Environmentally responsive hydrogel promotes vascular normalization to enhance STING anti-tumor immunity.

The immunosuppressive microenvironment of malignant tumors severely hampers the effectiveness of anti-tumor therapy. Moreover, abnormal tumor vasculature interacts with immune cells, forming a vicious cycle that further interferes with anti-tumor immunity and promotes tumor progression. Our pre-basic found excellent anti-tumor effects of c-di-AMP and RRx-001, respectively, and we further explored whether they could be combined synergistically for anti-tumor immunotherapy. We chose to load these two drugs on PVA-TSPBA hydrogel scaffolds that expressly release drugs within the tumor microenvironment by in situ injection. Studies have shown that c-di-AMP activates the STING pathway, enhances immune cell infiltration, and reverses tumor immunosuppression. Meanwhile, RRx-001 releases nitric oxide, which increases oxidative stress injury in tumor cells and promotes apoptosis. Moreover, the combination of the two presented more powerful pro-vascular normalization and reversed tumor immunosuppression than the drug alone. This study demonstrates a new design option for anti-tumor combination therapy and the potential of tumor environmentally responsive hydrogel scaffolds in combination with anti-tumor immunotherapy.

PI3K/AKT/mTORC1 signalling pathway regulates MMP9 gene activation via transcription factor NF-κB in mammary epithelial cells of dairy cows.

Matrix metalloproteinase 9 (MMP9) plays a pivotal role in mammary ductal morphogenesis, angiogenesis and glandular tissue architecture remodeling. However, the molecular mechanism of MMP9 expression in mammary epithelial cells of dairy cows remains unclear. This study aimed to explore the underlying mechanism of MMP9 expression. In this study, to determine whether the PI3K/AKT/mTORC1/NF-κB signalling pathway participates in the regulation of MMP9 expression, we treated mammary epithelial cells with specific pharmacological inhibitors of PI3K (LY294002), mTORC1 (Rapamycin) or NF-κB (Celastrol), respectively. Western blotting results indicated that LY294002, Rapamycin and Celastrol markedly decreased MMP9 expression and P65 nuclear translocation. Furthermore, we found that NF-κB (P65) overexpression resulted in elevated expression of MMP9 protein and activation of MMP9 promoter. In addition, we observed that Celastrol markedly decreases P65-overexpression-induced MMP9 promoter activity. Moreover, the results of the promoter assay indicated that the core regulation sequence for MMP9 promoter activation may be located at -420 ∼ -80 bp downstream from the transcription start site. These observations indicated that the PI3K/AKT/mTORC1 signalling pathway is involved in MMP9 expression by regulating MMP9 promoter activity via NF-κB in the mammary epithelial cells of dairy cows.

A Progressively Disassembled DNA Repair Inhibitors Nanosystem for the Treatment of BRCA Wild-Type Triple-Negative Breast Cancer.

Background: Olaparib, a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor has demonstrated promising efficacy in patients with triple-negative breast cancer (TNBC) carrying breast cancer gene (BRCA) mutations. However, its impact on BRCA wild-type (BRCAwt) TNBC is limited. Hence, it is crucial to sensitize BRCAwt TNBC cells to olaparib for effective clinical practice. Novobiocin, a DNA polymerase theta (POLθ) inhibitor, exhibits sensitivity towards BRCA-mutated cancer cells that have acquired resistance to PARP inhibitors. Although both of these DNA repair inhibitors demonstrate therapeutic efficacy in BRCA-mutated cancers, their nanomedicine formulations' antitumor effects on wild-type cancer remain unclear. Furthermore, ensuring effective drug accumulation and release at the cancer site is essential for the clinical application of olaparib. Materials and Methods: Herein, we designed a progressively disassembled nanosystem of DNA repair inhibitors as a novel strategy to enhance the effectiveness of olaparib in BRCAwt TNBC. The nanosystem enabled synergistic delivery of two DNA repair inhibitors olaparib and novobiocin, within an ultrathin silica framework interconnected by disulfide bonds. Results: The designed nanosystem demonstrated remarkable capabilities, including long-term molecular storage and specific drug release triggered by the tumor microenvironment. Furthermore, the nanosystem exhibited potent inhibitory effects on cell viability, enhanced accumulation of DNA damage, and promotion of apoptosis in BRCAwt TNBC cells. Additionally, the nanosystem effectively accumulated within BRCAwt TNBC, leading to significant growth inhibition and displaying vascular regulatory abilities as assessed by magnetic resonance imaging (MRI). Conclusion: Our results provided the inaugural evidence showcasing the potential of a progressively disassembled nanosystem of DNA repair inhibitors, as a promising strategy for the treatment of BRCA wild-type triple-negative breast cancer.

