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Topic Review
Small Peptides of Marine Origin
Cancer is one of the leading causes of death in the world, and antineoplastic drug research continues to be a major field in medicine development. The marine milieu has thousands of biological species that are a valuable source of novel functional proteins and peptides, which have been used in the treatment of many diseases, including cancer. In contrast with proteins and polypeptides, small peptides (with a molecular weight of less than 1000 Da) have overwhelming advantages, such as preferential and fast absorption, which can decrease the burden on human gastrointestinal function. Besides, these peptides are only connected by a few peptide bonds, and their small molecular weight makes it easy to modify and synthesize them. Specifically, small peptides can deliver nutrients and drugs to cells and tissues in the body. These characteristics make them stand out in relation to targeted drug therapy. Nowadays, the anticancer mechanisms of the small marine peptides are still largely not well understood; however, several marine peptides have been applied in preclinical treatment. 
  • 726
  • 10 Mar 2021
Topic Review
α-Helices in the T3SEs
Type III Secretion Systems (T3SSs) are multicomponent nanomachines located at the cell envelope of Gram-negative bacteria. Their main function is to transport bacterial proteins either extracellularly or directly into the eukaryotic host cell cytoplasm. Type III Secretion effectors (T3SEs), latest to be secreted T3S substrates, are destined to act at the eukaryotic host cell cytoplasm and occasionally at the nucleus, hijacking cellular processes through mimicking eukaryotic proteins. T3SE families adopt novel folds to target eukaryotic functions. These folds comprise a high helical content, which possibly reflects the specific requirements from T3SS effectors. In particular, effectors must (i) be able to be easily unfolded, (ii) cross the narrow T3S channel, (iii) be highly folded as soon as they will be found inside the host cell, in order to evade the host defense mechanisms, and (iv) display functional competence and structural plasticity in their final destination. α-helices can optimally fulfil these requirements.
  • 726
  • 06 Jun 2021
Topic Review Peer Reviewed
Trefoil Factor Family (TFF) Peptides
Trefoil factor family (TFF) peptides mainly consist of characteristic TFF domains, which contain about 40 amino acid residues, including 6 conserved cysteine residues. TFF peptides possess a single (mammalian TFF1 and TFF3), two (mammalian TFF2, Xenopus laevis xP2) or four TFF domains (X. laevis xP4). They exhibit lectin activities and are characteristic exocrine products of the mucous epithelia. Here, they play different roles for mucosal protection and the innate immune defense: TFF1 is a gastric tumor suppressor; TFF2 builds a lectin complex with the mucin MUC6, physically stabilizing the inner gastric mucus layer; and TFF3 forms a disulfide-linked heterodimer with IgG Fc binding protein (FCGBP), probably preventing the infiltration of microorganisms. Minor amounts of TFF peptides are endocrine products of the immune and nervous systems. Pathologically, TFF peptides are linked to inflammation. There are increasing indications that TFF peptides can antagonize cytokine receptors, such as receptors for IL-1β, IL-6, and TNFα (thereby acting as anti-inflammatory peptides). TFF peptides can probably also activate a variety of receptors, such as CXCR4. The TFF domain is a unique shuffled module which is also present in a number of mosaic proteins, such as zona pellucida proteins, sugar degrading enzymes and frog skin mucins. Here, their function seems to be defined by a lectin activity, which might even allow a role in fertilization.
  • 726
  • 13 Apr 2022
Topic Review
Nrf2 to Maintain Redox Homeostasis in Cardiometabolic Diseases
The transcription factor Nrf2 is a master regulator of multiple cytoprotective genes that maintain redox homeostasis and exert anti-inflammatory functions. The Nrf2-Keap1 signaling pathway is a paramount target of many cardioprotective strategies, because redox homeostasis is essential in cardiovascular health. Nrf2 gene variations, including single nucleotide polymorphisms (SNPs), are correlated with cardiometabolic diseases and drug responses. SNPs of Nrf2, KEAP1, and other related genes can impair the transcriptional activation or the activity of the resulting protein, exerting differential susceptibility to cardiometabolic disease progression and prevalence.
