Publications by authors named "Alexandra E Butler"

In the context of cell cycle inhibition, anti-proliferation, and the dysregulation observed in certain cancer pathologies, the protein p21 assumes a pivotal role. p21 links DNA damage responses to cellular processes such as apoptosis, senescence, and cell cycle arrest, primarily functioning as a regulator of the cell cycle. However, accumulating empirical evidence suggests that p21 is both directly and indirectly linked to a number of different metabolic processes.

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Article Synopsis
  • Microglial activation has been linked to neurodegenerative diseases like Alzheimer's and Parkinson's, but its role in metabolic disorders, particularly insulin resistance and type 2 diabetes, is gaining attention.
  • The text examines the biochemical pathways involved in this connection, including IKKβ/NF-κβ and IRS-1/PI3K/Akt, as well as the impact of non-coding RNAs on insulin resistance.
  • Finally, potential therapeutic strategies, both pharmaceutical and lifestyle-based, are discussed to reduce microglial activation and mitigate its effects on metabolism.
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Bilirubin (BR) is among the most potent endogenous antioxidants that originates from the heme catabolic pathway. Despite being considered as a dangerous and cytotoxic waste product at high concentrations, BR has potent antioxidant effects leading to the reduction of oxidative stress and inflammation, which play an important role in the development and progression of cancer. The purpose of this study is to introduce PEGylated BR nanoparticles (NPs), themselves or in combination with other anti-cancer agents.

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Background: Curcumin, a ubiquitous polyphenol in turmeric, possesses many anti-cancer and anti-inflammatory properties. These therapeutic effects are largely resultant of curcumin's ability to modulate global gene expression. Bioinformatics-based approaches for analyzing differential gene expression are effective tools in gaining a more profound understanding of the underlying mechanisms of action.

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Chronic pain remains a treatment challenge. Curcumin, a natural plant product found in the Curcuma genus, has been shown to possess anti-inflammatory, antioxidant, and neuroprotective properties. In this systematic review and meta-analysis, we aimed to evaluate the efficacy of curcumin and nano-curcumin for treating chronic pain in clinical and preclinical studies.

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Lipotoxicity is defined as a prolonged metabolic imbalance of lipids that results in ectopic fat distribution in peripheral organs such as the liver, heart, and kidney. The harmful consequences of excessive lipid accumulation in cardiomyocytes cause cardiac lipotoxicity, which alters the structure and function of the heart. Obesity and diabetes are linked to lipotoxic cardiomyopathy.

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Sodium glucose cotransporter 2 inhibitors (SGLT2is) are a newly developed class of anti-diabetics which exert potent hypoglycemic effects in the diabetic milieu. However, the evidence suggests that they also have extra-glycemic effects. The renin-angiotensin-aldosterone system (RAAS) is a hormonal system widely distributed in the body that is important for water and electrolyte homeostasis as well as renal and cardiovascular function.

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Article Synopsis
  • Type 2 diabetes (T2D) happens when the body can't make enough insulin, and it leads to problems in special cells in the pancreas called β-cells.
  • A harmful version of a protein called islet amyloid polypeptide (IAPP) builds up inside these β-cells, making them dysfunctional and causing issues in diabetes.
  • In a study with mice that have T2D symptoms, scientists found that early changes in cholesterol and lipids in these cells might be one of the first steps to the problems caused by misfolded IAPP.
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Vitamin D is proposed to have a protective effect against cardiovascular disease, though the mechanism is unclear. Vitamin D deficiency is common in polycystic ovary syndrome (PCOS), where it is strongly related to obesity, insulin resistance (IR) and risk of cardiovascular disease. To determine if the inherent pathophysiology of PCOS or vitamin D levels are linked to dysregulation of cardiovascular risk proteins (CVRPs), a study in non-obese women with PCOS and without IR was undertaken.

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Background: Perfluorinated alkyl acids (PFAAs) are persistent organic pollutants affected by BMI and ethnicity, with contradictory reports of association with vitamin D deficiency.

Methods: Twenty-nine Caucasian women with non-obese polycystic ovary syndrome (PCOS) and age- and BMI-matched Caucasian control women ( = 30) were recruited. Paired serum samples were analyzed for PFAAs ( = 13) using high-performance liquid chromatography-tandem mass spectrometry.

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: Hypoglycemia has been associated with cardiovascular events, and glucose variability has been suggested to be associated with increased cardiovascular risk. Therefore, in this study, we examined the effect on proteomic cardiovascular risk protein markers of (i) mild iatrogenic hypoglycemia and (ii) severe iatrogenic hypoglycemia followed by rebound hyperglycemia. : Two iatrogenic hypoglycemia studies were compared; firstly, mild hypoglycemia in 18 subjects (10 type 2 diabetes (T2D), 8 controls; blood glucose to 2.

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A variety of mechanisms and drugs have been shown to attenuate cardiovascular disease (CVD) onset and/or progression. Recent researchers have identified a potential role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in modulating lipid metabolism and reducing plasma low density lipoprotein (LDL) levels. PCSK9 is the central protein in the metabolism of LDL cholesterol (LDL-C) owing to its major function in LDL receptor (LDLR) degradation.

