Efficacy and safety evaluation of Ginkgo biloba dropping pill (GBDP) on stable angina pectoris complicated with depression: A placebo-controlled, randomized, double-blind, multicenter study.

BACKGROUND: Stable angina pectoris (SAP) is a clinical condition characterized by reversible and temporary myocardial ischemia and hypoxia. A majority of SAP patients also experience depressive disorders, which adversely affect their disease prognosis and overall quality of life. However, the clinical utility of existing antidepressants is constrained by their side effects. Ginkgo biloba dropping pill (GBDP), a Chinese patented medication, has demonstrated efficacy in the treatment of both coronary heart disease and mental disorders. This prospective, randomized, double-blind, multicenter clinical trial aimed to assess the effectiveness and safety of GBDP as an adjuvant therapy for SAP complicated by depression. METHODS: Participants were randomly assigned in a 1:1 ratio to receive either GBDP or a placebo (5 pills, three times a day) in addition to standard therapy for a duration of 12 weeks. The Seattle Angina Questionnaire (SAQ) was administered every 4 weeks during the treatment, and angina event frequency was assessed weekly. The 36-item Short-Form (SF-36) and Hamilton Depression Scale (HAMD) scores were measured both before and after the treatment. RESULTS: Out of the 72 patients, 68 (n = 34 per group) completed the entire study. At the first visit (4 weeks ± 3 days), the SAQ-Angina Stability score in the GBDP group was significantly higher than that in the placebo group (p < 0.05). While the average weekly frequency of angina episodes in the placebo group notably increased after 12 weeks of treatment (p < 0.05), it displayed an improving trend in the GBDP group (p > 0.05). By the endpoint, each subcategory score of SF-36 in the GBDP group exhibited significant improvement compared to baseline (p < 0.05). The comparison of score improvement between the two groups revealed that the SF-PCS score of the GBDP group was higher than that of the placebo group (p < 0.05). HAMD scores in both groups significantly increased after treatment (p < 0.05). No discernible difference in the incidence of adverse reactions was observed between the two groups (p > 0.05). CONCLUSION: In patients with SAP complicated by depression, GBDP, when combined with standard treatment, rapidly and safely alleviates angina pectoris symptoms. It demonstrates therapeutic potential in enhancing the quality of life and alleviating depressive symptoms.

Impact of inflammation and anti-inflammatory modalities on diabetic cardiomyopathy healing: From fundamental research to therapy.

Diabetic cardiomyopathy (DCM) is a prevalent cardiovascular complication of diabetes mellitus, characterized by high morbidity and mortality rates worldwide. However, treatment options for DCM remain limited. For decades, a substantial body of evidence has suggested that the inflammatory response plays a pivotal role in the development and progression of DCM. Notably, DCM is closely associated with alterations in inflammatory cells, exerting direct effects on major resident cells such as cardiomyocytes, vascular endothelial cells, and fibroblasts. These cellular changes subsequently contribute to the development of DCM. This article comprehensively analyzes cellular, animal, and human studies to summarize the latest insights into the impact of inflammation on DCM. Furthermore, the potential therapeutic effects of current anti-inflammatory drugs in the management of DCM are also taken into consideration. The ultimate goal of this work is to consolidate the existing literature on the inflammatory processes underlying DCM, providing clinicians with the necessary knowledge and tools to adopt a more efficient and evidence-based approach to managing this condition.

Efficacy and safety of Ginkgo biloba dropping pills in the treatment of coronary heart disease with stable angina pectoris and depression: study protocol for a randomised, placebo-controlled, parallel-group, double-blind and multicentre clinical trial.

