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Topic Review
STIM1 in Regulation of Cardiac Energy Substrate Preference
The heart requires a variety of energy substrates to maintain proper contractile function. Glucose and long-chain fatty acids (FA) are the major cardiac metabolic substrates under physiological conditions. Upon stress, a shift of cardiac substrate preference toward either glucose or FA is associated with cardiac diseases. For example, in pressure-overloaded hypertrophic hearts, there is a long-lasting substrate shift toward glucose, while in hearts with diabetic cardiomyopathy, the fuel is switched toward FA. Stromal interaction molecule 1 (STIM1), a well-established calcium (Ca2+) sensor of endoplasmic reticulum (ER) Ca2+ store, is increasingly recognized as a critical player in mediating both cardiac hypertrophy and diabetic cardiomyopathy. However, the cause–effect relationship between STIM1 and glucose/FA metabolism and the possible mechanisms by which STIM1 is involved in these cardiac metabolic diseases are poorly understood.
  • 931
  • 31 Aug 2023
Topic Review
Posttranslational Modifications in PD-L1 Turnover and Function
Programmed death-ligand 1 (PD-L1) is one of the most classic immune checkpoint molecules. Cancer cells express PD-L1 to inhibit the activity of effector T cells’ cytotoxicity through programmed death 1 (PD-1) engagement in exposure to inflammatory cytokines. PD-L1 expression levels on cancer cells might affect the clinical response to anti-PD-1/PD-L1 therapies. Hence, understanding molecular mechanisms for regulating PD-L1 expression is essential for improving the clinical response rate and efficacy of PD-1/PD-L1 blockade. Posttranslational modifications (PTMs), including phosphorylation, glycosylation, ubiquitination, and acetylation, regulate PD-L1 stability, cellular translocation, and interaction with its receptor. A coordinated positive and negative regulation via PTMs is required to ensure the balance and function of the PD-L1 protein. 
  • 930
  • 03 Dec 2021
Topic Review
Chronotherapy
Chronotherapy aims to understand the impact that biological rhythms have on the response to a therapy to optimize its action, maximize health benefits, and minimize possible adverse effects. Chronotherapy, or clinical chronopharmacology, study the impact that circadian rhythms have on the response to a drug to optimize its action, maximize health benefits and minimize possible adverse effects on the patient.
  • 930
  • 31 Oct 2022
Topic Review
Roles of Non-Coding RNA in Alzheimer’s Disease Pathophysiology
Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that is accompanied by deficits in memory and cognitive functions. The disease is pathologically characterised by the accumulation and aggregation of an extracellular peptide referred to as amyloid-β (Aβ) in the form of amyloid plaques and the intracellular aggregation of a hyperphosphorelated protein tau in the form of neurofibrillary tangles (NFTs) that cause neuroinflammation, synaptic dysfunction, and oxidative stress. The search for pathomechanisms leading to disease onset and progression has identified many key players that include genetic, epigenetic, behavioural, and environmental factors, which lend support to the fact that this is a multi-faceted disease where failure in various systems contributes to disease onset and progression. Although the vast majority of individuals present with the sporadic (non-genetic) form of the disease, dysfunctions in numerous protein-coding and non-coding genes have been implicated in mechanisms contributing to the disease.
  • 930
  • 25 Aug 2023
Topic Review
Ferroptosis in H9c2 Cardioblasts: Metabolome Analysis
Ferroptosis is a newly discovered iron-dependent non-apoptotic programmed cell death pathway. It is characterized by the accumulation of oxidized phospholipids due to the excessive oxygenation of polyunsaturated fatty acid (FA) residues of phospholipids by lipoxygenases and the limited capability of glutathione peroxidase 4 (GPX4) to neutralize oxidized phospholipids. Mitochondria play a central role in the pathogenesis of human diseases. They contain the main components and enzymes of the ferroptotic machinery, such as lipoxygenase, GPX4, GSH, glutamate, and iron. Mitochondria do not synthesize GSH and are therefore dependent on the synthesis of cytosolic GSH.  The effects of ferroptosis on the metabolome in H9c2 cardioblasts by gas chromatography-mass spectrophotometry (GC-MS) are described here.
  • 929
  • 29 Mar 2022
Topic Review
Biotechnologies in Perfume Manufacturing
The fragrance industry is increasingly turning to biotechnology to produce sustainable and high-quality fragrance ingredients. Microbial-based approaches have been found to be particularly promising, as they offer a more practical, economical and sustainable alternative to plant-based biotechnological methods for producing terpene derivatives of perfumery interest. Among the evaluated works, the heterologous expression of both terpene synthase and mevalonate pathway into Escherichia coli has shown the highest yields.
