Molecular hydrogen exerts its effect on multiple pathologies, including oxidative stress, inflammation, and apoptosis. However, its molecular mechanisms have not been fully elucidated. In order to explore the effects of molecular hydrogen, we meta-analysed gene expression profiles modulated by molecular hydrogen. We performed microarray analysis of the mouse liver with or without drinking hydrogen water. We also integrated two previously reported microarray datasets of the rat liver into meta-analyses. We used two categories of meta-analysis methods: the cross-platform method and the conventional meta-analysis method (Fisher's method). For each method, hydrogen-modulated pathways were analysed by (i) the hypergeometric test (HGT) in the class of over-representation analysis (ORA), (ii) the gene set enrichment analysis (GSEA) in the class of functional class scoring (FCS), and (iii) the signalling pathway impact analysis (SPIA), pathway regulation score (PRS), and others in the class of pathway topology-based approach (PTA). Pathways in the collagen biosynthesis and the heat-shock response were up-regulated according to (a) HGT with the cross-platform method, (b) GSEA with the cross-platform method, and (c) PRS with the cross-platform method. Pathways in cell cycles were down-regulated according to (a) HGT with the cross-platform method, (b) GSEA with the cross-platform method, and (d) GSEA with the conventional meta-analysis method. Because the heat-shock response leads to up-regulation of collagen biosynthesis and a transient arrest of cell cycles, induction of the heat-shock response is likely to be a primary event induced by molecular hydrogen in the liver of wild-type rodents.

Compared to other types of lung cancer, lung adenocarcinoma patients with a history of smoking have a poor prognosis during the treatment of lung cancer. How lung adenocarcinoma-related genes are differentially expressed between smoker and non-smoker patients has yet to be fully elucidated. We performed a meta-analysis of four publicly available microarray datasets related to lung adenocarcinoma tissue in patients with a history of smoking using R statistical software. The top 50 differentially expressed genes (DEGs) in smoking vs. non‑smoking patients are shown using heat maps. Additionally, we conducted KEGG and GO analyses. In addition, we performed a PPI network analysis for 8 genes that were selected during a previous analysis. We identified a total of 2,932 DEGs (1,806 upregulated, 1,126 downregulated) and five genes (CDC45, CDC20, ANAPC7, CDC6, ESPL1) that may link lung adenocarcinoma to smoking history. Our study may provide new insights into the complex mechanisms of lung adenocarcinoma in smoking patients, and our novel gene expression signatures will be useful for future clinical studies.

Gene expression connectivity mapping has gained much popularity in recent years with a number of successful applications in biomedical research testifying its utility and promise. A major application of connectivity mapping is the identification of small molecule compounds capable of inhibiting a disease state. In this study, we are additionally interested in small molecule compounds that may enhance a disease state or increase the risk of developing that disease. Using breast cancer as a case study, we aim to develop and test a methodology for identifying commonly prescribed drugs that may have a suppressing or inducing effect on the target disease (breast cancer).

An integrated analysis was performed with data from 4 phase 2 and phase 3 studies of tofogliflozin in which patients with type 2 diabetes mellitus received the sodium-glucose cotransporter 2 inhibitor tofogliflozin for up to 24 weeks. Sex differences, baseline haemoglobin A1c (HbA1c) and serum uric acid (UA) levels, and log10 -transformed urinary N-acetyl-β-D-glucosaminidase ratio were significantly correlated with the reduction in serum UA levels at both 4 and 24 weeks in multivariate analysis (respectively, P < .0001). The decrease in HbA1c levels was greatest in the group with the highest baseline HbA1c level (quartile 4; HbA1c > 8.6%) and lowest in the group with the lowest baseline HbA1c level (quartile 1; HbA1c ≤ 7.4%). The decrease in serum UA levels was greatest in the quartile 1 group and lowest in the quartile 4 group. In most groups, the maximum decrease in serum UA levels was seen in the first 4 weeks, while the maximum decrease in HbA1c was seen at week 24. Thus, serum UA levels were significantly decreased in patients with moderate HbA1c levels.

