MRPL21 promotes HCC proliferation through TP53 mutation-induced apoptotic resistance.

BACKGROUND AND AIMS: The specific mechanisms underlying the inhibition of hepatocellular carcinoma (HCC) proliferation and metastasis by mitochondrial apoptosis are not yet fully understood. However, it plays a vital role in suppressing HCC's ability to proliferate and spread. The involvement of MRPL21, a member within the family of mitochondrial ribosomal proteins (MRPs), is well-documented in both cellular apoptosis and energy metabolism. This study aims to explore and unravel the underlying mechanisms through which MRPL21 contributes to mitochondrial apoptosis and resistance against apoptosis in HCC. METHODS: To evaluate the level of MRPL21 expression at the gene and protein expression levels, analysis was performed on human liver samples and blood using techniques for quantification. A knockdown plasmid targeting MRPL21 was constructed to investigate its impact on the growth and apoptosis of hepatocellular carcinoma (HCC). To evaluate the impact of MRPL21 knockdown on hepatocellular carcinoma (HCC) cell proliferation and apoptosis, various assays were performed including CCK-8 assays, flow cytometry analysis, detection of reactive oxygen species (ROS), and assessment of mitochondrial membrane potential (MMP). Furthermore, the role of MRPL21 in TP53 mutation was examined using Nutlin-3. RESULTS: In HCC tissues and blood samples, an upregulation of MRPL21 expression was observed when compared to samples obtained from healthy individuals, and it is correlated with a poor prognosis for HCC. Silencing MRPL21 can effectively suppress Hep3B and HCCLM3 cells proliferation by modulating the mitochondrial membrane potential, it triggers the generation of reactive oxygen species (ROS), thereby leading to G0/G1 cell cycle arrest and initiation of early apoptosis. Furthermore, by inhibiting P53 activity, Nutlin-3 treatment can enhance MRPL21-deficiency-mediated apoptosis in Hep3B and HCCLM3 cells. CONCLUSION: Through its influence on TP53 mutation, MRPL21 promotes HCC proliferation and progression while conferring resistance to apoptosis. These findings suggest that MRPL21 holds promise as a valuable biomarker for the treatment of HCC.

The diapause-like colorectal cancer cells induced by SMC4 attenuation are characterized by low proliferation and chemotherapy insensitivity.

In response to adverse environmental conditions, embryonic development may reversibly cease, a process termed diapause. Recent reports connect this phenomenon with the non-genetic responses of tumors to chemotherapy, but the mechanisms involved are poorly understood. Here, we establish a multifarious role for SMC4 in the switching of colorectal cancer cells to a diapause-like state. SMC4 attenuation promotes the expression of three investment phase glycolysis enzymes increasing lactate production while also suppressing PGAM1. Resultant high lactate levels increase ABC transporter expression via histone lactylation, rendering tumor cells insensitive to chemotherapy. SMC4 acts as co-activator of PGAM1 transcription, and the coordinate loss of SMC4 and PGAM1 affects F-actin assembly, inducing cytokinesis failure and polyploidy, thereby inhibiting cell proliferation. These insights into the mechanisms underlying non-genetic chemotherapy resistance may have significant implications for the field, advancing our understanding of aerobic glycolysis functions in tumor and potentially informing future therapeutic strategies.

Fosaprepitant for postoperative nausea and vomiting in patients undergoing laparoscopic gastrointestinal surgery: a randomised trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a major problem after surgery. Even with double prophylactic therapy including dexamethasone and a 5-hydroxytryptamine-3 receptor antagonist, the incidence is still high in many at-risk patients. Fosaprepitant, a neurokinin-1 receptor antagonist, is an effective antiemetic, but its efficacy and safety in combination antiemetic therapy for preventing PONV remain unclear. METHODS: In this randomised, controlled, double-blind trial, 1154 participants at high risk of PONV and undergoing laparoscopic gastrointestinal surgery were randomly assigned to either a fosaprepitant group (n=577) receiving fosaprepitant 150 mg i.v. dissolved in 0.9% saline 150 ml, or a placebo group (n=577) receiving 0.9% saline 150 ml before anaesthesia induction. Dexamethasone 5 mg i.v. and palonosetron 0.075 i.v. mg were each administered in both groups. The primary outcome was the incidence of PONV (defined as nausea, retching, or vomiting) during the first 24 postoperative hours. RESULTS: The incidence of PONV during the first 24 postoperative hours was lower in the fosaprepitant group (32.4% vs 48.7%; adjusted risk difference -16.9% [95% confidence interval: -22.4 to -11.4%]; adjusted risk ratio 0.65 [95% CI: 0.57 to 0.76]; P<0.001). There were no differences in severe adverse events between groups, but the incidence of intraoperative hypotension was higher (38.0% vs 31.7%, P=0.026) and intraoperative hypertension (40.6% vs 49.2%, P=0.003) was lower in the fosaprepitant group. CONCLUSIONS: Fosaprepitant added to dexamethasone and palonosetron reduced the incidence of PONV in patients at high risk of PONV undergoing laparoscopic gastrointestinal surgery. Notably, it increased the incidence of intraoperative hypotension. CLINICAL TRIAL REGISTRATION: NCT04853147.

Magnetic Resonance Imaging (MRI) Differential Diagnosis of Meningiomas Using ANOVA.

This work explored the diagnostic value of different subtypes of meningiomas under T2WI low signal based on analysis of variance (ANOVA), and the expression differences of Ki67, VEGF, and P73 in different subtypes were analyzed. 67 patients with meningioma confirmed surgically and pathologically in hospital were selected as the research subjects, whose pathological classification occurs with obvious low signal on T2WI. First, the age distribution of the subjects and the distribution of different subtypes were counted. Then, ANOVA was adopted to analyze the MRI imaging signs of patients with different subtypes of meningioma. Finally, the differences of Ki67, VEGF, and P73 proteins and mRNA expression levels in different subtypes were detected via immunohistochemical assay and qPCR. The results showed that the proportion of patients with transitional meningioma was the most, which was 43.28%, while the proportion of patients with meningeal melanoma was the least, which was 7.46%. In patients with transitional meningioma, the MRI images showed mixed signals in different layers. Fibrous MRI images showed hyalinosis and calcification of collagen fibers in the tumor, with low T2WI signal. Sand-shape MRI images showed double low signals. MRI images of meningeal melanoma showed high signal on T1-weighted Imaging (T1WI) and low signal on T2WI. The protein expression and mRNA levels of Ki67 and P73 in transitional meningioma were evidently higher in contrast to those in fibrous meningioma (P < 0.05). The expression level of VEGF protein and mRNA in meningeal melanoma were notably higher in contrast to those in fibro meningioma (P < 0.05). It was revealed that the MRI images of the four subtypes of meningiomas under ANOVA-based T2WI low signal were quite different, and the expressions of Ki67, P73, and VEGF in different subtypes had significant differences. This work provided a reference basis for the preoperative diagnosis, treatment, and prognosis of meningiomas.

[Study on the preparation of nanometer oxide SnO2 gas-sensitive material by sol-gel method].

Based on the sol-gel method, nanosized SnO2 material was prepared, and its structure and properties were studied by XRD, UV and Raman spectra. The XRD result indicated that the SnO2 particles had an ideal nanosize. The diameter of SnO2 particles increased with raising the temperature. The Raman spectrum indicated that the SnO2 nanometer material annealed at low temperature had a large number of O-empties. The UV spectra showed that the sample had stable absorption properties although the particle size changed greatly in the annealed range of 300-500 degrees C. These properties might be utilized in enhancing the performance of SnO2 gas-sensitive devices.