Overexpression of programmed cell death ligand 1 reduces LPS-induced inflammatory cytokine upregulation and enhances osteo/odontogenic-differentiation of human dental pulp stem cells via upregulation of CCCTC-binding factor.

OBJECTIVE: The aim of this study was to explore the effect and mechanism of programmed cell death ligand 1 (PD-L1) in promoting the proliferation and osteo/odontogenic-differentiation of human dental pulp stem cells (hDPSCs) by mediating CCCTC-binding factor (CTCF) expression. DESIGN: The interaction between PD-L1 and CTCF was verified through co-immunoprecipitation. hDPSCs transfected with PD-L1 overexpression and CTCF knockdown vectors were treated with lipopolysaccharide or an osteogenic-inducing medium. Inflammatory cytokines and osteo/odontogenic-differentiation related genes were measured. Osteo/odontogenic-differentiation of hDPSCs was assessed using alkaline phosphatase (ALP) and alizarin red S staining. RESULTS: Overexpression of PD-L1 inhibited LPS-induced pro-inflammatory cytokine upregulation, cell proliferation, ALP activity, and calcium deposition in hDPSCs and elevated the expression of osteo/odontogenic-differentiation related genes; however, such expression patterns could be reversed by CTCF knockdown. Co-immunoprecipitation results confirmed the binding of PD-L1 to CTCF, indicating that PD-L1 overexpression in hDPSCs increases CTCF expression, thus inhibiting the inflammatory response and increasing osteo/odontogenic-differentiation of hDPSCs. CONCLUSION: PD-L1 overexpression in hDPSCs enhances the proliferation and osteo/odontogenic-differentiation of hDPSCs and inhibit the inflammatory response by upregulating CTCF expression.

Mechanistic regulation of FOXO transcription factors in the nucleus.

FOXO proteins represent evolutionarily conserved transcription factors (TFs) that play critical roles in responding to various physiological signals or pathological stimuli, either through transcription-dependent or -independent mechanisms. Dysfunction of these proteins have been implicated in numerous diseases, including cancer. Although the regulation of FOXO TFs shuttling between the cytoplasm and the nucleus has been extensively studied and reviewed, there's still a lack of a comprehensive review focusing on the intricate interactions between FOXO, DNA, and cofactors in the regulation of gene expression. In this review, we aim to summarize recent advances and provide a detailed understanding of the mechanism underlying FOXO proteins binding to target DNA. Additionally, we will discuss the challenges associated with pharmacological approaches in modulating FOXO function, and explore the dynamic association between TF, DNA, and RNA on chromatin. This review will contribute to a better understanding of mechanistic regulations of eukaryotic TFs within the nucleus.

The therapeutic efficacy of guided therapy for PCI after acute myocardial infarction: A meta-analysis.

OBJECTIVE: To systematically evaluate the effects of lead therapies on percutaneous coronary intervention (PCI) after acute myocardial infarction (AMI). METHODS: A randomized controlled trial (RCT) in the CNKI, Wanfang, VIP, ProQuest, PubMed, Cochrane Library, Scopus, and Web of Science databases was searched until January 2023. Two researchers strictly screened and checked the included literature, extracted relevant data, and used the Cochrane Manual to assess the risk quality of the literature. Using RevMan 5.3 software, Meta-analysis of 4 main outcome measures [cardiac function-related indicators, 6-minute walking distance (6 MWT), quality of life (SF-36), Seattle angina pectoris scale (SAQ)], and 3 secondary outcome measures [adverse event incidence, death incidence, and readmission rate]. RESULTS: 22 studies were finally included with 1754 subjects, but the overall quality of the included studies was not high. The results of the meta-analysis showed that, in the cardiac function-related indicators compared to controls, improved left ventricular ejection fraction (LVEF) index (MD = 1.42, 95%CI [-0.94, 3.79], P < .00001); however, compared with the Baduanjin group, Tai Chi ball + Baduanjin group and control group, there was no significant difference (P > .05); compared with the control group, the guidance therapy group improved the left ventricular end-diastolic volume (LVEDV) index (MD = -4.67, 95%CI [-6.8, -2.71], P < .00001). In comparison, the lead group improved the 6 MWT (MD = 69.44, 95%CI [30.12, 108.76], P < .00001); the SF-36 score (MD = 10.05, 95%CI [8.68, 11.42], P < .00001])and the SAQ score (MD = 6.2, 95%CI [3.97, 8.44], P < .00001). Among the secondary outcome measures, the incidence of adverse events was statistically significant (RR = 0.17, 95%CI [0.1, 0.32], P < .00001); statistically significant (RR = 0.29, 95%CI (0.1, 0.87), P < .00001); readmission (RR = 0.39, 95%CI [0.17, 0.87, 0.89], P < .00001). CONCLUSION: Based on the current study, combining conventional therapy/ exercise or using simple lead therapy after PCI can improve the treatment effect and improve the quality of life.

