Numerous clinical trials have examined the role of anthocyanins on cardiometabolic health, but their effects have not been quantitatively synthesized and systematically evaluated. The aim of our study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of anthocyanins on glycemic regulation and lipid profiles in both healthy populations and those with cardiometabolic diseases. The MEDLINE, EMBASE, Cochrane database, OVID EBM Reviews, and clinicaltrials.gov databases were searched until February 2017. RCTs with a duration of ≥2 wk that evaluated the effects of anthocyanins on glycemic control, insulin sensitivity, and lipids as either primary or secondary outcomes were included. The Cochrane Risk of Bias tool was used to assess the study quality. Standardized mean differences (SMDs) were determined by random-effects models. Meta-regression, sensitivity, and subgroup analyses were performed to explore the influence of covariates on the overall effects. Thirty-two RCTs (1491 participants) were eligible for meta-analysis. Anthocyanins significantly reduced fasting glucose (SMD: -0.31; 95% CI: -0.59, -0.04; = 80.7%), 2-h postprandial glucose (SMD: -0.82; 95% CI: -1.49, -0.15; = 77.7), glycated hemoglobin (SMD: -0.65; 95% CI: -1.00, -0.29; = 72.7%), total cholesterol (SMD: -0.33; 95% CI: -0.62, -0.03; = 86.9%), and LDL (SMD: -0.35; 95% CI: -0.66, -0.05; = 85.2%). Sensitivity analyses showed that the overall effects remained similar by excluding the trials with a high or unclear risk of bias. The significant improvements in glycemic control and lipids support the benefits of anthocyanins in the prevention and management of cardiometabolic disease. Further well-designed RCTs are needed to evaluate the long-term effects of anthocyanins on metabolic profiles and to explore the optimal formula and dosage. The protocol for this review was registered at https://www.crd.york.ac.uk/PROSPERO/#index.php as CRD42016033210.

Background and Objective. Now with more and more published systematic reviews of Complementary and Alternative Medicine (CAM) on adult cancer pain, it is necessary to use the methods of overview of systematic review to summarize available evidence, appraise the evidence level, and give suggestions to future research and practice. Methods. A comprehensive search (the Cochrane Library, PubMed, Embase, and ISI Web of Knowledge) was conducted to identify all systematic reviews or meta-analyses of CAM on adult cancer pain. And the evidence levels were evaluated using GRADE approach. Results. 27 systematic reviews were included. Based on available evidence, we could find that psychoeducational interventions, music interventions, acupuncture plus drug therapy, Chinese herbal medicine plus cancer therapy, compound kushen injection, reflexology, lycopene, TENS, qigong, cupping, cannabis, Reiki, homeopathy (Traumeel), and creative arts therapies might have beneficial effects on adult cancer pain. No benefits were found for acupuncture (versus drug therapy or shame acupuncture), and the results were inconsistent for massage therapy, transcutaneous electric nerve stimulation (TENS), and Viscum album L plus cancer treatment. However, the evidence levels for these interventions were low or moderate due to high risk of bias and/or small sample size of primary studies. Conclusion. CAM may be beneficial for alleviating cancer pain, but the evidence levels were found to be low or moderate. Future large and rigor randomized controlled studies are needed to confirm the benefits of CAM on adult cancer pain.

CTCF is an essential epigenetic regulator mediating chromatin insulation, long-range regulatory interactions, and the organization of large topological domains in the nucleus. Phenotypes of CTCF haploinsufficient mutations in humans, knockout in mice, and depletion in cells are often consistent with impaired genome stability, but a role of CTCF in genome maintenance has not been fully investigated. Here, we report that CTCF maintains genome stability, is recruited to sites of DNA damage, and promotes homologous recombination repair of DNA double-strand breaks (DSBs). CTCF depletion increased chromosomal instability, marked by chromosome breakage and end fusions, elevated genotoxic stress-induced genomic DNA fragmentation, and activated the ataxia telangiectasia mutated (ATM) kinase. We show that CTCF could be recruited to drug-induced 53BP1 foci and known fragile sites, as well as to I-SceI endonuclease-induced DSBs. Laser irradiation analysis revealed that this recruitment depends on ATM, Nijmegen breakage syndrome (NBS), and the zinc finger DNA-binding domain of CTCF. We demonstrate that CTCF knockdown impaired homologous recombination (HR) repair of DSBs. Consistent with this, CTCF knockdown reduced the formation of γ-radiation-induced Rad51 foci, as well as the recruitment of Rad51 to laser-irradiated sites of DNA lesions and to I-SceI-induced DSBs. We further show that CTCF is associated with DNA HR repair factors MDC1 and AGO2, and directly interacts with Rad51 via its C terminus. These analyses establish a direct, functional role of CTCF in DNA repair and provide a potential link between genome organization and genome stability.CTCF | chromatin | genome stability | DNA repair | homologous recombination

