EZH2 Promotes Multiple Myeloma Progression via STAT3 Pathway Activation.

BACKGROUND: Multiple myeloma (MM) is a malignant disorder of plasma cells in the bone marrow. MM causes the clonal proliferation of terminally differentiated plasma cells and the accumulation of monoclonal plasma cells. The enhancer of zeste homolog 2 (EZH2) has been proven to play a significant role in disease development and could act on the signal transducers and activators of the transcription 3 (STAT3) signaling pathway. This pathway contributes to the pathogenesis and maintenance of malignancies. This study aimed to explore the effect of EZH2 on MM progression and the role of the STAT3 pathway in this process. The goal was to increase knowledge and provide further insights about the pathogenesis of MM and identify novel targets for potential therapies. METHODS: The abnormal expression of EZH2 in MM cell lines was tested through real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and western blot analysis. Based on the MM cell line H929, transfection was used to modify EZH2 expression, followed by the subsequent evaluation of induced alteration in STAT3 activation. The STAT3 phosphorylation activator colivelin and inhibitor stattic were used for promoting and inhibiting the STAT3 activation, respectively. Colony-forming assay, transwell migration assay, and flow cytometry were used to explore cell proliferation, cell migration, and cell apoptosis, respectively. RESULTS: Both the EZH2 mRNA and protein were over-expressed in multiple MM cell lines including H929 (p < 0.001), U266 (p < 0.01), RPMI-8226 (p < 0.01) and MM.1S (p < 0.001). Increased EZH2 promoted cell proliferation (p < 0.001) and migration (p < 0.001) and simultaneously inhibited cell apoptosis (p < 0.001), which could be reversed by inhibited STAT3 activation (p < 0.001). In contrast, promoted STAT3 activation increased cell proliferation (p < 0.001) and migration (p < 0.001), while simultaneously inhibiting cell apoptosis (p < 0.001), despite decreased EZH2 expression. CONCLUSIONS: The effect of EZH2 and STAT3 pathways on MM regulation was revealed and verified. EZH2 promoted the progression of MM cells by activating the STAT3 pathway. The EZH2 and STAT3 pathways could be potential targets for effective MM treatment.

Analysis of Dietary and Nutritional Status of Tuberculosis Patients in Hulunbuir Region.

Objective: Tuberculosis (TB) is a major public health problem that affects millions of people worldwide. Malnutrition is a common complication of TB and can worsen the disease outcome. The purpose of this study was to investigate the dietary and nutritional status, as well as the dietary structure, of TB patients in Hulunbuir City, Inner Mongolia, China. Additionally, the study aimed to analyze the factors that influence the nutritional status in order to provide a theoretical foundation for the prevention and treatment of TB and related issues. Methods: A cross-sectional study was conducted on 334 randomly selected TB patients from Hulunbuir City Second Hospital. A questionnaire survey was administered to collect information on demographic characteristics, dietary habits, and food intake. Nutritional status was assessed by body mass index (BMI). Dietary diversity score (DDS) was calculated based on the number of food groups consumed in the previous 24 hours. Statistical analysis was performed using SPSS 20.0 software. Descriptive statistics employed rates and composition ratios, and categorical data was represented using frequencies and percentages. The chi-square test was used to analyze the association between nutritional status and other variables, with a significance level set at α=0.05. Multivariable ordinal logistic regression analysis was performed to identify the independent factors affecting the nutritional status of TB patients. Results: The univariate analysis revealed statistically significant differences (P < 0.05) in the nutritional status (as measured by BMI) among tuberculosis patients, considering ethnicity, educational level, smoking, meat-based diet, vegetable consumption, and DDS grading. No statistically significant differences were found regarding gender, age, marital status, occupation, sleep duration, alcohol consumption, and consumption of rice and flour dishes. Statistically significant variables from the univariate analysis were included in a multivariable ordinal logistic regression analysis model. The findings highlighted that educational level (high school or below), smoking, meat-based diet, DDS scores of 1-3, and a primarily vegetable-based diet had independent effects on the nutritional status of tuberculosis patients (all P < 0.05). No significant difference was found in nutritional status between the Han ethnic group and other ethnicities. Conclusion: The study revealed that the dietary and nutritional status of TB patients in Hulunbuir City was suboptimal and influenced by several factors. Smoking, meat-based diet, and low dietary diversity score were the primary risk factors for malnutrition among TB patients. The study suggests that nutritional education and intervention programs should be implemented for TB patients to improve their dietary quality and nutritional status.

Visible light-mediated synthesis of quinazolinones from benzyl bromides and 2-aminobenzamides without using any photocatalyst or additive.

This paper reports a novel method for the visible-light-mediated synthesis of quinazolinones from the reaction of benzyl bromides with 2-aminobenzamides. The reaction proceeded efficiently at room temperature upon irradiation with an 18 W blue light-emitting diode in air without photocatalysts or additives. By varying the solvent type, substrate molar ratio, and reaction time, the optimal reaction conditions, including the use of methanol solvent, room temperature, and reaction time of 28 h, were identified. Under these conditions, various quinazolinones were obtained using 18 substrates, with the highest yield of 93%. To determine the industrial value of the proposed method, a scale-up reaction was performed and 80% product yield was achieved. Mechanistic studies revealed that the reaction likely proceeded via a radical pathway and that the hydrogen bromide by-product generated during the first step of the reaction of benzyl bromide with 2-aminobenzamide promoted the subsequent step.

Research Progress of B-Cell Lymphoma/Leukemia-2 Inhibitor Combined with Azacytidine in the Targeted Therapy of Acute Myeloid Leukemia.

