Circular RNAs (circRNAs) are a class of noncoding RNA molecules with a covalently enclosed circular structure and are more stable than linear RNAs. CircRNAs possess unique characteristics and biological functions, playing key roles in the occurrence and development, proliferation, metastasis, invasion, and drug resistance of various types of cancer. Protein ubiquitination modification regulates the stability and functions of proteins through the ubiquitin-proteasome system (UPS), and affecting tumor-related signal transduction pathways. Interactions between circRNAs and UPS in cancer have attracted considerable interest. They may be novel biomarkers for cancer therapy and potential targets for mitigating tumors’ drug resistance. This article systematically reviews the molecular mechanism and clinical translational potential of circRNAs and protein ubiquitination modification in cancer and discusses their application prospects in diagnosis, treatment prognosis and overcoming drug resistance.

ObjectiveTo investigate the role and potential mechanism of microRNA-544 （miRNA-544） in lipopolysaccharide （LPS）-induced liver injury in mice with sepsis， and to provide a new target for the treatment of liver injury in sepsis. MethodsA total of 40 C57BL/6J mice were randomly divided into control group （intraperitoneal injection of normal saline）， model group （intraperitoneal injection of LPS at a dose of 5 mg/kg）， agonist group （intraperitoneal injection of LPS and miR-544 agonist at a dose of 5 mg/kg）， and miR-544 inhibitor group （intraperitoneal injection of LPS and miR-544 inhibitor at a dose of 5 mg/kg）， with 10 mice in each group. An automatic biochemical analyzer was used to measure the levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and total bilirubin （TBil） in serum and the liver； Western blot was used to measure the expression levels of monocyte chemotactic protein-1 （MCP-1）， CD16/32， and proteins associated with the NF-κB signaling pathway in the liver； q-PCR and ELISA were used to measure the expression levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in serum. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group of LPS-induced sepsis had a significant reduction in the expression level of miR-544 in serum and liver tissue （P0.01）， significant pathological changes of the liver （such as inflammatory cell infiltration and central vein congestion）， and significant increases in the levels of liver injury markers （ALT， AST， and TBil） in serum and the liver （all P0.001）， the expression levels of inflammatory factors （MCP-1， CD16/32， TNF-α， IL-6， and IL-1β） （all P0.01）， and the phosphorylation levels of key proteins of the NF-κB pathway （p-IKK， p-I-NF-κ， and p-p65） （all P0.01）. Compared with the model group， the miR-544 inhibitor group had a significant reduction in the expression level of miR-544 in serum and liver tissue （P0.01）， aggravated pathological changes of the liver， and significant increases in the levels of liver injury markers and inflammatory factors （ALT， AST， TBil， MCP-1， CD16/32， TNF-α， IL-6， and IL-1） （all P0.05）， as well as significant increases in the phosphorylation levels of key proteins of the NF-κB pathway （p-IKK， p-I-κB-α， and p-p65） （all P0.01）. On the contrary， the miR-544 agonist group had a significant increase in the expression level of miR-544 in serum and liver tissue （P0.01）， significant alleviation of liver pathological changes， and significant reductions in the levels of liver injury markers and inflammatory factors （ALT， AST， TBil， MCP-1， CD16/32， TNF-α， IL-6， and IL-1β） （all P0.05）， as well as significant reductions in the phosphorylation levels of key proteins of the NF-κB pathway （p-IKK， p-I-κB-α， and p-p65） （all P0.05）. ConclusionThis study shows that miR-544 can alleviate LPS-induced liver injury in mice with sepsis by inhibiting the expression of inflammatory-related proteins and the activation of the NF-κB signaling pathway.