Objective: In vitro and animal studies suggest that purified anthocyanins have favorable effects on metabolic profiles, but clinical trials have reported inconsistent findings. Furthermore, no study has been specifically conducted among individuals with prediabetes. The aim of this study was to investigate whether purified anthocyanins could improve cardiometabolic risk factors in Chinese adults with early untreated hyperglycemia. Research Design and Methods: This was a 12-week randomized, double-blind, placebo-controlled trial. A total of 160 participants aged 40–75 years with prediabetes or early untreated diabetes were randomly allocated to receive either purified anthocyanins (320 mg/day, n = 80) or placebo (n = 80) of identical appearance. A three-hour oral glucose tolerance test (OGTT) was performed, and cardiometabolic biomarkers (glycated hemoglobin A1c (HbA1c), fasting and postprandial glucose, insulin, C-peptide, and lipids) were measured at baseline and at the end of the trial. Results: A total of 138 subjects completed the protocol. Compared with placebo, purified anthocyanins moderately reduced HbA1c (−0.14%, 95% CI: −0.23~−0.04%; p = 0.005), low-density lipoprotein-c (LDL-c) (−0.2 mmol/L, 95% CI: −0.38~−0.01, p = 0.04), apolipoprotein A-1 (apo A1) (0.09 g/L, 95% CI: 0.02~0.17; p = 0.02), and apolipoprotein B (apo B) (−0.07 g/L, 95% CI: −0.13~−0.01; p = 0.01) according to intention-to-treat analysis. Subgroup analyses suggested that purified anthocyanins were more effective at improving glycemic control, insulin sensitivity, and lipids among patients with elevated metabolic markers. Conclusions: The 12-week randomized controlled trials (RCT) in Chinese adults with prediabetes or early untreated diabetes indicated that purified anthocyanins favorably affected glycemic control and lipid profile. Future studies of a longer duration that explore the dose-response relationship among patients with cardiometabolic disorders are needed to confirm our findings.

Matrix metalloproteinase-7 (MMP-7) is a secreted zinc- and calcium-dependent endopeptidase that degrades a broad range of extracellular matrix substrates and additional substrates. MMP-7 playsa crucial role in a diverse array of cellular processes and appears to be a key regulator of fibrosis in several diseases, including pulmonary fibrosis, liver fibrosis, and cystic fibrosis. In particular, the relationship between MMP-7 and kidney fibrosis has attracted significant attention in recent years. Growing evidence indicates that MMP-7 plays an important role in the pathogenesis of kidney fibrosis. Here, we summarize the recent progress in the understanding of the role of MMP-7 in kidney fibrosis. In particular, we discuss how MMP-7 contributes to kidney fibrotic lesions via the following three pathways: epithelial-mesenchymal transition (EMT), transforming growth factor-beta (TGF-β) signaling, and extracellular matrix (ECM) deposition. Further dissection of the crosstalk among and regulation of these pathways will help clinicians and researchers develop effective therapeutic approaches for treating chronic kidney disease.

