Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review).

Histone chaperones serve a pivotal role in maintaining human physiological processes. They interact with histones in a stable manner, ensuring the accurate and efficient execution of DNA replication, repair and transcription. Retinoblastoma binding protein (RBBP)4 and RBBP7 represent a crucial pair of histone chaperones, which not only govern the molecular behavior of histones H3 and H4, but also participate in the functions of several protein complexes, such as polycomb repressive complex 2 and nucleosome remodeling and deacetylase, thereby regulating the cell cycle, histone modifications, DNA damage and cell fate. A strong association has been indicated between RBBP4/7 and some major human diseases, such as cancer, age­related memory loss and infectious diseases. The present review assesses the molecular mechanisms of RBBP4/7 in regulating cellular biological processes, and focuses on the variations in RBBP4/7 expression and their potential mechanisms in various human diseases, thus providing new insights for their diagnosis and treatment.

Demand analysis of general practice patients for teaching clinic based on Kano model.

Background: General practice teaching clinics play a crucial role in the training of general practitioners, as they are more likely to enhance reception skills compared to traditional training methods. The quality of teaching clinics is largely determined by the level of patient acceptance. In recent years, the Kano model has become increasingly popular in the healthcare industry and has been used to enhance patient satisfaction. The objective of this study is to apply the Kano model to investigate the needs of patients in general practice teaching clinics and to rank the significance of each demand. This study will serve as a reference for enhancing the service quality of teaching clinics and advancing the field of general practice. Methods: A total of 101 patients of general practice at the Affiliated Hospital of Yangzhou University in Jiangsu province were selected using a random convenience sampling method to participate in a questionnaire survey. The questionnaire was designed by members of our team and was based on the Kano model. The study defined the service demand, assessed the impact of both satisfaction and dissatisfaction and created a matrix bubble diagram. Results: The study findings revealed that out of the 14 items of the general practice teaching clinic service demands, 1 item was categorized as a must-be requirement, 4 items were categorized as one-dimensional requirements, 2 items were categorized as an attractive requirement, 2 items were categorized as an indifferent requirement, and 5 items were categorized as mixed attributes. The findings of the matrix analysis showed that 4 items were situated in the area of one-dimensional attributes quadrant, 3 items were situated in the area of attractive attributes quadrant, 5 items were situated in the area of indifferent attributes quadrant, and 2 items were situated in the area of must-be attributes quadrant. Conclusion: The patients of general practice have positive attitudes toward teaching clinics. The findings can offer valuable insights for enhancing the quality of service and patient experience in general practice teaching clinics as well as for advancing the field of general practice.

Proteomic Investigation of the Antibacterial Mechanism of Cefiderocol against Escherichia coli.

This study aimed to investigate the antibacterial mechanism of cefiderocol (CFDC) using data-independent acquisition quantitative proteomics combined with cellular and molecular biological assays. Numerous differentially expressed proteins related to the production of NADH, reduced cofactor flavin adenine dinucleotide (FADH2), NADPH and reactive oxygen species (ROS), iron-sulfur cluster binding, and iron ion homeostasis were found to be upregulated by CFDC. Furthermore, parallel reaction monitoring analysis validated these results. Meanwhile, we confirmed that the levels of NADH, ROS, H2O2, and iron ions were induced by CFDC, and the sensitivity of Escherichia coli to CFDC was inhibited by the antioxidant vitamin C, N-acetyl-l-cysteine, and deferoxamine. Moreover, deferoxamine also suppressed the H2O2 stress induced by CFDC. In addition, knockout of the NADH-quinone oxidoreductase genes (nuoA, nuoC, nuoE, nuoF, nuoG, nuoJ, nuoL, nuoM) in the respiratory chain attenuated the sensitivity of E. coli to CFDC far beyond the effects of cefepime and ceftazidime; in particular, the E. coli BW25113 ΔnuoJ strain produced 60-fold increases in MIC to CFDC compared to that of the wild-type E. coli BW25113 strain. The present study revealed that CFDC exerts its antibacterial effects by inducing ROS stress by elevating the levels of NADH and iron ions in E. coli. IMPORTANCE CFDC was the first FDA-approved siderophore cephalosporin antibiotic in 2019 and is known for its Trojan horse tactics and broad antimicrobial activity against Gram-negative bacteria. However, its antibacterial mechanism is not fully understood, and whether it has an impact on in vivo iron ion homeostasis remains unknown. To comprehensively reveal the antibacterial mechanisms of CFDC, data-independent acquisition quantitative proteomics combined with cellular and molecular biological assays were performed in this study. The findings will further facilitate our understanding of the antibacterial mechanism of CFDC and may provide a theoretical foundation for controlling CFDC resistance in the future.

Observation of Efficacy of Internet-Based Chronic Disease Management Model Combined with Modified Therapy of Bushenyiliu Decoction in Treating Patients with Type 2 Diabetes Mellitus and Prostate Cancer and Its Effect on Disease Control Rate.

