Alexandra E. Butler

Increased Chromogranin A-Positive Hormone-Negative Cells in Chronic Pancreatitis

ContextnChronic pancreatitis (CP) is characterized by inflammation, fibrosis, and a loss of pancreatic acinar cells, which can result in exocrine and eventually endocrine deficiency. Pancreatitis has been reported to induce formation of new endocrine cells (neogenesis) in mice. Our recent data have implicated chromogranin A-positive hormone-negative (CPHN) cells as potential evidence of neogenesis in humans.nnnObjectivenWe sought to establish if CPHN cells were more abundant in CP in humans.nnnDesign, Setting, and ParticipantsnWe investigated the frequency and distribution of CPHN cells and the expression of the chemokine C-X-C motif ligand 10 (CXCL10) and its receptor chemokine C-X-C motif receptor 3 in pancreas of nondiabetic subjects with CP.nnnResultsnCPHN cell frequency in islets was increased sevenfold in CP [2.1% ± 0.67% vs 0.35% ± 0.09% CPHN cells in islets, CP vs nonpancreatitis (NP), P < 0.01], as were the CPHN cells found as scattered cells in the exocrine areas (17.4 ± 2.9 vs 4.2 ± 0.6, CP vs NP, P < 0.001). Polyhormonal endocrine cells were also increased in CP (2.7 ± 1.2 vs 0.1 ± 0.04, CP vs NP, % of polyhormonal cells of total endocrine cells, P < 0.01), as was expression of CXCL10 in α and β cells.nnnConclusionnThere is increased islet endogenous expression of the inflammation marker CXCL10 in islets in the setting of nondiabetic CP and an increase in polyhormonal (insulin-glucagon expressing) cells. The increase in CPHN cells in CP, often in a lobular distribution, may indicate foci of attempted endocrine cell regeneration.

Curcumin in heart failure: A choice for complementary therapy?

Graphical abstract Figure. No caption available. ABSTRACT Heart failure is a major public health concern and one of the most common reasons for a cardiac hospital admission. Heart failure may be classified as having a reduced or preserved ejection fraction and its severity is based on the symptom score. Given the aging population, it is predicted that admissions with heart failure will increase. Whilst pharmacological therapy has improved the associated morbidity and mortality, there is a need for additional therapies to improve the clinical outcome as the death rate remains high. Curcumin is a natural product derived from turmeric that appears to have cardiovascular benefit through a number of mechanisms. In this review, we have assessed the mechanisms by which curcumin may exert its effects in different models of heart failure and show that it has promise as a complementary treatment in heart failure.

The versatile role of curcumin in cancer prevention and treatment: A focus on PI3K/AKT pathway.

Despite significant advances in treatment modalities, millions of cancer‐related deaths continue to occur annually, often as a consequence of developing resistance against the range of available chemotherapeutic drugs. Furthermore, available anti‐cancer chemotherapeutic agents show limited efficacy, often have severe side effects, and are expensive. Thus, the discovery of pharmacological agents that do not have these disadvantages is necessary. Curcumin, a polyphenolic compound derived from turmeric (Curcumin longa L.), is one such agent that has been widely studied for its anti‐inflammatory and/or anti‐cancer effects. Curcumin exerts its anti‐cancer effect by suppressing the initiation, progression, and metastasis of a variety of cancers and appears to inhibit carcinogenesis by affecting two main processes: angiogenesis and tumor growth. These anti‐cancer effects are largely mediated via negative regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other oncogenic molecules. The PI3K/AKT pathway is commonly activated in cancer initiation and progression. Considered to be the key signaling pathway, the phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (AKT) pathway therefore represents a key target for cancer therapeutics. In the current review, we focus upon curcumins targeting of PI3K/AKT in different malignancies to effect inhibition of cancer development and progression.

Sodium-glucose cotransporter 2 inhibitors and inflammation in chronic kidney disease: Possible molecular pathways: YARIBEYGI et al.

Clinical trials with sodium–glucose cotransporter 2 (SGLT2) inhibitors (empagliflozin, dapagliflozin, and canagliflozin) have shown a decrease in the progression of chronic kidney disease (CKD). SGLT2 inhibitors represent a new category of oral antidiabetic agents that can also reduce systolic and diastolic blood pressure, as well as serum uric acid, and improve the glomerular filtration rate. Apart from affecting renal hemodynamics and glycotoxicity, evidence suggests that SGLT2 inhibitors may be renoprotective due to their effects on inflammation in renal tissues. Inflammatory responses play a prominent role in the pathophysiology of CKD as several structural and functional disorders of renal failure are strongly related to the overproduction of proinflammatory mediators. The present review discusses the anti‐inflammatory properties of SGLT2 inhibitors. The different molecular pathways through which SGLT2 inhibitors may affect inflammation in the kidneys are also commented upon.

Effects of antidiabetic drugs on NLRP3 inflammasome activity, with a focus on diabetic kidneys

Inflammatory responses have a pivotal role in the development of diabetic nephropathy (DN). The nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is a newly recognized and potent inflammatory mediator that induces inflammatory responses in several disorders, including DN. The suppression of procytokine release and inflammatory response is integral to the prevention of complications arising from the inflammatory process. In this review, we discuss the role of the NLRP3 inflammasome in the pathogenesis of DN, focusing on its effects on interleukin (IL)-1β and IL-18. Furthermore, we review the potential anti-inflammatory effects of antidiabetic drugs used in routine clinical practice, such as insulin, biguanides, Sodium-glucose co-transporter-2 (SGLT2) inhibitors, sulfonylureas, thiazolidinediones, and dipeptidyl peptidase-4 (DPP-4) inhibitors. In addition, we discuss whether these drugs can also modulate NLRP3 inflammasome activity in renal tissues.