BackgroundBone cancer pain is currently a major clinical challenge for the management of cancer patients, and the cellular and molecular mechanisms underlying the spinal sensitization remain unclear. While several studies demonstrated the critical role of proteinase-activated receptor (PAR2) in the pathogenesis of several types of inflammatory or neuropathic pain, the involvement of spinal PAR2 and the pertinent signaling in the central sensitization is not determined yet in the rodent model of bone cancer pain.FindingsImplantation of tumor cells into the tibias induced significant thermal hyperalgesia and mechanical allodynia, and enhanced glutamatergic strength in the ipsilateral dorsal horn. Significantly increased brain-derived neurotrophic factor (BDNF) expression was detected in the dorsal horn, and blockade of spinal BDNF signaling attenuated the enhancement of glutamatergic strength, thermal hyperalgesia and mechanical allodynia in the rats with bone cancer pain. Significantly increased spinal PAR2 expression was also observed, and inhibition of PAR2 signaling ameliorated BDNF upsurge, enhanced glutamatergic strength, and thermal hyperalgesia and mechanical allodynia. Inhibition of NF-κB pathway, the downstream of PAR2 signaling, also significantly decreased the spinal BDNF expression, glutamatergic strength of dorsal horn neurons, and thermal hyperalgesia and mechanical allodynia.ConclusionThe present study demonstrated that activation of PAR2 triggered NF-κB signaling and significantly upregulated the BDNF function, which critically contributed to the enhancement of glutamatergic transmission in spinal dorsal horn and thermal and mechanical hypersensitivity in the rats with bone cancer. This indicated that PAR2 - NF-κB signaling might become a novel target for the treatment of pain in patients with bone cancer.

Signal transducer and activator of transcription 3 (STAT3) is a pleiotropic signaling mediator of many cytokines, including interleukin-6 (IL-6) and IL-10. STAT3 is known to play critical roles in cell growth, proliferation, differentiation, immunity and inflammatory responses. The objective of this study was to determine the effect of porcine reproductive and respiratory syndrome virus (PRRSV) infection on the STAT3 signaling since PRRSV induces a weak protective immune response in host animals. We report here that PRRSV infection of MARC-145 cells and primary porcine pulmonary alveolar macrophages led to significant reduction of STAT3 protein level. Several strains of both PRRSV type 1 and type 2 led to a similar reduction of STAT3 protein level but had a minimal effect on its transcripts. The PRRSV-mediated STAT3 reduction was in a dose-dependent manner as the STAT3 level decreased, along with incremental amounts of PRRSV inocula. Further study showed that nonstructural protein 5 (nsp5) of PRRSV induced the STAT3 degradation by increasing its polyubiquitination level and shortening its half-life from 24 h to ϳ3.5 h. The C-terminal domain of nsp5 was shown to be required for the STAT3 degradation. Moreover, the STAT3 signaling in the cells transfected with nsp5 plasmid was significantly inhibited. These results indicate that PRRSV antagonizes the STAT3 signaling by accelerating STAT3 degradation via the ubiquitin-proteasomal pathway. This study provides insight into the PRRSV interference with the JAK/STAT3 signaling, leading to perturbation of the host innate and adaptive immune responses. IMPORTANCEThe typical features of immune responses in PRRSV-infected pigs are delayed onset and low levels of virus neutralizing antibodies, as well as weak cellmediated immunity. Lymphocyte development and differentiation rely on cytokines, many of which signal through the JAK/STAT signaling pathway to exert their biological effects. Here, we discovered that PRRSV antagonizes the JAK/STAT3 signaling by inducing degradation of STAT3, a master transcription activator involved in multiple cellular processes and the host immune responses. The nsp5 protein of PRRSV is responsible for the accelerated STAT3 degradation. The PRRSV-mediated antagonizing STAT3 could lead to suppression of a broad spectrum of cytokines and growth factors to allow virus replication and spread in host animals. This may be one of the reasons for the PRRSV interference with the innate immunity and its poor elicitation of protective immunity. This finding provides insight into PRRSV pathogenesis and its interference with the host immune responses.

Background: Metastasis in breast cancer is a vital concern in treatment because most women with primary breast cancer have micrometastases to distant sites at diagnosis. As a member of the inhibitor of apoptosis protein (IAP) family, survivin has been proposed as an attractive target for new anticancer interventions. In this study, we investigated the role of the plasmid encoding the phosphorylation-defective mouse survivin threonine 34→alanine mutant (Msurvivin T34A plasmid) in suppressing both murine primary breast carcinomas and pulmonary metastases.