Objective: The interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) signaling pathway plays an important role in the development of tumors. Increased IL-33 levels promote the proliferation of tumor cells. This article aims to screen and express nanoantibodies targeting interleukin IL-33, block the transduction of the IL-33/ST2 signaling pathway by binding to IL-33, regulate inflammatory responses, and prevent tumor deterioration. Methods: Nanoantibody sequences that specifically bind to interleukin IL-33 were screened from a large-capacity natural phage nanoantibody library by panning, enrichment verification and screening, and two NbIL-33 nanoantibodies with different amino acid sequences were obtained; the NbIL-33 nanoantibody sequence was amplified from the phage plasmid pMECS by PCR technology, and the nanoantibody sequence was connected to the expression vector pMal-c4x by plasmid construction method and transformed into the expression strain BL21 (DE3) to obtain the soluble fusion expression strain of NbIL-33 and MBP tag protein: Ni-NTA affinity chromatography was used to purify NbA1 fusion protein and NbE12 fusion protein; ELISA method was used to detect the specificity, affinity and thermal stability of NbIL-33; CCK8 method was used to detect the inhibitory effect of NbIL-33 on IL-33-induced human breast cancer cell proliferation. Results: By screening the nanoantibody sequence that specifically binds to interleukin IL-33 from the natural phage nanoantibody library, two NbIL-33 nanoantibodies with different amino acid sequences were obtained, named NbA1 and NbE12 respectively; they were expressed in E.coli BL21, and two nanoantibodies with a purity of more than 90% were obtained by Ni-NTA affinity chromatography. ELISA showed that both NbA1 and NbE12 could bind to IL-33, and their affinity constants Ka values were (6.068±2.58)×105 mol/L and (2.17±0.37)×106 mol/L, respectively; CCK8 assay proved that both NbA1 and NbE12 had an inhibitory effect on IL-33-induced human breast cancer cell proliferation, and the inhibitory effect of NbA1 was greater than that of NbE12. Conclusion: In this study, two IL33-targeting nanoantibody sequences were screened from the natural phage nanoantibody library, and the NbIL-33 fusion protein expression strain was constructed. Non-fusion proteins NbA1 and NbE12 with a purity greater than 90% were purified by Ni-NTA affinity chromatography, and their biological functions were preliminarily studied, laying the foundation for the tumor treatment strategy targeting IL-33.
Objective: This study aims to explore the characteristic genes and potential mechanisms of ferroptosis-related idiopathic pulmonary fibrosis (IPF). Methods: To construct a ferroptosis-related IPF risk model (Fer-Score) by using WGCNA and ssGSEA. Subsequently analyzed immune cell infiltration and pathway enrichment in different risk subtypes. The LASSO algorithm was employed to screen ferroptosis-related genes characteristic of IPF and assess the correlation between immune cell infiltration abundance, key pathway scores and characteristic genes. Finally, we validated the expression of characteristic genes and conducted functional studies using an IPF cell model. Results: Nine ferroptosis-related IPF genes were identified for constructing the Fer-Score. The risk scores of different subtypes of Fer-Score showed significant difference, with the model achieving an area under the ROC curve of 0.917 7 and 0.937 5 for the discovery and validation sets, respectively. Immune infiltration analysis revealed significant correlations between enrichment scores and memory B cells, dendritic cells, resting NK cells, monocytes, and neutrophils. Pathway enrichment analysis identified 24 pathways significantly enriched by GSEA, seven of which were notably related to immune cell infiltration. Combined LASSO algorithm and Pearson correlation analysis identified MEG8, ALOX15, and ADAM23 as characteristic genes contributing to IPF. Cell experiments showed that ADAM23 was significantly overexpressed in the IPF cell model, and knockdown of ADAM23 inhibited LPS induced proliferation and migration of BEAS-2Bs cells. Conclusion: Knockdown of ADAM23 can inhibit the progression of IPF potentially by regulating metabolism-related pathways to influence the infiltration patterns of five types of immune cells. Thereby ADAM23 may contribute to the occurrence of IPF.
Currently, the incidence and mortality rates of tumors are increasing. Traditional tumor diagnosis and treatment methods have many limitations, while photodynamic therapy (PDT), as an emerging tumor treatment method, has attracted more and more attention due to its unique advantages. PDT relies on the photophysical and photochemical actions of photosensitizers under specific wavelengths of light to produce a series of reactive oxygen species (ROS) that induce tumor cell death. Corrole, due to its unique optical properties, selectivity for tumor tissues, rich potential for chemical modification, and good biocompatibility, has broad application prospects in photodynamic therapy. This article provides a systematic review of the synthesis of corrole-based compounds and their progress in tumor treatment.