How Nanotherapeutic Platforms Play a Key Role in Glioma? A Comprehensive Review of Literature.

Glioblastoma (GBM), a highly aggressive form of brain cancer, is considered one of the deadliest cancers, and even with the most advanced medical treatments, most affected patients have a poor prognosis. However, recent advances in nanotechnology offer promising avenues for the development of versatile therapeutic and diagnostic nanoplatforms that can deliver drugs to brain tumor sites through the blood-brain barrier (BBB). Despite these breakthroughs, the use of nanoplatforms in GBM therapy has been a subject of great controversy due to concerns over the biosafety of these nanoplatforms. In recent years, biomimetic nanoplatforms have gained unprecedented attention in the biomedical field. With advantages such as extended circulation times, and improved immune evasion and active targeting compared to conventional nanosystems, bionanoparticles have shown great potential for use in biomedical applications. In this prospective article, we endeavor to comprehensively review the application of bionanomaterials in the treatment of glioma, focusing on the rational design of multifunctional nanoplatforms to facilitate BBB infiltration, promote efficient accumulation in the tumor, enable precise tumor imaging, and achieve remarkable tumor suppression. Furthermore, we discuss the challenges and future trends in this field. Through careful design and optimization of nanoplatforms, researchers are paving the way toward safer and more effective therapies for GBM patients. The development of biomimetic nanoplatform applications for glioma therapy is a promising avenue for precision medicine, which could ultimately improve patient outcomes and quality of life.

Qiqilian ameliorates vascular endothelial dysfunction by inhibiting NLRP3-ASC inflammasome activation in vivo and in vitro.

CONTEXT: Previous studies have highlighted significant therapeutic effects of Qiqilian (QQL) capsule on hypertension in spontaneously hypertensive rats (SHRs); however, its underlying molecular mechanism remains unclear. OBEJECTIVE: We investigated the potential mechanism by which QQL improves hypertension-induced vascular endothelial dysfunction (VED). MATERIALS AND METHODS: In vivo, SHRs were divided into four groups (20 per group) and were administered gradient doses of QQL (0, 0.3, 0.6, and 1.2 g/kg) for 8 weeks, while Wistar Kyoto rats were used as normal control. The vascular injury extent, IL-1ß and IL-18 levels, NLRP3, ASC and caspase-1 contents were examined. In vitro, the effects of QQL-medicated serum on angiotensin II (AngII)-induced inflammatory and autophagy in human umbilical vein endothelial cells (HUVECs) were assessed. RESULT: Compared with the SHR group, QQL significantly decreased thickness (125.50 to 105.45 µm) and collagen density (8.61 to 3.20%) of arterial vessels, and reduced serum IL-1ß (96.25 to 46.13 pg/mL) and IL-18 (345.01 to 162.63 pg/mL) levels. The NLRP3 and ACS expression in arterial vessels were downregulated (0.21- and 0.16-fold, respectively) in the QQL-HD group compared with the SHR group. In vitro, QQL treatment restored NLRP3 and ASC expression, which was downregulated approximately 2-fold compared with that of AngII-induced HUVECs. Furthermore, QQL decreased LC3II and increased p62 contents (p < 0.05), indicating a reduction in autophagosome accumulation. These effects were inhibited by the autophagy agonist rapamycin and enhanced by the autophagy inhibitor chloroquine. CONCLUSION: QQL effectively attenuated endothelial injury and inflammation by inhibiting AngII-induced excessive autophagy, which serves as a potential therapeutic strategy for hypertension.

Gut microbiota in Chinese and Japanese patients with cardiovascular diseases: a systematic review and meta-analysis.

