Ribosome is an intracellular ribonucleoprotein particle that serves as the site of protein biosynthesis. Ribosomal dysfunction caused by mutations in genes encoding ribosomal proteins (RPs) and ribosome biogenesis factors (RBFs) can lead to a spectrum of diseases, collectively known as ribosomopathy. Phase separation is a thermodynamic process that produces multiple phases from a homogeneous mixture. The formation of membraneless organelles and intracellular structures, including ribosomes and nucleoli, cannot occur without the involvement of phase separation. Here, ribosome structure, biogenesis, and their relationship with ribosomopathy are systematically reviewed. The tissue specificity of ribosomopathy and the role of phase separation in ribosomopathy are particularly discussed, which may offer some clues for understanding the mechanisms of ribosomopathy. Then, some new ideas for the prevention, diagnosis, and treatment of ribosomopathy are provided.
Humans ; Ribosomes/physiology* ; Ribosomal Proteins/metabolism* ; Mutation ; Animals ; Cell Nucleolus/metabolism* ; Protein Biosynthesis ; Phase Separation

Objective:To explore the effects of quercetin on autophagy and proliferation in HBV-positive liver cancer HCCLM3 cells based on STING signaling and its underlying mechanism.Methods:HCCLM3 cells were treated with quercetin (50 μmol/L or 100 μmol/L), designated as the 50 μmol/L group and 100 μmol/L group, respectively. The inhibitory effect of quercetin on HCCLM3 cells was detected using the CCK-8 method. A scratch assay was conducted to assess the impact of quercetin on the migration ability of HCCLM3 cells. A CCK8 and ROS kit was used to detect the effect of quercetin on the levels of reactive oxygen species in HCCLM3 cells. Western blotting was employed to measure the effect of quercetin on the expression of STING signaling and autophagy-related proteins in HCCLM3 cells. RNA interference technology was used to assess the effects of STING signaling inhibition on the expression of autophagy-related proteins and reactive oxygen species levels in HCCLM3 cells. The combined effects of STING activators and quercetin on HCCLM3 cell proliferation and autophagy were evaluated. The t-test was used to detect data differences between two groups, while ANOVA was employed for comparisons among multiple groups, followed by the SNK- q test for further pairwise comparisons. Results:Compared with the control group, quercetin (50 μmol/L and 100 μmol/L groups) significantly inhibited HCCLM3 cell survival activity in a dose-dependent manner (control group: 100%; 50 μmol/L group: 75.25%; 100 μmol/L group: 50.36%, P<0.01 ). Quercetin inhibited HCCLM3 cell migration in a dose-dependent manner (>2 h, control group: 187.16 μm; 50 μmol/L group: 145.22 μm; 100 μmol/L group: 88.21 μm, P<0.01), which significantly increased intracellular reactive oxygen species (ROS) levels in HCCLM3 cells (control group: 1.00; 50 μmol/L group: 1.565; 100 μmol/L group: 2.175, P<0.01). The phosphorylation level of STING was significantly increased ( P<0.01), and the expression of autophagy-related protein microtubule-related protein 1A/1B light chain 3 (LC3) protein was significantly promoted ( P<0.01). Compared with the quercetin group, the cell viability of the small interfering-STING+quercetin group was increased (quercetin group: 56.3%; small interfering-STING+quercetin group: 85.7%, P<0.05), while the expression of autophagy-related protein LC3 was decreased. Compared with the quercetin group, the cell viability of the quercetin+STING activator group was further decreased (quercetin group: 56.7%; quercetin+STING activator group: 35.4%, P<0.01), and the expression levels of STING and autophagy protein LC3 were significantly increased ( P<0.05). Conclusions:STING signaling-regulated cell autophagy mediates the inhibitory effect of quercetin on the proliferation of HCCLM3 cells, and this effect is enhanced after administration of the STING agonist.