MicroRNAs: Novel Molecular Targets and Response Modulators of Statin Therapy

Cardiovascular disease (CVD) is a major cause of death globally. Addressing cardiovascular risk factors, particularly dyslipidemia, represents the most robust clinical strategy towards reducing the CVD burden. Statins inhibit 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and represent the main therapeutic approach for lowering cholesterol and reducing plaque formation/rupture. The protective effects of statins extend beyond lowering cholesterol. MicroRNAs (miRNAs or miRs), small noncoding regulatory RNAs, likely mediate the positive pleiotropic effects of statins via modulation of lipid metabolism, enhancement of endothelial function, inhibition of inflammation, improvement of plaque stability, and immune regulation. miRNAs are implicated in statin-related interindividual variations in therapeutic response, directly via HMG-CoA reductase, or indirectly through targeting cytochrome P450 3A (CYP3A) functionality and proprotein convertase subtilisin/kexin type9 (PCSK9) biology.

The therapeutic and diagnostic role of exosomes in cardiovascular diseases

Exosomes are nano-sized membranous vesicles that are secreted by cells. They have an important role in transferring proteins, mRNA, miRNA and other bioactive molecules between cells and regulate gene expression in recipient cells. Therefore, exosomes are a mechanism by which communication between cells is achieved and they are involved in a wide range of physiological processes, especially those requiring cell-cell communication. In the cardiovascular system, exosomes are associated with endothelial cells, cardiac myocytes, vascular cells, stem and progenitor cells, and play an essential role in development, injury and disease of the cardiovascular system. In recent years, accumulating evidence implicates exosomes in the development and progression of cardiovascular disease. Additionally, exosomal microRNAs are considered to be key players in cardiac regeneration and confer cardioprotective and regenerative properties on both cardiac and non-cardiac cells and, additionally, stem and progenitor cells. Notably, miRNAs may be isolated from blood and offer a potential source of novel diagnostic and prognostic biomarkers for cardiovascular disease. In this review, we summarize and assess the functional roles of exosomes in cardiovascular physiology, cell-to-cell communication and cardio-protective effects in cardiovascular disease.

Efficacy of artichoke leaf extract in non‐alcoholic fatty liver disease: A pilot double‐blind randomized controlled trial

Non‐alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and is potentially treatable, though there are few therapeutic agents available. Artichoke leaf extract (ALE) has shown potential as a hepatoprotective agent. This study sought to determine if ALE had therapeutic utility in patients with established NAFLD. In this randomized double‐blind placebo‐controlled parallel‐group trial, 100 subjects with ultrasound‐diagnosed NAFLD were randomized to either ALE 600 mg daily or placebo for a 2‐month period. NAFLD response was assessed by liver ultrasound and serological markers including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and AST to platelet ratio index (APRI) score. Ninety patients completed the study (49 ALE and 41 placebo) with no side effects reported. ALE treatment compared with placebo: Doppler sonography showed increased hepatic vein flow (p < .001), reduced portal vein diameter (p < .001) and liver size (p < .001), reduction in serum ALT (p < .001) and AST (p < .001) levels, improvement in AST/ALT ratio and APRI scores (p < .01), and reduction in total bilirubin. ALE supplementation reduced total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, non‐high‐density lipoprotein cholesterol, and triglyceride concentrations (p = .01). This study has shown beneficial effects of ALE supplementation on both ultrasound liver parameters and liver serum parameters (ALT, AST, APRI ratio, and total bilirubin) in patients with NAFLD.

Modulation of heat shock proteins by statins

Graphical abstract Figure. No caption available. &NA; Heat shock proteins (HSP or stress proteins) are intracellular molecules that participate in physiological cell metabolism and growth, although they are known to be involved in many stress conditions. Statins inhibit the action of the enzyme 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMG‐CoA), which is important in the synthesis of cholesterol and essential isoprenoid intermediates, thereby lowering circulating low‐density lipoprotein cholesterol (LDL), a major risk factor for cardiovascular disease (CVD). This review provides new insights into the mechanisms of action of statins in the regulation of HSPs. A better understanding of this involvement can help in development of new and more effective treatment strategies for CVD.

Therapeutic potential of curcumin in diabetic complications

ABSTRACT Diabetes mellitus is an extremely prevalent endocrine disease and a major global public health concern. Diabetic complications, such as retinopathy, nephropathy, neuropathy and cardiovascular disease, are common and majorly impact a patient’s quality of life. Curcumin, the major active component of turmeric, possesses extensive known pharmacological properties, including anti‐inflammatory, antioxidant, and antitumor effects. Increasing evidence suggests that curcumin may offer protection against diabetic complications. The current review focuses on the possible molecular targets and pathways involved in diabetic complications and, in particular, the multi‐target approach of curcumin in attenuating diabetic nephropathy, retinopathy, and neuropathy.