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.

We provide an update to a network meta-analysis evaluating the relative efficacy of nintedanib + docetaxel versus other second-line agents in adenocarcinoma histology non-small-cell lung cancer.

Due to recent advancements in the understanding of the molecular pathogenesis of B-cell malignancies, there has been an explosion of innovative agents in development. The purpose of this review is to efficiently summarize novel therapies with activity in indolent non-Hodgkin lymphoma (iNHL) targeting surface antigens, signaling pathways, and the tumor microenvironment. Areas covered: A literature search was performed to identify preclinical data and clinical trials focused on the use of targeted therapies in iNHL subtypes including follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Classes reviewed include monoclonal antibodies, antibody-drug conjugates, immunomodulatory agents, B-cell receptor pathway inhibitors, Bcl-2 inhibitors, checkpoint inhibitors, chromatin and epigenetic modulating agents, and CAR T-cells. Expert commentary: Opinions regarding strategies to address the prioritization of novel agents entering clinical development, the determination of rational combination therapy, the development of novel endpoints to expedite clinical development, and the movement towards novel consolidative approaches with immuno- and cellular therapy in an attempt to provide curative treatment options are provided. Also, the economic impact of indefinite therapy is discussed.

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.

Myasthenia gravis (MG) is a rare debilitating autoimmune neuromuscular disorder. Many studies have focused on the mechanism and treatment strategies of MG. However, the exact pathogenesis of MG and effective treatment strategies remain unclear. Recent studies have indicated that microRNAs (miRNAs or miRs) can regulate the pathological pathways of MG, suggesting their potential role in novel treatments. In the present study, we created a comprehensive catalog of experimentally confirmed MG risk genes and miRNAs by manually mining published literature and public databases. Based on these genes and miRNAs, we identified 41 MG risk pathways and 105 approved drugs that can affect these pathways. Some important MG-related pathways, such as hsa04060 (cytokine-cytokine receptor interaction) and hsa05200 (pathway in cancer), were found to be regulated by MG risk miRNAs and drugs. Furthermore, we constructed an miRNA-regulated drug-pathway network and identified miRNAs and drugs that synergistically regulate key MG pathways and biological processes. We developed a drug repurposing strategy to identify 25 drug repurposing candidates for MG; several of these drugs, such as rituximab, adalimumab, sunitinib, and muromonab, have the potential to be novel MG treatment drugs. This study provides novel insight into the pathogenesis of MG and potential drug candidates for MG were identified.

Developments in the diagnosis and treatment of colorectal cancer (CRC) have been made in the last decade, but the overall survival rate of patients with CRC has not improved dramatically. Genetic and epigenetic events contribute to CRC pathogenesis. Tumor heterogeneity results in a range of prognoses and responses to CRC management and therapy. Epigenetic biomarkers have potential in CRC diagnosis and in measuring response to therapy. Combining information from genetic and epigenetic alterations provides an opportunity to predict response to therapy. Epigenetic biomarkers can be used in disease stratification, which also helps in designing therapeutic approaches for CRC. Challenges in the understanding of CRC development and gaps in knowledge are discussed.

Therapy for the myelodysplastic syndromes (MDS) is an evolving area of research which has made significant use of the increased understanding of the complex biology of these disorders. Novel agents targeting multiple pathogenic pathways are being actively tested in preclinical and clinical settings and hold the potential to be available to clinicians before long.