Objective:To explore the effects of quercetin on autophagy and proliferation in HBV-positive liver cancer HCCLM3 cells based on STING signaling and its underlying mechanism.Methods:HCCLM3 cells were treated with quercetin (50 μmol/L or 100 μmol/L), designated as the 50 μmol/L group and 100 μmol/L group, respectively. The inhibitory effect of quercetin on HCCLM3 cells was detected using the CCK-8 method. A scratch assay was conducted to assess the impact of quercetin on the migration ability of HCCLM3 cells. A CCK8 and ROS kit was used to detect the effect of quercetin on the levels of reactive oxygen species in HCCLM3 cells. Western blotting was employed to measure the effect of quercetin on the expression of STING signaling and autophagy-related proteins in HCCLM3 cells. RNA interference technology was used to assess the effects of STING signaling inhibition on the expression of autophagy-related proteins and reactive oxygen species levels in HCCLM3 cells. The combined effects of STING activators and quercetin on HCCLM3 cell proliferation and autophagy were evaluated. The t-test was used to detect data differences between two groups, while ANOVA was employed for comparisons among multiple groups, followed by the SNK- q test for further pairwise comparisons. Results:Compared with the control group, quercetin (50 μmol/L and 100 μmol/L groups) significantly inhibited HCCLM3 cell survival activity in a dose-dependent manner (control group: 100%; 50 μmol/L group: 75.25%; 100 μmol/L group: 50.36%, P<0.01 ). Quercetin inhibited HCCLM3 cell migration in a dose-dependent manner (>2 h, control group: 187.16 μm; 50 μmol/L group: 145.22 μm; 100 μmol/L group: 88.21 μm, P<0.01), which significantly increased intracellular reactive oxygen species (ROS) levels in HCCLM3 cells (control group: 1.00; 50 μmol/L group: 1.565; 100 μmol/L group: 2.175, P<0.01). The phosphorylation level of STING was significantly increased ( P<0.01), and the expression of autophagy-related protein microtubule-related protein 1A/1B light chain 3 (LC3) protein was significantly promoted ( P<0.01). Compared with the quercetin group, the cell viability of the small interfering-STING+quercetin group was increased (quercetin group: 56.3%; small interfering-STING+quercetin group: 85.7%, P<0.05), while the expression of autophagy-related protein LC3 was decreased. Compared with the quercetin group, the cell viability of the quercetin+STING activator group was further decreased (quercetin group: 56.7%; quercetin+STING activator group: 35.4%, P<0.01), and the expression levels of STING and autophagy protein LC3 were significantly increased ( P<0.05). Conclusions:STING signaling-regulated cell autophagy mediates the inhibitory effect of quercetin on the proliferation of HCCLM3 cells, and this effect is enhanced after administration of the STING agonist.

Objective To investigate the role of RNA-binding motif protein X-linked(RBMX)in regulating the proliferation,migration,invasion and glycolysis in human bladder cancer cells.Methods A lentivirus vectors system and RNA interference technique were used to construct bladder cancer 1376 and UC-3 cell models with RBMX overexpression and knockdown,respectively,and successful cell modeling was verified using RT-qPCR and Western blotting.Proliferation and colony forming ability of the cells were evaluated using EdU assay and colony-forming assay,and cell migration and invasion abilities were determined using Transwell experiment.The expressions of glycolysis-related proteins M1 pyruvate kinase(PKM1)and M2 pyruvate kinase(PKM2)were detected using Western blotting.The effects of RBMX overexpression and knockdown on glycolysis in the bladder cancer cells were assessed using glucose and lactic acid detection kits.Results RT-qPCR and Western blotting confirmed successful construction of 1376 and UC-3 cell models with RBMX overexpression and knockdown.RBMX overexpression significantly inhibited the proliferation,clone formation,migration and invasion of bladder cancer cells,while RBMX knockdown produced the opposite effects.Western blotting results showed that RBMX overexpression increased the expression of PKM1 and decreased the expression of PKM2,while RBMX knockdown produced the opposite effects.Glucose consumption and lactate production levels were significantly lowered in the cells with RBMX overexpression(P<0.05)but increased significantly following RBMX knockdown(P<0.05).Conclusion RBMX overexpression inhibits bladder cancer progression and lowers glycolysis level in bladder cancer cells by downregulating PKM2 expression,suggesting the potential of RBMX as a molecular target for diagnosis and treatment of bladder cancer.

