期刊：
CURRENT NEUROPHARMACOLOGY,2024年22(10):1672-1696 ISSN：1570-159X
作者机构：
Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and
Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese Medicine and Western Medicine,
Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Third-Grade
Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine,
College of Medicine and Health Sciences, China Three Gorges University, Yichang, Hubei 443002, China;Department of Neurosurgery, First Affiliated
Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410007, China;School
of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;[Gong, Lipeng; Liang, Junjie; Xie, Letian] Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and
Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese Medicine and Western Medicine,
Hunan University of Chinese Medicine, Changsha, Hunan 410208, China
摘要：
Ischemic stroke is a leading cause of disability and death worldwide. However, the clinical efficacy of recanalization therapy as a preferred option is significantly hindered by reperfusion injury. The transformation between different phenotypes of gliocytes is closely associated with cerebral ischemia/ reperfusion injury (CI/RI). Moreover, gliocyte polarization induces metabolic reprogramming, which refers to the shift in gliocyte phenotype and the overall transformation of the metabolic network to compensate for energy demand and building block requirements during CI/RI caused by hypoxia, energy deficiency, and oxidative stress. Within microglia, the pro-inflammatory phenotype exhibits upregulated glycolysis, pentose phosphate pathway, fatty acid synthesis, and glutamine synthesis, whereas the anti-inflammatory phenotype demonstrates enhanced mitochondrial oxidative phosphorylation and fatty acid oxidation. Reactive astrocytes display increased glycolysis but impaired glycogenolysis and reduced glutamate uptake after CI/RI. There is mounting evidence suggesting that manipulation of energy metabolism homeostasis can induce microglial cells and astrocytes to switch from neurotoxic to neuroprotective phenotypes. A comprehensive understanding of underlying mechanisms and manipulation strategies targeting metabolic pathways could potentially enable gliocytes to be reprogrammed toward beneficial functions while opening new therapeutic avenues for CI/RI treatment. This review provides an overview of current insights into metabolic reprogramming mechanisms in microglia and astrocytes within the pathophysiological context of CI/RI, along with potential pharmacological targets. Herein, we emphasize the potential of metabolic reprogramming of gliocytes as a therapeutic target for CI/RI and aim to offer a novel perspective in the treatment of CI/RI.
关键词：
Chinese herbal compound;Large intestine cancer;AOM/DSS-Induced colorectal cancer mice;16S rRNA;Inflammation
摘要：
This study was conducted to observe the effect of Chinese herbal compound on the treatment of colon cancer using AOM/DSS-induced C57BL/6J colon cancer mice and to validate potential influence on intestinal flora of mice. A colorectal cancer (CRC) mouse model was built with a total of 50 C57BL/6J mice that were induced by administrating AOM/DSS. These experimental animals were split up into 5 groups, a control group, a model group, and low-, medium- and high-dose Chinese herbal compound groups. All mice were given Chinese herbal compound treatment, and the colon tissues of each group were harvested with the length measured and the number of colon polyps accounted. The Ki-67 expression in the colon tissues was detected via immuno-histochemistry. Relative quantification of the expression of genes and proteins was determined through qPCR and WB assays. Contents of IL-6, TNF-α, IFN-γ, and IL-10 in serum and colon tissues of mice were determined by ELISA. An additional 16S rRNA sequencing analysis was implemented for the identification of mouse intestinal flora. The results suggested that all low-, medium- or high-dose Chinese herbal compound could markedly inhibit the shortening of colon length and significant number reduction of colon polyps in the model group. The relative expression of genes and proteins (PCNA, Muc16, and MMP-9) associated with proliferation in mouse colon tissues were inhibited. In addition, compared with the model group, the contents of IL-6, TNF-α, and IFN-γ in serum and colon tissues were substantially decreased in the high-dose Chinese herbal compound group, thereby reducing the structure damage in colon tissues and the infiltration degree of inflammatory cells. Besides, the expression of TLR4/MyD88/NF-κB protein was markedly decreased. The 16S rRNA sequencing analysis demonstrated that mice in the model group had decreased intestinal flora diversity, and there were significant changes in flora abundance and amino acid metabolism between the control group and the model group. Taken together, the treatment of Chinese herbal compound against CRC in this study might be regulated by the TLR4/MyD88/NF-κB signaling pathway, and the imbalance in intestinal flora was also closely related to CRC occurrence.
作者机构：
[Zheng, Yu; Zheng, Huizhen] Hunan Univ Chinese Med, Clin Coll Chinese Med 1, Changsha 410007, Peoples R China.;[Zheng, Yu; Zheng, Huizhen; Guo, Zhihua] Hunan Univ Chinese Med, Coll Chinese Med, Changsha 410208, Peoples R China.
通讯机构：
[Guo, ZH ] H;Hunan Univ Chinese Med, Coll Chinese Med, Changsha 410208, Peoples R China.