We have previously reported surrogate biomarkers of VEGF pathway activities with the potential to provide predictive information for anti-VEGF therapies. The aim of this study was to systematically evaluate a new VEGF-dependent gene signature (VDGs) in relation to molecular subtypes of ovarian cancer and patient prognosis. Using microarray profiling and cross-species analysis, we identified 140-gene mouse VDGs and corresponding 139-gene human VDGs, which displayed enrichment of vasculature and basement membrane genes. In patients who received bevacizumab therapy and showed partial response, the expressions of VDGs (summarized to yield VDGs scores) were markedly decreased in post-treatment biopsies compared with pre-treatment baselines. In contrast, VDGs scores were not significantly altered following bevacizumab treatment in patients with stable or progressive disease. Analysis of VDGs in ovarian cancer showed that VDGs as a prognostic signature was able to predict patient outcome. Correlation estimation of VDGs scores and molecular features revealed that VDGs was overrepresented in mesenchymal subtype and BRCA mutation carriers. These findings highlighted the prognostic role of VEGF-mediated angiogenesis in ovarian cancer, and proposed a VEGF-dependent gene signature as a molecular basis for developing novel diagnostic strategies to aid patient selection for VEGF-targeted agents.

Differential gene expression analyses to investigate multiple sclerosis (MS) molecular pathogenesis cannot detect genes harboring genetic and/or epigenetic modifications that change the gene functions without affecting their expression. Differential co-expression network approaches may capture changes in functional interactions resulting from these alterations. We re-analyzed 595 mRNA arrays from publicly available datasets by studying changes in gene co-expression networks in MS and in response to interferon (IFN)-β treatment. Interestingly, MS networks show a reduced connectivity relative to the healthy condition, and the treatment activates the transcription of genes and increases their connectivity in MS patients. Importantly, the analysis of changes in gene connectivity in MS patients provides new evidence of association for genes already implicated in MS by single-nucleotide polymorphism studies and that do not show differential expression. This is the case of amiloride-sensitive cation channel 1 neuronal (ACCN1) that shows a reduced number of interacting partners in MS networks, and it is known for its role in synaptic transmission and central nervous system (CNS) development. Furthermore, our study confirms a deregulation of the vitamin D system: among the transcription factors that potentially regulate the deregulated genes, we find TCF3 and SP1 that are both involved in vitamin D3-induced p27Kip1 expression. Unveiling differential network properties allows us to gain systems-level insights into disease mechanisms and may suggest putative targets for the treatment.

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.

The increasing use of engineered nanomaterials (ENMs) of varying physical and chemical characteristics poses a great challenge for screening and assessing the potential pathology induced by these materials, necessitating novel toxicological approaches. Toxicogenomics measures changes in mRNA levels in cells and tissues following exposure to toxic substances. The resulting information on altered gene expression profiles, associated pathways, and the doses at which these changes occur, are used to identify the underlying mechanisms of toxicity and to predict disease outcomes. We evaluated the applicability of toxicogenomics data in identifying potential lung-specific (genomic datasets are currently available from experiments where mice have been exposed to various ENMs through this common route of exposure) disease outcomes following exposure to ENMs.

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.

Prenatal alcohol exposure (PAE) can result in an array of morphological, behavioral, and neurobiological deficits that can range in their severity. Despite extensive research in the field and a significant progress made, especially in understanding the range of possible malformations and neurobehavioral abnormalities, the molecular mechanisms of alcohol responses in development are still not well understood. There have been multiple transcriptomic studies looking at the changes in gene expression after PAE in animal models; however, there is a limited apparent consensus among the reported findings. In an effort to address this issue, we performed a comprehensive re-analysis and meta-analysis of all suitable, publically available expression data sets.

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.

Metformin is effective for the treatment of polycystic ovary syndrome, but conflicting results regarding its effect on adipocytokine levels (adiponectin, resistin, visfatin, and leptin) in patients with polycystic ovary syndrome receiving metformin treatment have been reported. To provide high-quality evidence about the effect of metformin treatment on adipocytokines in patients with polycystic ovary syndrome, relevant studies that assessed the levels of adipocytokines (adiponectin, resistin, visfatin, and leptin) in patients with polycystic ovary syndrome receiving treatment with metformin administration were reviewed and analyzed.