Polyphenols in bee products and prevention of cell senescence.

Sustaining the continuity of cells and their homeostasis throughout the lifespan is compulsory for the survival of an organism. Cellular senescence is one of mechanisms involved in cell homeostasis and survival, and plays both important and detrimental roles in the maintenance of malfunctioned and normal cells. However, when exposed to various insults (genetic, metabolic and environmental), the cells undergo oxidative stress which may induce premature senescence, or so-called stress-induced premature senescence. Many age-related diseases are associated with premature senescence. Hence, there is growing interest in the intake of natural sources such as dietary food, which has protective functions on human health and diseases as well as on premature senescence. There are many natural food sources which have beneficial effects on delaying cell senescence, of which bee products are one of them. Bee products (honey, propolis, royal jelly, bee pollen, bee bread, venom and wax) are rich in polyphenols, a compound that exerts powerful antioxidant actions against oxidative stress and is able to delay premature senescence that is linked to ageing. This review describes the factors triggering senescence, the biomarkers involved and the prevention of senescence by the polyphenols present in bee products. Thus, it is hoped that this will provide new insights into the clinical management of age-related diseases.

Effects of honey supplementation on safety profiles among postmenopausal breast cancer patients.

OBJECTIVES: In this study, we aimed to determine the effect of honey supplementation on the safety profiles of postmenopausal breast cancer patients. METHODS: Seventy-two postmenopausal women with stage I, II, or III breast cancer from the Oncology Clinic, Universiti Sains Malaysia Hospital were treated with anastrozole (1 mg/day). Patients were randomly assigned to one of the two groups (n = 36/group): a control group (no honey) and a honey group (20 g/day of honey for 12 weeks). Fasting blood samples were obtained pre- and post-intervention to investigate differences in the haematological, renal, and liver profiles of patients in both the groups. RESULTS: Post-intervention, alanine aminotransferase levels were significantly higher in the control group than in the honey group. In the honey group, white blood cell counts, platelet counts, and creatinine levels were significantly higher following honey supplementation for 12 weeks. Nevertheless, the values were still within normal ranges. CONCLUSIONS: The present study suggests that honey supplementation of 20 g/day for 12 weeks is safe and beneficial for postmenopausal breast cancer patients.

Epigenomic approach in understanding Alzheimer's disease and type 2 diabetes mellitus.

Cognitive decline is a debilitating feature of Alzheimer's disease (AD). The causes leading to such impairment are still poorly understood and effective treatments for AD are still unavailable. Type 2 diabetes mellitus (T2DM) has been identified as a risk factor for AD due to desensitisation of insulin receptors in the brain. Recent studies have suggested that epigenetic mechanisms may also play a pivotal role in the pathogenesis of both AD and T2DM. This article describes the correlation between AD and T2DM and provides the insights to the epigenetics of AD. Currently, more research is needed to clarify the exact role of epigenetic regulation in the course and development of AD and also in relation to insulin. Research conducted especially in the earlier stages of the disease could provide more insight into its underlying pathophysiology to help in early diagnosis and the development of more effective treatment strategies.

Humanin: a possible linkage between Alzheimer's disease and type 2 diabetes.

The prevalence of Alzheimer's disease (AD) is higher among type 2 diabetes mellitus (T2DM) patients. In T2DM patients, the progression of AD is more rapid. Furthermore, several pathophysiological pathways are common to AD and T2DM. Humanin is a recently introduced, mitochondrial-derived peptide with neuroprotective effects. Humanin can alter the mechanisms involved in AD and T2DM pathogenesis. Insulin resistance as well as oxidative stress has been shown to be associated with increased amyloid deposition in brain neurons and islet beta cells. Moreover, advanced glycation end products and lipid metabolism disorders are common pathways of oxidative stress and low-grade systemic inflammation in AD and T2DM. These common pathways may explain AD and T2DM pathogenesis and suggest common treatments for both diseases. Treatments for T2DM and AD attempt to slow cognitive decline, and recent investigations have focused on agents that may alter pathways common to AD and T2DM pathogenesis. Non-steroidal antiinflammatory drugs, such as interleukin-1 antagonists and statins, are possible drug candidates for both AD and T2DM.

Quinoline derivatives: candidate drugs for a class B G-protein coupled receptor, the calcitonin gene-related peptide receptor, a cause of migraines.

Class B G-protein coupled receptors are involved in a wide variety of diseases and are a major focus in drug design. Migraines are a common problem, and one of their major causative agents is the class B G-protein coupled receptor, Calcitonin gene-related peptide (CGRP) receptor, a target for competitive drug discovery. The calcitonin receptor-like receptor generates complexes with a receptor activity-modifying protein, which determines the type of receptor protein formed. The CGRP receptor comprises a complex formed from the calcitonin receptor-like receptor and receptor activity-modifying protein 1. In this study, an in silico docking approach was used to target the calcitonin receptor-like receptor in the bound form with receptor activity-modifying protein 1 (CGRP receptor), as well as in the unbound form. In both cases, the resulting inhibitors bound to the same cavity of the calcitonin receptor-like receptor. The twelve evaluated compounds were competitive inhibitors and showed efficient inhibitory activity against the CGRP receptor and Calcitonin receptor-like receptor. The two studied quinoline derivatives demonstrated potentially ideal inhibitory activity in terms of binding interactions and low range nano-molar inhibition constants. These compounds could prove helpful in designing drugs for the effective treatment of migraines. We propose that quinoline derivatives possess inhibitory activity by disturbing CGRP binding in the trigeminovascular system and may be considered for further preclinical appraisal for the treatment of migraines.