  • 929
  • 09 May 2023
Topic Review
Epigenetic and Epitranscriptomic Control in Prostate Cancer
The initiation of prostate cancer has been long associated with DNA copy-number alterations, the loss of specific chromosomal regions and gene fusions, and driver mutations, especially those of the Androgen Receptor. Non-mutational events, particularly DNA and RNA epigenetic dysregulation, are emerging as key players in tumorigenesis. Researchers summarize the molecular changes linked to epigenetic and epitranscriptomic dysregulation in prostate cancer and the role that alterations to DNA and RNA modifications play in the initiation and progression of prostate cancer.
  • 928
  • 17 Mar 2022
Topic Review
Mechanism of Action of the Plagiochilins
Plagiochilin A functions as an inhibitor of the termination phase of cytokinesis: the membrane abscission stage. This unique, innovative mechanism of action, coupled with its marked anticancer action, notably against prostate cancer cells, make plagiochilin A an interesting lead molecule for the development of novel anticancer agents. There are known options to increase its potency, as deduced from structure–activity relationships. The analysis shed light on this family of bryophyte species and the little-known group of bioactive terpenoid plagiochilins. Plagiochilin A and derivatives shall be further exploited for the design of novel anticancer targeting the cytokinesis pathway.
  • 928
  • 24 Mar 2023
Topic Review
Targeting Iron-Sulfur Clusters in Cancer
Iron dysregulation is a hallmark of cancer, characterized by an overexpression of genes involved in iron metabolism and iron-sulfur cluster (ISC) biogenesis. Dysregulated iron homeostasis increases intracellular labile iron, which may lead to the formation of excess cytotoxic radicals and make it vulnerable to various types of regulated cell death, including ferroptosis. The inhibition of ISC synthesis triggers the iron starvation response, increasing lipid peroxidation and ferroptosis in cancer cells treated with oxidative stress-inducing agents. Various methods, such as redox operations, iron chelation, and iron replacement with redox-inert metals, can destabilize or limit ISC formation and function, providing potential therapeutic strategies for cancer treatment. Targeting ISCs to induce ferroptosis represents a promising approach in cancer therapy.
  • 928
  • 01 Aug 2023
Topic Review
Prion p53
p53 is a 393-amino-acids-long transcription factor composed of a globular DNA binding domain flanked by a transcription activation domain in N-terminal and a tetramerization domain in the C-terminal part of the protein and is active in a homo-tetrameric state.
  • 927
  • 12 Mar 2021
Topic Review
Hydrogen Sulfide in Mammalian Cells
Hydrogen sulfide (H2S) was recognized as a gaseous signaling molecule, similar to nitric oxide (-NO) and carbon monoxide (CO). It's important to provide an overview of the formation of hydrogen sulfide (H2S) in the human body. H2S is synthesized by enzymatic processes involving cysteine and several enzymes, including cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), cysteine aminotransferase (CAT), 3-mercaptopyruvate sulfurtransferase (3MST) and D-amino acid oxidase (DAO). The physiological and pathological effects of hydrogen sulfide (H2S) on various systems in the human body have led to extensive research efforts to develop appropriate methods to deliver H2S under conditions that mimic physiological settings and respond to various stimuli. These functions span a wide spectrum, ranging from effects on the endocrine system and cellular lifespan to protection of liver and kidney function. The exact physiological and hazardous thresholds of hydrogen sulfide (H2S) in the human body are currently not well understood and need to be researched in depth. 
  • 926
  • 18 Dec 2023
Topic Review
Role of Yes-Associated Protein in Breast Cancer
The hippo/yes-associated protein (YAP) protein is a critical oncogenic mediator within the Hippo signaling pathway and has been implicated in various cancer types. In breast cancer, it frequently becomes activated, thereby contributing to developing drug-resistance mechanisms. Studies have underscored the intricate interplay between YAP and ferroptosis within the breast tumor microenvironment. YAP exerts a negative regulatory effect on ferroptosis, promoting cancer cell survival and drug resistance.
  • 926
  • 17 Jan 2024
Topic Review
Up-Frameshift Protein 1 in Human Disorders
Up-frameshift protein 1 (UPF1) plays the role of a vital controller for transcripts, ready to react in the event of an incorrect translation mechanism. It is well known as one of the key elements involved in mRNA decay pathways and participates in transcript and protein quality control in several different aspects. Firstly, UPF1 specifically degrades premature termination codon (PTC)-containing products in a nonsense-mediated mRNA decay (NMD)-coupled manner. Additionally, UPF1 can potentially act as an E3 ligase and degrade target proteins independently from mRNA decay pathways. Thus, UPF1 protects cells against the accumulation of misfolded polypeptides. However, this multitasking protein may still hide many of its functions and abilities.
