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 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.
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.
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.
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.
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.
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.
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 analyze the expression and significance of NF-κBp65 and autophagy-related proteins Beclin1 and p62 in patients with papillary thyroid carcinoma (PTC).MethodsOne hundred and sixty cases of PTC patients' tumor tissue specimens and paracancerous tissue specimens in our hospital from March 2013 to February 2015 were collected, and 90 cases of cervical lymph node metastasis tissue specimens of the above patients were collected. The expressions of NF-κBp65, Beclin1 and p62 in PTC tissues, metastatic lymph node tissues and paracancerous tissues were detected by immunohistochemical method, and the relationship between the above indexes and the clinicopathological characteristics and prognosis of PTC patients was analyzed.ResultsThe positive rates of expression of NF-kappa Bp65 and p62 in PTC tissues and metastatic lymph node tissues were higher than those in paracancerous tissues (P<0.05). The expression rate of Beclin1 in PTC tissues and metastatic lymph node tissues was lower than that in paracancerous tissues (P<0.05). The positive rate of NF-κBp65 expression in PTC tissues was not related to the clinicopathological characteristics of patients (P>0.05). The expression of p62 decreased with the increase of tumor differentiation (P<0.05). The expression of Beclin1 in patients with stage Ⅲ+Ⅳ and lymph node metastasis were lower than those in patients with stage Ⅰ+Ⅱ and without lymph node metastasis (P<0.05), while the expression of p62 was opposite. Spearman correlation analysis showed that the expression of Beclin1 and p62 in PTC tissues was negatively correlated (r=–0.656, P<0.01). In metastatic lymph node tissues, the expression of Beclin1 and p62 was also negatively correlated (r=–0.562, P<0.01). The 3-year survival rates of patients with positive expression of p62 and NF-κBp65 in PTC tissues were lower than that of patients with negative expression (P<0.05). The 3-year survival rate of patients with positive expression of Becrin1 was higher than that of negative expression (P<0.05). TNM stage, lymph node metastasis, NF-κBp65 and p62 were independent risk factors for PTC prognosis, and Beclin1 was protective factor.ConclusionsNF-κBp65 and p62 are highly expressed in PTC tissues and lymph node metastasis tissues, while Beclin1 is poorly expressed, which could be used as independent prognostic factors for PTC patients. In addition, Beclin1 and p62 are related to PTC biological behavior and may become potential indicators for PTC diagnosis.
Objective To investigate whether miRNA (miR)-34a mediates oxaliplatin (OXA) resistance of colon cancer cells by inhibiting macroautophagy via the transforming growth factor (TGF)-β/Smad4 pathway. Methods miR-34a expression levels were detected in colon cancer tissues and colon cancer cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Computational search, functional luciferase assay, and Western blotting method were used to demonstrate the downstream target of miR-34a in colon cancer cells. Cell viability was measured with cell counting kit-8. Apoptosis and macroautophagy of colon cancer cells were analyzed by flow cytometry and transmission electron microscopy, and expressions of Beclin1 and LC3Ⅱ protein were detected by Western blotting method. Results Expression of miR-34a was significantly reduced while expressions of TGF-β and Smad4 mRNA were increased in colon cancer patients treated with OXA-based chemotherapy. OXA treatment also resulted in decreased miR-34a expression levels and increased TGF-β and Smad4 expression levels in both parental cells and the OXA-resistant colon cancer cells. Activation of macroautophagy contributed to OXA resistance in colon cancer cells. Expression levels of Smad4 and miR-34a in colon cancer patients had a significant inverse correlation and overexpressing miR-34a inhibited macroautophagy activation by directly targeting Smad4 through the TGF-β/Smad4 pathway. OXA-induced downregulation of miR-34a and increased drug resistance by activating macroautophagy in colon cancer cells. Conclusion miR-34a mediates OXA resistance of colon cancer by inhibiting autophagy via the TGF-β/Smad4 pathway.