OBJECTIVE: To explore the role of CDGSH iron-sulfur domain 2 (CISD2) in patients with sepsis-related myocardial injury (SMI) and its predictive value for 28-day prognosis and myocardial damage through clinical studies and cell experiments. METHODS: A retrospective study was conducted. Adult patients diagnosed with sepsis admitted to the critical care medicine of Third Affiliated Hospital of Qiqihar Medical University from January 2023 to January 2024 were enrolled. The clinical data, laboratory indicators, expression level of CISD2 mRNA in peripheral blood mononuclear cells (PBMC) 24 hours after admission, and 28 days prognosis were collected. Patients were divided into SMI group [left ventricular ejection fraction (LVEF) < 0.50 or LVEF decreased by ≥ 10% from baseline] and sepsis non-myocardial injury group based on LVEF. The expression levels of CISD2 mRNA were compared between the two groups, and the correlation between CISD2 and myocardial injury was analyzed. Patients were divided into the low-expression group (CISD2 mRNA < 0.5 copy/μL) and the high-expression group (CISD2 mRNA ≥ 0.5 copy/μL) based on the expression of CISD2 mRNA, and into the survival group and the death group based on the prognosis at 28 days. The clinical characteristics were analyzed between the groups. Multivariate Logistic regression was used to analyze the independent predictors of 28-day mortality in patients with sepsis. The predictive value of CISD2 for myocardial damage and 28-day prognosis in patients with sepsis were evaluated by using the receiver operator characteristic curve (ROC curve). In addition, in vitro experiments using human AC16 cardiomyocytes was conducted. The cells were divided into control group, lipopolysaccharide (LPS) group, the LPS+transfection group with overexpression of CISD2 plasmid (LPS+p-CISD2 group), and the LPS + transfection group with negative control plasmid (LPS+p-NC group). The mRNA expression of CISD2 in cells were detected by real-time quantitative polymerase chain reaction (RT-qPCR), the protein expression of CISD2 in cells were detected by Western blotting, and the cell viability was determined by cell counting kit-8 (CCK-8). RESULTS: A total of 85 sepsis patients were included, with 32 developing myocardial injury and 53 without myocardial injury. There were 40 cases of low expression of CISD2 and 45 cases of high expression of CISD2. At 28 days, 60 cases survived and 25 cases died. The mRNA expression of CISD2 in the SMI group was significantly lower than that in the sepsis non-myocardial injury group (copy/μL: 0.41±0.09 vs. 0.92±0.13, P < 0.05). CISD2 was significantly correlated with myocardial injury in patients with sepsis (r = 0.729, P < 0.05). The proportion of LVEF < 0.50 (67.50% vs. 11.11%), sequential organ failure score (SOFA: 15.63±2.15 vs. 11.12±1.52), and acute physiology and chronic health evaluation II (APACHEII: 29.49±3.51 vs. 22.41±2.61) in the CISD2 low-expression group were significantly higher than those in the CISD2 high-expression group (all P < 0.05), while there were no significantly differences in other indicators. The Kaplan-Meier survival curve showed that the 28-day survival time of sepsis patients with in the CISD2 low-expression group was significantly shorter than that in the CISD2 high-expression group (Log-rank test: χ ² = 5.601, P < 0.05). The proportion of CISD2 low-expression and the proportion of LVEF < 0.50 in the survival group were both higher than those in the death group (80.00% vs. 33.33%, 64.00% vs. 26.67%, both P < 0.05), while there were no significantly differences in other indicators. Multivariate Logistic regression analysis showed that CIDS2 and LVEF were independent predictive factors for 28-day mortality in patients with sepsis [CIDS2: odds ratio (OR) = 3.400, 95% confidence interval (95%CI) was 1.026-11.264, P = 0.045; LVEF: OR = 2.905, 95%CI was 1.029-8.199, P = 0.044]. ROC curve analysis showed that when CISD2 was expressed at a low level, patients with sepsis were at high risk of death within 28 days and myocardial injury. The sensitivity of CISD2 in predicting the 28-day mortality of patients with sepsis was 80.00%, and the specificity was 66.67%, and the area under the curve (AUC) was 0.733 (95%CI was 0.626-0.823). The sensitivity of CISD2 in predicting myocardial injury in patients with sepsis was 83.87%, the specificity was 74.07%, and the AUC was 0.790 (95%CI was 0.688-0.871). In addition, compared with the control group, the mRNA and protein expressions of CISD2 as well as the cell activity in the LPS group were significantly decreased. The mRNA and protein expressions of CISD2 and the activity of cardiomyocytes transfected with p-CISD2 were significantly increased. CONCLUSIONS CISD2 plays a protective role in sepsis-associated myocardial injury and has good predictive value for 28-day prognosis and myocardial injury.
Humans ; Sepsis/metabolism* ; Prognosis ; Retrospective Studies ; Male ; Female ; Middle Aged ; RNA, Messenger/genetics* ; Aged ; Myocardium/metabolism*

OBJECTIVETo study the effects of Yanshu injection on the combined treatment in the advanced primary liver cancer.

METHODEighty-five cases of advanced primary liver cancer were treated with Yanshu injection combining with chemotherapy or only chemotherapy. The curative effects, pain genesic rate, one year survival rate, survival quality of life and cell immune functions were observed.

RESULTThe remission rate and one year survival rate of the trial group were 60.5% and 51.2%, respectively, and were significantly higher than those (45.2% and 40.5%) of the control group (P < 0.05). The pain relief rate of the trial group was significantly higher than that of the control group (P < 0.05). The improvement of the quality of life was higher than that of the contral group (P < 0.01). The ability of the T-cell subgroup and NK-cell of the trail group were significantly difference between pre-and post-treatment (P < 0.01 or 0.05); however, that of the control group was no obviously change.

CONCLUSIONYanshu injection combination with chemotherapy can raise the curative effect, one year survival rate and cellular immune function, reduce pain genesic rate and toxicity of chemotherapy, and improve the quality of life of the patients with advanced primary liver cancer, which is worthy to be recommended for clinical application.

Adult ; Aged ; Antineoplastic Agents, Phytogenic ; administration & dosage ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; therapeutic use ; Female ; Humans ; Injections, Intravenous ; Liver Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Phytotherapy ; Plants, Medicinal ; chemistry ; Quality of Life ; Sophora ; chemistry ; Survival Rate