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Topic Review
Circadian Rhythms
Infertility represents a growing health problem in industrialized countries. Thus, a greater understanding of the molecular networks involved in this disease could be critical for the development of new therapies. A recent finding revealed that circadian rhythmicity disruption is one of the main causes of poor reproductive outcome. The circadian clock system beats circadian rhythms and modulates several physiological functions such as the sleep-wake cycle, body temperature, heart rate, and hormones secretion, all of which enable the body to function in response to a 24 h cycle. This intricated machinery is driven by specific genes, called “clock genes” that fine-tune body homeostasis. Stress of modern lifestyle can determine changes in hormone secretion, favoring the onset of infertility-related conditions that might reflect disfunctions within the hypothalamic–pituitary–gonadal axis. Consequently, the loss of rhythmicity in the suprachiasmatic nuclei might affect pulsatile sexual hormones release. Herein, we provide an overview of the recent findings, in both animal models and humans, about how fertility is influenced by circadian rhythm. In addition, we explore the complex interaction among hormones, fertility and the circadian clock. A deeper analysis of these interactions might lead to novel insights that could ameliorate the therapeutic management of infertility and related disorders.
  • 2.0K
  • 02 Feb 2021
Topic Review
Germ Cell Development
Mechanistic understanding of germ cell formation at a genome-scale level can aid in developing novel therapeutic strategies for infertility. Germ cell formation is a complex process that is regulated by various mechanisms, including epigenetic regulation, germ cell-specific gene transcription, and meiosis.
  • 1.9K
  • 11 Mar 2021
Topic Review
Liver Metastatic Breast Cancer
The median overall survival of patients with metastatic breast cancer is only 2–3 years, and for patients with untreated liver metastasis, it is as short as 4–8 months. Improving the survival of women with breast cancer requires more effective anti-cancer strategies, especially for metastatic disease. Nutrients can influence tumor microenvironments, and cancer metabolism can be manipulated via dietary modification to enhance anti-cancer strategies. Yet, there are no standard evidence-based recommendations for diet therapies before or during cancer treatment, and few studies provide definitive data that certain diets can mediate tumor progression or therapeutic effectiveness in human cancer. This review focuses on metastatic breast cancer, in particular liver metastatic forms, and recent studies on the impact of diets on disease progression and treatment.
  • 1.9K
  • 22 Jul 2022
Topic Review
Obesity
Obesity, a complex and multifactorial disease associated with excessive adiposity or body fat, currently affects over a third of the world’s population. Obesity is closely related to a significant increase in the morbidity risk of chronic diseases, such as disability, depression, type 2 diabetes, hypertension, cardiovascular diseases, cancers, and mortality, thus representing a serious public health problem. According to the World Health Organization (WHO), the body mass index (BMI) is used as a tool to assess overweight or obesity; a BMI ≥ 40 kg/m2 is characteristic of severe obesity. Rare genetic obesity disorders are characterized by mutations of genes strongly involved in the central or peripheral regulation of energy balance. These mutations are effective in causing the early onset of severe obesity and insatiable hunger (hyperphagia), suggesting that the genetic component can contribute to 40–70% of obesity.”
  • 1.9K
  • 13 Jan 2022
Topic Review
T2DM and the Gut Microbiota
Type 2 Diabetes Mellitus (T2DM) affects over 9% of the United States population alone, constitutes a cause for ensuing cardiovascular disease, and is typically closely linked to obesity status. While obesity has long been perceived to stem from a sedentary lifestyle and high fat intake there is increasing evidence supporting the idea that this is a more complex issue than initially thought. The human gut microbiome has been a recent point of investigation due to the idea that it may be closely linked to T2DM. The aforementioned high fat diets can impact the gut microbiome in a significant way, altering the demography of the gut’s microflora, hence shifting the gut into a state of dysbiosis. Dysbiosis is a state that favors the initiation of a cascade inducing metabolic deregulation, increasing inflammation and insulin resistance systemically. Below the relationship of the microbiome to T2DM is briefly discussed.
  • 1.8K
  • 29 Oct 2020
Topic Review
Endocrine Disrupting Chemicals
Endocrine-disrupting chemicals (EDCs) are exogenous substances able to mimic or to interfere with the endocrine system, thus altering key biological processes such as organ development, reproduction, immunity, metabolism and behavior. High concentrations of EDCs are found in several everyday products including plastic bottles and food containers and they could be easily absorbed by dietary intake. In recent years, considerable interest has been raised regarding the biological effects of EDCs, particularly Bisphenol A (BPA) and phthalates, on human pregnancy and fetal development. Several evidence obtained on in vitro and animal models as well as by epidemiologic and population studies strongly indicated that endocrine disruptors could negatively impact fetal and placental health by interfering with the embryonic developing epigenome, thus establishing disease paths into adulthood. Moreover, EDCs could cause and/or contribute to the onset of severe gestational conditions as Preeclampsia (PE), Fetal Growth Restriction (FGR) and gestational diabetes in pregnancy, as well as obesity, diabetes and cardiovascular complications in reproductive age. Therefore, despite contrasting data being present in the literature, endocrine disruptors must be considered as a therapeutic target. Future actions aimed at reducing or eliminating EDC exposure during the perinatal period are mandatory to guarantee pregnancy success and preserve fetal and adult health.