  • 726
  • 21 Mar 2022
Topic Review
Forms of Parkinson Disease Epigenetic Aspects
Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting approximately 1% of the population over the age of 50. PD is the second most common neurodegenerative disorder, and the estimated prevalence is 94 cases per 100,000 people, or approximately 0.3 percent in the general population 40 years of age and older. The yearly incidence of new cases ranges from 8 to 18.6 per 100,000 person-years. PD is clinically characterized by uncontrollable tremors at rest, rigidity, slowness of movement and postural impairment. In addition to violations of motor function, PD is accompanied by gastrointestinal, olfactory, sleep, and cognitive pathologies and other disorders. PD is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). These neurons release dopamine (DA) from nerve endings in the striatum and control muscle tone and multiple brain functions including a broad array of behavioral processes such as mood, reward, addiction, and stress. Morphologically PD is characterized by the presence of intracellular inclusions called Lewy bodies (LB) consisting mainly of aggregated α-synuclein (αSyn) inside nerve cells including SNpc. The onset of PD is dependent on both genetic and environmental factors. The latter can alter gene expression by causing epigenetic changes, such as DNA methylation, and the post-translational modification of histones and non-coding RNAs (ncRNAs, the most studied of which are microRNAs or miRNAs). The regulation of genes responsible for monogenic forms of PD may also be involved in sporadic PD.
  • 726
  • 12 Sep 2023
Topic Review
Nutriepigenomics in Environmental-Associated Oxidative Stress
Complex molecular mechanisms define our responses to environmental stimuli. Beyond the DNA sequence itself, epigenetic machinery orchestrates changes in gene expression induced by diet, physical activity, stress and pollution, among others. Importantly, nutrition has a strong impact on epigenetic players and, consequently, sustains a promising role in the regulation of cellular responses such as oxidative stress. As oxidative stress is a natural physiological process where the presence of reactive oxygen-derived species and nitrogen-derived species overcomes the uptake strategy of antioxidant defenses, it plays an essential role in epigenetic changes induced by environmental pollutants and culminates in signaling the disruption of redox control. 
  • 726
  • 18 Apr 2023
Topic Review
Exosomes Diversity
Cells can communicate through special “messages in the bottle”, which are recorded in the bloodstream inside vesicles, namely exosomes. The exosomes are nanovesicles of 30–100 nm in diameter that carry functionally active biological material, such as proteins, messanger RNA (mRNAs), and micro RNA (miRNAs). Therefore, they are able to transfer specific signals from a parental cell of origin to the surrounding cells in the microenvironment and to distant organs through the circulatory and lymphatic stream. More and more interest is rising for the pathological role of exosomes produced by cancer cells and for their potential use in tumor monitoring and patient follow up. In particular, the exosomes could be an appropriate index of proliferation and cancer cell communication for monitoring the minimal residual disease, which cannot be easily detectable by common diagnostic and monitoring techniques. The lack of unequivocal markers for tumor-derived exosomes calls for new strategies for exosomes profile characterization aimed at the adoption of exosomes as an official tumor biomarker for tumor progression monitoring.
  • 725
  • 21 Nov 2020
Topic Review
Lactoferrin and Its Derived Peptides
Lf is bacteriostatic and/or bactericidal, can stimulate cell proliferation and differentiation, facilitate iron absorption, improve neural development and cognition, promote bone growth, prevent cancer and exert anti-inflammatory and immunoregulatory effects.
