The role of nesfatin-1 in glucose homeostasis has been investigated previously. However, although numerous studies have examined the relationships between circulating nesfatin-1 levels and type 2 diabetes, the conclusions are contradictory. We aimed to probe the relationship between circulating nesfatin-1 levels and type 2 diabetes by meta-analysis. Seven studies including 328 type 2 diabetes patients and 294 control subjects were included. Although there was no obvious difference in circulating nesfatin-1 levels between patients with type 2 diabetes and the control group (MD = -0.04; 95% CI = -0.32 to -0.23), subgroup analysis showed higher nesfatin-1 levels in newly diagnosed type 2 diabetes patients (MD = 0.59; 95% CI = 0.45 to 0.74) and significantly lower nesfatin-1 levels in type 2 diabetes patients receiving antidiabetic treatment (MD = -0.26; 95% CI = -0.33 to -0.20). In conclusion, the analysis supports a relationship between circulating nesfatin-1 levels and type 2 diabetes, where newly diagnosed type 2 diabetes was associated with an elevated Nesfatin-1 level, and type 2 diabetes patients receiving antidiabetic treatment showed lower circulating nesfatin-1 levels.

The placenta is the first human organ to reach full development during pregnancy. It serves as a barrier but also as an interchange surface. Epigenetic changes observed in placental tissue may reflect intrauterine insults while also pointing to physiological pathways altered under exposure to such environmental threats. By means of a systematic search of the literature, 39 papers assessing human placental epigenetic signatures in association with either (i) psychosocial stress, (ii) maternal psychopathology, (iii) maternal smoking during pregnancy, and (iv) exposure to environmental pollutants, were identified. Their findings revealed placental tissue as a unique source of epigenetic variability that does not correlate with epigenetic patterns observed in maternal or newborn blood, tissues which are typically analyzed regarding prenatal stress. Studies regarding prenatal stress and psychopathology during pregnancy were scarce and exploratory in nature revealing inconsistent findings. Of note, there was a marked tendency towards placental hypomethylation in studies assessing either tobacco use during pregnancy or exposure to environmental pollutants suggesting the interaction between contaminant-derived metabolites and epigenetic machinery. This review highlights the need for further prospective longitudinal studies assessing long-term health effects of placental epigenetic signatures derived from exposure to several prenatal stressors.

Resistance to platinum-based chemotherapy is the major barrier to treating high-grade serous ovarian cancer (HGS-OvCa). To improve HGS-OvCa patient prognosis, it is critical to identify the underlying mechanisms that promote platinum resistance. The goal of the present study was to identify a lncRNA-mRNA co-expression network and key lncRNAs that predict resistance to platinum-based chemotherapy in ovarian cancer patients. By systematically analyzing the expression profiles of lncRNAs and mRNAs in HGS-OvCa samples from the Cancer Genome Atlas (TCGA), we revealed that lncRNAs play important roles in platinum resistance in HGS-OvCa patients and delineate a lncRNA-mRNA co-expression network in HGS-OvCa patients who exhibit platinum resistance. Within the platinum resistance-specific lncRNA-mRNA network, 35 lncRNAs and 270 mRNAs showed 124 significant lncRNA-mRNA co-expression relationships. Pathway analysis revealed that lncRNAs in the platinum resistance network may participate in platinum resistance by regulating metabolic pathways. Moreover, HGS-OvCa patients with low lncRNA RP5-1120P11.1 expression showed a poorer prognosis than those with high lncRNA RP5-1120P11.1 expression in TCGA dataset (P = 2.74 × 10-5, log rank test), which was also validated in the GSE63885 dataset (P = 0.0242, log rank test). Network and function analysis revealed that lncRNA RP5-1120P11.1 regulates many cancer-related signaling pathways, such as the PI3K-AKT signaling pathway (P = 1.02 × 10-5, hypergeometric test) and the Jak-STAT signaling pathway (P = 1.71 × 10-4, hypergeometric test). Particularly, lncRNA RP5-1120P11.1 expression is significantly positively correlated with ABCC10 gene expression (P = 3.89 × 10-3, Pearson correlation test). Both lncRNA RP5-1120P11.1 and ABCC10 were down-regulated in platinum-resistant HGS-OvCa patients, and RP5-1120P11.1 is located near ABCC10 on chromosome 6. Gene ABCC10 has been implicated in resistance to docetaxel treatment. The present study paves the way for investigating lncRNA functions in platinum drug resistance and identifying lncRNAs with prognostic and therapeutic potential in HGS-OvCa.