Objective: To compare the efficacy of transcatheter arterial chemoembolization (TACE) combined with hepatic arterial infusion chemotherapy (HAIC) versus TACE alone in the treatment of advanced hepatocellular carcinoma (HCC). Methods: Retrospective clinical data from 156 patients diagnosed with advanced HCC and treated either with TACE combined with HAIC (55 cases) or TACE alone (101 cases) in the First Affiliated Hospital of Jinan University between March 2018 and October 2021 were collected. Propensity score matching (PSM) was employed to minimize between-group differences. Overall survival (OS), progression-free survival (PFS), tumor response rate, and adverse reaction rates were compared. Results: In the pre-adjusted PSM cohort, the TACE-HAIC group demonstrated significantly longer median OS (19.7 months vs. 9.8 months, P=0.010) and median PFS (10.7 months vs. 5.1 months, P=0.008) compared to the TACE alone group. Although the objective response rate (ORR) did not significantly differ between groups (23.6% vs. 20.2%, P=0.303), the disease control rate (DCR) was higher in the TACE-HAIC group (72.7% vs. 65.8%, P=0.024). After 1∶1 propensity score matching, a matched cohort of 78 cases showed that the TACE-HAIC group had significantly better median OS (19.1 months vs. 7.4 months) and median PFS (10.7 months vs. 5.0 months) than the TACE alone group (P<0.05). The combined treatment also exhibited advantages in overall response rate and DCR, with comparable incidence of adverse reactions between groups (P>0.05). Conclusion: The combination of TACE and HAIC offers superior survival benefits and tumor response rates compared to traditional TACE alone in treating advanced HCC, with good tolerability.
Objective: To evaluate the clinical efficacy of intelligent controlled pressure ureterorenoscopy in treating polycystic kidney disease with renal calculi. Methods: A retrospective analysis was conducted on the clinical data of three patients with polycystic kidney disease and renal calculi treated in the first affiliated hospital of Jinan University between June 2022 and September 2023. Intelligent controlled pressure ureterorenoscopy was performed, and the treatment outcomes and incidence of complications were analyzed. Results: All three patients were male, with an average age of (51.00±6.08) years old. The average surface area of the stones in (4.75±4.53) cm2. Two patients had stones on the left side, and one had stones on the right side. All three patients exhibited varying degrees of renal hydronephrosis. All three surgeries were successfully completed. The average operative time was (195.30±65.61) min. No active bleeding occurred during or after the surgery. None of the patients experienced complications such as sepsis, organ injury, or irrigation fluid absorption syndrome. Routine blood and biochemical tests were conducted on the first day post-surgery. The average decrease in hemoglobin was (9.73±13.35) g/L, and no patient required blood transfusion. The average postoperative serum creatinine level was (265.10±194.28) μmol/L. Conclusion: Intelligent controlled pressure ureterorenoscopy is a safe and effective treatment for polycystic kidney with renal calculi.
Objective: To compare the predictive value of decision tree and Logistic regression model for pregnancy outcomes in in vitro fertilization-embryo transfer (IVF-ET) patients. Methods: A total of 350 patients undergoing IVF-ET in Heping Hospital of Changzhi Medical College from January 2021 to October 2022 were included in the study, and were divided into pregnancy success group (215 patients) and pregnancy failure group (135 patients) according to pregnancy outcome. Clinical data of patients were collected, Logistic regression and decision tree models were established to predict pregnancy outcomes of IVF-ET patients, and decision tree analysis models (decision tree 1 and decision tree 2) were established under the condition of whether the results of Logistic regression were based, and receiver operating characteristic (ROC) curve was used to evaluate the prediction effect of the model. Results: Of the 350 patients, 61.43% had successful pregnancy, and the 38.57% had failed pregnancy. In the pregnancy failure group, the age ≥35 years, infertility years ≥5 years, cycle times ≥1, the proportion of patients with mental disorders and serum progesterone level on HCG day were higher than those in the pregnancy success group, and the proportion of patients with egg number ≥10, fertilization rate ≥75%, endometrial thickness on HCG day and high-quality embryo number were lower than those in the pregnancy success group (P<0.05). Multivariate Logistic regression analysis showed that age, serum progesterone level on HCG day, number of high-quality embryos and mental disorders were all influencing factors of pregnancy outcome in IVF-ET patients (P<0.05). Decision tree model showed that age, serum progesterone level on HCG day and number of high-quality embryos were influencing factors of pregnancy outcome in IVF-ET patients. The AUC of Logistic regression model was 0.832, and the prediction sensitivity, specificity and accuracy were 87.3%, 71.4% and 83.5%, respectively. The AUC of decision tree 1 was 0.859, and the prediction sensitivity, specificity and accuracy were 85.1%, 76.8% and 85.6%, respectively. The AUC of decision tree 2 was 0.820, and the prediction sensitivity, specificity and accuracy were 83.7%, 73.2% and 82.4%, respectively. The AUC of decision tree 1 was greater than that of decision tree 2 (P<0.05), but there was no statistical significance compared with that of Logistic regression model (P>0.05). Conclusion: Both Logistic model and decision tree model have certain predictive value for pregnancy outcome of IVF-ET patients.