BACKGROUND: Cardiovascular disease (CVD) is a major threat to public health. OBJECTIVE: Compare the gut microbial composition between Chinese and Japanese patients with cardiovascular diseases and healthy subjects. STUDY SELECTION: Observational studies with Chinese and Japanese populations. Reviews, duplicate, book chapters, and other irrelevant studies were excluded. DATA EXTRACTION: Independent searching by two investigators (LLJ, HJL). DATA SYNTHESIS: Data from eleven studies (with 960 subjects) were included for the meta-analysis. The meta-analysis showed that the abundance of Firmicutes in patients with cardiovascular disease was [ES=0.42, 95%CI, (0.34, 0.50), P<.01], while the abundance of Firmicutes in control subjects was [ES=0.36, 95%CI, (0.23, 0.49), P<.01] (ES: effect size). When compared to control subjects, the differential expression of Firmicutes abundance in patients with CVDs was [MD = 15.21, 95%CI (8.95, 21.48), P<.01] (MD: mean difference). The ratio of Firmicutes abundance in patients with CVDs to the control subjects was [RR=1.28, 95%CI (0.98, 1.67), P=.07]. The ratio of Firmicutes in coronary heart disease (CHD) patients and controls was [RR=1.42, 95%CI (1.05, 1.94), P=.02]. Firmicutes/Bacteroidetes ratio is [OR=1.64 95%CI (1.11, 2.42), P=.01]. CONCLUSION: Our data show that patients with cardiovascular disease had higher levels of gut Firmicutes when compared to healthy controls. In addition, gut microbial dysbiosis was present in patients with cardiovascular diseases. LIMITATIONS: Due to limited quality and quantity of selected studies, conclusions from the current study need to be validated by future studies. CONFLICT OF INTEREST: None.

Nanomaterial-Based Antivascular Therapy in the Multimodal Treatment of Cancer.

Abnormal tumor vasculature and a hypoxic tumor microenvironment (TME) limit the effectiveness of conventional cancer treatment. Recent studies have shown that antivascular strategies that focus on antagonizing the hypoxic TME and promoting vessel normalization effectively synergize to increase the antitumor efficacy of conventional therapeutic regimens. By integrating multiple therapeutic agents, well-designed nanomaterials exhibit great advantages in achieving higher drug delivery efficiency and can be used as multimodal therapy with reduced systemic toxicity. In this review, strategies for the nanomaterial-based administration of antivascular therapy combined with other common tumor treatments, including immunotherapy, chemotherapy, phototherapy, radiotherapy, and interventional therapy, are summarized. In particular, the administration of intravascular therapy and other therapies with the use of versatile nanodrugs is also described. This review provides a reference for the development of multifunctional nanotheranostic platforms for effective antivascular therapy in combined anticancer treatments.

Prolactin regulates RANKL expression via signal transducer and activator of transcription 5a signaling in mammary epithelial cells of dairy cows.

Receptor of activated nuclear factor kappa B ligand (RANKL) is regulated by prolactin in the mammary gland. However, the intrinsic molecular mechanism is not well understood. Herein, mammary epithelial cells (MECs) of dairy cows were isolated to characterize the molecular mechanism of prolactin in vitro. We demonstrated that prolactin stimulation increased the expression of RANKL in MECs. Moreover, the expression of RANKL induced by prolactin was inhibited by the prolactin receptor or signal transducer and activator of transcription 5A (STAT5a) knockdown. Furthermore, prolactin markedly increased RANKL-Luciferase reporter activity in MECs. We identified a putative gamma-interferon activated site (GAS) in the region between residues -883 to -239 bp of the RANKL promoter. Subsequently, we found that the mutated GAS sequence failed to respond to prolactin stimulation. In addition, STAT5a knockdown markedly decreased prolactin-stimulated RANKL promoter activity. Western blot results revealed that RANKL overexpression markedly decreased the STAT5a phosphorylation level in MECs. These findings indicate that prolactin could regulate RANKL promoter activity via STAT5a, contributing to increased RANKL expression in MECs. RANKL may have a negative regulatory effect on STAT5a activity.

Towards a Machine Learning-Based Digital Twin for Non-Invasive Human Bio-Signal Fusion.

Human bio-signal fusion is considered a critical technological solution that needs to be advanced to enable modern and secure digital health and well-being applications in the metaverse. To support such efforts, we propose a new data-driven digital twin (DT) system to fuse three human physiological bio-signals: heart rate (HR), breathing rate (BR), and blood oxygen saturation level (SpO2). To accomplish this goal, we design a computer vision technology based on the non-invasive photoplethysmography (PPG) technique to extract raw time-series bio-signal data from facial video frames. Then, we implement machine learning (ML) technology to model and measure the bio-signals. We accurately demonstrate the digital twin capability in the modelling and measuring of three human bio-signals, HR, BR, and SpO2, and achieve strong performance compared to the ground-truth values. This research sets the foundation and the path forward for realizing a holistic human health and well-being DT model for real-world medical applications.