Biomaterial cues can act as potent regulators of cell niche and microenvironment. Epigenetic regulation plays an important role in cell functions, including proliferation, differentiation, and reprogramming. It is now well appreciated that biomaterials can alter epigenetic states of cells. In this study, we systematically reviewed the underlying epigenetic mechanisms of how different biomaterial cues, including material chemistry, topography, elasticity, and mechanical stimulus, influence cell functions, such as nuclear deformation, cell proliferation, differentiation, and reprogramming, to summarize the differences and similarities among each biomaterial cues and their mechanisms, and to find common and unique properties of different biomaterial cues. Moreover, this work aims to establish a mechanogenomic map facilitating highly functionalized biomaterial design, and renders new thoughts of epigenetic regulation in controlling cell fates in disease treatment and regenerative medicine.

This systematic review examines the efficacy and safety of whole body vibration (WBV) on fracture healing. A systematic literature search was conducted with relevant keywords in PubMed and Embase, independently, by two reviewers. Original animal and clinical studies about WBV effects on fracture healing with available full-text and written in English were included. Information was extracted from the included studies for review. In total, 19 articles about pre-clinical studies were selected. Various vibration regimes are reported; of those, the frequencies of 35 Hz and 50 Hz show better results than others. Most of the studies show positive effects on fracture healing after vibration treatment and the responses to vibration are better in ovariectomised (OVX) animals than non-OVX ones. However, several studies provide insufficient evidence to support an improvement of fracture healing after vibration and one study even reports disruption of fracture healing after vibration. In three studies, vibration results in positive effects on angiogenesis at the fracture site and surrounding muscles during fracture healing. No serious complications or side effects of vibration are found in these studies. WBV is suggested to be beneficial in improving fracture healing in animals without safety problem reported. In order to apply vibration on fractured patients, more well-designed randomised controlled clinical trials are needed to examine its efficacy, regimes and safety.

To undertake a systematic review and meta-analysis of randomized controlled trials of the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) therapy on serum C-reactive protein (CRP) concentrations.

To date, no drug has been proven to be neuroprotective or disease-modifying for Parkinson's disease (PD) in clinical trials. Here, we aimed to assess preclinical evidence of Ginsenosides-Rg1 (G-Rg1), a potential neuroprotectant, for experimental PD and its possible mechanisms. Eligible studies were identified by searching six electronic databases from their inception to August 2016. Twenty-five eligible studies involving 516 animals were identified. The quality score of these studies ranged from 3 to 7. Compared with the control group, two out of the 12 studies of MPTP-induced PD showed significant effects of G-Rg1 for improving the rotarod test (P < 0.01), two studies for improving the swim-score values (P < 0.01), six studies for improving the level of TH protein expression (P < 0.01), and two studies for increasing the expression of TH mRNA in the substantia nigra of mice (P < 0.01). The studies reported that G-Rg1 exerted potential neuroprotective effects on PD model through different mechanisms as antineuroinflammatory activities (n = 10), antioxidant stress (n = 3), and antiapoptosis (n = 11). In conclusion, G-Rg1 exerted potential neuroprotective functions against PD largely by antineuroinflammatory, antioxidative, and antiapoptotic effects. G-Rg1 as a promising neuroprotectant for PD needs further confirmation by clinical trials.

The appropriate selection of reference genes for the normalization of non-biological variance in reverse transcription real-time quantitative PCR (RT-qPCR) is essential for the accurate interpretation of the collected data. The use of multiple validated reference genes has been shown to substantially increase the robustness of the normalization. It is therefore considered good practice to validate putative genes under specific conditions, determine the optimal number of genes to be employed, and report the method or methods used. Under this premise, we assessed the current state of reference gene based normalization in RT-qPCR bivalve ecotoxicology studies (post 2011), employing a systematic quantitative literature review. A total of 52 papers met our criteria and were analysed for genes used, the use of multiple reference genes, as well as the validation method employed. We further critically discuss methods for reference gene validation based on a case study using copper exposed primary hemocytes from the marine bivalve Ruditapes philippinarum; including the established algorithms geNorm, NormFinder and BestKeeper, as well as the popular online tool RefFinder. We identified that RT-qPCR normalization is largely performed using single reference genes, while less than 40% of the studies attempted to experimentally validate the expression stability of the genes used. 18s rRNA and β-Actin were the most popular genes, yet their un-validated use did introduce artefactual variance that altered the interpretation of the resulting data. Our findings further suggest that combining the results from multiple individual algorithms and calculating the overall best-ranked gene, as computed by the RefFinder tool, does not by default lead to the identification of the most suitable reference genes.