  • 1.8K
  • 27 Oct 2020
Topic Review
AMP-activated Protein Kinase
We live and to do so we must breathe and eat, so are we a combination of what we eat and breathe? Here we will consider this question, and the role in this respect of the AMP-activated protein kinase (AMPK). Emerging evidence suggests that AMPK facilitates central and peripheral reflexes that coordinate breathing and oxygen supply, and contributes to central regulation of feeding and food choice. We propose, therefore, that oxygen supply to the body is aligned with not only the quantity we eat, but also nutrient-based diet selection, and that the cell-specific expression pattern of AMPK subunit isoforms is critical to appropriate system alignment in this respect. If this is the case, then aberrant cell-specific changes in the expression of AMPK subunit isoforms could give rise, in part, to known associations between a wide variety of conditions associated with metabolic disorder.
  • 1.8K
  • 10 May 2021
Topic Review
Genetics of Primary Aldosteronism
Primary aldosteronism (PA) is the most common form of secondary hypertension, with a prevalence of 5–10% among patients with hypertension. PA is mainly classified into two subtypes: aldosterone-producing adenoma (APA) and bilateral idiopathic hyperaldosteronism. Recent developments in genetic analysis have facilitated the discovery of mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, CACNA1H, CLCN2, and CTNNB1 in sporadic or familial forms of PA in the last decade. These findings have greatly advanced our understanding of the mechanism of excess aldosterone synthesis, particularly in APA. Most of the causative genes encode ion channels or pumps, and their mutations lead to depolarization of the cell membrane due to impairment of ion transport. Depolarization activates voltage-gated Ca2+ channels and intracellular calcium signaling and promotes the transcription of aldosterone synthase, resulting in overproduction of aldosterone. 
  • 1.7K
  • 07 May 2021
Topic Review
SIRT1-NF-κB Axis
Inflammation is an adaptive response triggered by harmful conditions or stimuli, such as an infection or tissue damage pursuing homeostasis reestablishment. Liver diseases cause approximately 2 million deaths per year worldwide and hepatic inflammation is a common factor to all of them, being the main driver of hepatic tissue damage and causing progression from NAFLD (non-alcoholic fatty liver disease) to NASH (non-alcoholic steatohepatitis), cirrhosis and, ultimately, HCC (hepatocellular carcinoma). The metabolic sensor SIRT1, a class III histone deacetylase with strong expression in metabolic tissues such as liver, and transcription factor NF-κB, a master regulator of inflammatory response, show an antagonistic relationship in controlling inflammation. For this reason, SIRT1 targeting is emerging as a potential strategy to improve different metabolic and/or inflammatory pathologies. In this review, we explore diverse upstream regulators and some natural/synthetic activators of SIRT1 as possible therapeutic treatment for liver diseases.
  • 1.7K
  • 27 Oct 2020
Topic Review
HDAC3 Complex and Nuclear Hormone Receptors
Histone deacetylase 3 is the core component of the nuclear receptor corepressor complex, and plays a central role in transcriptional repression mediated by nuclear hormone receptors. 
  • 1.7K
  • 08 Oct 2021
Topic Review
Vitamin D Deficiency
Vitamin D was found to counteract insulin resistance via  participation in the maintenance of normal resting reactive oxygen species level and regulation of Ca2+ level in many cell types. Both genomic and non-genomic action of vitamin D is directed to insulin signaling. Thereby, vitamin D  reduces the extent of pathologies associated with insulin resistance such as oxidative stress and inflammation. Therefore, the beneficial actions of vitamin D include an improvement of glucose and lipid metabolism in insulin-sensitive tissues, and in consequence the diminish of insulin resistance.
  • 1.7K
  • 30 Sep 2020
Topic Review
Metabolic Reprogramming in Cancer Cells
Cancer cells alter metabolic processes to sustain their characteristic uncontrolled growth and proliferation. Altered metabolic flux in cancer is controlled by tumor-host cell interactions, key oncogenes, tumor suppressors, and other regulatory molecules, including non-coding RNAs. Changes to metabolic pathways in cancer are dynamic, exhibit plasticity, and are often dependent on the type of tumor and the tumor microenvironment, leading in a shift of thought from the Warburg Effect and the “reverse Warburg Effect” to metabolic plasticity. 
