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.

The accumulation of chronic or severe acute DNA and cellular damage in oral mucosa cells is one of the main factors that help initiate a wide range of malignant lesions in the oral cavity. There has been considerable controversy in the literature about the effect of such sustained genotoxic and cytotoxic damage to oral mucosa cells.

Breast cancer (BrCa) and diabetes mellitus (DM) are two major heath problems in women and the general population. This study explores the association between DM and breast cancer patients' survival outcomes, as well as the potential therapeutic merits of metformin.

Despite recent advances in the understanding of the biology of renal cell carcinoma (RCC), successful surgical treatment and implementation of novel‑targeted therapies, the prognosis for RCC patients remains poor. Late presentation, tumor heterogeneity and in particular the lack of molecular biomarkers for early detection, classification and the surveillance of RCC treatments are major obstacles. The increasing knowledge regarding the functional role of microRNAs (miRNAs) in pathophysiological processes may provide an important link to the identification of suitable therapeutic targets and diagnostic/prognostic biomarkers for RCC. The aim of this review was to provide new insight into the function of miRNAs in the pathogenesis of RCC and to emphasize their potential as diagnostic and prognostic markers, as well as therapeutic targets.

The "classic" endocannabinoid (eCB) system includes the cannabinoid receptors CB1 and CB2, the eCB ligands anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their metabolic enzymes. An emerging literature documents the "eCB deficiency syndrome" as an etiology in migraine, fibromyalgia, irritable bowel syndrome, psychological disorders, and other conditions. We performed a systematic review of clinical interventions that enhance the eCB system--ways to upregulate cannabinoid receptors, increase ligand synthesis, or inhibit ligand degradation.

Psychosis is associated with an elevated risk for cardiovascular disease. We reviewed evidence for a causal association between experimentally controlled antipsychotic drug exposure and a change in the expression of genes relevant to cardiovascular disease in human cell lines. Reports from SCOPUS - V.4 (Elsevier) and MEDLINE (ISI) were assessed for global or candidate gene expression analysis, tissue and cell type, tissue source or cell line, antipsychotic drug and dosage, length of drug exposure and statistically significant fold change in gene expression after drug exposure; 29 eligible studies analysed gene expression in the brain, eye (as a model of neuronal cells), heart, kidney (as a model of any cell), liver, pancreas or skin. Antipsychotic drugs alter the expression of numerous genes related to cardiovascular health, including genes under the control of the sterol regulatory element binding protein transcription factors that control lipid and fatty acid biosynthesis.

To assess the current literature on the impact of rheumatoid arthritis (RA) treatments on the humoral response to pneumococcal and influenza vaccines.

Human epidermal growth factor receptor 2 (HER2) is overexpresed in 15-20% of all breast cancers. Treatment with trastuzumab has led to an improved outcome and prolonged survival of HER2-positive breast cancer patients and today the drug is established as standard of care in both the adjuvant and metastatic settings. However, trastuzumab resistance is common and a major focus in the treatment of HER2-positive breast cancer has been developing therapeutic agents to either potentiate the effect of trastuzumab or to target cells which have become resistant to trastuzumab. The present review addresses efficacy and toxicity of dual targeting in HER2-positive breast cancer.

Observational and preclinical studies suggested an association between the expression of thymidylate synthase (TS) and clinical effects of pemetrexed-based chemotherapy in non-small-cell lung cancer (NSCLC) patients. However, the predictive value of TS for pemetrexed-containing chemotherapy regimen remained controversial. The aim of the study was to further appraise the association between the expression of TS and clinical efficacy pemetrexed-based chemotherapy in NSCLC patients.

Carcinogenesis is a complex process involving both genetic and epigenetic mechanisms. The cellular molecular epigenetic machinery, including histone modifications, is associated with changes in gene expression induced by exposure to environmental agents. In this paper, we systematically reviewed publications regarding the effects of xenobiotic stressors, mainly heavy metal exposure, on specific histone modifications. We included a total of 18 publications describing the effect of environmental stressors on histone structure modifications. We then constructed an interaction map to visualize the effect of environmental exposure(s) on specific histone modifications. In the studies we considered, a total of 20 modifications were reported, of which H3Me3K4 and H3Me2K9 were the most frequently studied histone modifications. These modifications were affected mostly by heavy metals and ethanol exposure. Based on the interaction map, we explored the molecular mechanisms mediating the histone modifications induced by environmental stressors in the respective selected studies. This resulted in the identification of seven target proteins and two families of proteins mediating the effects of environmental stressors on histone modifications. This review contributes to the understanding of environmental exposure and its possible effects on cancer risk by inducing changes in histone modifications and hence gene expression.

Many primary studies have considered the association of polymorphisms of folate metabolism and response to 5-fluorouracil (5-FU) and capecitabine in patients with colorectal cancer. The conclusions from these studies have been conflicting and few have considered large cohorts of patients. Therefore, we have completed a systematic review and meta-analyses to summarize some of the findings to date. We conducted searches for any studies that had addressed the prognostic value of genotype analysis of thymidylate synthetase (TYMS), Methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR).

