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Topic Review
Sodium-Glucose Co-Transporter-2 Inhibitors on Diuretic Resistance in HF
Heart failure (HF) is a chronic disorder of the cardiovascular (CV) system and remains a major cause of morbidity and mortality worldwide. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are beneficial for patients suffering from type 2 diabetes mellitus (T2DM) or established cardiovascular disease (CVD), mainly HF, by reducing CVD-related morbidity and mortality.
  • 44
  • 26 Mar 2024
Topic Review
IGF-II–Insulin Receptor Isoform-A Autocrine Signal in Cancer
Insulin receptor overexpression is a common event in human cancer. Its overexpression is associated with a relative increase in the expression of its isoform A (IRA), a shorter variant lacking 11 aa in the extracellular domain, conferring high affinity for the binding of IGF-II along with added intracellular signaling specificity for this ligand. Since IGF-II is secreted by the vast majority of malignant solid cancers, where it establishes autocrine stimuli, the co-expression of IGF-II and IRA in cancer provides specific advantages such as apoptosis escape, growth, and proliferation to those cancers bearing such a co-expression pattern.
  • 49
  • 13 Mar 2024
Topic Review
Autocrine IGF-II-Associated Cancers
The paraneoplastic syndrome referred in the literature as non-islet-cell tumor hypoglycemia (NICTH) and extra-pancreatic tumor hypoglycemia (EPTH) was first reported almost a century ago, and the role of cancer-secreted IGF-II in causing this blood glucose-lowering condition has been widely established. The landscape emerging, based on molecular and cellular findings, supports a broader role for IGF-II in cancer biology beyond its involvement in the paraneoplastic syndrome. In particular, a few key findings are constantly observed during tumorigenesis, (a) a relative and absolute increase in fetal insulin receptor isoform (IRA) content, with (b) an increase in IGF-II high-molecular weight cancer-variants (big-IGF-II), and (c) a stage-progressive increase in the IGF-II autocrine signal in the cancer cell, mostly during the transition from benign to malignant growth. An increasing and still under-exploited combinatorial pattern of the IGF-II signal in cancer is shaping up in the literature with respect to its transducing receptorial system and effector intracellular network. Interestingly, while surgical and clinical reports have traditionally restricted IGF-II secretion to a small number of solid malignancies displaying paraneoplastic hypoglycemia, a retrospective literature analysis, along with publicly available expression data from patient-derived cancer cell lines conveyed in the present perspective, clearly suggests that IGF-II expression in cancer is a much more common event, especially in overt malignancy.
  • 66
  • 08 Mar 2024
Topic Review
Gut Microbiota, Inflammation, and Obesity
The increased prevalence of obesity and several other metabolic disorders, including diabetes and non-alcoholic fatty liver disease, has reached global pandemic proportions. Lifestyle changes may result in a persistent positive energy balance, hastening the onset of these age-related disorders and consequently leading to a diminished lifespan. Although suggestions have been raised on the possible link between obesity and the gut microbiota, progress has been hampered due to the extensive diversity and complexities of the gut microbiota. Being recognized as a potential biomarker owing to its pivotal role in metabolic activities, the dysregulation of the gut microbiota can give rise to a persistent low-grade inflammatory state associated with chronic diseases during aging.
  • 60
  • 06 Mar 2024
Topic Review
Etiopathogenic Factors for Obesity
Obesity is an abnormal or excessive accumulation of fat that represents a health risk, and it is characterized by reaching a body mass index (BMI) equal to or greater than 30 kg/m2. Obesity is a chronic disease of multifactorial etiology that involves an energy imbalance, genetic and epigenetic factors, alterations in glucose and lipid metabolism, disorders of adipose tissue functioning, neuroendocrine dysregulation, and alterations in the intestinal microbiota, among others.
  • 143
  • 05 Mar 2024
Topic Review
Type 2 Diabetes: Beta Cell Compensation and Death
Type 2 diabetes (T2D) has become a worldwide epidemic, primarily driven by obesity from overnutrition and sedentariness. Physiologically, T2D manifests as an inability of the pancreatic beta cells to produce and secrete a sufficient bolus of insulin to elicit a response in target cells to transport glucose from the blood and properly regulate glucose levels. Insulin is synthesized in the endoplasmic reticulum (ER) of pancreatic beta cells where it undergoes a series of post-translational modifications to form mature insulin. Insulin resistance requires more insulin to be produced by beta cells to compensate for these desensitized cells. Consequently, this compensation causes additional strain on beta cells. This stress primarily originates from the ER and can also trigger oxidative stress. These cellular stresses can lead to beta cell decompensation, manifested by dysfunction and eventually a loss of beta cell mass.
  • 98
  • 04 Mar 2024
Topic Review
Complications of Obesity in Children
The increasing incidence of obesity in the pediatric population requires attention to its serious complications. It turns out that in addition to typical, well-known metabolic complications, obesity as a systemic disease carries the risk of equally serious, although less obvious, non-metabolic complications, such as cardiovascular diseases, polycystic ovary syndrome, chronic kidney disease, asthma, thyroid dysfunction, immunologic and dermatologic conditions, and mental health problems. They can affect almost all systems of the young body and also leave their mark in adulthood. In addition, obesity also contributes to the exacerbation of existing childhood diseases. 
  • 60
  • 28 Feb 2024
Topic Review
Preclinical and Clinical Endeavors Targeting Mitochondria
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons, for which current treatment options are limited. Recent studies have shed light on the role of mitochondria in ALS pathogenesis, making them an attractive therapeutic intervention target.
  • 158
  • 26 Feb 2024
Topic Review
Thyroid Hormone Activity in the Brain
Thyroid hormones (THs) are essential in normal brain development, and cognitive and emotional functions. THs act through a cascade of events including uptake by the target cells by specific cell membrane transporters, activation or inactivation by deiodinase enzymes, and interaction with nuclear thyroid hormone receptors. Several thyroid responsive genes have been described in the developing and in the adult brain and many studies have demonstrated a systemic or local reduction in TH availability in neurologic disease and after brain injury.
  • 184
  • 22 Feb 2024
Topic Review
Irisin in Women’s Life Span
Since its discovery, irisin has attracted much attention for its potential involvement in metabolic and reproductive diseases. It appears to play an important role in different physiological and pathological conditions that can involve women throughout their entire lives. Irisin appears to be an important factor for the hypothalamic–pituitary–gonadal axis activation, and it seems to play a role in the timing of puberty onset. Additionally, serum irisin levels have been proposed as a biomarker for predicting the future development of gestational diabetes (GDM). Its role in polycystic ovary syndrome (PCOS) is still controversial, although an “irisin resistance” mechanism has been hypothesized. Beyond its influence on metabolism, irisin also appears to influence bone health. Irisin levels are inversely correlated with the prevalence of fractures in postmenopausal women. Similar mechanisms have also been postulated in young women with functional hypothalamic amenorrhea (FHA).
  • 58
  • 20 Feb 2024
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