Objective To investigate the role of RNA-binding motif protein X-linked(RBMX)in regulating the proliferation,migration,invasion and glycolysis in human bladder cancer cells.Methods A lentivirus vectors system and RNA interference technique were used to construct bladder cancer 1376 and UC-3 cell models with RBMX overexpression and knockdown,respectively,and successful cell modeling was verified using RT-qPCR and Western blotting.Proliferation and colony forming ability of the cells were evaluated using EdU assay and colony-forming assay,and cell migration and invasion abilities were determined using Transwell experiment.The expressions of glycolysis-related proteins M1 pyruvate kinase(PKM1)and M2 pyruvate kinase(PKM2)were detected using Western blotting.The effects of RBMX overexpression and knockdown on glycolysis in the bladder cancer cells were assessed using glucose and lactic acid detection kits.Results RT-qPCR and Western blotting confirmed successful construction of 1376 and UC-3 cell models with RBMX overexpression and knockdown.RBMX overexpression significantly inhibited the proliferation,clone formation,migration and invasion of bladder cancer cells,while RBMX knockdown produced the opposite effects.Western blotting results showed that RBMX overexpression increased the expression of PKM1 and decreased the expression of PKM2,while RBMX knockdown produced the opposite effects.Glucose consumption and lactate production levels were significantly lowered in the cells with RBMX overexpression(P<0.05)but increased significantly following RBMX knockdown(P<0.05).Conclusion RBMX overexpression inhibits bladder cancer progression and lowers glycolysis level in bladder cancer cells by downregulating PKM2 expression,suggesting the potential of RBMX as a molecular target for diagnosis and treatment of bladder cancer.

Objective:To analyze the effect of perioperative SEPT9 level in peripheral blood on long-term prognosis of patients with colorectal tumors. Methods:Retrospectively analyzed the data of 334 patients with colorectal cancer admitted to the Department of Anus & Intestine Surgery from January 2017 to December 2022, including 197 male patients and 137 female patients, aged 29 to 83 (62.8±10.7) years. Positive group was consisted of 241 patients with positive SEPT9 before surgery, while negative group was consisted of 93 patients with negative SEPT9 before surgery. Among the positive group, 169 cases turned negative for SEPT9 on the one week after surgery (transnegative group), and another 72 cases did not turn negative (non negative group). Univariate and multivariate analysis of clinical general data were carried out to screen out the risk factors affecting the long-term prognosis of colorectal cancer patients after surgery. The survival curve was calculated by Kaplan-Meier method, and the Log-rank test was used to compare the difference in survival rate between groups. Results:All patients′ overall median survival time was 67 months, and the 1, 3 and 5 years overall survival rate was 91.9%, 70.9% and 57.1%. The results of multi-factor analysis showed that whether the tumor had lymph node metastasis, TNM stage, and preoperative SEPT9 methylation status were independent risk factors affecting the long-term prognosis of colorectal cancer ( P=0.004, <0.001, 0.041), while for patients with preoperative SEPT9 positive, TNM stage of tumor and whether SEPT9 turned negative after surgery were independent risk factors for prognosis ( P=0.026, 0.001). The median survival time of patients in positive group and negative group was 63 months and 71 months, respectively. The 1, 3 and 5 year survival rates after surgery were 90.4%, 67.0%, 55.0% and 95.7%, 79.1% and 64.6%, respectively( P=0.007). The median survival time of the patients in the transnegative group and nonnegative group was 45 months and 62 months, respectively. The 1, 3 and 5-year survival rates were 83.2%, 60.5%, 48.1% and 93.5%, 72.9%, 63.5%( P<0.001). Conclusions:Perioperative SEPT9 level is correlated with long-term prognosis of CRC patients, and patients with negative SEPT9 before surgery have better prognosis than those with positive SEPT9. Preoperative positive patients who do not turn negative after surgery often indicate poor prognosis of tumor.