Emdogain is a commercial product of unknown composition and is clinically used to induce periodontal regeneration. This study aims to review current knowledge of the in vitro effects of Emdogain on oral tissues and, in particular, factors related to carcinoma. A systematic approach was used to review studies from the Embase and Pubmed databases; a total of 76 studies were included. These comprised in vitro studies of the cytokines in, or regulated by, Emdogain and assays designed to study the effects of EMD on human cells in oral tissues or malignant cells. Several studies have shown that EMD regulates the proliferation, migration, adhesion, gene expression, and cytokine production of (pre-)osteoblasts, periodontal fibroblasts, and gingival fibroblasts. However, the effects of EMD on malignant oral cells are not well understood. EMD seems to have broad regulatory effects on malignant cells and on several carcinoma-related factors. Evidence suggests that patients with premalignant or malignant mucosal lesions should not be treated with EMD.

Alcohol dependence is a major disease burden of adults in modern society worldwide. There is no cure for alcohol dependence. In this study, we have examined the molecular targets of ethanol-induced toxicity in humans based on a systematic review of literature data and then discussed current and potential therapeutic targets for alcohol abuse and dependence. Using human samples with ethanol exposure, microarray analyses of gene expression have shown that numerous genes are up- and/or down-regulated by alcohol exposure. The ethanol-responsive genes mainly encode functional proteins such as proteins involved in nucleic acid binding, transcription factors, selected regulatory molecules, and receptors. These genes are also correlated with important biological pathways, such as angiogenesis, integrin signalling pathway, inflammation, wnt signaling pathway, platelet-derived growth factor signaling pathway, p53 pathway, epidermal growth factor receptor signaling pathway and apoptosis signaling pathway. Currently, only three medications were approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcohol abuse and alcohol dependence, including the aldehyde dehydrogenase inhibitor disulfiram, the micro-opioid receptor antagonist naltrexone, and the N-methyl-D-aspartate (NMDA) receptor inhibitor acamprosate (oral and injectable extended-release formulations). In addition, a number of agents are being investigated as novel treatments for alcohol abuse and dependence. These include selective 5-HT reuptake inhibitors (e.g. fluoxetine), 5-HT(1) receptor agonists (e.g. buspirone), 5-HT(2) receptor antagonists (e.g. ritanserin), 5-HT(3) receptor antagonists (e.g. ondansetron), dopamine receptor antagonists (e.g. aripiprazole and quetiapine), dopamine receptor agonists (e.g. bromocriptine), GABA(B) receptor agonists (e.g. baclofen), and cannabinoid-1 (CB(1)) receptor antagonists. Some of these agents have shown promising efficacy in initial clinical studies. However, further randomized studies with larger samples are warranted to establish their efficacy and safety profiles in the treatment of alcohol dependence.

Considerable interest in the efficacy of rituximab (a monoclonal CD20 antibody) in patients with systemic lupus erythematosus (SLE) has been generated due to its unique mode of action, culminating in a series of randomized and open trials, and case reports. However, this use is off-license and two significant RCTs have reported negative findings, reopening the debate on clinical benefit. This review of the available data suggests that rituximab induces B-cell depletion in 95% of patients, and a significant reduction in disease activity is achieved with a relatively good safety profile in patients with SLE.

Natural products represent a rich reservoir of potential small chemical molecules exhibiting antiproliferation and anticancer properties. An example is berberine, a protoberberine alkaloid widely distributed in medical plants used in traditional Chinese prescriptions. Recent advances have shown that berberine exerts anticancer activities both in vitro and in vivo through different mechanisms. Berberine shows inhibitory effects on the proliferation and reproduction of certain tumorigenic microorganisms and viruses, such as Heliobacter pylori and hepatitis B virus. Transcriptional regulation of some oncogene and carcinogenesis-related gene expression and interaction with both DNA and RNA are also well documented. Besides, berberine is a broad spectrum enzyme inhibitor, which affects N-acetyltransferase, cyclooxygenase-2, and topoisomerase activities and gene/protein expression. These actions, together with the regulation of reactive oxygen species production, mitochondrial transmembrane potential, and nuclear factor-kappaB activation might underlie its antiproliferative and proapoptotic effects. More importantly, the suppression of tumor growth and metastasis, the beneficial application in combined medication, and the improvement of multidrug resistance both in vivo and in vitro clearly show its potential as an alternative medicine for tumor chemotherapy.

Chondroitin sulfate has been shown to relieve pain and improve functional limitation in patients with osteoarthritis (OA) of the knee in numerous clinical trials and meta-analyses. Its role as a potential structure-modifying drug for knee OA, however, remains controversial.

Enzastaurin is a novel antineoplastic and antiangiogenic agent that acts through inhibition of protein kinase C (PKC).