How do periodontal infections affect the onset and progression of Alzheimer's disease?

Chronic infection can cause slow progressive dementia, cortical atrophy and amyloid deposition in the atrophic form of general paresis. Due to the fact that specific bacterial ligands can increase the expression of proinflammatory molecules that can activate innate and adaptive immune systems, inflammation may play a significant role in the pathogenesis of Alzheimer's disease (AD). Furthermore, there is a significant association between AD and various types of spirochete. Periodontitis is a prevalent and persistent peripheral infection that is associated with gram-negative anaerobic bacteria and is capable of showing localized and systemic infections in the host. Periodontal disease related pathogens and their inflammatory products contribute to systemic inflammation and the pathogenesis of AD. In this minireview, we propose a hypothetical link between periodontitis, type 2 diabetes and AD. We also present the possible mechanistic links between periodontitis-related inflammation, type 2 diabetes and AD. Since this condition is treatable, periodontitis may be a readily-modifiable risk factor for AD.

Genomic linkage between Alzheimer's disease and type 2 diabetes.

Alzheimer's disease (AD) is a major health concern that affects nearly every society worldwide. The disease is an irreversible, progressive and age-related neurodegenerative disorder. It is characterized by impaired cognitive function and the diffuse deposition of amyloid plaques and neurofibrillary tangles. The causes of AD and the underlying mechanisms that trigger the onset of the disease are still a matter of debate. Several epidemiological studies have shown that the development of AD is associated with type 2 diabetes mellitus (T2D). In this review, we provide evidence for the link between T2D and AD, highlighting the critical role of insulin in the pathogenesis of these diseases, and we provide information on the genes that might be involved in the interplay between these two disorders. New insight into the complex biology of AD is necessary for the early diagnosis of the disease, the development of novel drug therapies and the prevention of these health issues.

The role of viruses in neurodegenerative and neurobehavioral diseases.

Neurodegenerative and neurobehavioral diseases may be caused by chronic and neuropathic viral infections and may result in a loss of neurons and axons in the central nervous system that increases with age. To date, there is evidence of systemic viral infections that occur with some neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, autism spectrum disorders, and HIV-associated neurocognitive disorders. With increasing lifespan, the incidence of neurodegenerative diseases increases consistently. Neurodegenerative diseases affect approximately 37 million people worldwide and are an important cause of mortality. In addition to established non-viral-induced reasons for neurodegenerative diseases, neuropathic infections and viruses associated with neurodegenerative diseases have been proposed. Neuronal degeneration can be either directly or indirectly affected by viral infection. Viruses that attack the human immune system can also affect the nervous system and interfere with classical pathways of neurodegenerative diseases. Viruses can enter the central nervous system, but the exact mechanism cannot be understood well. Various studies have supported viral- and non-viral-mediated neurodegeneration at the cellular, molecular, genomic and proteomic levels. The main focus of this review is to illustrate the association between viral infections and both neurodegenerative and neurobehavioral diseases, so that the possible mechanism and pathway of neurodegenerative diseases can be better explained. This information will strengthen new concepts and ideas for neurodegenerative and neurobehavioral disease treatment.

A nanotechnological approach to the management of Alzheimer disease and type 2 diabetes.

Alzheimer's disease (AD) and type 2 diabetes (T2D) are both prevalent in older individuals and have gained significant attention due to alarming rates of increase. The high incidences of these diseases pose a great socioeconomic burden and cause major public health concerns worldwide. A number of studies have established potential links between AD and T2D, supporting the hypothesis that T2D is linked with an increased risk of AD and that controlling diabetes could have a positive impact on the prevention of AD. At present, both diseases lack precise diagnostic approaches for early intervention and effective cure. Further, the currently available diagnostic tools for AD screening are insufficiently sensitive and robust for preventive measures. Although several drugs are used for the treatment of both these diseases, none of these drugs offers complete remission of the disease, merely symptomatic relief. Moreover, these drugs have limited efficacy because of problems such as conventional drug delivery systems beyond the blood brain barrier, a lack of target specificity and diminished potency. From this perspective, the emerging field of nanotechnology has offered new techniques and tools to overcome these challenges. In this review, we discuss the direct and indirect limitations of existing therapies and describe alternative potential nanotechnological approaches that could be utilized to overcome these limitations. New insight in the field of nanomedicine is necessary for early diagnosis, the development of novel drug therapies, the action of drugs and prevention, as well as for gaining an in-depth understanding of the complex biology of both diseases.

Current view from Alzheimer disease to type 2 diabetes mellitus.

Alzheimer's disease (AD) is a neurodegenerative disorder that leads to memory problems. It has been associated with type 2 diabetes mellitus at both the molecular and biochemical level. Pancreatic cells have molecular similarities to the brain at the transcriptomic and proteomic levels. Several genes have been reported to be responsible for both AD and diabetes. Currently, no proper treatment is available but various therapeutic approaches are utilized worldwide for the management of these disorders and may be nanoparticles and herbal treatment of Bacopa monnieri will make promise for the treatment of AD in future. The formation of amyloids in neurons and the formation of amylin in pancreatic cells are potential links between these two disorders, which can be silent killers.