Adjuvant chemotherapy with melatonin for targeting human cancers: A review

Melatonin is a multifunctional hormone that has long been known for its antitumoral effects. An advantage of the application of melatonin in cancer therapy is its ability to differentially influence tumors from normal cells. In this review, the roles of melatonin adjuvant therapy in human cancer are discussed. Combination of melatonin with chemotherapy could provide synergistic antitumoral outcomes and resolve drug resistance in affected patients. This combination reduces the dosage for chemotherapeutic agents with the subsequent attenuation of side effects related to these drugs on normal cells around tumor and on healthy organs. The combination therapy increases the rate of survival and improves the quality of life in affected patients. Cancer cell viability is reduced after application of the combinational melatonin therapy. Melatonin does all these functions by adjusting the signals involved in cancer progression, re-establishing the dark/light circadian rhythm, and disrupting the redox system for cancer cells. To achieve effective therapeutic outcomes, melatonin concentration along with the time of incubation for this indoleamine needs to be adjusted. Importantly, a special focus is required to be made on choosing an appropriate chemotherapy agent for using in combination with melatonin. Because of different sensitivities of cancer cells for melatonin combination therapy, cancer-specific targeted therapy is also needed to be considered. For this review, the PubMed database was searched for relevant articles based on the quality of journals, the novelty of articles published by the journals, and the number of citations per year focusing only on human cancers.     

Mechanisms of statin-induced new-onset diabetes

Statins, with their lipid-lowering properties, are a first-line therapy for the prevention of cardiovascular diseases. Recent evidence, however, suggests that statins can increase the risk of new-onset diabetes (NOD). The molecular mechanisms of statin-induced NOD are not precisely known, although some pathophysiologic mechanisms have been suggested. Specific to the beta cell, these mechanisms include alterations in insulin secretion, changes in ion channels, modulation of signaling pathways, and inflammation/oxidative stress. Outwith the beta cell, other suggested mechanisms involve adipocytes, including alterations in adipocyte differentiation and modulation of leptin and adiponectin, and genetic and epigenetic mechanisms, including alterations in microRNA. The evidence supporting these and other mechanisms will be discussed. Greater understanding of the underlying mechanisms linking the onset of diabetes to statin therapy is essential and clinically relevant, as it may enable novel preventative or therapeutic approaches to be instituted and guide the production of a new generation of statins lacking this side effect.     

Positive correlation between vitamin D receptor gene TaqI variant and gastric cancer predisposition in a sample of Iranian population

Gastric cancer is the second cause of cancer-related mortality and the fourth most common cancers worldwide. Owing to the immune modulatory effect of vitamin D in the body, the role of vitamin D receptor gene in vitamin D regulation receives a great deal of research interest. The aim of the current study was to highlight the association between two variants of TaqI and FokI in the vitamin D receptor gene and gastric cancer predisposition in a sample of South Khorasan population. The present investigation consisted of 69 patients affected with gastric cancer and 100 healthy individuals. The genomic DNA was extracted by salting out the protocol from peripheral venous blood. Genotyping of TaqI and FokI variants were performed by PCR-RFLP method. Our findings manifested that TC genotype of TaqI polymorphism was statistically significant between the case and the control groups (p = 0.002). Moreover, the frequency of TC + CC genotypes was statistically significant between the two groups (p = 0.009). Furthermore, we could not find any meaningful association between FokI variant and the participant groups. The present results declared that, in our population, TC genotype of TaqI polymorphism has an association with gastric cancer susceptibility. In addition, more investigation with greater sample sizes is needed to confirm our results.     

Amelioration of regulatory T cells by Lactobacillus delbrueckii and Lactobacillus rhamnosus in pristane-induced lupus mice model

