EGCG) on chondrocyte senescence and its mechanism. Methods The chondrocytes were isolated from the articular cartilage of 4-week-old Sprague Dawley rats, and cultured with type Ⅱcollagenase and passaged. The cells were identified by toluidine blue staining, alcian blue staining, and immunocytochemical staining for type Ⅱ collagen. The second passage (P2) cells were divided into blank control group, 10 ng/mL IL-1β group, and 6.25, 12.5, 25.0, 50.0, 100.0, and 200.0 μmol/L EGCG+10 ng/mL IL-1β group. The chondrocyte activity was measured with cell counting kit 8 after 24 hours of corresponding culture, and the optimal drug concentration of EGCG was selected for the subsequent experiment. The P2 chondrocytes were further divided into blank control group (group A), 10 ng/mL IL-1β group (group B), EGCG+10 ng/mL IL-1β group (group C), and EGCG+10 ng/mL IL-1β+5 mmol/L 3-methyladenine (3-MA) group (group D). After cultured, the degree of cell senescence was detected by β-galactosidase staining, the autophagy by monodansylcadaverine method, and the expression levels of chondrocyte-related genes [type Ⅱ collagen, matrix metalloproteinase 3 (MMP-3), MMP-13] by real-time fluorescent quantitative PCR, the expression levels of chondrocyte-related proteins (Beclin-1, LC3, MMP-3, MMP-13, type Ⅱ collagen, P16, mTOR, AKT) by Western blot. Results The cultured cells were identified as chondrocytes. Compared with the blank control group, the cell activity of 10 ng/mL IL-1β group significantly decreased (P<0.05). Compared with the 10 ng/mL IL-1β group, the cell activity of EGCG+10 ng/mL IL-1β groups increased, and the 50.0, 100.0, and 200.0 μmol/L EGCG significantly promoted the activity of chondrocytes (P<0.05). The 100.0 μmol/L EGCG was selected for subsequent experiments. Compared with group A, the cells in group B showed senescence changes. Compared with group B, the senescence rate of chondrocytes in group C decreased, autophagy increased, the relative expression of type Ⅱ collagen mRNA increased, and relative expressions of MMP-3 and MMP-13 mRNAs decreased; the relative expressions of Beclin-1, LC3, and type Ⅱ collagen proteins increased, but the relative expressions of P16, MMP-3, MMP-13, mTOR, and AKT proteins decreased; the above differences were significant (P<0.05). Compared with group C, when 3-MA was added in group D, the senescence rate of chondrocytes increased, autophagy decreased, and the relative expressions of the target proteins and mRNAs showed an opposite trend (P<0.05). ConclusionEGCG regulates the autophagy of chondrocytes through the PI3K/AKT/mTOR signaling pathway and exerts anti-senescence effects.
Neuropathic pain (NP) is a pathological state caused by damage or disease to the somatosensory nervous system. Programmed cell death (PCD) is an orderly process of cell death regulated by both intrinsic signals and external stimuli. In recent years, an increasing number of studies have shown that PCD plays a key regulatory role in the pathogenesis of NP. This article reviews the molecular mechanisms of various types of PCD and their specific roles in NP, in order to provide new research directions for the prevention, diagnosis, and treatment of NP.
ObjectiveTo investigate the mechanism of early vascularization of the tissue engineered bone in the treatment of rabbit radial bone defect by local injection of angiopoietin 2 (Ang-2).MethodsForty-eight New Zealand white rabbits were established unilateral 1.5 cm long radius defect models. After implantation of hydroxyapatite/collagen scaffolds in bone defects, the rabbits were randomly divided into 2 groups: control group (group A) and Ang-2 group (group B) were daily injected with 1 mL normal saline and 1 mL saline-soluble 400 ng/mL Ang-2 at the bone defect within 2 weeks after operation, respectively. Western blot was used to detect the expressions of autophagy related protein [microtubule associated protein 1 light chain 3 (LC3), Beclin-1], angiogenesis related protein [vascular endothelial growth factor (VEGF)], and autophagy degradable substrate protein (SQSTMl/p62) in callus. X-ray films examination and Lane-Sandhu X-ray scoring were performed to evaluate the bone defect repair at 4, 8, and 12 weeks after operation. The rabbits were sacrificed at 12 weeks after operation for gross observation, and the angiogenesis of bone defect area was observed by HE staining.ResultsWestern blot assay showed that the relative expressions of LC3-Ⅱ/LC3-Ⅰ, Beclin-1, and VEGF in group B were significantly higher than those in group A, and the relative expression of SQSTMl/p62 was significantly lower than that in group A (P<0.05). Radiographic and gross observation of specimens showed that only a few callus were formed in group A, the bone defect was not repaired; more callus were formed and complete repair of bone defect was observed in group B. The Lane-Sandhu scores in group B were significantly higher than those in group A at 4, 8, and 12 weeks after operation (P<0.05). HE staining showed that the Harvard tubes in group B were well arranged and the number of new vessels was significantly higher than that in group A (t=–11.879, P=0.000).ConclusionLocal injection of appropriate concentration of Ang-2 may promote early vascularization and bone defect repair of tissue engineered bone in rabbits by enhancing autophagy.
Atherosclerotic cardiovascular disease (ASCVD) is a disease caused by the accumulation of atherosclerotic plaques that leads to arterial hardening and impairment of contractility. Proprotein convertase subtilisin/kexin type 9 (PCSK9) can increase low-density lipoprotein cholesterol levels in plasma, which accelerates the development and progression of ASCVD. This article intends to review the biological characteristics and functional mechanisms of PCSK9, elucidate its impact on the development and progression of ASCVD, provide research literature support for the diagnosis and treatment of such diseases and improving the prognosis of patients.