  • 925
  • 18 May 2023
Topic Review
Role of SCAP/SREBP in Hepatic Steatosis
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a unique, multi-factorial condition with several phases of progression including steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Sterol element binding protein 1c (SREBP1c) is the main transcription factor involved in regulating hepatic de novo lipogenesis. This transcription factor is synthesized as an inactive precursor, and its proteolytic maturation is initiated in the membrane of the endoplasmic reticulum upon stimulation by insulin. SREBP cleavage activating protein (SCAP) is required as a chaperon protein to escort SREBP from the endoplasmic reticulum and to facilitate the proteolytic release of the N-terminal domain of SREBP into the Golgi. SCAP inhibition prevents activation of SREBP and inhibits the expression of genes involved in triglyceride and fatty acid synthesis, resulting in the inhibition of de novo lipogenesis.
  • 925
  • 24 Jan 2024
Topic Review
Microalgae n-3 PUFAs
N-3 polyunsaturated fatty acids (n-3 PUFAs), and especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential compounds for human health. They have been proven to act positively on a panel of diseases and have interesting anti-oxidative, anti-inflammatory or anti-cancer properties. For these reasons, they are receiving more and more attention in recent years, especially future food or feed development. EPA and DHA come mainly from marine sources like fish or seaweed. Unfortunately, due to global warming, these compounds are becoming scarce for humans because of overfishing and stock reduction. Although increasing in recent years, aquaculture appears insufficient to meet the increasing requirements of these healthy molecules for humans. One alternative resides in the cultivation of microalgae, the initial producers of EPA and DHA. They are also rich in biochemicals with interesting properties.
  • 924
  • 25 Apr 2021
Topic Review
Intelligent Nanobiosensors for SARS-CoV-2 Diagnosis
The novel coronavirus appeared to be a milder infection initially, but the unexpected outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly called COVID-19, was transmitted all over the world in late 2019 and caused a pandemic. Human health has been disastrously affected by SARS-CoV-2, which is still evolving and causing more serious concerns, leading to the innumerable loss of lives. Smart and intelligent nanomaterial-enabled biosensors (nanobiosensors) have already proven their utility for the diagnosis of several viral infections, as various detection strategies based on nanobiosensor devices are already present, and several other methods are also being investigated by researchers for the determination of SARS-CoV-2 disease.
  • 924
  • 19 Aug 2022
Topic Review
Pim Kinases
Pim Kinases; Pim-1, Pim-2, and Pim-3, are a family of constitutively active serine/threonine kinases, widely associated with cell survival, proliferation, and migration. Historically considered to be functionally redundant, independent roles for the individual isoforms have been described. Whilst most established for their role in cancer progression, there is also increasing evidence for wider pathological roles of Pim kinases within the context of cardiovascular disease, including inflammation, thrombosis, and cardiac injury.
  • 924
  • 08 Aug 2023
Topic Review
Long Non-Coding RNAs in Alzheimer’s Disease
Accurate and early prediction of risk is an important strategy to alleviate the Alzheimer’s Disease (AD) burden. Neuroinflammation is a major factor prompting the onset of the disease. Inflammation exerts its toxic effect via multiple mechanisms. Amongst others, alteration of gene expression via modulation of non-coding RNAs (ncRNAs), such as miRNAs. Recent evidence supports that inflammation can also affect long non-coding RNA (lncRNA) expression. 
  • 923
  • 15 Dec 2022
Topic Review
Histone Demethylases: Insights into Human
Histone methylation is a three-step process that includes the integral roles of “writers”, or histone methyltransferases (HMTs), “readers,” or histone methylation-recognizing proteins, and “erasers,” or histone demethylases (HDMs). Histone methylation and demethylation regulate genes, either by relaxing histone tails to permit transcription factors and other proteins to contact the DNA, or by wrapping histone tails around the DNA, thereby blocking access. These changes impact nucleosomal characteristics and, henceforth, their interactions with other proteins.
  • 923
  • 25 Jun 2023
Topic Review
PPARα-Lysosomal Crosstalk in NAFLD
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors which belong to the nuclear hormone receptor superfamily. They regulate key aspects of energy metabolism within cells. Recently, PPARα has been implicated in the regulation of autophagy-lysosomal function, which plays a key role in cellular energy metabolism. PPARα transcriptionally upregulates several genes involved in the autophagy-lysosomal degradative pathway that participates in lipolysis of triglycerides within the hepatocytes. Interestingly, a reciprocal regulation of PPARα nuclear action by autophagy-lysosomal activity also exists with implications in lipid metabolism. This review succinctly discusses the unique relationship between PPARα nuclear action and lysosomal activity and explores its impact on hepatic lipid homeostasis under pathological conditions such as non-alcoholic fatty liver disease (NAFLD).
  • 922
  • 29 Oct 2020
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