BACKGROUND: Coronary heart disease(CHD) with stable angina pectoris is a common cardiovascular disease. It has been reported that 10%-81.4% of these patients suffer from psychological conditions,such as depression, which has been associated with more frequent angina, lower treatment satisfaction and lower perceived quality of life. Ginkgo biloba extract (GBE), the raw material of Ginkgo biloba dropping pills (GBDPs), is widely used to treat various conditions, including cardiovascular disease, ischaemic cerebrovascular disease, and depression. This clinical trial aimed to examine the efficacy and safety of GBDPs in improving the frequency of angina pectoris and the life quality of patients with stable angina pectoris and depression symptoms. METHODS: This randomised, double-blind, placebo-controlled, parallel-group and multicentre clinical trial will be conducted in four medical centres in China. We aim to recruit approximately 72 participants aged 18-75 years with depression and coronary heart disease with stable angina pectoris. Based on conventional drug treatment, participants will be randomly assignedto the treatment group (GBDPs group; n=36) or the control group (placebo group; n=36) at a 1:1 allocation ratio. After randomisation,follow-up will be done at 4 weeks, 8 weeks and 12 weeks (±3 days). Additionally, 30 healthy individuals will be enrolled to investigate the underlying pharmacological mechanisms of the effects of GBE. The primary outcomes will be the Seattle Angina Questionnaire score and the frequency of angina pectoris-related symptoms each week. The secondary outcomes will include the 36-item Short Form Health Survey quality-of-life scale, Hamilton Depression Scale and composite endpoint incidence of major adverse cardiovascular events. ETHICS AND DISSEMINATION: This trial has been approved by the Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (approval number: ZYYECK [2020]030). Written informed consent will be obtained from all participants. The results of this trial will be publicly shared through academic conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04529148 and ChiCTR2200066908.

LncRNA MHRT Prevents Angiotensin II-Induced Myocardial Oxidative Stress and NLRP3 Inflammasome via Nrf2 Activation.

The development of angiotensin II (Ang II)-induced cardiomyopathies is reportedly mediated via oxidative stress and inflammation. Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of cellular antioxidant defense, and reactive oxygen species (ROS) can activate the NLRP3 inflammasome. MHRT is a newly discovered lncRNA exhibiting cardioprotective effects, demonstrated by inhibiting myocardial hypertrophy via Brg1 and myocardial apoptosis via Nrf2 upregulation. However, the underlying mechanism of MHRT remains unclear. We explored the potential protective effects of MHRT against Ang II-induced myocardial oxidative stress and NLRP3-mediated inflammation by targeting Nrf2. Chronic Ang II administration induced NLRP3 inflammasome activation (increased NLRP3, caspase-1 and interleukin-1ß expression), oxidative stress (increased 3-nitrotyrosine and 4-hydroxy-2-nonenal), cardiac dysfunction and decreased MHRT and Nrf2 expression. Lentivirus-mediated MHRT overexpression inhibited Ang II (100 nM)-induced oxidative stress and NLRP3 inflammasome activation in AC16 human cardiomyocyte cells. Mechanistically, MHRT overexpression upregulated the expression and function of Nrf2, as determined by the increased transcription of downstream genes HO-1 and CAT, subsequently decreasing intracellular ROS accumulation and inhibiting the expression of thioredoxin-interacting protein (NLRP3 activator) and its direct binding to NLRP3. Accordingly, MHRT could protect against Ang II-induced myocardial injury by decreasing oxidative stress and NLRP3 inflammasome activation via Nrf2 activation.

Efficacy and Safety of QiShen YiQi Dripping Pills in the Treatment of Coronary Heart Disease Complicating Chronic Heart Failure (Syndrome of Qi Deficiency with Blood Stasis): Study Protocol for a Randomized, Placebo-Controlled, Double-Blind and Multi-Centre Phase II Clinical Trial.

Background: Heart failure (HF) is a serious and terminal stage of various cardiac diseases and the most common complication of coronary heart disease (CHD). Previous clinical studies have shown that Qishen Yiqi dropping pills (QSYQ) have the effect of treating chronic heart failure. This study aims to evaluate the clinical efficacy, safety and optimal effective dose of QSYQ in treating CHD complicating chronic HF with reduced ejection fraction (HFrEF). Methods: We will conduct a randomized, double-blind, placebo controlled, multicenter clinical trial. A total of 228 individuals from 16 hospitals in China will be randomly assigned to the low-dose, high-dose, and placebo groups in a ratio of 1:1:1. The trial consists of a screening period (standard medical treatment for at least 2 weeks) and a 12-week treatment period. After randomization, follow-up will be conducted at the 4th, 8th and 12th week. The primary outcomes will be the 6-Minute Walk Test (6MWT) at Week 12. Secondary outcomes will include 6MWT distance at Week 4 and 8, New York Heart Association (NYHA) functional classification, Traditional Chinese Medicine (TCM) Syndrome score, echocardiography indices, N-terminal pro-B-type natriuretic peptide (NT-proBNP), oxyhemoglobin saturation, Minnesota living with heart failure questionnaire (MLHFQ) score, grasp strength body mass index test and cardiovascular adverse events (AE). Ethics and Dissemination: This trial has been approved by the Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (approval number: ZYYEC [2021]005). Written informed consent will be obtained from all participants. The results of this trial will be publicly shared through academic conferences and peer-reviewed journals. Study Registration: Clinical Trials Registry (NCT04983043, Date: 07/08/2021, https://clinicaltrials.gov/ct2/show/NCT04983043).

