Quercetin inhibited cadmium-induced autophagy in the mouse kidney via inhibition of oxidative stress.

The objective of the current study was to explore the inhibitory effects of quercetin on cadmium-induced autophagy in mouse kidneys. Mice were intraperitoneally injected with cadmium and quercetin once daily for 3 days. The LC3-II/ß-actin ratio was used as the autophagy marker, and autophagy was observed by transmission electron microscopy. Oxidative stress was investigated in terms of reactive oxygen species, total antioxidant capacity, and malondialdehyde. Cadmium significantly induced typical autophagosome formation, increased the LC3-II/ß-actin ratio, reactive oxygen species level, and malondialdehyde content, and decreased total antioxidant capacity. Interestingly, quercetin markedly decreased the cadmium-induced LC3-II/ß-actin ratio, reactive oxygen species levels, and malondialdehyde content, and simultaneously increased total antioxidant capacity. Cadmium can inhibit total antioxidant capacity, produce a large amount of reactive oxygen species, lead to oxidative stress, and promote lipid peroxidation, eventually inducing autophagy in mouse kidneys. Quercetin could inhibit cadmium-induced autophagy via inhibition of oxidative stress. This study may provide a theoretical basis for the treatment of cadmium injury.

[Effect of colon cancer cell-derived IL-1α on the migration and proliferation of vascular endothelial cells].

OBJECTIVE: To explore the effect of colon cancer cell-derived interleukin-1α on the migration and proliferation of human umbilical vein endothelial cells as well as the role of IL-1α and IL-1ra in the angiogenesis process. METHODS: Western blot was used to detect the expression of IL-1α and IL-1R1 protein in the colon cancer cell lines with different liver metastatic potential. We also examined how IL-1α and IL-1ra influence the proliferation and migration of umbilical vascular endothelial cells assessed by PreMix WST-1 assay and migration assay, respectively. Double layer culture technique was used to detect the effect of IL-1α on the proliferation and migration of vascular endothelial cells and the effect of IL-1ra on the vascular endothelial cells. RESULTS: Western blot analysis showed that IL-1α protein was only detected in highly metastatic colon cancer HT-29 and WiDr cells, but not in the lowly metastatic CaCo-2 and CoLo320 cells.Migration assay showed that there were significant differences in the number of penetrated cells between the control (17.9±3.6) and 1 ng/ml rIL-1α group (23.2±4.2), 10 ng/ml rIL-1α group (31.7±4.5), and 100 ng/ml rIL-1α group (38.6±4.9), showing that it was positively correlated with the increasing concentration of rIL-1α (P<0.01 for all). The proliferation assay showed that the absorbance values were 1.37±0.18 in the control group, and 1.79±0.14 in the 1 ng/ml rIL-1α group, 2.14±0.17 in the 10 ng/ml rIL-1α group, and 2.21±0.23 in the 100 ng/ml rIL-1α group, showing a positive correlation with the increasing concentration of rIL-1α(P<0.01 for all). IL-1ra significantly inhibited the proliferation and migration of vascular endothelial cells (P<0.01). The levels of VEGF protein were (1.697±0.072) ng/ml, (3.507±0.064)ng/ml and (4.139±0.039)ng/ml in the control, HUVECs+ IL-1α and HUVECs+ HT-29 co-culture system groups, respectively, showing a significant difference between the control and HUVECs+ 10 pg/ml rIL-1α groups and between the control and HUVECs+ HT-29 groups (P<0.01 for both). CONCLUSIONS: Our findings indicate that colon cancer cell-derived IL-1α plays an important role in the liver metastasis of colon cancer through increased VEGF level of the colon cancer cells and enhanced vascular endothelial cells proliferation, migration and angiogenesis, while IL-1ra can suppress the effect of IL-1α and inhibit the angiogenesis in colon cancer.

lncRNA TUSC7 regulates oxidative stress level by targeting miR-23b in colorectal cancer and thus inhibits cell proliferation, migration and invasion.

