Molecular Mechanisms by Which Imeglimin Improves Glucose Homeostasis.

Despite different classes of antidiabetic medications available for the management of patients with diabetes, efforts are underway to identify novel and safer antihyperglycemic agents with higher potency and increased tolerability. Imeglimin is a promising antidiabetic agent that has shown to have significant antihyperglycemic effects in studies, although it has not been approved yet. There is growing evidence that imeglimin improves glucose homeostasis in the diabetic milieu; however, the precise molecular mechanisms are still not elucidated.

Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disorder characterized by chronic hyperglycemia and an inadequate response to circulatory insulin by peripheral tissues resulting in insulin resistance. Insulin resistance has a complex pathophysiology, and it is contributed to by multiple factors including oxidative stress. Oxidative stress refers to an imbalance between free radical production and the antioxidant system leading to a reduction of peripheral insulin sensitivity and contributing to the development of T2DM via several molecular mechanisms.

Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects.

Intensive diabetes control has been associated with increased mortality in type 2 diabetes (T2DM); this has been suggested to be due to increased hypoglycemia. We measured hypoglycemia-induced changes in endothelial parameters, oxidative stress markers and inflammation at baseline and after a 24-hour period in type 2 diabetic (T2DM) subjects versus age-matched controls. Case-control study: 10 T2DM and 8 control subjects.

Antipsychotic Drugs and Risk of Developing Venous Thromboembolism and Pulmonary Embolism: A Systematic Review and Meta-Analysis.

Background: Antipsychotic (AP) medications are the cornerstone treatment for schizophrenia and some other psychiatric diseases. However, some observational studies suggest that these medications might increase the risk of venous thromboembolism (VTE) and pulmonary embolism (PE).

Objectives: The aim of this study was to assess whether AP medications are associated with the development of VTE or PE, and to assess the risk based on any type of AP drugs, quality of studies and after adjustment of risk factors.

Utilization of Lipid-based Nanoparticles to Improve the Therapeutic Benefits of Bortezomib.

Cancer is a condition where there is an uncontrolled growth of cells resulting in high mortality. It is the second most frequent cause of death worldwide. Bortezomib (BTZ) is a Proteasome Inhibitor (PI) that is used for the treatment of a variety of cancers.

Incretins and microRNAs: Interactions and physiological relevance.

MicroRNAs (miRNA) are one class of the small regulatory RNAs that can impact the expression of numerous genes including incretin hormones and their G protein-coupled receptors. Incretin peptides, including GLP-1, GLP-2, and GIP, are released from the gastrointestinal tract and have an crucial role in the glucose hemostasis and pancreatic beta-cell function. These hormones and their analogs with a longer half-life, glucagon like peptide-1 receptor agonists (GLP1RA), modify the expression of miRNAs.

MicroRNA-mediated regulation of Nrf2 signaling pathway: Implications in disease therapy and protection against oxidative stress.

MicroRNAs (miRs) are small non-coding pieces of RNA that are involved in a variety of physiologic processes such as apoptosis, cell proliferation, cell differentiation, cell cycle and cell survival. These multifunctional nucleotides are also capable of preventing oxidative damages by modulating antioxidant defense systems in a variety of milieu, such as in diabetes. Although the exact molecular mechanisms by which miRs modulate the antioxidant defense elements are unclear, some evidence suggests that they may exert these effects via nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.

The molecular mechanisms by which vitamin D improve glucose homeostasis: A mechanistic review.

Diabetes mellitus (DM) is a complex metabolic disorder involving multiple deleterious molecular pathways and cellular defects leading to disturbance in the biologic milieu. It is currently a global health concern with growing incidence, especially among younger adults. There is an unmet need to find new therapeutic targets for the management of diabetes.

Newly diagnosed abnormal glucose tolerance determines post-MI prognosis in patients with hospital related hyperglycaemia but without known diabetes.

Aims: Investigate if abnormal glucose tolerance (AGT) affects post-myocardial infarction (MI) prognosis in patients with hospital-related hyperglycaemia (HRH) but without known diabetes mellitus (KDM).