Identification of optimal reference genes for gene expression normalization in human osteosarcoma cell lines under proliferative conditions.

The molecular pathogenesis and therapeutic target research studies on osteosarcoma (OS) have developed well during the last few years using various OS cell lines with reverse transcription quantitative polymerase chain reaction (RT-qPCR). However, the identification of suitable reference genes of RT-qPCR for OS cell lines has not been reported. Here, we conducted the normalization research of 12 reference genes (GAPDH, ACTB, 18S, B2M, ALAS1, GUSB, HPRT1, HMBS, PPIA, PUM1, RPL29, and TBP) for gene expression analysis in four kinds of human OS cell lines (U2OS, Saos-2, HOS, and MG-63) to improve the investigation of molecular mechanisms and the accuracy of diagnosis and prognostic molecular targets of OS. The gene expression stability and applicability of the 12 reference gene candidates were determined using geNorm, NormFinder, and BestKeeper software. The results indicated that PUM1 and the combination of PPIA + ALAS1 were recommended as the optimal reference gene in these four different sources of human OS cell lines under proliferative conditions. The present study identified the most suitable reference genes and reference gene combinations for OS cell lines under proliferative conditions in order to use in gene expression profile analysis. A reliable standardized method has the potential to improve the understanding of the biological mechanisms underlying OS in the future.

3D-printed bioactive ceramic scaffolds with MoSe2 nanocrystals as photothermal agents for bone tumor therapy.

Large scale bone defects after bone tumor resection are difficult to reconstruct and repair, and there is also the possibility of tumor recurrence. Photothermal therapy (PTT) has the function of inhibiting tumor cells, but the risk of damage to normal cells is the main factor limiting the clinical application of PTT drugs, and most of them have a weak effect on regeneration for bone defects. Therefore, specific biomaterials that simultaneously eliminate bone tumors, have low toxicity, and promote osteogenesis have attracted considerable attention. In this paper, we successfully fabricated bioactive bredigite scaffolds (MS-BRT) functionalized with MoSe2 nanocrystals using a combination of 3D printing and hydrothermal methods. MS-BRT scaffolds not only have low toxicity and good osteogenic ability, but also have the ability to kill bone tumors by photothermal therapy. Using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and an infrared thermal camera, MoSe2 nanocrystals were demonstrated to be successfully modified on the surface of BRT scaffolds. The MoSe2 nanocrystals endow the scaffolds with excellent photothermal properties, which can be well controlled by varying the hydrothermal reaction time and laser power density. Furthermore, the MS-BRT scaffolds can effectively kill MG-63 and HeLa cells and promote the adhesion and proliferation of osteoblasts. The performance of osteoblastic activity was assessed by alkaline phosphatase staining and alizarin red S staining, which results suggest that both MS-BRT and BRT have favorable osteogenic properties. This study combines the photothermal properties of semiconducting MoSe2 nanocrystals with the osteogenic activity of bioceramic scaffolds for the first time, providing a broader perspective for the development of novel biomaterials with dual functions of bone tumor treatment and bone regeneration.

Yellow-Green Luminescence Due to Polarity-Dependent Incorporation of Carbon Impurities in Self-Assembled GaN Microdisk.

