RNA methylation, homologous recombination repair and therapeutic resistance.

Homologous recombination (HR) repair of DNA double-strand breaks (DSBs) is critical for maintaining genomic integrity and stability. Defects in HR increase the risk of tumorigenesis. However, many human tumors exhibit enhanced HR repair capabilities, consequently endowing tumor cells with resistance to DNA-damaging chemotherapy and radiotherapy. This review summarizes the role of RNA methylation in HR repair and therapeutic resistance in human tumors. We also analyzed the interactions between RNA methylation and other HR-modulating modifications including histone acetylation, histone deacetylation, ubiquitination, deubiquitination, protein arginine methylation, and gene transcription. This review proposes that targeting RNA methylation is a promising approach to overcoming HR-mediated therapeutic resistance.

Risk factors for fluoropyrimidine-induced cardiotoxicity in colorectal cancer: A retrospective cohort study and establishment of a prediction nomogram for 5-FU induced cardiotoxicity.

Background: Fluoropyrimidine is an important component of systemic chemotherapy for colorectal cancer (CRC). Fluoropyrimidine-induced cardiotoxicity (FIC) may result in delay and discontinuation of chemotherapy and, in severe cases, can even be life-threatening. To date, risk factors for FIC have not been well identified. This cohort study aimed to identify the predictors of FIC in CRC patients and develop a risk prediction nomogram model. Methods: Between January 1, 2018 and December 31, 2020, colorectal cancer patients who received 5-fluoropyrimidine(5-Fu)/capecitabine-based chemotherapy in Affiliated Cancer Hospital of Guizhou Medical University were included. FIC was defined as an adverse cardiovascular event related to fluoropyrimidine that occurred during or within four weeks of completing chemotherapy. Risk factors were determined by LASSO algorithm and multivariate logistic regression analysis. Nomogram for predicting 5-Fu-induced cardiotoxicity was established and internally validated. The concordance index (C-index) and calibration curve were used to evaluate the nomogram's discrimination and accuracy. Results: A total of 916 patients were included for analysis, and 200 [21.8%,95% confidence interval (CI):19.12%-24.47%] experienced FIC. LASSO algorithm and multivariate logistic regression analysis determined that chemotherapy ≤3 cycles (OR=4.694, 95%CI=3.184-6.92), age≥ 60 (OR=1.678, 95%CI=1.143-2.464), BMI>22.97 (OR=1.77, 95%CI=1.202-2.606), and simultaneous use of bevacizumab (OR=2.922, 95%CI=1.835-4.653) were significant risk factors, and were included in the prediction model for 5-Fu induced cardiotoxicity. The C-index (95%CI) was 0.751 (0.706-0.795) by internal validation. For patients treated with capecitabine-based regimen, the incidence of FIC increased with the absolute value of neutrophils (OR=5.177, 95%CI=1.684-15.549) and eosinophils (OR=3.377,95% CI=1.237-9.22). Conclusions: Our study identified risk factors for FIC and established a prediction nomogram model based on chemotherapy cycle, age, BMI and use of target therapy for 5-FU induced Cardiotoxicity. The discriminative prediction model can be used for patient counselling and risk-stratification before undergoing chemotherapy in colorectal cancer.

Effect of cefuroxime intracameral injection antibiotic prophylactic on postoperative endophthalmitis wound post-cataract: A meta-analysis.

To assess the impact of cefuroxime injection of intracameral prophylaxis antibiotic on after endophthalmitis operative wound following surgery of cataract, we conducted a meta-analysis. A thorough review of the literature up to July 2022 revealed that there were 1 167 197 participants with surgery of cataract at the start of the research; 1 004 425 of these subjects received an injection of intracameral of cefuroxime, while 162 772 did not get an antibiotic as a control. Using dichotomous approaches and a random or fixed-effect model, odds ratios (OR) with 95% confidence intervals (CIs) were estimated to evaluate the impact of cefuroxime injection of intracameral prophylaxis antibiotic on after endophthalmitis operative wound following surgery of cataract. When comparing no antibiotic in participants who had surgery of cataract, the cefuroxime injection of intracameral significantly reduced the after endophthalmitis operative wound (OR, 0.14; 95% CI, 0.07-0.29, P = 0.001) with high heterogeneity (I2 = 95%). When comparing participants who received no antibiotic after surgery of cataract, the after endophthalmitis operative wound from the cefuroxime injection of intracameral was considerably lower. Although none of the 22 studies encompassed in the meta-analysis had a study with a small sample size, it is nevertheless advisable to proceed with caution when analysing the results.

Everolimus Reverses Palbociclib Resistance in ER+ Human Breast Cancer Cells by Inhibiting Phosphatidylinositol 3-Kinase(PI3K)/Akt/Mammalian Target of Rapamycin (mTOR) Pathway.