Metal-Cyclic Dinucleotide Nanomodulator-Stimulated STING Signaling for Strengthened Radioimmunotherapy of Large Tumor.

Combined treatment of immunotherapy and radiotherapy shows promising therapeutic effects for the regression of a variety of cancers. However, even multi-modality therapies often fail to antagonize the regression of large tumors due to the extremely immunosuppressive tumor microenvironment (TME). Here, a radioimmunotherapeutic paradigm based on stimulator of interferon genes (STING)-dependent signaling is applied to preclude large tumor progression by utilizing the metal-cyclic dinucleotide (CDN) nanoplatform, which integrates STING agonist c-di-AMP and immunomodulating microelement manganese (II) within the tannic acid nanostructure (TMA-NPs). As observed by magnetic resonance imaging, the localized administration of TMA-NPs effectively relieves hypoxia within TME and causes radical oxygen species overproduction and apoptosis in cancer cells after exposure to X-ray irradiation. The DNA fragments released from the apoptotic cells after the combined treatment augment the production of endogenous CDNs in cancer cells, hence significantly activating the STING-mediated pathway for stronger anti-tumor immunity. The localized therapy of TMA-NPs + X-ray not only inhibits the primary large tumor progression but also retards distant tumor growth by promoting dendritic cell maturation and activating cytotoxic immune cells whil suppressing immunosuppressive cells. Therefore, this work represents the combinatorial potency of TMA-NPs and X-rays on large tumor regression through strengthened STING-mediated radioimmunotherapeutics.

Comparative Transcriptome Sequencing Analysis of Hirudo nipponia in Different Growth Periods.

Hirudo nipponia is the only blood-sucking leech included in Chinese Pharmacopoeia having distinct features of anticoagulation, exorcizing blood stasis, and promoting menstruation. Despite such significant characteristics, very little is known about its molecular genetics and related physiological mechanisms. In this study, the transcriptomes of H. nipponia at three developmental stages (larvae, young, and adults), revealed a total of 1,348 differentially expressed genes (DEGs), 223 differentially expressed lncRNAs, and 88 novel mRNAs. A significant diverse gene expression patterns were observed at different developmental stages which were analyzed by differential gene expression trends, and the overall gene expression trends consist of three overall down-regulated trends, and two overall up-regulated trends. Furthermore, the GO and KEGG enrichment functional annotation analysis revealed that these DEGs were mainly associated with protein hydrolysis, signal transduction, energy metabolism, and lipid metabolism while growth, development, metabolism, and reproduction-related DEGs were also found. Additionally, real-time quantitative PCR results confirmed deep sequencing results based on the relative expression levels of nine randomly selected genes. This is the first transcriptome-based comprehensive study of H. irudo nipponia at different developmental stages which provided considerable deep understanding related to gene expression patterns and their relevant developmental pathways, neurodevelopmental and reproductive characteristics of the leech.

Comprehensive Transcriptome Sequencing Analysis of Hirudinaria manillensis in Different Growth Periods.

Medical leeches are widely been used in biochemical and clinical medical studies, helping to restore blood circulation to grafted or severely injured tissue. Mostly, adult leeches are being used in the traditional pharmacopeia, but the gene expression profiling of leeches in different growth periods is not well-reported. So, in this study, we used transcriptome analysis to analyze the comparative gene expression patterns of Hirudinaria manillensis (H. manillensis) in different growth periods, including larval, young, and adult stages. We constructed 24 cDNA libraries from H. manillensis larval, young, and adult stages, and about 54,639,118 sequences were generated, 18,106 mRNA transcripts of which 958 novel mRNAs and 491 lncRNAs were also assembled as well. Furthermore, the results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the differentially upregulated genes from the larval to adult stages were enriched in pathways such as cilium, myofibril, contractile fiber, cytoskeleton proteins, dilated cardiomyopathy, adrenergic signaling in cardiomyocytes, etc. Moreover, in the adult stages, a significant increase in the expression of the Hirudin-HM (HIRM2) genes was detected. In addition, our comparative transcriptome profiling data from different growth stages of H. manillensis also identified a large number of DEGs and DElncRNAs which were tentatively found to be associated with the growth of H. manillensis; as it grew, the muscle-related gene expression increased, while the lipid metabolism and need for stimulation and nutrition-related genes decreased. Similarly, the higher expression of HIRM2 might attribute to the high expression of protein disulfide isomerase gene family (PDI) family genes in adulthood, which provides an important clue that why adult leeches rather than young leeches are widely used in clinical therapeutics and traditional Chinese medicine.