Yellow-green luminescence (YGL) competes with near-bandgap emission (NBE) for carrier recombination channels, thereby reducing device efficiency; yet uncovering the origin of YGL remains a major challenge. In this paper, nearly stress-free and low dislocation density self-assembled GaN microdisks were synthesized by Na-flux method. The YGL of GaN microdisks highly depend on their polar facets. Variable accelerating voltage/power CL, variable temperature PL, and Raman spectroscopy are further performed to clarify the origin of polarity dependence of GaN microdisk YGL behavior, which indicates its independence of dislocations, surface effects, stress, crystalline quality, and gallium vacancies. It was found that the incorporation ability of carbon impurities in the polar (0001) facet is greater than that in the semipolar (101̅1) facets, producing higher content of CN or CNON defects, resulting in a more pronounced YGL in the polar (0001) facet of GaN.

Analysis of the lncRNA-Associated Competing Endogenous RNA (ceRNA) Network for Tendinopathy.

Background: We aimed to construct the lncRNA-associated competing endogenous RNA (ceRNA) network and distinguish feature lncRNAs associated with tendinopathy. Methods: We downloaded the gene profile of GSE26051 from the Gene Expression Omnibus (GEO), including 23 normal samples and 23 diseased tendons. Differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) were identified, and functional and pathway enrichment analyses were performed. Protein-protein interaction (PPI) network was constructed and further analyzed by module mining. Moreover, a ceRNA regulatory network was constructed based on the identified lncRNA-mRNA coexpression relationship pairs and miRNA-mRNA regulation pairs. Results: We identified 1117 DEmRNAs and 57 DElncRNAs from the GEO data. The downregulated DEmRNAs were particularly associated with muscle contraction and muscle filament, while the upregulated ones were linked to extracellular matrix organization and cell adhesion. From the PPI network, 11 modules were extracted. Genes in MCODE 2 (such as TPM4) were significantly involved in cardiomyopathy, and genes in MCODE 4 (such as COL4A3 and COL4A4) were involved in focal adhesion, ECM-receptor interaction, and PI3K-Akt signaling pathway. The ceRNA network contained 7 lncRNAs (MIR133A1HG, LINC01405, PRKCQ-AS1, C10orf71-AS1, MBNL1-AS1, HOTAIRM1, and DNM3OS), 63 mRNAs, and 41 miRNAs. Downregulated lncRNA MIR133A1HG could competitively bind with hsa-miR-659-3p and hsa-miR-218-1-3p to regulate the TPM3. Meanwhile, MIR133A1HG could competitively bind with hsa-miR-1179 to regulate the COL4A3. Downregulated C10orf71-AS1 could competitively bind with hsa-miR-130a-5p to regulate the COL4A4. Conclusions: Seven important lncRNAs, particularly MIR133A1HG and C10orf71-AS1, were found associated with tendinopathy according to the lncRNA-associated ceRNA network.

A Simplified Herbal Formula Improves Cardiac Function and Reduces Inflammation in Mice Through the TLR-Mediated NF-κB Signaling Pathway.

Nuanxinkang tablet (NXK), a Chinese herbal formula, can improve heart function and quality of life in patients with chronic heart failure (CHF). However, the mechanisms of action of NXK are not fully understood. In this study, we investigated the effects of NXK on inflammation in the CHF mouse model. This model was established by transverse aortic constriction (TAC) and treated with NXK for 8 weeks. Then, the cardiac function and myocardial fibrosis were evaluated. The monocytes/macrophages were evaluated by immunofluorescence. The mRNA levels of IL-1ß, IL-6, TNF-α, ICAM-1, and VCAM-1 were measured by quantitative real-time polymerase chain reaction (qRT-PCR), while TLR4, MyD88, NF-κB p65, P-IκBα, TLR2, TLR7 and TLR9 protein levels were evaluated by Western blot. The results showed that NXK improved the left ventricular ejection fraction (LVEF) and left ventricular end-systolic dimension, reversed myocardial fibrosis, and inhibited pro-inflammatory (CD11b + Ly6C+) monocytes/macrophages in the TAC mouse model. NXK also reduced the mRNA and protein levels of the above markers. Taken together, NXK improved heart function and reduced inflammation through the TLR-mediated NF-κB signaling pathway, suggesting that it might be used as an innovative treatment strategy for CHF.

PELO facilitates PLK1-induced the ubiquitination and degradation of Smad4 and promotes the progression of prostate cancer.