Effect of repetition of rTMS at different frequencies on the efficacy of swallowing disorders after stroke: A systematic review and meta-analysis.

BACKGROUND: To systematically evaluate the curative effect of repeated transcranial magnetic stimulation at different frequencies on swallowing disorders after stroke. METHODS: A search was conducted for randomized controlled trials of repeated transcranial magnetic stimulation for stroke patients in CNKI, Wanfang, VIP, ProQuest, PubMed, Cochrane Library, Scopus, and Web of Science databases until December 2022. The 2 researchers strictly screened and checked the included documents, extracted relevant data, assessed the risk quality of the literature using the Cochrane manual, and conducted a network meta-analysis of the data using State16.0. RESULTS: Eighteen studies included 680 participants. The results of the reticular meta-analysis showed that in the leakage-aspiration scale (PAS) indicators, 1 Hz, 3 Hz, 5 Hz, and 10 Hz were all better treatment effects compared with the control group, and there was a statistically significant difference (P < .05). In the standard swallowing function assessment (SSA) index, 3 Hz, 5 Hz, and 10 Hz compared with the control group were statistically significant (P < .05); there was no difference between 1 Hz and the control group (P > .05). The cumulative probability ranking results showed that the intervention effect of 3 Hz was the best in the PAS index, much greater than that of other frequencies, and the intervention effects of 10 Hz and 5 Hz were similar. For the SSA index, the intervention effect was optimal at 10 Hz, followed by 5 Hz. Note that the treatment effect of 1 Hz ranked last, even lower than that of the control group. The results of the 5 Hz treatment site grouping analysis showed that the affected side was > bilateral > healthy in PAS and > bilateral > healthy in SSA. CONCLUSION SUBSECTIONS: Based on the current study, the optimal frequency and site selection results of the 2 evaluation indicators are not uniform, but from the combination of the 2 evaluation indicators, the treatment effect of 10H is good, and the effect of bilateral stimulation for the selection of stimulation sites is good. The above conclusions need to be verified in high-quality studies.

The progress of molecules and strategies for the treatment of HBV infection.

Hepatitis B virus infections have always been associated with high levels of mortality. In 2019, hepatitis B virus (HBV)-related diseases resulted in approximately 555,000 deaths globally. In view of its high lethality, the treatment of HBV infections has always presented a huge challenge. The World Health Organization (WHO) came up with ambitious targets for the elimination of hepatitis B as a major public health threat by 2030. To accomplish this goal, one of the WHO's strategies is to develop curative treatments for HBV infections. Current treatments in a clinical setting included 1 year of pegylated interferon alpha (PEG-IFNα) and long-term nucleoside analogues (NAs). Although both treatments have demonstrated outstanding antiviral effects, it has been difficult to develop a cure for HBV. The reason for this is that covalently closed circular DNA (cccDNA), integrated HBV DNA, the high viral burden, and the impaired host immune responses all hinder the development of a cure for HBV. To overcome these problems, there are clinical trials on a number of antiviral molecules being carried out, all -showing promising results so far. In this review, we summarize the functions and mechanisms of action of various synthetic molecules, natural products, traditional Chinese herbal medicines, as clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR/Cas)-based systems, zinc finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs), all of which could destroy the stability of the HBV life cycle. In addition, we discuss the functions of immune modulators, which can enhance or activate the host immune system, as well some representative natural products with anti-HBV effects.

Chemoproteomic and Transcriptomic Analysis Reveals that O-GlcNAc Regulates Mouse Embryonic Stem Cell Fate through the Pluripotency Network.