BACKGROUND Palbociclib, a specific inhibitor of CDK4/6, has been shown to provide a survival benefit in hormone receptor-positive advanced breast cancer; however, its resistance and related mechanisms are unclear. MATERIAL AND METHODS In this study, we constructed palbociclib-resistant hormone receptor-positive breast cancer cells (MCF-7-P) via culturing with palbociclib for at least 6 months. Quantitative real-time PCR (qRT-PCR) and western blot were used to detect the expression of stemness markers in MCF-7-P and MCF-7 cells. Additionally, cell spheroid formation, Transwell migration, ALDH1 activity, and flow cytometry assays were performed to detect stemness and migration ability of MCF-7-P cells, and the effects of everolimus on MCF-7-P cells stemness and migration ability. Growth inhibition assay was used to examine the effect of everolimus on the sensitivity of palbociclib in MCF-7-P and MCF-7 cells. RESULTS MCF-7-P cells had stronger stemness and higher expression of ABCG2 and MDR1. Moreover, PI3K/Akt/mTOR signaling was hyper-activated in MCF-7-P cells. Additionally, everolimus, which is a mTOR inhibitor, attenuated MCF-7-P cells stemness and re-sensitized MCF-7-P cells to palbociclib. Importantly, everolimus enhanced the antitumor effect of palbociclib in palbociclib-sensitive hormone receptor-positive cells (MCF-7 cells). CONCLUSIONS These findings provide a rationale for future clinical trials of palbociclib and everolimus combination-based therapy in hormone receptor-positive breast cancer.

Efficacy and Mechanism of Cinnamon Essential Oil on Inhibition of Colletotrichum acutatum Isolated From 'Hongyang' Kiwifruit.

In this study, one of the dominant pathogens, which caused postharvest diseases such as anthracnose, was isolated from decayed 'Hongyang' kiwifruit. It was identified as Colletotrichum acutatum by its morphological characteristics and standard internal transcribed spacer ribosomal DNA sequence. Further, the efficacy and possible mechanism of cinnamon essential oil on inhibition of C. acutatum were investigated. Results showed that C. acutatum was dose-dependently inhibited by cinnamon essential oil. Meanwhile, the mycelial growth and spore germination of C. acutatum were completely inhibited at the concentrations of 0.200 µL/mL and 0.175 µL/mL (v/v), respectively. Indeed, both minimal inhibitory and minimum fungicidal concentrations of cinnamon essential oil were measured as 0.200 µL/mL. Additionally, the possible antifungal mechanism of cinnamon essential oil on C. acutatum was demonstrated. Results showed that the cinnamon essential oil could destroy the cell membrane integrity of C. acutatum, and the structure of cell membrane was changed. Indeed, the cell cytoplasm including soluble protein, sugar, and nucleic acid was released, which significantly changed the extracellular conductivity. Results suggested that the cinnamon essential oil exerted great potential to be used as a natural and efficient preservative for kiwifruit postharvest storage, which were helpful for the better understanding of the efficacy and mechanism of cinnamon essential oil on inhibition of pathogens isolated from decayed 'Hongyang' kiwifruit.

Structural organization of hepatic portal vein in rat with special reference to musculature, intimal folds, and endothelial cell alignment.

Structural organization of hepatic portal vein (HPV) was examined in adult rats by means of light and electron microscopy. Three characteristic features were found in the wall structure of rat HPV. (1) Tunica media consisted of two kinds of smooth muscle. The inner circular smooth muscle (CSM) was composed with one or two layer of smooth muscle cells, and was found in the entire length of the HPV and its tributaries. The outer longitudinal smooth muscle (LSM) was limited to a specific region of HPV; in particular it was well-developed at distal half of HPV. CSM counteracts luminal hydrostatic pressure to prevent circumferential hyperextension of venous wall, whereas LSM is likely to counteract a tractive force produced by gravity and movement of small intestine. (2) Intima of HPV showed a unique feature, intimal folds, which protruded into the lumen and were aligned almost circumferentially. Intimal folds were found only at the same region where the LSM was well-developed. Thus, LSM is presumably involved in the formation of intimal folds. (3) The endothelial cells between intimal folds were circumferentially aligned along the folds, although those in the other regions of HPV were arrayed along the longitudinal axis of HPV or the direction of blood flow as reported in other kinds of blood vessel. This finding implied that the circumferential blood flow locally occurs on the surface of intima between the intimal folds.

[Study on transplantation of marrow stromal stem cells into acellular extra cellular matrix in mice [corrected]].

OBJECTIVE: To study the integration of mice [corrected] marrow stromal stem cells (MSCs) after transplantation into acellular extracellular matrix (AECM). METHODS: We got 16 femurs from 8 Kunming mice [corrected], the femurs were treated by Triton X-100 to get AECM, MSCs were collected from femoral marrow of 20 Kunming rats about a mouth old by PBS 4 ml, centrifuged and primary cultured in bottles, then the mice [corrected] MSCs were transplanted into AECM at a concentration of 5 x 10(6)/ml and cultured for 7 days. The integration of the donor cells was observed using one phase contrast microscope, a light microscope and a scanning electron microscope (SEM). RESULTS: In AECM bone lacunas there were MSCs nuclei stained blue. The nuclei were unevenly distributed in AECM with more in the peripheral AECM than in the central AECM and with more in the layer near culture medium than in the layer far away from culture medium. AECM possessed a good spatial scaffold structure, the marrow stromal stem cells were well integrated into AECM. CONCLUSION: AECM can be used as a good scaffold material for tissue engineered bone construction.