Chinese Herb Jiedu Huayu Granules Inhibiting Immune and Inflammatory Response of Rats with Acute Liver Failure by Regulating the NF-κB Signaling Pathway.

Objective: To research the influence of Chinese medicine Jiedu Huayu granules (JDHY) on the immune response and inflammatory response of rats with acute liver failure (ALF) and investigate its related mechanism. Methods: Rats were randomly divided into 4 groups: control group (n = 6) were injected with the same amount of normal saline; ALF group (n = 10) were injected intraperitoneally with D-GaIN (700 mg/kg) and LPS (10 µg/kg); ALF+JDHY group (n = 10) were given JDHY 57.55 g/kg/d by gavage for 7 days and injected intraperitoneally with D-GaIN/LPS after the last dose; and ALF+BAY group (n = 10) were given BAY 10 mg/kg/d by gavage for 7 days and injected intraperitoneally with D-GaIN/LPS after the last dose. Changes in liver function and coagulation function were examined in rat serum; the pathological varieties of liver tissues were verified by HE staining; immunohistochemistry was utilized to determine the ratio of PCNA and F4/80 in liver tissues; the flow cytometry was applied to determine the ratio of CD4+/CD8+ cells in peripheral blood mononuclear cells (PBMCs); ELISA and qRT-PCR were utilized to check the level of IL-10, IL-6, IL-13, IL-1ß, TNF-α, IFN-γ, and CD163 in serum and liver cells. Western blot was adopted to check the expression of apoptotic protein and expression and NF-κB pathway-related protein expression. Results: JDHY and BAY could decline the expression of AST, ALT, ALP, and TBiL in ALF rat serum significantly (P < 0.01), increase PTA and PLT (P < 0.01), and mitigate liver tissue damage. Besides, JDHY and BAY could reduce the apoptosis and improve the proliferation of the liver cells in rats with ALF; meanwhile, the ratio of CD4+ cells and F4/80 cells was reduced while CD8+ cells were increased (P < 0.01). Further, JDHY and BAY could reduce the level of IFN-γ, IL-6, IL-1ß, and TNF-α while increasing the level of IL-10 and IL-13 (P < 0.01). Additionally, the expression of sCD163 in serum and CD163 expression in liver tissues increased (P < 0.01). The result of western blot confirmed that JDHY could inhibit the phosphorylated expression of NF-κB, IKßα, and IKKß in the ALF rat tissues. Conclusions: JDHY can upregulate the level of CD163/sCD163 by the NF-κB signaling pathway, thereby regulating immune response, inhibiting inflammatory response, and ultimately improving ALF in the rats.

Identification of key genes associated with the progression of liver fibrosis to hepatocellular carcinoma based on iTRAQ proteomics and GEO database.

INTRODUCTION AND OBJECTIVE: Liver fibrosis (LF) often leads to cirrhosis and even hepatocellular carcinoma (HCC), but the molecular mechanism remains unclear. The aims of the present study were to identify potential biomarkers for the progression of LF to HCC and explore the associated molecular mechanisms. MATERIALS AND METHODS: The isobaric tags for relative and absolute quantitation (iTRAQ) was used to detect changes in the protein expression profiles of liver tissues and to screen the differentially expressed proteins (DEPs). The differentially expressed genes (DEGs) of LF rats and patients were screened by Gene Expression Database (GEO). Subsequently, the clinicopathological analysis of the overlapping genes in different pathological stages in HCC patients based on GEPIA database was conducted. RESULTS: iTRAQ proteomic analysis revealed 689, 749 and 585 DEPs in the 6W, 8W and 12W groups, respectively. ALDH2, SLC27A5 and ASNS were not only the DEPs found in rats with LF with different stages but were also the DEGs related to the pathological stages and survival in patients with HCC. CONCLUSIONS: ALDH2, SLC27A5 and ASNS were the potential biomarkers associated with the progression of LF to HCC.