  • 725
  • 29 Dec 2020
Topic Review
Ubisol-Q10 for Neurodegenerative Disease Treatment
It is well established and accepted that excessive oxidative stress is a key contributor to neurodegenerative diseases, driving interest in the development and application of redox therapies including the use of coenzyme-Q10 (CoQ10). However, in several human clinical trials, CoQ10 has failed to show efficacy, possibly due to poor tissue penetration and inability to deliver it parenterally. Ubisol-Q10 is a nanomicellar, water-dispersible formulation of CoQ10 that was created by combining CoQ10 with an amphiphilic and self-emulsifying molecule of polyoxyethanyl α-tocopheryl sebacate (PTS). This stable formulation is suitable for parenteral delivery and when tested at micromolar concentrations (well within FDA guidelines), it showed unprecedented neuroprotection, both in cellular models and animal models of chronic progressive neurodegeneration of both Parkinson’s and Alzheimer’s type. Systemic application of Ubisol-Q10 in drinking water stopped further progression of ongoing neurodegeneration as long as Ubisol-Q10 was provided. Mechanistically, this treatment with Ubisol-Q10 mobilized astroglia response in the CNS, quenched reactive oxygen species, prevented cell senescence, activated autophagy, reduced inflammation, and stabilized mitochondria. Importantly, these biochemical outcomes are accompanied by a significant improvement in behavioral deficits typically observed in animals with Parkinson’s and Alzheimer’s disease. Thus, Ubisol-Q10 is a promising candidate for developing a disease-modifying therapeutic intervention for neurodegenerative diseases that can be easily administered as drinking tonic.
  • 725
  • 20 May 2021
Topic Review
Autophagy and Flavonoids
Autophagy, which is a conserved biological process and essential mechanism in maintaining homeostasis and metabolic balance, enables cells to degrade cytoplasmic constituents through lysosomes, recycle nutrients, and survive during starvation. Autophagy exerts an anticarcinogenic role in normal cells and inhibits the malignant transformation of cells. On the other hand, aberrations in autophagy are involved in gene derangements, cell metabolism, the process of tumor immune surveillance, invasion and metastasis, and tumor drug-resistance. Therefore, autophagy-targeted drugs may function as anti-tumor agents. Accumulating evidence suggests that flavonoids have anticarcinogenic properties, including those relating to cellular proliferation inhibition, the induction of apoptosis, autophagy, necrosis, cell cycle arrest, senescence, the impairment of cell migration, invasion, tumor angiogenesis, and the reduction of multidrug resistance in tumor cells. Flavonoids, which are a group of natural polyphenolic compounds characterized by multiple targets that participate in multiple pathways, have been widely studied in different models for autophagy modulation. However, flavonoid-induced autophagy commonly interacts with other mechanisms, comprehensively influencing the anticancer effect. Accordingly, targeted autophagy may become the core mechanism of flavonoids in the treatment of tumors.
  • 724
  • 05 Feb 2021
Topic Review
Insights into the Pharmacological Effects of Flavonoids
Flavonoids are widely occurring secondary metabolites of plants. Currently, there is a trend of article numbers increasing, which focuses on the computer modeling of flavonoid interactions with biological targets. Such studies help to accumulatethe data on lead compounds that can find medicinal implementation, including COVID-19. Flavanonol taxifolin demonstrated wound-healing activity. Luteolin, apigenin, and wogonin, which can be classified as flavones, show induced neutrophil apoptosis and have potential as neutrophil apoptosis-inducing anti-inflammatory, proresolution agents.
  • 724
  • 10 Jun 2022
Topic Review
NF-κB and Human Cancer
Transcription factor NF-κB has been extensively studied for its varied roles in cancer since its initial characterization as a potent retroviral oncogene several decades ago. It is now clear that NF-κB plays a major role in a large variety of human cancers, including especially ones of immune cell origin. NF-κB is generally constitutively or aberrantly activated in human cancers where it is involved.
  • 723
  • 25 Dec 2021
Topic Review
MicroRNA Modulation
The prevalence of obesity has dramatically increased over the last decades. Weight loss obtained through diet and exercise leads to a  significant decrease in morbidity and mortality. Recently, there has been growing interest in the possible beneficial effects of dietary supplements (DSs), including polyphenols, fatty acids, and other plant-derived substances, as adjuvants in the management of obesity and metabolic diseases. Specifically, polyphenols, widely spread in vegetables and fruits, significantly modulate adipose tissue activities,  contrasting inflammation and improving insulin sensitivity in preclinical and clinical studies. Remarkably, polyphenols are involved in complex microRNA networks, which play crucial roles in metabolic processes. The administration of different polyphenols and other plant-derived compounds led to significant changes in the microRNA expression profile in peripheral tissues in a growing number of preclinical studies. In particular, these compounds were able to revert obesity-induced microRNA dysregulation, leading to the inhibition of adipogenesis and the induction of weight loss. Furthermore, through microRNA modulation, they attenuated key metabolic alterations, including insulin resistance and lipid anomalies, in animal models of obesity. Some of them were also able to reduce proinflammatory cytokines in adipose tissue. The aim of this review is to summarize current evidence about the effect of plant-derived DSs on microRNA expression in obesity.