Methods: Post-MI survivors without KDM underwent pre-discharge oral glucose tolerance test. Cardiovascular death and non-fatal re-infarction (MACE) were recorded.

Neuromodulatory effects of anti-diabetes medications: A mechanistic review.

Diabetes mellitus is a potent upstream event in the molecular pathophysiology which gives rise to various diabetes-related complications. There are several classes of anti-diabetic medications that have been developed to normalize blood glucose concentrations through a variety of molecular mechanisms. Beyond glucose-lowering effects, these agents may also provide further therapeutic potential.

The effects of statins on microglial cells to protect against neurodegenerative disorders: A mechanistic review.

Microglia are the primary innate immune system cells in the central nervous system (CNS). They are crucial for the immunity, neurogenesis, synaptogenesis, neurotrophic support, phagocytosis of cellular debris, and maintaining the CNS integrity and homeostasis. Invasion by pathogens as well as in CNS injuries and damages results in activation of microglia known as microgliosis.

Anti-inflammatory potentials of incretin-based therapies used in the management of diabetes.

GLP-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase 4 inhibitors (DPP-4i) are two classes of antidiabetic agents used in the management of diabetes based on incretin hormones. There is emerging evidence that they have anti-inflammatory effects. Since most long-term complications of diabetes have a background of chronic inflammation, these agents may be beneficial against diabetic complications not only due to their hypoglycemic potential but also via their anti-inflammatory effects.

Physiologically relevant screening of polyphenol-rich commercial preparations for bioactivity in vascular endothelial cells and application to healthy volunteers: A viable workflow and a cautionary tale.

This study describes the screening of 13 commercially-available plant extracts for pharmacological activity modulating vascular function using an endothelial cell model. A French maritime pine bark extract (FMPBE) was found to have the greatest effect upon nitric oxide availability in control (181% ± 36% of untreated cells) and dysfunctional cells (132% ± 8% of untreated control cells). In healthy volunteers, the FMPBE increased plasma nitrite concentrations 8 h post-consumption compared to baseline (baseline corrected median 1.

Comparative Evaluation of Biomarkers of Inflammation Among Indian Women With Polycystic Ovary Syndrome (PCOS) Consuming Vegetarian vs. Non-vegetarian Diet.

Sub-inflammation and insulin resistance characterize women with PCOS. Data on dietary modulation of inflammation among PCOS women is scant, particularly from Indian subcontinent. The present study aimed to assess the effect of plant based vs.

Going to extremes: the Goldilocks/Lagom principle and data distribution.

Numerical data in biology and medicine are commonly presented as mean or median with error or confidence limits, to the exclusion of individual values. Analysis of our own and others' data indicates that this practice risks excluding 'Goldilocks' effects in which a biological variable falls within a range between 'too much' and 'too little' with a region between where its function is 'just right'; a concept captured by the Swedish term 'Lagom'. This was confirmed by a narrative search of the literature using the PubMed database, which revealed numerous relationships of biological and clinical phenomena of the Goldilocks/Lagom form including quantitative and qualitative examples from the health and social sciences.

Molecular mechanisms by which SGLT2 inhibitors can induce insulin sensitivity in diabetic milieu: A mechanistic review.

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are a relatively newer class of anti-hyperglycemic medications that reduce blood glucose by inhibition of renal glucose re-uptake, thereby increasing urinary glucose excretion. Although glycosuria is the primary mechanism of action of these agents, there is some evidence suggesting they can reduce insulin resistance and induce peripheral insulin sensitivity. Identifying the molecular mechanisms by which these medications improve glucose homeostasis can help us to develop newer forms of SGLT2i with lesser side effects.

Expression of microRNA in follicular fluid in women with and without PCOS.

Several studies have shown the expression of small non-coding microRNA (miRNA) changes in PCOS and their expression in follicular fluid has been described, though the number of studies remains small. In this prospective cohort study, miRNA were measured using quantitative polymerase chain reaction (qPCR) in 29 weight and aged matched anovulatory women with PCOS and 30 women without from follicular fluid taken at the time of oocyte retrieval who were undergoing in vitro fertilization (IVF); miRNA levels were determined from a miRNA data set. 176 miRNA were detected, of which 29 differed significantly between normal women and PCOS women.