OBJECTIVE: Currently, multiple studies have shown that long non-coding ribonucleic acid TUSC7 exerts an anti-tumor effect in a variety of cancers. However, the function and underlying regulatory mechanism of lncRNA TUSC7 in CRC remain unclear. METHODS: The relative fluorescence intensity of MMP9 in the cancer and in peritoneal tissues was measured by immunofluorescence. Peritoneal macrophages in BALB/c mice were sorted out using flow cytometry. The abdominal circumference of mice was measured. Moreover, the correlation between TUSC7 and miR-23b was detected by diluciferase experiment and the expressions of TUSC7 and miR-23b were analyzed using real-time fluorescence quantitative PCR. Last, the effect of TUSC7 on peritoneal macrophages was detected. RESULTS: The relative fluorescence intensity of MMP9 in cancer was significantly stronger than that it in the surrounding tissues. Measurements of abdominal circumference in mice showed that TUSC7 inhibited the metastasis of CRC. The results of dual luciferase assay and RT-qPCR experiment showed that TUSC7 could target and inhibit miR-23b. The expressions of P22, P47, gp91, p-STAT6, p-STAT3, IL-4 and IL-10 were remarkably increased in TUSC7 OE group compared with those in NC group, while the expressions of p-SHP2, MMP2 and MMP9 were evidently reduced in contrast with those in NC group. The viability, proliferation, migration and invasion of CRC cells could be inhibited by TUSC7 OE, which was reversed by TUSC7 KD. CONCLUSION: LncRNA TUSC7 can regulate the oxidative stress level and promote the M2 polarization of macrophages through targeting miR-23b of peritoneal macrophage in CRC, thus inhibiting cell proliferation, migration and invasion.

Effects of natural orifice transluminal endoscopic radical resection of the colon and targeted therapy on immune response and blood CA199 and CA242 levels in colorectal cancer.

To examine the effect of natural orifice transluminal endoscopic radical resection combined with targeted therapy on the immune system and serum levels of CA199 and CA242 in individuals with colorectal cancer. We enrolled 90 patients admitted to our hospital with a diagnosis of colorectal cancer between February 2020 and May 2022 and divided them into 2 groups according to the treatment methods: observation group (n = 45) and control group (n = 45). Patients in the control group underwent conventional laparoscopic radical resection of the colon followed by targeted therapy, whereas those in the observation group underwent natural orifice transluminal endoscopic radical resection of the colon and targeted therapy. Serum CA199 and CA242 levels, incidence of adverse events, clinical efficacy, perioperative indicators, and immune function indicators were compared between the 2 groups. The objective response rate (ORR) and disease control rate (DCR) were significantly higher in the observation group than in the control group (60.00% vs 35.6%, P = .020, and 91.1% vs 64.44%, P = .002, respectively). Compared with the control group, the observation group was associated with less blood loss (P = .003), shorter operation time (P = .011), shorter first exhaust time (P = .042), shorter borborygmus recovery time (P = .042), and shorter length of hospital stay (P = .020). After treatment, the CD3 + (P = .020), CD4 + (P = .008), and CD4+/CD8 + (P = .035) counts were lower, whereas the IgG (P = .014), IgM (P = .019), and IgA (P = .038) counts were higher in the observation group than in the control group. CA199 (P = .009) and CA242 (P = .001) levels were lower in the observation group than in the control group. The groups did not differ significantly in the incidence of adverse events (P = .842). The combination of natural orifice transluminal endoscopic radical resection for colorectal cancer and targeted therapy can shorten hospital stay, improve immune function, lower serum levels of CA199 and CA242, and exhibit good clinical efficacy.

Magnetic Resonance Imaging and Serum AFP-L3 and GP-73 in the Diagnosis of Primary Liver Cancer.

Objective: To investigate the combined application value of magnetic resonance imaging (MRI) combined with serum alpha-fetoprotein (AFP)-L3 and Golgi protein (GP)-73 in the diagnosis of primary liver cancer. Methods: The data of 200 patients with suspected liver cancer admitted to our hospital from February 2020 to February 2021 were retrospectively analyzed, and they were randomly divided into an experimental group and a control group, with 100 cases in each group. The experimental group received a combined detection of MRI with serum AFP-L3 and GP-73, and the control group adopted traditional diagnostic methods (spiral computed tomography and serum AFP). The diagnostic yields of the two groups were compared. Surgical resection was performed after the diagnosis of primary liver cancer, and the correlation between the efficacy and combined detection of MRI with serum AFP-L3 and GP-73 levels was analyzed. Results: The two groups presented comparable general information (P >0.05). The surgical results showed 160 cases of primary liver cancer, including 75 cases in the experimental group and 85 cases in the control group, and 40 cases of benign liver lesions. The diagnostic accuracy of the experimental group (73/75, 95%) was significantly higher than that of the control group (76/85, 86%) (P < 0.05). The serum levels of AFP-L3, GP-73, and AFP in patients with primary liver cancer were remarkably decreased after surgery (P < 0.001). The preoperative and postoperative AFP-L3, GP-73, and AFP levels of patients with primary liver cancer were significantly higher than those of patients with benign liver lesions. The AUC (95% CI) for the combined detection of MRI and serum AFP-L3 and GP-73 levels in patients with surgically confirmed primary liver cancer was 0.747 (0.619-0.874). Conclusion: MRI combined with serum AFP-L3 and GP-73 presents favorable diagnostic efficiency in the diagnosis of primary liver cancer, which is worthy of clinical application.