关键词：
Bayesian model;Clinical efficacy;Heart failure with (mildly) reduced ejection fraction;Network meta-analysis;Traditional Chinese medicine injection
摘要：
BACKGROUND: More than half of all heart failure (HF) patients have heart failure with reduced ejection fraction (HFrEF) or mildly reduced ejection fraction (HFmrEF). The combination of traditional Chinese medicine injections (TCMIs) with Western medicine treatment (WMT) has been reported to have better efficacy than using WMT alone. However, the positive effects of TCMIs combined with WMT on HFrEF and HFmrEF require more comprehensive and systematic evidence and warrant further investigation. METHODS: The NMA searched eight databases, including four English and four Chinese, from database creation to November 10, 2022. We used the Cochrane Risk of Bias tool (ROB 2) to assess the selected studies' quality. OpenBUGS and STATA 17.0 were used for network meta-analysis. RESULTS: The 101 RCTs were included in the systematic review. Studies have shown that when combined with any of the five TCMIs, WMT was more efficient than WMT alone. Shenmai injection (SMI)+WMT may be the best treatment for clinical effectiveness rate (CER) improvement and b-type natriuretic peptide (BNP) reduction. Huangqi injection (HQI)+WMT was the best treatment for improving left ventricular ejection fraction (LVEF). Danhong injection (DHI)+WMT may be the best treatment for lowering left ventricular end-diastolic dimension (LVEDD). Xinmailong injection (XMLI)+WMT was likely the best treatment for increasing the 6-min walking test (6MWT). In addition, XMLI had the lowest incidence of adverse reactions (3.38%). CONCLUSIONS: Shenfu injection (SFI), SMI, DHI, XMLI, and HQI combined with WMT have stronger efficiency in treating HFrEF and HFmrEF. However, as all studies were conducted in China, this review is limited by the inevitable selection bias, and further high-quality multicenter randomized controlled trials (RCTs) are required.
期刊：
Supportive Care in Cancer,2024年32(2):136 ISSN：0941-4355
通讯作者：
So, WKW
作者机构：
[Xu, Binbin] Hunan Univ Chinese Med, Sch Nursing, Changsha, Peoples R China.;[So, Winnie K. W.; Choi, Kai Chow; Xu, Binbin; So, WKW] Chinese Univ Hong Kong, Nethersole Sch Nursing, Hong Kong, Peoples R China.
通讯机构：
[So, WKW ] C;Chinese Univ Hong Kong, Nethersole Sch Nursing, Hong Kong, Peoples R China.
关键词：
COmprehensive Score for financial Toxicity;Cut-off score;Cost-related treatment nonadherence;Health-related quality of life;Cancer;Chinese
摘要：
PURPOSE: This study aimed to determine a cut-off for the simplified Chinese version of the COmprehensive Score for financial Toxicity (COST) that could identify cost-related treatment nonadherence among Chinese patients with cancer. The study also sought to validate this cut-off score by using it to assess impaired health-related quality of life (HRQoL) in the same population. METHODS: A secondary analysis was conducted using data from a cross-sectional survey of 1208 Chinese patients with cancer who were recruited from 12 hospitals in six cities across three provinces of the Chinese mainland. Sociodemographic information and data on financial toxicity (FT), cost-related treatment nonadherence, and HRQoL were used in the analysis. Receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off for the simplified Chinese version of the COST. RESULTS: The ROC analysis identified a COST cut-off of 18.5 for identifying cost-related treatment nonadherence, yielding a sensitivity of 76.5% and specificity of 71.4%. In the validation study, this cut-off score yielded a sensitivity of 64.2% and a specificity of 67.1% for identifying impaired HRQoL. CONCLUSION: Early and dynamic assessment of cancer-related FT in routine clinical practice may play a crucial role in the early identification and management of FT. Accordingly, a COST cut-off of 18.5 was identified to indicate cost-related treatment nonadherence and impaired HRQoL in a population of patients with cancer from the Chinese mainland. This finding may facilitate the implementation of universal FT screening among patients with cancer in specific settings such as the Chinese mainland.
期刊：
BRIEFINGS IN BIOINFORMATICS,2024年25(2) ISSN：1467-5463
通讯作者：
Changning Liu
作者机构：
[Zexin Zhang; Jing Li; Changning Liu] CAS Key Laboratory of Tropical Plant Resources and Sustainable Use , Yunnan Key Laboratory of Crop Wild Relatives Omics, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming 650223 , China;[Wen Chen] Hunan Provincial Key Laboratory of Vascular Biology and Translational Medicine , School of Medicine, Hunan University of Chinese Medicine, Changsha 410208 , China;College of Life Sciences, University of Chinese Academy of Sciences , Beijing 100049 , China;[Zitian Yang] CAS Key Laboratory of Tropical Plant Resources and Sustainable Use , Yunnan Key Laboratory of Crop Wild Relatives Omics, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming 650223 , China<&wdkj&>College of Life Sciences, University of Chinese Academy of Sciences , Beijing 100049 , China
通讯机构：
[Changning Liu] C;CAS Key Laboratory of Tropical Plant Resources and Sustainable Use , Yunnan Key Laboratory of Crop Wild Relatives Omics, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming 650223 , China
关键词：
CRISPR/Cas9;machine learning;lncRNA;sgRNA
摘要：
CRISPR/Cas9 is a promising RNA-guided genome editing technology, which consists of a Cas9 nuclease and a single-guide RNA (sgRNA). So far, a number of sgRNA prediction softwares have been developed. However, they were usually designed for protein-coding genes without considering that long non-coding RNA (lncRNA) genes may have different characteristics. In this study, we first evaluated the performances of a series of known sgRNA-designing tools in the context of both coding and non-coding datasets. Meanwhile, we analyzed the underpinnings of their varied performances on the sgRNA’s specificity for lncRNA including nucleic acid sequence, genome location and editing mechanism preference. Furthermore, we introduce a support vector machine-based machine learning algorithm named CRISPRlnc, which aims to model both CRISPR knock-out (CRISPRko) and CRISPR inhibition (CRISPRi) mechanisms to predict the on-target activity of targets. CRISPRlnc combined the paired-sgRNA design and off-target analysis to achieve one-stop design of CRISPR/Cas9 sgRNAs for non-coding genes. Performance comparison on multiple datasets showed that CRISPRlnc was far superior to existing methods for both CRISPRko and CRISPRi mechanisms during the lncRNA-specific sgRNA design. To maximize the availability of CRISPRlnc, we developed a web server (http://predict.crisprlnc.cc) and made it available for download on GitHub.