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Glomerular hyperfiltration (GH) has been reported to be higher in women with polycystic ovary syndrome (PCOS) and is an independent risk factor for renal function deterioration, metabolic, and cardiovascular disease. The aim of this study was to determine GH in type A PCOS subjects and to identify whether inflammatory markers, markers of CKD, renal tubule injury markers, and complement system proteins were associated. In addition, a secondary cohort study was performed to determine if the eGFR had altered over time.

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Diabetes mellitus (DM) is comprised of two predominant subtypes: type 1 diabetes mellitus (T1DM), accounting for approximately 5 % of cases worldwide and resulting from autoimmune destruction of insulin-producing β-cells, and type 2 (T2DM), accounting for approximately 95 % of cases globally and characterized by the inability of pancreatic β-cells to meet the demand for insulin due to a relative β-cell deficit in the setting of peripheral insulin resistance. Both types of DM involve derangement of glucose metabolism and are metabolic diseases generally considered to be initiated by a combination of genetic and environmental factors. Viruses have been reported to play a role as infectious etiological factors in the initiation of both types of DM in predisposed individuals.

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Objective: The hemoglobin A1c (HbA1c) diagnostic threshold for type 2 diabetes (T2D) of 6.5 % (48 mmol/mol) was based on the prevalence of retinopathy found in populations not known to have T2D. It is unclear if nephropathy has a similar HbA1c threshold, partly because it is a rarer complication of early diabetes.

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Exosomes are extracellular vesicles of endosomal origin, ranging from 30 to 150 nm in diameter, that mediate intercellular transfer of various biomolecules, such as proteins, lipids, nucleic acids, and metabolites. They modulate the functions of recipient cells and participate in diverse physiological and pathological processes, such as immune responses, cell-cell communication, carcinogenesis, and viral infection. Stem cells (SCs) are pluripotent or multipotent cells that can differentiate into various cell types.

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Backgrounds: Non-alcoholic fatty liver disease (NAFLD) is a common condition affecting >25 % of the population worldwide. This disorder ranges in severity from simple steatosis (fat accumulation) to severe steatohepatitis (inflammation), fibrosis and, at its end-stage, liver cancer. A number of studies have identified overexpression of several key genes that are critical in the initiation and progression of NAFLD.

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Article Synopsis
  • * RNA-based therapies, especially using microRNAs and small interfering RNAs (siRNAs), have shown potential for treating various diseases, including cardiovascular disease (CVD).
  • * Despite their promise, RNA therapies face challenges like poor binding, instability, delivery issues, immune responses, and unintended effects, which need to be addressed for effective medication development.
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Background: MicroRNAs (miRNAs) are promising therapeutic agents for non-alcoholic fatty liver disease (NAFLD). This study aimed to identify key genes/proteins involved in NAFLD pathogenesis and progression and to evaluate miRNAs influencing their expression.

Methods: Gene expression profiles from datasets GSE151158, GSE163211, GSE135251, GSE167523, GSE46300, and online databases were analyzed to identify significant NAFLD-related genes.

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Dysregulated Alzheimer's disease (AD)-associated protein expression is reported in polycystic ovary syndrome (PCOS), paralleling the expression reported in type 2 diabetes (T2D). We hypothesized, however, that these proteins would not differ between women with non-obese and non-insulin resistant PCOS compared to matched control subjects. We measured plasma amyloid-related proteins levels (Amyloid-precursor protein (APP), alpha-synuclein (SNCA), amyloid P-component (APCS), Pappalysin (PAPPA), Microtubule-associated protein tau (MAPT), apolipoprotein E (apoE), apoE2, apoE3, apoE4, Serum amyloid A (SAA), Noggin (NOG) and apoA1) in weight and aged-matched non-obese PCOS ( = 24) and control ( = 24) women.

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Aims: In this narrative review, we have analyzed and synthesized current studies relating to the effects of anti-diabetic drugs on traumatic brain injury (TBI) complications.

Methods: Eligible studies were collected from Scopus, Google Scholar, PubMed, and Cochrane Library for clinical, in-vivo, and in-vitro studies published on the impact of anti-diabetic drugs on TBI.

Results: Traumatic brain injury (TBI) is a serious brain disease that is caused by any type of trauma.

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Polycystic ovary syndrome (PCOS) is the most common endocrine condition in women of reproductive age, and several risk factors found in PCOS are associated with an increased risk of Alzheimer's disease (AD). Proteins increased in AD have been reported to include fibronectin (FN) fragments 3 and 4 (FN1.3 and FN1.

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Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disease in females of reproductive age, affecting 4-20% of pre-menopausal women worldwide. MicroRNAs (miRNAs) are endogenous, single-stranded, non-coding, regulatory ribonucleic acid molecules found in eukaryotic cells. Abnormal miRNA expression has been associated with several diseases and could possibly explain their underlying pathophysiology.

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Ferroptosis is a recently identified form of cell death characterized by iron accumulation and lipid peroxidation. Unlike apoptosis, necrosis, and autophagy, ferroptosis operates through a distinct molecular pathway. Curcumin, derived from turmeric rhizomes, is a natural compound with diverse therapeutic benefits, including neuroprotective, anti-metabolic syndrome, anti-inflammatory, and anti-cancer properties.

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