The Effect of Type-2 Diabetes on Cognitive Status and the Role of Anti-diabetes Medications.

Type-2 diabetes mellitus prevalence is constantly increasing; this is explained by the increase of its risk factors and the amelioration of its management. Therefore, people are living longer with diabetes mellitus, which, in turn, has revealed new complications of the disease. Dementia is represented mainly by Alzheimer's disease and is an interesting topic of study. Accordingly, statistics have shown that dementia incidence is doubled in diabetic patients. The establishment of a relation between type-2 diabetes mellitus was studied on several levels in both humans and animal subjects. First, insulin receptors were found in the brain, especially the hippocampus, and insulin transport to the brain is mainly accomplished through the blood-brain barrier. Secondly, several studies showed that insulin affects multiple neurotransmitters in favor of promoting memory and cognition status. Thirdly, multiple pathological studies showed that insulin and Alzheimer's disease share many common lesions in the brain, such as beta-amyloid plaques, amylin-Aß plaques, hyper-phosphorylated tau protein, and brain atrophy, especially in the hippocampus. After recognizing the positive effect of insulin on cognitive status, and the harmful effect of insulin resistance on cognitive status, multiple studies were focused on the role of anti-diabetes medications in fighting dementia. Consequently, these studies showed a positive impact of oral anti-diabetes medication, as well as insulin in limiting the progression of dementia and promoting cognitive status. Moreover, their effects were also noticed on limiting the pathological lesions of Alzheimer's disease. Accordingly, we can consider type-2 diabetes mellitus as a risk factor for dementia and Alzheimer's disease. Therefore, this can be used on the pharmaceutical level by the promising implication of antidiabetics as a treatment of dementia and Alzheimer's disease or at least to limit its progression. However, multiple clinical studies should be dedicated to proving the true benefits of anti-diabetes medications in treating dementia before they can be used in reality.

Melatonin-A New Prospect in Prostate and Breast Cancer Management.

Cancer is a known cause of mortality globally. The management of cancer has been influenced periodically by diverse scientific research for early detection to promote remission and improve quality of life. One of these advancements is the prospect of melatonin (n-acetyl-5-methoxytryptamine) in managing prostate and breast cancers. Melatonin exerts its oncostatic effect by inhibiting angiogenesis, preventing cancer spread and growth, and improving the sensitivity of cancer cells to radiation and chemotherapy in both prostate and breast cancer. This review aims to highlight some of the current studies on melatonin's effect on prostate and breast cancers. We reviewed articles and two randomized controlled trials (RCT) that highlighted the mechanism of melatonin in combating tumorigenesis of these cancers. Articles and RCT studies were obtained by searching PubMed using regular and Medical Subject Heading (MeSH) keyword search strategy. The majority of the articles reviewed supported the use of melatonin in cancer management since inhibition of angiogenesis, cancer proliferation, invasion of normal cells by tumor cells, and improvement in chemotherapeutic and radiation therapy were achieved with its use. In addition, melatonin was also protective against prostate and breast cancers in the general population. Despite the benefits of melatonin in cancer management, most of the studies done were in vivo and in vitro studies, and more studies in human subjects are encouraged to confirm the positive therapeutic use of melatonin.

Iron Deficiency-Induced Changes in the Hippocampus, Corpus Striatum, and Monoamines Levels That Lead to Anxiety, Depression, Sleep Disorders, and Psychotic Disorders.

Iron deficiency anemia caused by severe iron deficiency in infancy is associated with poor health and severe neurological impairment such as mental, motor, social, emotional, neurophysiological, and neurocognitive dysfunction. The behavioral effects of iron deficiency can present themselves in infancy, but they are also found in adulthood. Some behaviors can start in childhood but persist throughout adulthood. The behaviors that are particularly often seen in infants and children include wariness and hesitance, lack of positive affect, and diminished social engagement. The affected behaviors in adults include anxiety, depression, higher complex cogitative tasks, and other psychological disorders. The mechanisms of how iron deficiency affects behavior include affecting the hippocampus, the corpus striatum, and certain neurotransmitters. The hippocampus is a brain region that is essential for memory, learning, and other purposes. The hippocampus is very sensitive to lack of Iron during early development. The corpus striatum dispatches dopamine-rich projects to the prefrontal cortex, and it is involved in controlling executive activities such as planning, inhibitory control, sustained attention, working memory, regulation of emotion, memory storage and retrieval, motivation, and reward. Iron deficiency has been known to cause changes in behavioral and developmental aspects by affecting neurotransmitters such as serotonin, noradrenaline, and dopamine. Iron deficiency causes behavior changes that can present in infancy and, even if corrected postnatally, it can have long-lasting effects well into adulthood.