Objective:To explore the effect of the developmental stages and quality on pregnancy outcome and birth outcome, and provide evidence for single blastocyst selection in frozen-thawed cycles.Methods:A retrospective cohort study analysis was performed on the data of patients with a total of 893 cycles who underwent single blastocyst transfer in frozen-thawed cycles in the Center for Reproductive Medicine, Qingyuan People's Hospital from January 2013 to June 2021. The cycles were divided into day 5 (D5) and day 6 (D6) groups according to the time of blastocyst formation. Then the two groups were divided into four subgroups according to the quality of blastocyst, namely, D5 good-quality embryo subgroup, D5 non-good-quality embryo subgroup, D6 good-quality embryo subgroup and D6 non-good-quality embryo subgroup. The general data, clinical outcomes and neonatal outcomes of each group were compared.Results:1) The clinical pregnancy rate [60.14% (332/552)], the implantation rate [60.14% (332/552)] and the live birth rate [47.64% (263/552)] in D5 group were significantly higher than those in D6 group [45.75% (156/341), 45.75% (156/341), 36.36% (124/341), all P<0.001], but there were no significant differences in body mass index, duration of infertility, intimal thickness of transplantation day and miscarriage rate between the two groups (all P>0.05). In addition, there were also no significant differences in birth weight, low birth weight rate, fetal macrosomia rate and male/female ratio (all P>0.05). 2) There were significant differences in clinical pregnancy rate [61.00% (294/482), 54.29% (38/70), 51.00% (127/249), 31.52% (29/92)] and live birth rate [48.96% (236/482), 38.57% (27/70), 41.37% (103/249), 22.83% (21/92)] among D5 good-quality embryo subgroup, D5 non-good-quality embryo subgroup, D6 good-quality embryo subgroup and D6 non-good-quality embryo subgroup (all P<0.001). D5 good-quality embryo subgroup had the highest clinical pregnancy rate and live birth rate, while D6 non-good-quality embryo subgroup had the lowest clinical pregnancy rate and live birth rate. There were also no significant differences in birth weight, fetal macrosomia rate and male/female ratio among the four subgroups (all P>0.05), while there was a significant difference in low birth weight rate [5.08% (12/236), 0 (0/27), 4.85% (5/103), 23.81% (5/21)] among the four subgroups ( P=0.014). 3) There were no significant differences in clinical pregnancy rate and live birth rate between D5 non-good-quality embryo subgroup and D6 good-quality embryo subgroup (all P>0.05). The clinical pregnancy rate and the live birth rate of 4BC in D5 were lower than those of 4AA, 4AB and 4BA in D6, while the miscarriage rate of 4BC in D5 was higher than that of 4AA, 4AB and 4BA in D6, but there were no significant differences (all P>0.05).The clinical pregnancy rate and the live birth rate of 4BC in D5 were higher than those of 4BB in D6, but there were no significant differences (all P>0.05). Conclusion:In the frozen-thawed cycle of single blastocyst transplantation, D5 good-quality blastocysts are preferred. When faced with D5 non-good-quality embryos and D6 good-quality embryos, the optimal choice was D6 4AA>D6 4BA>D6 4AB>D5 4BC>D6 4BB.