Self-renewal and differentiation of embryonic stem cells (ESCs) are influenced by protein O-linked ß-N-acetylglucosamine (O-GlcNAc) modification, but the underlying mechanism remains incompletely understood. Herein, we report the identification of 979 O-GlcNAcylated proteins and 1340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. In addition to OCT4 and SOX2, the third core pluripotency transcription factor (PTF) NANOG was found to be modified and functionally regulated by O-GlcNAc. Upon differentiation along the neuronal lineage, the O-GlcNAc stoichiometry at 123 sites of 83 proteins-several of which were PTFs-was found to decline. Transcriptomic profiling reveals 2456 differentially expressed genes responsive to OGT inhibition during differentiation, of which 901 are target genes of core PTFs. By acting on the core PTF network, suppression of O-GlcNAcylation upregulates neuron-related genes, thus contributing to mESC fate determination.

Cytomembrane visualization using Stokes parameter confocal microscopy.

A new, to the best of our knowledge, method for Stokes vector imaging is proposed to achieve imaging and dynamic monitoring of a non-labeled cytomembrane. In this work, a polarization state vector is described by a Stokes vector and expressed in chrominance space. A physical quantity called polarization chromaticity value (PCV) corresponding to a Stokes vector is used as the imaging parameter to perform Stokes vector imaging. By using the PCV imaging technique, the Stokes vector can be expressed in three-dimensional real space rather than in a Poincare sphere. Furthermore, a four-way Stokes parameter confocal microscopy system is designed to measure four Stokes parameters simultaneously and obtain micro-imaging. Label-free living onion cell membranes and their plasmolysis process are selected as the representative micro-anisotropy experimental analysis. It is proved that PCV imaging can perform visualization of cytomembranes, and further, microscopic orientation is demonstrated. The prospect of universal measurement of anisotropy details for analysis and diagnosis is provided.

Quantitative and Site-Specific Chemoproteomic Profiling of Protein O-GlcNAcylation in the Cell Cycle.

Mammalian cell cycle is a central process for tissue growth and maintenance. Protein O-linked ß-N-acetylglucosamine (O-GlcNAc) modification has been found to occur on several important cell cycle regulators. However, the O-GlcNAcylated proteome has not been extensively profiled during cell cycle progression. Herein, we report a quantitative profiling of protein O-GlcNAcylation sites in cell proliferation, by using an O-GlcNAc chemoproteomic strategy. In HeLa cells, a total of 902, 439, and 872 high-confidence O-GlcNAcylation sites distributed on 414, 265, and 425 proteins are identified in the interphase, early mitosis, and mitotic exit stages, respectively. The identified O-GlcNAcylation events occur on a variety of important regulators, which are involved in the processes of cell division, DNA repair, and cell death. Furthermore, we show that O-GlcNAcylation is dynamically regulated in a cell cycle stage-dependent manner. Our results provide a valuable resource for investigating the functional roles of O-GlcNAc in the mammalian cell cycle.

[Clinical observation on acupuncture for treatment of abdominal postoperative pain].

OBJECTIVE: To compare the therapeutic effects between acupuncture based on syndrome differentiation and analgesic on abdominal postoperative pain. METHODS: One hundred cases of abdominal postoperative pain were randomly divided into two groups, 50 cases in each one. In acupuncture group, the treatment was applied according to meridian differentiation and point selection on the affected meridian. Ashi points near to the incision as the main points and those closely connected with Zangfu functions were selected, such as Yanglingquan (GB 34), Taichong (LR 3) and Zusanli (ST 36), etc. In medication group, muscular injection of Bucinnazine was administered. The severity of pain was evaluated with Visual Analogue Scale (VAS) before and after treatment. RESULTS: The remarkably effective rate in acupuncture group was 60.0% (30/50), which was markedly better than that 28.0% (14/50) in medication group (P < 0.01). VAS scores in 30 min and 4 h after treatment as well as 24 h after operation in two groups were all reduced remarkably as compared with those before treatment (all P < 0.01), indicating the satisfactory analgesia in treatment. VAS scores in acupuncture group were lower apparently than those in medication group in 30 min and 4 h after treatment (P < 0.01,P < 0.05). CONCLUSION: Acupuncture has quick analgesia in treatment of abdominal postoperative pain, which is superior to muscular injection of Bucinnazine because of its advantages of long-term and significant efficacy.