Objective: To investigate the efficacy and safety of azacytidine and B-cell lymphoma/leukemia-2 inhibitors in the treatment of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Methods: The clinical data of 31 patients with AML/MDS who were clearly diagnosed with AML/MDS were analyzed from 2018.10 to 2021.02, and the total amount of azacyclonol and B-cell lymphoma/leukemia-2 inhibitor was used for single or combined chemotherapy, with a total amount of 75 mg/m2 ∗7 d, divided into 7-10 days of continuous subcutaneous injection, every 28-30 days for a course of treatment. Overall response rate (ORR), median survival, poor response, and genetic mutations were observed. Results: A total of 104 courses of treatment were completed in 31 patients, the median course was 3 (1-12), and 6 patients who did not complete 2 courses of treatment were not counted in the statistics. After 2 courses, ORR was 72.0%, CRES was 2 (8.0%), mCR was 16 (64.0%), disease stable was 5 (20.0%), treatment failures were 2 (8.0%), mortality was 40.0%, and median survival time was >5 months. Single-agent and combined ORR was 64.3% and 81.8%, respectively, with median survival of 7.25 and 9 months; ORR for MDS and AML was 66.7% and 76.9%, respectively, median survival of 8 and 11 months was 66.7% and 80.0% of ORRs at 260 and V60 years, respectively, and median survival of 7 and 11.5 months; MDS-EB-1. The ORR of MDS-EB-2 was 75.0% and 62.5%, respectively, with median survival times of 11.5 and 6.5 months. During 2 courses and 4 courses, the rate of transfusion dependence was 64.0% and 55.5%, respectively. Fifteen cases were detected by second-generation sequencing, and the results were 14 cases of combined gene mutations. Conclusion: Azacytidine and B-cell lymphoma/leukemia-2 inhibitors have good efficacy and high safety in the treatment of AML and MDS, and the combined treatment is better than that of monotherapy, but the side effects of combination therapy are large.

Rhizosphere-Associated Microbiomes of Rice (Oryza sativa L.) Under the Effect of Increased Nitrogen Fertilization.

Crops assemble and rely on rhizosphere-associated microbiomes for plant nutrition, which is crucial to their productivity. Historically, excessive nitrogen fertilization did not result in continuously increasing yields but rather caused environmental issues. A comprehensive understanding should be developed regarding the ways in which crops shape rhizosphere-associated microbiomes under conditions of increased nitrogen fertilization. In this study, we applied 16S and 18S ribosomal RNA gene profiling to characterize bacterial and fungal communities in bulk and rhizosphere soil of rice subjected to three levels of nitrogen fertilization for 5 years. Soil biochemical properties were characterized, and carbon-, nitrogen-, and phosphorus-related soil enzyme activities were investigated, by assays. Increasing nitrogen fertilization led to a decreasing trend in the variation of microbial community structures and demonstrated a more definite influence on fungal rather than bacterial community compositions and functions. Changes in the level of nitrogen fertilization significantly affected chemical properties such as soil pH, nutrient content, and microbial biomass levels in both rhizosphere and bulk soil. Soil enzyme activity levels varied substantially across nitrogen fertilization intensities and correlated more with the fungal than with the bacterial community. Our results indicated that increased nitrogen input drives alterations in the structures and functions of microbial communities, properties of soil carbon, nitrogen, and phosphorus, as well as enzyme activities. These results provide novel insights into the associations among increased nitrogen input, changes in biochemical properties, and shifts in microbial communities in the rhizosphere of agriculturally intensive ecosystems.

[Study on RNA interference silencing hMSH2 induces the reversal chemo-resistance of ovarian carcinoma cell line OC3/TAX300].

OBJECTIVE: To investigate the reversal effect of hMSH2 small interference RNA(siRNA) on chemo-resistance of ovarian carcinoma cell line OC3/TAX300, explore the clinical significance. METHODS: The specific hMSH2 siRNA (experimental group) and non-specific hMSH2 siRNA (negative control group) was designed, synthesized and transfected into ovarian carcinoma cell line OC3/TAX300. The expression mRNA and protein levels of hMSH2 were detected by real-time reverse transcription (RT)-PCR and western blot. The cell proliferation was detected by methyl thiazolyl tetrazolium(MTT) method after 12, 24, 48, 72 hours of 2 µg/ml taxol, the apoptosis rate after 24, 48 hours of 2 µg/ml taxol was analyzed by flow cytometry. Morphological changes and ultramicrostructure of cells after 48 hours of 2 µg/ml taxol were observed with transmission electron microscope. RESULTS: (1) The mRNA levels of hMSH2 were 0.004 ± 0.000, 0.053 ± 0.006 and 0.057 ± 0.012 in experimental group, negative control group and non-infected group, respectively. The protein levels of hMSH2 were 0.19 ± 0.04, 1.00 ± 0.07 and 0.95 ± 0.03 in experimental group, negative control group and non-infected group, respectively. (2) Compared with the non-infected group and the negative control group. The cell proliferation was effectively inhibited after 12, 24, 48, 72 hours of 2 µg/ml taxol (P < 0.05). The cell cycle was arrested at G2/M phase, the apoptotic rate was significantly increased after 24, 48 hours of 2 µg/ml taxol (P < 0.05). The experimental group after 48 hours of 2 µg/ml taxol was found to have more visible cell shrinkage, more serious chromatin margination, nucleus condensation, fragmentation and apoptotic body formation, nucleolus disappeared, markedly swollen mitochondria, mitochondrial cristae disappeared and other signs of apoptosis. While the nucleus was located in the cells of the central and nucleolus is clear, only mild chromatin pyknosis and marginalized, mild swelling of mitochondria in the control group and blank group. CONCLUSION: siRNA targeting hMSH2 may reverse the chemo-resistance of ovarian carcinoma cell line OC3/TAX300 and may become a treatment or a new direction in the adjuvant therapy of ovarian cancer.