Objective: To explore the correlation between C-reactive protein clearance rate (CRPc) and airway hyperresponsiveness (AHR) in acute bronchitis patients, in order to provide a reference for clinical diagnosis of AHR degree in acute bronchitis patients. Methods: A total of 182 patients with acute bronchitis admitted to Luzhou Hospital of Traditional Chinese Medicine from June 2020 to June 2023 were selected as the study objects, and were divided into group A: mild (n=67), group B: moderate (n=59), and group C: severe (n=56) according to the different degrees of AHR. The method of 1∶1 orientation matching was used to adjust the balance of patient data. All patients underwent lung examination, fasting blood was collected in the morning, and serum indexes of patients were detected by enzyme-linked immunosorbent assay. CRP level and CRPc were detected within 24 h and after admission and 3, 5, and 7 d after treatment. Multivariate Logistic regression analysis was conducted to analyze the correlation between CRPc and AHR degree, analyze the clinical factors affecting AHR degree, construct the corresponding prediction model and evaluate. Results: After 1∶1 orientation matching, 47 patients with mild, moderate and severe AHR with no statistical difference in various indicators before treatment were obtained. After treatment, the levels of FEV1/FVC, MVV, interferon-γ (IFN-γ), IL-10 and PD20FEV1 in the 3 groups were increased, while the levels of CRP, YKL-39 and LTE4 were decreased, indicating a significant improvement effect. In addition, the levels of FEV1/FVC, MVV, IFN-γ, IL-10 and PD20FEV1 in group A were higher than those in the other two groups, while the levels of CRP, YKL-39 and LTE4 were lower than those in the other two groups, and the improvement effect was better. The CRPc of group A, B and C after 7 d of treatment were (70.66±14.85)%, (60.55±15.52)% and (48.24±14.47)%, respectively, and the CRPc of group A were significantly higher than those of the other two groups. Multivariate Logistic regression analysis showed that CRPc-3 (OR=0.85, 95%CI: 0.69-0.87), CRPc-5 (OR=0.92, 95%CI: 0.77-0.95) and CRPc-7 (OR=0.96, 95%CI: 0.89-0.98) were correlated with the degree of AHR in patients. YKL-39 and LTE4 are risk factors (OR>1) for developing severe AHR, while CRPc-3, CRPc-5, CRPc-7, IFN-γ and PD20FEV1 are protective factors (OR<1) for developing severe AHR. All 7 factors have high predictive value for the risk of developing severe AHR, but the combined detection has the highest predictive value. A model built by combining the above 7 factors: Logit(P)=-2.036-0.449 (CRPc-3)-0.507(CRPc-5)-0.114(CRPc-7)-0.464(IFN-γ)+0.449(LTE4)+0.622(YKL-39)-0.200(PD20FEV1). When P=0.90, the Yoden index is the highest and the prediction effect is the best with prediction accuracy 83.10%, sensitivity 93.71%, and specificity 78.52%. Conclusion: Patients with mild AHR had higher CRPc than those with moderate and severe AHR, CRPc-3, CRPc-5 and CRPc-7 were correlated with the degree of AHR.
Objective: To screen an extract against Streptococcus agalactiae and Streptococcus iniae from Artemisia argyi Levl. et Vant, and to explore its in vitro antimicrobial activity and mechanism. Methods: The agar plate diffusion method was used to screen for Artemisia argyi Levl. et Vant extracts with excellent in vitro antibacterial effects. Subsequently, the minimum inhibitory concentration against Streptococcus agalactiae and Streptococcus iniae was determined. By observing the formation of biofilms, the hydrophobicity and relative conductivity of bacterial surfaces treated with the extract, and the structure of bacterial cells, its antibacterial mechanisms were explored. Results: The selected Artemisia argyi Levl. et Vant extract with good antibacterial effect was Artemisia argyi water extract (AWE). AWE can increase cell membrane permeability by inhibiting the formation of bacterial biofilm, reducing surface hydrophobicity, and increasing relative conductivity, thereby damaging bacterial cell membrane and bacterial structure. Conclusion: AWE is an excellent antibacterial extract of Artemisia argyi Levl. et Vant, which has the potential to serve as a natural antibacterial agent for Streptococcus agalactiae and Streptococcus iniae.