Objective:To explore the effect of the developmental stages and quality on pregnancy outcome and birth outcome, and provide evidence for single blastocyst selection in frozen-thawed cycles.Methods:A retrospective cohort study analysis was performed on the data of patients with a total of 893 cycles who underwent single blastocyst transfer in frozen-thawed cycles in the Center for Reproductive Medicine, Qingyuan People's Hospital from January 2013 to June 2021. The cycles were divided into day 5 (D5) and day 6 (D6) groups according to the time of blastocyst formation. Then the two groups were divided into four subgroups according to the quality of blastocyst, namely, D5 good-quality embryo subgroup, D5 non-good-quality embryo subgroup, D6 good-quality embryo subgroup and D6 non-good-quality embryo subgroup. The general data, clinical outcomes and neonatal outcomes of each group were compared.Results:1) The clinical pregnancy rate [60.14% (332/552)], the implantation rate [60.14% (332/552)] and the live birth rate [47.64% (263/552)] in D5 group were significantly higher than those in D6 group [45.75% (156/341), 45.75% (156/341), 36.36% (124/341), all P<0.001], but there were no significant differences in body mass index, duration of infertility, intimal thickness of transplantation day and miscarriage rate between the two groups (all P>0.05). In addition, there were also no significant differences in birth weight, low birth weight rate, fetal macrosomia rate and male/female ratio (all P>0.05). 2) There were significant differences in clinical pregnancy rate [61.00% (294/482), 54.29% (38/70), 51.00% (127/249), 31.52% (29/92)] and live birth rate [48.96% (236/482), 38.57% (27/70), 41.37% (103/249), 22.83% (21/92)] among D5 good-quality embryo subgroup, D5 non-good-quality embryo subgroup, D6 good-quality embryo subgroup and D6 non-good-quality embryo subgroup (all P<0.001). D5 good-quality embryo subgroup had the highest clinical pregnancy rate and live birth rate, while D6 non-good-quality embryo subgroup had the lowest clinical pregnancy rate and live birth rate. There were also no significant differences in birth weight, fetal macrosomia rate and male/female ratio among the four subgroups (all P>0.05), while there was a significant difference in low birth weight rate [5.08% (12/236), 0 (0/27), 4.85% (5/103), 23.81% (5/21)] among the four subgroups ( P=0.014). 3) There were no significant differences in clinical pregnancy rate and live birth rate between D5 non-good-quality embryo subgroup and D6 good-quality embryo subgroup (all P>0.05). The clinical pregnancy rate and the live birth rate of 4BC in D5 were lower than those of 4AA, 4AB and 4BA in D6, while the miscarriage rate of 4BC in D5 was higher than that of 4AA, 4AB and 4BA in D6, but there were no significant differences (all P>0.05).The clinical pregnancy rate and the live birth rate of 4BC in D5 were higher than those of 4BB in D6, but there were no significant differences (all P>0.05). Conclusion:In the frozen-thawed cycle of single blastocyst transplantation, D5 good-quality blastocysts are preferred. When faced with D5 non-good-quality embryos and D6 good-quality embryos, the optimal choice was D6 4AA>D6 4BA>D6 4AB>D5 4BC>D6 4BB.

Colorectal cancer is a common tumor of the digestive system with a high degree of malignancy. Most patients are in the advanced stages of the disease when they develop symptoms. Although the detection rate of traditional screening methods is improving with advances in imaging and the popularity of colonoscopy, the diagnosis of early, asymptomatic colon cancer is still unsatisfactory. Therefore, it is particularly important to further study the occurrence and development mechanism of colorectal cancer and obtain new ideas for the diagnosis and treatment.? In recent years, with the deepening of epigenetics research, the role of DNA methylation in the pathogenesis of colorectal cancer has gradually attracted attention. This paper will review the research progress of DNA methylation in colorectal cancer′s diagnosis and treatment.

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.
Aggrecans/metabolism* ; Animals ; Cartilage, Articular/metabolism* ; Chondrocytes/pathology* ; Cytoskeletal Proteins/metabolism* ; Mice ; Muscle Proteins/metabolism* ; Osteoarthritis/pathology* ; Temporomandibular Joint/pathology*