Molecular mechanisms underlying hematophagia revealed by comparative analyses of leech genomes.

BACKGROUND: Leeches have been used in traditional Chinese medicine since prehistoric times to treat a spectrum of ailments, but very little is known about their physiological, genetic, and evolutionary characteristics. FINDINGS: We sequenced and assembled chromosome-level genomes of 3 leech species (bloodsucking Hirudo nipponia and Hirudinaria manillensis and nonbloodsucking Whitmania pigra). The dynamic population histories and genome-wide expression patterns of the 2 bloodsucking leech species were found to be similar. A combined analysis of the genomic and transcriptional data revealed that the bloodsucking leeches have a presumably enhanced auditory sense for prey location in relatively deep fresh water. The copy number of genes related to anticoagulation, analgesia, and anti-inflammation increased in the bloodsucking leeches, and their gene expressions responded dynamically to the bloodsucking process. Furthermore, the expanded FBN1 gene family may help in rapid body swelling of leeches after bloodsucking, and the expanded GLB3 gene family may be associated with long-term storage of prey blood in a leech's body. CONCLUSIONS: The high-quality reference genomes and comprehensive datasets obtained in this study may facilitate innovations in the artificial culture and strain optimization of leeches.

Association between Toll-like receptor gene polymorphisms and risk of Helicobacter pylori infection: A protocol for systematic review and meta-analysis.

BACKGROUND: There were many case-control studies performed the association between TLRs gene polymorphisms and the correlation of Helicobactor pylori infection, these results were inconformity. Therefore, a comprehensive meta-analysis was performed to evaluate the TLRs gene polymorphism and susceptibility to H. pylori infection. METHODS: Eligible studies were searched from PubMed, EMBASE, Web of science, Cochrane library, CNKI, CBM, Wan Fang Database and VIP Database, all the databases were searched from inception to December 2020. OR with the corresponding 95% CI were presented as associations between certain TLR gene polymorphism and the risk of H. pylori infection, all the included data will be analyzed with the software of Review Manager 5.2 and STATA 14.2. RESULTS: This study will provide a high-quality evidence to find the TLR gene polymorphisms with H. pylori infection susceptibility. CONCLUSION: This study will explore which TLR genotype increase the risk of H. pylori infection.

Effects of salvianolic acid B on liver fibrosis: A protocol for systematic review and meta analysis.

BACKGROUND: Liver fibrosis is a pathological change existing in most chronic liver diseases, which leads to abnormal changes in liver tissue structure and affects the normal physiological function of liver. Without effectively control, liver fibrosis can develop into cirrhosis and increase the risk of liver cancer. Salvianolic acid B (Sal B) is the main active component in the water-soluble extract from Salvia miltiorrhiza, which is a traditional Chinese medicine usually used for treating cardiovascular and liver diseases. It is reported that Sal B shown a good action against liver fibrosis via numerous signaling pathways, which indicate that Sal B is a potential candidate drug for the treatment of liver fibrosis. METHODS: We searched the related researches from the following electronic databases: PubMed, EMBASE, Web of science, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Wan fang Database for Chinese Technical Periodicals and VIP Database. All the databases were searched from inception to December 2019. No restriction of language, publication date, or publication status. PICO of this systematic review are shown as flowing: P, preclinical studies which evaluated the effects of Sal B on the animal models of liver fibrosis with controlled studies; I, received Sal B as only treat in any dose; C, received normal saline, distilled water, or no treatment; O, the primary outcome include measure will be the decrease in liver fibrosis score, and the secondary outcomes include the index of liver fibrosis. All the included data will be analyzed with the software of Review Manager 5.2 and STATA 14.2. DISCUSSION: The purpose of this study is to conduct a systematic review and meta-analysis to assess the effects on anti-liver fibrosis of Sal B, and this will be contribute to drug development and pathological mechanisms of clinical research. TRIAL REGISTRATION: INPLASY202050101, registered on 28/5/2020.

Quercetin for myocardial ischemia reperfusion injury: A protocol for systematic review and meta-analysis.