OBJECTIVE: To explore the efficacy of Internet-based chronic disease management model combined with the modified therapy of Bushenyiliu decoction in treating patients with type 2 diabetes mellitus (T2DM) and prostate cancer and its effect on disease control rate (DCR). METHODS: 120 patients with T2DM and prostate cancer admitted to the Affiliated Hospital of Yangzhou University, Yangzhou First People's Hospital, from February 2019 to February 2020, were retrospectively analyzed and equally divided into the experimental group and the control group according to their admission order. Conventional treatment combined with the modified therapy of Bushenyiliu decoction was performed on all patients for 3 months, and the Internet-based chronic disease management model was adopted for patients in the experimental group additionally, so as to compare their short-term effect, survival time, disease progression, blood glucose indicators, immune function indicators, and type 2 Diabetes Self-Care Scale (2-DSCS) scores. RESULTS: Compared with the control group, the experimental group obtained significantly higher DCR and objective remission rate (ORR) (P < 0.05), higher survival time and disease progression (P < 0.001), better blood glucose indicators and immune function indicators (P < 0.001), and higher 2-DSCS scores (P < 0.001) after treatment. CONCLUSION: Combining the Internet-based chronic disease management model with the modified therapy of Bushenyiliu decoction can effectively enhance the self-care ability of patients with T2DM and prostate cancer, improve their blood glucose level, promote their body immunity, and comprehensively optimize the cancer control effect, which should be promoted in practice.

Screening of Methylation Gene Sites as Prognostic Signature in Lung Adenocarcinoma.

PURPOSE: Most lung adenocarcinoma (LUAD) patients are diagnosed at the advanced stage and have poor prognosis. DNA methylation plays an important role in the prognosis prediction of cancers. The objective of this study was to identify new DNA methylation sites as biomarkers for LUAD prognosis. MATERIALS AND METHODS: We downloaded DNA methylation data from The Cancer Genome Atlas data portal. Cox proportional hazard regression model and random survival forest algorithm were applied to identify the DNA-methylation sites. Methylation of sites were validated in the Gene Expression Omnibus cohorts. Function annotation were done to explore the biological function of DNA methylated sites signature. RESULTS: Six DNA methylation sites were identified as prognosis signature. The signature yielded acceptable discrimination between the high-risk group and low-risk group. The discrimination effect of this DNA methylation signature for the OS was obvious, with a median OS of 21.89 months vs. 17.74 months for high-risk vs. low-risk groups. This prognostic prediction model was validated by the test group and GEO dataset. The predictive survival value was higher for the prognostic prediction model than that for the tumor node metastasis stage. Adjuvant hemotherapy could not affect the prediction of the signature. Functional analysis indicated that these signature genes were involved in protein binding and cytoplasm. CONCLUSION: We identified the prognostic signature for LUAD by combining six DNA methylation sites. This could service as potential robust and specificity signature in the prognosis prediction of LUAD.

Angiotensin-(1-7) attenuates angiotensin II-induced cardiac hypertrophy via a Sirt3-dependent mechanism.

The objectives of the present study were to investigate the effect of ANG-(1-7) on the development of cardiac hypertrophy and to identify the intracellular mechanism underlying this action of ANG-(1-7). Blood pressure and heart rate were recorded using radiotelemetry before and after chronic subcutaneous infusion of control (PBS), ANG II, ANG-(1-7), or ANG II + ANG-(1-7) for 4 wk in normotensive rats. Chronic administration of ANG-(1-7) did not affect either basal blood pressure or the ANG II-induced elevation in blood pressure. However, ANG-(1-7) significantly attenuated ANG II-induced cardiac hypertrophy and perivascular fibrosis in these rats. These effects of ANG-(1-7) were confirmed in cultured cardiomyocytes, in which ANG-(1-7) significantly attenuated ANG II-induced increases in cell size. This protective effect of ANG-(1-7) was significantly attenuated by pretreatment with A779 (a Mas receptor antagonist) or Mito-TEMPO (a mitochondria-targeting superoxide scavenger) as well as blockade of Sirt3 (a deacetylation-acting protein) by viral vector-mediated overexpression of sirtuin (Sirt)3 short hairpin (sh)RNA. Western blot analysis demonstrated that treatment with ANG-(1-7) dramatically increased Sirt3 expression. In addition, ANG-(1-7) attenuated the ANG II-induced increase in mitochondrial ROS generation, an effect that was abolished by A779 or Sirt3 shRNA. Moreover, ANG-(1-7) increased FoxO3a deacetylation and SOD2 expression, and these effects were blocked by Sirt3 shRNA. In summary, the protective effects of ANG-(1-7) on ANG II-induced cardiac hypertrophy and increased mitochondrial ROS production are mediated by elevated SOD2 expression via stimulation of Sirt3-dependent deacetylation of FoxO3a in cardiomyocytes. Thus, activation of the ANG-(1-7)/Sirt3 signaling pathway could be a novel therapeutic strategy in the management of cardiac hypertrophy and associated complications.NEW & NOTEWORTHY Chronic subcutaneous ANG-(1-7) has no effect on ANG II-induced elevations in blood pressure but significantly attenuates ANG II-induced cardiac hypertrophy and fibrosis by a mitochondrial ROS-dependent mechanism. This protective effect of ANG-(1-7) against the action of ANG II action is mediated by stimulation of sirtuin-3-mediated deacetylation of FoxO3a, which triggers SOD2 expression.