PLK1 and Smad4 are two important factors in prostate cancer initiation and progression. They have been reported to play the opposite role in Pten-deleted mice, one is an oncogene, the other is a tumor suppressor. Moreover, they could reversely regulate the PI3K/AKT/mTOR pathway and the activation of MYC. However, the connections between PLK1 and Smad4 have never been studied. Here, we showed that PLK1 could interact with Smad4 and promote the ubiquitination and degradation of Smad4 in PCa cells. PLK1 and PELO could bind to different domains of Smad4 and formed a protein complex. PELO facilitated the degradation of Smad4 through cooperating with PLK1, thereby resulting in proliferation and metastasis of prostate cancer cell. Changes in protein levels of Smad4 led to the alteration of biological function that caused by PLK1 in prostate cancer cells. Further studies showed that PELO upregulation was positively associated with high grade PCa and knockdown of PELO expression significantly decreased PCa cell proliferation and metastasis in vitro and vivo. PELO knockdown in PCa cells could enhance the tumor suppressive role of PLK1 inhibitor. In addition, blocking the interaction between PELO and Smad4 by using specific peptide could effectively inhibit PCa cell metastasis ability in vitro and vivo. Overall, these findings identified a novel regulatory relationship among PLK1, Smad4 and PELO, and provided a potential therapeutic strategy for advanced PCa therapy by co-targeting PLK1 and PELO.

Curative efficacy of surgical procedures for older patients with femoral neck fracture: a network meta-analysis and systematic review.

BACKGROUND: Femoral neck fractures have a higher incidence in older people with poor prognosis, inducing serious social problems. Common treatment methods include total hip arthroplasty, bipolar hemiarthroplasty, double-screw fixation, multiple-screw fixation, and dynamic hip system. METHODS: We searched through four electronic databases, including PubMed, Web of Science, Cochrane Library, and Embase databases, for articles regarding femoral neck fractures, bone screw, and hip prosthesis published up to February 11, 2020. All included articles were used for quality evaluation and data extraction. Extracted data were expressed as odds ratios or weighted mean differences, with 95% confidence intervals. We conducted a network meta-analysis for Harris hip score, complications, 1-year mortality rate, reoperation rate, intraoperative blood loss, and duration of operation using STATA version 16.0 software. RESULTS: Twenty-two randomized controlled trials and nine cohort studies included in this study involved 3861 patients. Total hip arthroplasty significantly improved the postoperative function of patients with femoral neck fractures. The surface under the cumulative ranking curve value of the Harris hip score for more than 1 year after total hip arthroplasty was 98.2. CONCLUSIONS: This meta-analysis indicated no significant difference in mortality among different treatment groups. Total hip arthroplasty can provide satisfactory outcomes in hip joint function, and double-screw fixation results in the lowest intraoperative risk. In general, total hip arthroplasty results in a lower incidence of adverse events and is especially recommended for patients with femoral neck fractures. This article has been retrospectively registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) on November 27, 2020. Registration number: INPLASY2020110123.

Thermal migration towards constructing W-W dual-sites for boosted alkaline hydrogen evolution reaction.

Tungsten carbides, featured by their Pt-like electronic structure, have long been advocated as potential replacements for the benchmark Pt-group catalysts in hydrogen evolution reaction. However, tungsten-carbide catalysts usually exhibit poor alkaline HER performance because of the sluggish hydrogen desorption behavior and possible corrosion problem of tungsten atoms by the produced hydroxyl intermediates. Herein, we report the synthesis of tungsten atomic clusters anchored on P-doped carbon materials via a thermal-migration strategy using tungsten single atoms as the parent material, which is evidenced to have the most favorable Pt-like electronic structure by in-situ variable-temperature near ambient pressure X-ray photoelectron spectroscopy measurements. Accordingly, tungsten atomic clusters show markedly enhanced alkaline HER activity with an ultralow overpotential of 53 mV at 10 mA/cm2 and a Tafel slope as low as 38 mV/dec. These findings may provide a feasible route towards the rational design of atomic-cluster catalysts with high alkaline hydrogen evolution activity.