  • 1.6K
  • 27 Jul 2021
Topic Review
Pancreatic β-Cell Dysfunction
Under healthy conditions, pancreatic β-cells produce and secrete the insulin hormone in response to blood glucose levels. Under diabetic conditions, however, β-cells are compelled to continuously secrete larger amounts of insulin to reduce blood glucose levels, and thereby, the β-cell function is debilitated in the long run.
  • 1.6K
  • 30 Dec 2020
Topic Review
Hypothalamic Regulation of Corticotropin-Releasing Factor under Stress
Stress response is considered the physiological and behavioral response to internal or external stimulus. Corticotropin-releasing factor (CRF) in the hypothalamus plays a central role in regulating the stress response. CRF stimulates adrenocorticotropic hormone (ACTH) release from the anterior pituitary. ACTH stimulates glucocorticoid secretion from the adrenal glands. Glucocorticoids are essential for stress coping, stress resilience, and homeostasis.
  • 1.5K
  • 27 Nov 2021
Topic Review
Regulation of Mitochondrial Ca2+
Mitochondria, as the main site of cellular energy metabolism and the generation of oxygen free radicals, are the key switch for mitochondria-mediated endogenous apoptosis. Ca2+ is not only an important messenger for cell proliferation, but it is also an indispensable signal for cell death. Ca2+ participates in and plays a crucial role in the energy metabolism, physiology, and pathology of mitochondria. Mitochondria control the uptake and release of Ca2+ through channels/transporters, such as the mitochondrial calcium uniporter (MCU), and influence the concentration of Ca2+ in both mitochondria and cytoplasm, thereby regulating cellular Ca2+ homeostasis. Mitochondrial Ca2+ transport-related processes are involved in important biological processes of tumor cells including proliferation, metabolism, and apoptosis.
  • 1.5K
  • 30 Jun 2022
Topic Review
Sphingolipids and DNA Damage Response
Sphingolipids are essential structural components of biological membranes that mediate a wide array of physiological functions such as inflammation, cell proliferation, survival, senescence, and death. An emerging body of evidence suggests that bioactive sphingolipids modulate the DNA damage response (DDR) induced by genotoxic stress and therein determine cell fate.
  • 1.5K
  • 16 Jul 2020
Topic Review
Iron Deficiency in Celiac Disease
Iron deficiency anemia (IDA) is the most recognized type of anemia in patients with celiac disease (CD) and may be present in over half of patients at the time of diagnosis. Folate and vitamin B12 malabsorption, nutritional deficiencies, inflammation, blood loss, development of refractory CD, and concomitant Heliobacter pylori infection are other causes of anemia in such patients. The decision to replenish iron stores and the route of administration (oral or intravenous) are controversial due, in part, to questions surrounding the optimal formulation and route of administration.
  • 1.5K
  • 09 Oct 2021
Topic Review
Thyroid Hormone Signaling
Thyroid hormones (TH) perform a plethora of actions in numerous tissues and induce an overall increase in metabolism, with an augmentation in energy demand and oxygen expenditure. Oxidants are required for normal thyroid-cell proliferation, as well as for the synthesis of the main hormones secreted by the thyroid gland, triiodothyronine (T3) and thyroxine (T4). 
  • 1.5K
  • 16 Jun 2023
Topic Review
Nitric Oxide in Different Cancer Types
Nitric oxide (NO) is a short-lived, ubiquitous signaling molecule that affects numerous critical functions in the body. There are markedly conflicting findings in the literature regarding the bimodal effects of NO in carcinogenesis and tumor progression, which has important consequences for treatment. 
  • 1.5K
  • 16 Jan 2023
Topic Review
Inappropriate Secretion of Thyroid-Stimulating Hormone
The term “inappropriate secretion of thyroid-stimulating hormone; IST” was proposed by Gershengorn and Weintraub in 1975. In a subsequent report, IST was described as a condition characterized by elevated serum levels of immunoreactive thyroid-stimulating hormone (TSH) in the presence of elevated free thyroid hormone concentrations. Similarly, the term "syndrome of IST (SITSH)" is widely used in Japan to refer to a closely related condition; however, unlike that for IST, an elevated serum free triiodothyronine concentration is not a requisite criterion for SITSH diagnosis. IST or SITSH is an important indicator of resistance to thyroid hormone β (RTHβ) caused by germline mutations in genes encoding thyroid hormone receptor β (TRβ) and TSH-secreting pituitary adenoma.
  • 1.5K
  • 12 Aug 2021
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