Regulatory T cells (Tregs) play an indispensable role in the control of immune responses and induction of peripheral tolerance. Dysregulation of Tregs is involved in the pathogenesis of systemic lupus erythematosus (SLE). Tolerogenic probiotics have shown beneficial effects in the control of autoimmune diseases. We evaluated the prophylactic and therapeutic effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on Tregs and their related molecules in pristane-induced lupus mice model. Fifty-four female BALB/c mice (3–5 weeks) were randomly divided into nine groups. Lupus was induced in all groups using pristane. Prophylactic groups were treated from Day 0 (at the time of pristane injection) and treatment groups were treated 2 months later with L. rhamnosus, L. delbrueckii, mix of both probiotics, and prednisolone. One group was considered as SLE-induced control group without any treatment. Presence of antinuclear antibodies (ANA), antidouble-stranded DNA (anti-dsDNA), antiribonucleoprotein (anti-RNP), proteinuria, and serum level of creatinine, urea, the expression of forkhead box P3 (Foxp3), interleukin 6 (IL-6), IL-10, transforming growth factor β, and the number of Tregs were determined. SLE induction by pristane led to the formation of lipogranuloma, presence of ANA, anti-dsDNA, and anti-RNP. Probiotics consumption decreased the level of lipogranuloma, ANA, and anti-dsDNA. In addition, in probiotics receiving groups, Tregs and the expression level of Foxp3 increased, while IL-6 decreased. The effect of probiotics in the prophylactic group was more prominent. The results may indicate the effectiveness of L. delbrueckii and L. rhamnosus in the enhancement of Tregs and the decrease of inflammatory cytokines and disease severity in SLE-induced mice.     

Stem cell therapy: A novel approach for myocardial infarction

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Until recently, it was thought that myocardium was not able to repair itself, but studies have now shown that resident cardiac stem cells have regenerative capacity, and stem cell therapy may be a novel approach for cardiac muscle repair and regeneration. Stem cell-derived paracrine factors have been shown to regulate ventricular remodeling, inflammation, apoptosis, cardiomyocytes regeneration, and neovascularization in regions of infarcted cardiac tissue. In this review, we summarize the evidence from cellular, animal, and clinical studies supporting the potential clinical significance of stem cell therapy as a novel therapeutic approach for the treatment of MI.     

Evaluation of the neuroprotective effects of electromagnetic fields and coenzyme Q10 on hippocampal injury in mouse

Electromagnetic fields (EMFs) are reported to interfere with chemical reactions involving free radical production. Coenzyme Q₁₀ (CoQ10) is a strong antioxidant with some neuroprotective activities. The purpose of this study was to examine and compare the neuroprotective effects of EMF and CoQ10 in a mouse model of hippocampal injury. Hippocampal injury was induced in mature female mice (25–30 g), using an intraperitoneal injection of trimethyltin hydroxide (TMT; 2.5 mg/kg). The experimental groups were exposed to EMF at a frequency of 50 Hz and intensity of 5.9 mT for 7 hr daily over 1 week or treated with CoQ10 (10 mg/kg) for 2 weeks following TMT injection. A Morris water maze apparatus was used to assess learning and spatial memory. Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) tests were also performed for the histopathological analysis of the hippocampus. Antiapoptotic genes were studied, using the Western blot technique. The water maze test showed memory improvement following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Nissl staining and TUNEL tests indicated a decline in necrotic and apoptotic cell count following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Western blot study indicated the upregulation of antiapoptotic genes in treatment with CoQ10, as well as coadministration. Also, treatment with EMF had no significant effects on reducing damage induced by TMT in the hippocampus. According to the results, EMF had no significant neuroprotective effects in comparison with CoQ10 on hippocampal injury in mice. Nevertheless, coadministration of EMF and CoQ10 could improve the neuroprotective effects of CoQ10.     

The role of microRNAs in prostate cancer migration,invasion, and metastasis

Prostate cancer (PCa) is considered the most prevalent malignancy and the second major cause of cancer-related death in males from Western countries. PCa exhibits variable clinical pictures, ranging from dormant to highly metastatic cancer. PCa suffers from poor prognosis and diagnosis markers, and novel biomarkers are required to define disease stages and to design appropriate therapeutic approach by considering the possible genomic and epigenomic differences. MicroRNAs (miRNAs) comprise a class of small noncoding RNAs, which have remarkable functions in cell formation, differentiation, and cancer development and contribute in these processes through controlling the expressions of protein-coding genes by repressing translation or breaking down the messenger RNA in a sequence-specific method. miRNAs in cancer are able to reflect informative data about the current status of disease and this might benefit PCa prognosis and diagnosis since that is concerned to PCa patients and we intend to highlight it in this paper.