Study of the biological characteristics of human umbilical cord mesenchymal stem cells after long-time cryopreservation.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) have considerable potential in cell therapy. Cryopreservation represents the gold standard in cell storage, but its effect on hUC-MSCs is still not well understood. The aim of this study was to investigate the effect of one year of cryopreservation and thawing on the biological characteristics of hUC-MSCs from the same donors. Fresh hUC-MSCs were cryopreserved in commercial freezing medium (serum-free CellBanker 2) at passage 2. After one year of cryopreservation, the hUC-MSCs were thawed and subcultured to passage 4. The comparison was performed in terms of followings: cell count, viability, morphology, proliferation capacity, differentiation potential and chromosomal stability. The total cell count and viability of hUC-MSCs before and after one year of cryopreservation were 1 × 107 and 96.34% and 0.943 × 107 and 93.81%, respectively. Cryopreserved and fresh hUC-MSCs displayed a similar cell doubling times, expressed the markers CD73, CD90, CD105 and were negative for the markers CD34, CD45, and HLA-DR. Karyotypes were found to be normal after one year of cryopreservation. The trilineage differentiation properties were maintained after cryopreservation. However, when compared to freshly isolated hUC-MSCs from the same donor, cryopreserved hUC-MSCs exhibited decreased expression of osteogenesis- and chondrogenesis-related genes including Runx2, Sox9, and Col1a1, and increased expression of adipogenesis-related genes. These results demonstrated that cryopreservation did not affect cell morphology, surface marker expression, cell viability, proliferative capacity, or chromosomal stability. However, the osteogenic and chondrogenic differentiation capacities of cryopreserved hUC-MSCs were slightly reduced compared with those of fresh cells from the same donor.

Hemgn Protects Hematopoietic Stem and Progenitor Cells Against Transplantation Stress Through Negatively Regulating IFN-γ Signaling.

Hematopoietic stem and progenitor cells (HSPCs) possess the remarkable ability to regenerate the whole blood system in response to ablated stress demands. Delineating the mechanisms that maintain HSPCs during regenerative stresses is increasingly important. Here, it is shown that Hemgn is significantly induced by hematopoietic stresses including irradiation and bone marrow transplantation (BMT). Hemgn deficiency does not disturb steady-state hematopoiesis in young mice. Hemgn-/- HSPCs display defective engraftment activity during BMT with reduced homing and survival and increased apoptosis. Transcriptome profiling analysis reveals that upregulated genes in transplanted Hemgn-/- HSPCs are enriched for gene sets related to interferon gamma (IFN-γ) signaling. Hemgn-/- HSPCs show enhanced responses to IFN-γ treatment and increased aging over time. Blocking IFN-γ signaling in irradiated recipients either pharmacologically or genetically rescues Hemgn-/- HSPCs engraftment defect. Mechanistical studies reveal that Hemgn deficiency sustain nuclear Stat1 tyrosine phosphorylation via suppressing T-cell protein tyrosine phosphatase TC45 activity. Spermidine, a selective activator of TC45, rescues exacerbated phenotype of HSPCs in IFN-γ-treated Hemgn-/- mice. Collectively, these results identify that Hemgn is a critical regulator for successful engraftment and reconstitution of HSPCs in mice through negatively regulating IFN-γ signaling. Targeted Hemgn may be used to improve conditioning regimens and engraftment during HSPCs transplantation.

Large Multicohort Study Reveals a Prostate Cancer Susceptibility Allele at 5p15 Regulating TERT via Androgen Signaling-Orchestrated Chromatin Binding of E2F1 and MYC.

Aberrant telomerase reverse transcriptase (TERT) expression is crucial for tumor survival and cancer cells escaping apoptosis. Multiple TERT-locus variants at 5p15 have been discovered in association with cancer risk, yet the underlying mechanisms and clinical impacts remain unclear. Here, our association studies showed that the TERT promoter variant rs2853669 confers a risk of prostate cancer (PCa) in different ethnic groups. Further functional investigation revealed that the allele-specific binding of MYC and E2F1 at TERT promoter variant rs2853669 associates with elevated level of TERT in PCa. Mechanistically, androgen stimulations promoted the binding of MYC to allele T of rs2853669, thereby activating TERT, whereas hormone deprivations enhanced E2F1 binding at allele C of rs2853669, thus upregulating TERT expression. Notably, E2F1 could cooperate with AR signaling to regulate MYC expression. Clinical data demonstrated synergistic effects of MYC/E2F1/TERT expression or with the TT and CC genotype of rs2853669 on PCa prognosis and severity. Strikingly, single-nucleotide editing assays showed that the CC genotype of rs2853669 obviously promotes epithelial-mesenchymal transition (EMT) and the development of castration-resistant PCa (CRPC), confirmed by unbiased global transcriptome profiling. Our findings thus provided compelling evidence for understanding the roles of noncoding variations coordinated with androgen signaling and oncogenic transcription factors in mis-regulating TERT expression and driving PCa.