Cell transfer-based immunotherapies in cancer: A review.

In cell transfer therapy (CTT), immune cells such as innate immune-derived natural killer cells and dendritic cells as well as acquired immune-related T lymphocytes such as tumor-infiltrating lymphocytes and cytokine-activated or genetically modified peripheral blood T cells are used in the management of cancer. These therapies are increasingly becoming the most used treatment modality in cancer after tumor resection, chemotherapy, and radiotherapy. In adoptive cell transfer, the lymphocytes isolated from either a donor or the patient are modified ex vivo and reinfused to target malignant cells.

The effect of C-peptide on diabetic nephropathy: A review of molecular mechanisms.

C-peptide is a small peptide connecting two chains of proinsulin molecule and is dissociated before the release of insulin. It is secreted in an equimolar amount to insulin from the pancreatic beta-cells into the circulation. Recent evidence demonstrates that it has other physiologic activities beyond its structural function.

Effects of curcumin on mitochondria in neurodegenerative diseases.

Neurodegenerative diseases (NDs) result from progressive deterioration of selectively susceptible neuron populations in different central nervous system (CNS) regions. NDs are classified in accordance with the primary clinical manifestations (e.g.

Anti-fibrotic effects of curcumin and some of its analogues in the heart.

Cardiac fibrosis stems from the changes in the expression of fibrotic genes in cardiac fibroblasts (CFs) in response to the tissue damage induced by various cardiovascular diseases (CVDs) leading to their transformation into active myofibroblasts, which produce high amounts of extracellular matrix (ECM) proteins leading, in turn, to excessive deposition of ECM in cardiac tissue. The excessive accumulation of ECM elements causes heart stiffness, tissue scarring, electrical conduction disruption and finally cardiac dysfunction and heart failure. Curcumin (Cur; also known as diferuloylmethane) is a polyphenol compound extracted from rhizomes of Curcuma longa with an influence on an extensive spectrum of biological phenomena including cell proliferation, differentiation, inflammation, pathogenesis, chemoprevention, apoptosis, angiogenesis and cardiac pathological changes.

Treatment of genitourinary syndrome of menopause: the potential effects of intravaginal ultralow-concentration oestriol and intravaginal dehydroepiandrosterone on quality of life and sexual function.

The climacteric is considered a natural phase in a woman's aging process and is defined as the period starting from the decline in ovarian activity until after the end of ovarian function. Genitourinary syndrome of menopause (GSM) is commonly observed in menopausal women and is characterised by a collection of symptoms resulting from changes to the internal and external genitalia as well as the lower urinary tract. Several studies have demonstrated the close association between sexual dysfunction and symptoms related to GSM.

Alterations in long noncoding RNAs in women with and without polycystic ovarian syndrome.

Unlabelled: Long noncoding RNAs (lncRNAs) are RNA transcripts over 200 nucleotides long that are not translated into protein; however, there is increasing evidence of their regulatory functions. To date, there are few studies measuring lncRNA in control women or women with polycystic ovary syndrome (PCOS).

Objective: To determine lncRNA differences between PCOS and control women.

The CD105:CD106 microparticle ratio is CD106 dominant in polycystic ovary syndrome compared to type 2 diabetes and healthy subjects.

Background: A retrospective analysis was carried out from patients and controls during the past 5 years from a series of studies investigating endothelial microparticles (MP).

Methods: In total, 319 samples from 207 individuals were included in this analysis, from patients with type 2 diabetes (T2D, n = 105), women with polycystic ovary syndrome (PCOS, n = 145) and healthy volunteers (n = 69). All data were generated via the same flow cytometry protocol with the same antibody clones.

Therapeutic effects of Crocin in autoimmune diseases: A review.

The immune system when acts against selfmolecules results in an imbalance in immunologic tolerance leading to the development of several autoimmune diseases (ADs) such as rheumatoid arthritis, asthma, ulcerative colitis, type 1 diabetes, and multiple sclerosis. Improved recognition of the mechanisms of ADs has led to the advancement of the management of these diseases. The principal mediators of ADs are inflammatory molecules.