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 review the mechanism and effects of cell autophagy in the pathophysiology changes of peripheral nerve injury. Methods The recent literature about cell autophagy in peripheral nerve injury and regeneration was extensively reviewed and summarized. Results The researches through drugs intervention and gene knockout techniques have confirmed that the Schwann cell autophagy influences the myelin degeneration, debris clearance, inflammatory cells infiltration, and axon regeneration through JNK/c-Jun pathway. To adjust autophagy process could slow down the Wallerian degeneration, maintain the integrity of injured nerve, while the effect on axon regeneration is still controversial. Conclusion The Schwann cell autophagy plays a key role in the pathophysiology changes of peripheral nerve injury, the further study of its mechanism could provide new methods for the therapy of peripheral nerve injury.
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.
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.
ObjectiveTo explore the effects of PKD1 gene on mouse aortic smooth muscle (MOVAS) cells autophagy.MethodsThe shRNA and over-expression lentiviral vectors for the target gene of PKD1 were constructed. MOVAS cells were infected by a number of successful packaging shRNA (PKD1 knockdown) or ETS-1 (PKD1 over-expressing) lentiviral vectors, and qPCR was used to test interference and over-expressing effects. Then qPCR and Western blotting were used to detect the expression levels of autophagy markers including Atg5, Beclin1 and LC3 in control group, shPKD1 group and ETS-1 group.ResultsCompared with the control group, PKD1 mRNA level was decreased in the shPKD1 group (P<0.05); ETS-1 and PKD1 mRNA levels were increased in the ETS-1 group (P<0.05). In contrast with the control group, the mRNA levels of autophagy markers including Atg5 (P<0.05) and Beclin1 (P<0.01) were obviously decreased in the shPKD1 group, but they were obviously increased in the ETS-1 group (P<0.001). Protein levels of Atg5, Beclin1 and LC3 were significantly decreased in the shPKD1 group (P<0.05), but they were increased obviously in the ETS-1 group (P<0.05) in contrast with the control group.ConclusionPKD1 gene is involved in MOVAS cells autophagy, low expression of PKD1 gene can inhibit autophagy and high expression of PKD1 promotes autophagy in vascular smooth muscle cells.
ObjectiveTo summarize the mechanism of hydrogen sulfide (H2S) in regulating autophagy and ameliorating multi-organ dysfunction in the treatment of sepsis.MethodThe relevant literatures at home and abroad in recent years were systematically searched and read to review the mechanism of H2S in regulating autophagy and ameliorating multi-organ dysfunction during sepsis.ResultsAs a new medical gas signal molecule, H2S could regulate autophagy by regulating multiple signal pathways such as Nrf2, NF-κB, MAPK, AMPK, etc., then ameliorated multi-organ dysfunction in sepsis.ConclusionH2S inhibits inflammation, oxidative stress, and apoptosis by regulating autophagy, thus ameliorating multi-organ dysfunction in sepsis, which is expected to become an effective therapeutic target for sepsis.
Nuclear receptors are transcriptional regulators involved in almost all biological processes such as cell growth, differentiation, apoptosis, substance metabolism and tumor formation, and they can be regulated by small molecules that bind to them. Autophagy is a special way of programmed cell death and it is a highly conserved metabolic process. Once autophagy defects or excessive autophagy occur, the disease will develop. In recent years, numerous studies have shown that nuclear receptors are related to autophagy. Therefore, this paper mainly reviews the research progress on nuclear receptors involved in the regulation of autophagy, and focuses on the mechanism of several nuclear receptors involved in the regulation of autophagy, aiming at understanding the molecular basis of how nuclear receptors participate in regulating autophagy, as well as providing possible ideas and strategies for the treatment of corresponding diseases.
ObjectiveTo investigate the mechanism of magnesium sulfate in protecting rabbit cartilage by initiating autophagy.MethodsTwenty-four adult female New Zealand rabbits were used to prepare post-traumatic osteoarthritis (PTOA) models by anterior cruciate ligament transection. Then, the PTOA models were randomly divided into PTOA group, distilled water group, and magnesium sulfate group, with 8 rabbits in each group. Immediately after operation, the distilled water group and the magnesium sulfate group were injected with 0.5 mL distilled water and 20 mmol/L magnesium sulfate solution in the joint cavity 3 times a week for 4 weeks, respectively. The PTOA group was not treated. The general condition of the animals was observed after operation. After 4 weeks, the expressions of tumor necrosis factor α (TNF-α) and collagen typeⅡ in the joint fluid and the expression of collagen type Ⅱ in venous blood were detected by ELISA assay. The protein expressions of transient receptor potential channel vanilloid 5 (TRPV5) and microtubule associated protein 1 light chain 3 (LC3; LC3-Ⅱ/LC3-Ⅰ) in femoral cartilage were detected by Western blot. The mRNA expressions of interleukin 1β (IL-1β), TNF-α, matrix metalloproteinases 3 (MMP-3) in synovial tissue and collagen type Ⅱ, Aggrecan (AGN), SOX9 in cartilage tissue were detected by real-time fluorescence quantitative PCR. Cartilage tissue sections were stained with HE staining, Masson staining, and Alcian blue staining and scored according to the modified histological osteoarthritis (OA) score.ResultsAll animals survived until the experiment was completed. Compared with the other two groups, the expression of TNF-α in joint effusion and collagen type Ⅱ in joint effusion and venous blood were decreased in magnesium sulfate group; the protein expression of TRPV5 decreased, and the ratio of LC3-Ⅱ/LC3-Ⅰ increased significantly; the mRNA expressions of IL-1β, TNF-α, and MMP-3 in synovial tissue were decreased, and the mRNA expressions of collagen type Ⅱ, AGN, and SOX9 in cartilage tissue were increased; OA scores also decreased significantly. All differences were statistically significant (P<0.05). There was no significant difference in the above indicators between the PTOA group and the distilled water group (P>0.05).ConclusionIntra-articular injection of magnesium sulfate can reduce intra-articular inflammation, reduce the loss of collagen type Ⅱ and AGN, and is beneficial to cartilage regeneration in rabbits. The mechanism may be related to the initiation of chondroautophagy by inhibiting the calcium channel TRPV5.
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.
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.