Optimized CRISPR/Cas9-mediated single nucleotide mutation in adherent cancer cell lines.

CRISPR/Cas9 is an efficient, accurate, and optimizable genome-editing tool. Here, we present a modified CRISPR/Cas9 genome-editing protocol for single nucleotide mutation in adherent cell lines. The protocol was adapted to focus on ease of use and efficiency. The protocol here describes how to generate a single nucleotide mutation in cultured 22Rv1 cells. We have also used the protocol in other adherent cell types. Thus, the protocol can be applied to assessing the effect of non-coding single nucleotide polymorphisms (SNPs) in a variety of cell types. For complete details on the use and execution of this protocol, please refer to Gao et al. (2018).

Effectiveness and safety of Xinyin tablet in treatment of chronic heart failure: A protocol of systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Xinyin Tablet (XYT) has been widely used in the treatment of CHF, Which helping to improve the clinical symptoms, enhance exercise, and even may improve the long-term prognosis of patients. However, the exact effectiveness and safety of XYT for CHF has not be comprehensively researched, so we want to generalize the effectiveness and safety of XYT for CHF through the meta-analysis, which may benefit the design of future clinical trials and provide valuable references. METHODS: This protocol complies with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. From the inception until September 2020, a systematic and comprehensive electronic search about Relevant randomized controlled trials will be conducted in 4 English literature databases and 4 Chinese literature databases. The registration number: INPLASY2020100015. 2 investigators will be arranged to deal with the study selection and data extraction independently. The New York Heart Function Classification, traditional Chinese medicine (TCM) symptom scores, the scores of quality of life, 6-min walk distance (6MWD), etc. will be systematically measured as outcomes. At last, the data will be handled by Review Manager 5.3 and Stata 15.0. RESULTS AND CONCLUSION: This study is hoping to provide a high-level evidence to prove the therapeutic effect of XYT on CHF, which may enhance the application of Chinese medicine.

Nrf2 participates in the anti-apoptotic role of zinc in Type 2 diabetic nephropathy through Wnt/ß-catenin signaling pathway.

Zinc (Zn), as an essential trace element, has been approved to serve many roles in diabetic studies. Also Zn deficiency will aggravate renal damage in diabetes through suppression of nuclear factor-erythroid 2-related factor 2 (Nrf2) expression and function. The purpose of this study was to illustrate the role of Zn in renal apoptosis in diabetes and whether Nrf2 participated in the process. Type 2 diabetes mice model was induced by a single dose of streptozotocin (STZ) injection after high-fat diet (HFD) feeding for 3 months, then the mice were given diets supplemented with different concentrations of Zn (control, 30 ppm; low-concentration, 0.85 ppm). After 12-week treatment, morphology and associated protein expressions were examined. The results showed that low Zn diet significantly aggravated the level of renal apoptosis during diabetes, performed as the upregulation of caspase-3 expression. In addition, either low Zn diet or diabetes or both dramatically decreased the expression of Nrf2 and P-AKT in kidney. Moreover, the expression of ß-catenin in kidney was increased markedly in diabetic groups. Mechanistic study applying human renal tubular epithelial cells (HK11) confirmed the role of Nrf2, as silencing Nrf2 expression abolished Zn supplementation protection against high sugar + high fat + low Zn-induced apoptosis and downregulation of ß-catenin expression. All these results suggest that Nrf2 plays a key role in Zn protection against Type 2 diabetes induced renal apoptosis, which might be through Wnt/ß-catenin signaling pathway.