Objective: To isolate terpenoids from supercritical carbon dioxide extracts of Artemisia argyi L. and evaluae their anti-inflammatory and anti-tumour activities, in order to provide a basis for the development of highly effective and low-toxicity anti-inflammatory and anti-tumour drug leads. Methods: The essential oil was extracted by supercritical carbon dioxide extraction technique after crushing the air-dried Artemisia argyi leaves. The crude extracts of essential oil were separated and purified using various separation chromatographic columns (silica gel columns, ODS, MCI, LH-20, semi-preparative HPLC, etc). The structures of the isolated compounds were identified by nuclear magnetic resonance spectroscopy. The anti-inflammatory activity of the compounds on the lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model was determined by the Griess method; the anti-tumor activity of the compounds and their toxicity to normal cells were determined by the CCK8 method. Results: Twenty-eight monomer compounds were isolated from Artemisia argyi leaves, including 3 monoterpenes, 21 sesquiterpenes, 1 diterpene compound and 3 aliphatic alcohols compounds. Compounds 4, 5, 6, 9, 10, 14 and 15 were found to have anti-inflammatory activity, among which compounds 4, 9 and 15 showed significant anti-inflammatory activity, with IC50s of (1.8±0.3) μmol/L, (1.2±0.1) μmol/L, (1.5±0.2) μmol/L, and CC50s of (28.6±1.5) μmol/L, (15.6±0.6) μmol/L, (18.9±0.7) μmol/L. Compounds 4, 5, 6, 9 and 14 possessed anti-tumour activity, of which compounds 4 and 5 were more significant, the IC50s were (5.9±0.6) μmol/L, (6.3±0.1) μmol/L and (13.5±0.9) μmol/L, (20.5±0.6) μmol/L for tumour cells U251 and A549, and the CC50s were (41.0±1.2) μmol/L and (37.4±0.2) μmol/L for normal cells BV2, which provided a certain degree of safety. Conclusion: A total of 28 compounds were isolated from the supercritical carbon dioxide extract of Artemisia argyi L. Compounds 1, 9, 11, 12, 23, and 24 were isolated from Artemisia argyi L for the first time. Compounds 4, 9, and 15 showed significant anti-inflammatory activity, while compounds 4 and 5 had significant anti-tumor activity and had pharmacological value for further study.
Objective: To investigate the active anti-neuroinflammatory components and mechanisms of Artemisia vulgaris L. from Tangyin, providing a theoretical basis for the discovery of lead compounds and the development of anti-neuroinflammatory drugs from this plant. Methods: Terpenoids from Artemisia vulgaris L. were isolated using open column chromatography and high-performance liquid chromatography (HPLC), and their structures and configurations were identified using nuclear magnetic resonance (NMR) spectroscopy. The CCK8 method was utilized to assess the effect of compounds on cellular proliferation capacity. The content of NO in cells was detected by the Griess assay, while the mRNA expression levels of inflammatory cytokines TNF-α, IL-6, and IL-1β were assessed by RT-qPCR. Protein levels of TNF-α and IL-6 were determined by ELISA. Furthermore, Western Blot analysis was employed to determine the expression levels of relevant proteins within the PI3K/AKT/mTOR and NF-κB signaling pathways. Results: Nineteen compounds were isolated and identified from the active fraction of Artemisia vulgaris L. with anti-neuroinflammatory activity. Among them, artemvulactone U(AU) had no obvious inhibitory effect on the growth of BV-2 cells, as determined by the CCK-8 assay. Notably, AU also demonstrated the most significant inhibition of NO production, as evidenced by the Griess assay. RT-qPCR and ELISA results indicated that AU suppressed the LPS-induced expression of inflammatory cytokines TNF-α, IL-6, and IL-1β. Western blot analysis revealed that AU alleviated neuroinflammation by downregulating the expression of INOS and COX-2. Furthermore, Western blot analysis suggesting that its anti-inflammatory activity may be mediated through modulation of the PI3K/AKT/mTOR and NF-κB signaling pathways.Conclusion: The compound artemvulactone U isolated from the petroleum ether fraction of Artemisia vulgaris L.has good anti-neuroinflammatory activity and holds the potential for further research and development as an anti-inflammatory agent.
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