BACKGROUND: At present, there is no effective therapy for preventing myocardial ischemia reperfusion injury (MIRI), and it is inevitable. The methods how to effectively decrease MIRI have attracted the attention of medical researches in recent years. Quercetin is a part of natural flavonoids in plant polyphenols. Many studies have found that quercetin has a positive effect on MIRI. METHODS: In order to clarify the effectiveness and potential mechanisms of quercetin for MIRI animals, we searched for animal studies of quercetin for MIRI in Wanfang data Information, Chinese National Knowledge Infrastructure, VIP information database, China Biology Medicine disc, EMBASE, PubMed, and Web of Science. Participant intervention comparator outcomes of this study are as flowing: P, rats in MIRI; I, received quercetin treatment merely; C, received only vehicle or no treatment; O, Main outcomes are myocardial infarction size and markers of myocardial injury. Additional outcomes are serum indices or protein levels tied to the mechanisms of quercetin in myocardial l/R injury. Review Manager 5.2 software and Stata14.0 will be used for data analysis. SYRCLE's risk of bias tool will be used for risk of bias analysis of animal studies. DISCUSSION: This preclinical systematic review and meta-analysis will evaluate the effects and mechanisms of quercetin for MIRI animals, and provide more evidence-based guidance for transforming basic research into clinical treatment. TRIAL REGISTRATION: INPLASY202050067, registered on 16/5/2020.

Enolase 1 Correlated With Cancer Progression and Immune-Infiltrating in Multiple Cancer Types: A Pan-Cancer Analysis.

Enolase 1 (ENO1) is an oxidative stress protein expressed in endothelial cells. This study aimed to investigate the correlation of ENO1 with prognosis, tumor stage, and levels of tumor-infiltrating immune cells in multiple cancers. ENO1 expression and its influence on tumor stage and clinical prognosis were analyzed by UCSC Xena browser, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), and GTEx Portal. The ENO1 mutation analysis was performed by cBio Portal, and demonstrated ENO1 mutation (1.8%) did not impact on tumor prognosis. The relationship between ENO1 expression and tumor immunity was analyzed by Tumor Immune Estimation Resource (TIMER) and GEPIA. The potential functions of ENO1 in pathways were investigated by Gene Set Enrichment Analysis. ENO1 expression was significantly different in tumor and corresponding normal tissues. ENO1 expression in multiple tumor tissues correlated with prognosis and stage. ENO1 showed correlation with immune infiltrates including B cells, CD8+ and CD4+ T cells, macrophages, neutrophils, and dendritic cells, and tumor purity. ENO1 was proved to be involved in DNA replication, cell cycle, apoptosis, glycolysis process, and other processes. These findings indicate that ENO1 is a potential prognostic biomarker that correlates with cancer progression immune infiltration.

Lack of association between ALOX5AP genetic polymorphisms and risk of ischemic stroke: evidence from meta-analyses.

BACKGROUND: In recent years, there has been substantial research evaluating the relationship between arachidonate 5-lipoxygenase-activating protein (ALOX5AP) polymorphisms and ischemic stroke (IS). The objective of this study was to systematically review and analyze the existing evidence. METHODS: A comprehensive search of major electronic databases for studies published between 1990 and 2018 was carried out. Data were synthesized as OR and 95% CI using fixed-effects and random-effects models. RESULTS: A total of 30 studies were available for analysis. The aggregate sample size across all studies was 32,782 (16,294 cases and 16,488 controls). We found no association of the ALOX5AP rs10507391 (OR=1.03 for A allele vs T allele; 95% CI: 0.93-1.14; P=0.557), rs4769874 (OR=1.13 for A allele vs G allele; 95% CI: 1.00-1.28; P=0.050), rs9551963 (OR=1.03 for A allele vs C allele; 95% CI: 0.96-1.11; P=0.372), rs17222814 (OR=1.09 for A allele vs G allele; 95% CI: 0.96-1.24; P=0.195), rs17222919 (OR=0.89 for G allele vs T allele; 95% CI: 0.75-1.06; P=0.175), and rs4073259 (OR=1.20 for A allele vs G allele; 95% CI: 1.00-1.45; P=0.056) polymorphisms with IS risk. Haplotype analysis also did not yield significant findings for the HapA (rs17222814G-rs10507391T-rs4769874G-rs9551963A; OR=1.20; 95% CI: 0.91-1.56; P=0.192) and HapB (rs17216473A-rs10507391A-rs9315050A-rs17222842G; OR=1.11; 95% CI: 0.90-1.38; P=0.339) haplotypes. CONCLUSION: Current evidence does not support an association of rs10507391, rs4769874, rs9551963, rs17222814, rs17222919, rs4073259, and HapA and HapB with IS risk.