Insulin Resistance, Hyperandrogenism, and Its Associated Symptoms Are the Precipitating Factors for Depression in Women With Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) is a combination of many symptoms resulting from hormonal imbalance, metabolic syndromes, hyperandrogenism, and anovulation. This paper explores the various etiopathology and mechanisms causing depression in women with PCOS and how to prevent and treat PCOS-induced depression. Women with PCOS present with multiple symptoms such as acne, hirsutism, androgenic alopecia, obesity, menstrual irregularities, infertility, and mood disturbances like depression and anxiety. Depression is the most common psychological problem faced by women with PCOS. The various pathophysiological mechanisms that lead to depression are Insulin resistance, disturbance in the hypothalamic pituitary adrenal (HPA) axis, hyperandrogenism and its clinical presentation, obesity, and infertility. Lifestyle modifications such as dietary changes and weight loss play a significant role in preventing and managing PCOS-induced depression. Cognitive behavioral therapy (CBT) and lifestyle modification have shown to be effective measures for weight loss in obese women with PCOS. Antidepressants also play a part in treating PCOS-induced depression. Over the last decade, the number of cases of depression in women with PCOS has increased. This paper provides detailed data on the fundamental causes of depression in women with PCOS to facilitate a more straightforward treatment approach.

Role of Selective Sodium-Glucose Co-Transporter-2 Inhibitors in Managing Cardio-Renal Complications in Type 2 Diabetes Mellitus: Beyond Glycemic Control.

Chronic kidney disease (CKD) and cardiovascular complications are the leading causes of death in type 2 diabetes mellitus. Apart from the standard therapy, which includes angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), lipid-lowering medication, and anti-platelet therapy, the new group of drugs termed the 'sodium-glucose co-transporter-2 (SGLT2) inhibitors' have shown promising results in managing complications arising from the cardiovascular and renal systems in diabetics. This article attempts to highlight the role and mechanism of action of this class of drugs.   We reviewed 127 articles and analyses of randomized controlled trials using several drugs in the SGLT2 inhibitor family (sotagliflozin, canagliflozin, dapagliflozin, tofogliflozin) over the past five years, out of which 58 met the criteria and aim of the study. These articles were retrieved from PubMed, Google Scholar, and Medline data sources and assessed for quality using the assessment of multiple systematic reviews (AMSTAR) checklist and Cochrane risk-of-bias tool. Results from the review showed significant benefits in reducing progressive renal decline, blood pressure control, heart failure hospitalization, death from renal or cardiovascular complications, myocardial infarction, and stroke. This benefit is also seen in non-diabetic patients, hence postulating that these effects may not be solely due to glycemic control. There are several mechanisms with which it achieves this benefit with the most significant being its role on intraglomerular pressure. Other pathways include blood pressure control, natriuresis, ventricular remodeling, erythropoiesis, lipid metabolism, plasma volume, and electrolyte imbalance.   It is clear that the role of SGLT2 inhibitors isn't limited to glycemic control and they can achieve a wide array of functions by affecting different systems. More studies need to be done to completely understand this medication to improve the quality of life in diabetic and non-diabetic patients living with CKD and cardiovascular complications. The pharmacokinetics of this drug could also help set the basis for newer medications.

Effectiveness of Stem Cell Therapies in Improving Clinical Outcomes in Patients With Heart Failure.

Heart failure (HF), continuing to be a notable cause of morbidity and mortality worldwide, also is a noteworthy economic burden to the patients. Current medical management of HF has poor efficacy to completely arrest or reverse the progression to end-stage disease. As the option of cardiac transplantation remains limited to few patients, the stem cell approach continues to be a promising one in developing a novel therapy in the treatment of HF. This review attempts to discuss and compare the outcomes of numerous clinical trials that involved treatment of HF of variable etiologies with stem cells of numerous lineages such as bone marrow-derived cells (BMCs), mesenchymal stem cells (MSCs), cardiosphere derived progenitor cells (CDCs), etc. We reviewed articles and randomized controlled trials (RCT) that used stem cells to treat heart failure. The articles and RCT studies were obtained through a search on PubMed and Medline databases and performed using regular and medical subject heading (MeSH) keyword search strategy. A total of 17 trial-based studies, along with other articles that met the aim of the review, were selected. A discussion of the findings from major clinical trials such as the C-CURE, CHART-1, POSEIDON, POSEIDON-DCM, TAC-HFT, and other small scale trials highlights the change in functional and mechanical parameters of HF, namely, left ventricular ejection fraction (LVEF), end-diastolic volume (EDV), end-systolic volume (ESV), 6-minute walking test distance (6MWTD), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and assessment of New York heart association (NYHA) class of heart failure, and Minnesota Living with Heart Failure Questionnaire (MLHFQ) score to reflect improvement in quality of life (QoL) of patients. Out of the studies analyzed, the majority reported significant improvements in at least two of the parameters mentioned above. However, more phase three randomized trials are required to compare the efficacy of multiple lineages of stem cells, factoring in molecular and dosage factors to develop a standardized therapy.