Epigenetic mechanisms are important for the regulation of gene expression and differentiation in the fetus and the newborn child. Symptoms of maternal depression and antidepressant use affects up to 20 % of pregnant women, and may lead to epigenetic changes with life-long impact on child health. The aim of this review is to investigate whether there is an association between exposure to maternal antidepressants during pregnancy and epigenetic changes in the newborn.

Aberrant DNA methylation has been identified as a key molecular event regulating the pathogenesis of myelodysplastic syndromes (MDS); myeloid neoplasms with an inherent risk of transformation to acute myeloid leukemia (AML). Based on the above findings, DNA hypomethylating agents (HMA) have been widely used to treat AML and MDS, especially in elderly patients and in those who are not eligible for allogeneic stem cell transplantation (SCT). Our goal was to determine if there is any therapeutic advantage of HMA vs. conventional care regimens (CCR) and indirectly compare the efficacy of azacitidine and decitabine in this patient population.

Medullary thyroid carcinoma (MTC) originates from the parafollicular C cells of the thyroid gland. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC. Germline activating mutations of this gene have been reported in about 88-98% of familial MTCs, while somatic mutations of RET gene have been detected in about 23-70% of sporadic forms. Although these genetic events are well characterized, much less is known about the role of epigenetic abnormalities in MTC.

Curcumin is a bioactive polyphenol occurring in the rhizomes of Curcuma longa. It is well-reputed for its chemopreventive and anticancer properties; however, recent evidence has revealed numerous biological and pharmacological effects of curcumin that are relevant to the treatment of non-cancer diseases. Mechanistically, curcumin exerts its pharmacological effects through anti-inflammatory and antioxidant mechanisms via interaction with different signaling molecules and transcription factors. In addition, epigenetic modulators such as microRNAs (miRs) have emerged as novel targets of curcumin. Curcumin was found to modulate the expression of several pathogenic miRs in brain, ocular, renal, and liver diseases. The present systematic review was conducted to identify miRs that are regulated by curcumin in non-cancer diseases.

Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as "carcinogenic to humans" (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments.

A significant residual cardiovascular risk is consistently observed in patients treated with statins. A combined treatment with fibrates reduces cardiovascular events in very high-risk patients. Because this is apparently unconnected to an improvement in lipid-related outcomes we hypothesized that the cardioprotective effects of fibrates might be associated with an improvement in paraoxonase-1 (PON1) status.

Gallbladder carcinoma is a rare, aggressive malignancy of the biliary tract associated with a poor prognosis. Despite the deployment of targeted therapies that have demonstrated marked survival benefits in many tumor types, traditional cytotoxic chemotherapy has remained the mainstay of treatment for unresectable and metastatic gallbladder cancer.

Arsenic is ubiquitously present in human lives, including in the environment and organisms, and has divergent effects between different cells and tissues and between different exposure times and doses. These observed effects have been attributed to the nuclear transcription factor kappa B(NF-κB) signaling pathway. Herein, a meta-analysis was performed by independently searching databases including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze effects of arsenic exposure on NF-κB signaling. Compared to controls, in the exposed group, p-IκB levels were found to be 8.13-fold higher (95% CI, 2.40-13.85; Z = 2.78; p = 0.005), IκB levels were 16.19-fold lower (95% CI, -27.44--4.94; Z = 2.78; p = 0.005), and NF-κBp65 levels were 0.77-fold higher (95% CI, 0.13-1.42; Z = 2.34; p = 0.02) for normal cells and tissue, while NF-κBp65 levels were 4.90-fold lower (95% CI, -8.49-1.31; Z = 2.62; p = 0.009), NF-κB activity was 2.45-fold lower (95% CI, -3.66-1.25; Z = 4.00; p < 0.0001), and DNA-binding activity of NF-κB was 9.75-fold lower (95% CI, -18.66-4.54; Z = 2.15; p = 0.03) for abnormal cells and tissue. Short exposure to high arsenic doses activated the NF-κB signaling pathway, while long exposure to low arsenic doses suppressed NF-κB signaling pathway activation. These findings may provide a theoretical basis for injurious and therapeutic mechanisms of divergent effects of arsenic.

Mitochondrial diseases are a group of heterogeneous disorders for which no curative therapy is currently available. Several drugs are currently being pursued as candidates to correct the underlying biochemistry that causes mitochondrial dysfunction.

Guidelines on the diagnosis and treatment of iron deficiency (ID) vary widely across indications.

Decreased activity of the enzyme paraoxonase-1 (PON1) has been demonstrated in cardiovascular diseases. Statins, the forefront of pharmacotherapy for dyslipidemia, have been shown to enhance PON1 activity but clinical findings have not been conclusive.

To report on molecular mechanisms of fetal hemoglobin (HbF) induction by hydroxyurea (HU) for the treatment of sickle cell disease.