  • 723
  • 29 Jan 2021
Topic Review
Epidermal Stem Cells
The skin surface is modified by numerous appendages. These structures arise from epithelial stem cells (SCs) through the induction of epidermal placodes as a result of local signalling interplay with mesenchymal cells based on the Wnt–(Dkk4)–Eda–Shh cascade. Slight modifications of the cascade, with the participation of antagonistic signalling, decide whether multipotent epidermal SCs develop in interfollicular epidermis, scales, hair/feather follicles, nails or skin glands. 
  • 722
  • 05 Jan 2021
Topic Review
Chemotherapy-Induced Neuropathic Pain
Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of chemotherapics such as taxanes, vinca alkaloids, and platinum compounds. The pathways described so far are diverse and target various components of the peripheral Nervous System (PNS). Among the contributors to neuropathic pain, inflammation has been indicated as a powerful driver of CIPN.
  • 722
  • 28 Mar 2022
Topic Review
S-adenosyl-l-homocysteine Hydrolase
S-adenosyl-l-homocysteine hydrolase (SAHase) is a major regulator of cellular methylation reactions that occur in eukaryotic and prokaryotic organisms. SAHase activity is also a significant source of l-homocysteine and adenosine, two compounds involved in numerous vital, as well as pathological processes. Therefore, apart from cellular methylation, the enzyme may also influence other processes important for the physiology of particular organisms.
  • 721
  • 17 Feb 2021
Topic Review
Mitochondrial Calcium
Mitochondria calcium is a double-edged sword. The low levels of calcium are essential to maintain optimal rates of ATP production, extreme levels of calcium overcoming the mitochondrial calcium retention capacity leads to loss of mitochondrial function. In moderate amounts, ATP synthesis rates are inhibited in a calcium-titratable manner.
  • 721
  • 31 Jan 2023
Topic Review
Dietary Phytochemicals in Skin Cancer
Human skin is continuously subjected to environmental stresses, as well as extrinsic and intrinsic noxious agents. Although skin adopts various molecular mechanisms to maintain homeostasis, excessive and repeated stresses can overwhelm these systems, leading to serious cutaneous damage, including both melanoma and non-melanoma skin cancers. Phytochemicals present in the diet possess the desirable effects of protecting the skin from damaging free radicals as well as other benefits. Dietary phytochemicals appear to be effective in preventing skin cancer and are inexpensive, widely available, and well tolerated. Multiple in vitro and in vivo studies have demonstrated the significant anti-inflammatory, antioxidant, and anti-angiogenic characteristics of dietary phytochemicals against skin malignancy. Moreover, dietary phytochemicals affect multiple important cellular processes including cell cycle, angiogenesis, and metastasis to control skin cancer progression. Herein, we discuss the advantages of key dietary phytochemicals in whole fruits and vegetables, their bioavailability, and underlying molecular mechanisms for preventing skin cancer. Current challenges and future prospects for research are also reviewed. To date, most of the chemoprevention investigations have been conducted preclinically, and additional clinical trials are required to conform and validate the preclinical results in humans.
  • 720
  • 27 May 2021
Topic Review
Impact of TRAP1 on Cancer Metabolism
The Hsp90 chaperone TNF-receptor-associated protein-1 (TRAP1) is primarily localized to the mitochondria and controls both cellular metabolic reprogramming and mitochondrial apoptosis. TRAP1 upregulation facilitates the growth and progression of many cancers by promoting glycolytic metabolism and antagonizing the mitochondrial permeability transition that precedes multiple cell death pathways. TRAP1 attenuation induces apoptosis in cellular models of cancer, identifying TRAP1 as a potential therapeutic target in cancer. Similar to cytosolic Hsp90 proteins, TRAP1 is also subject to post-translational modifications (PTM) that regulate its function and mediate its impact on downstream effectors, or ‘clients’.
  • 720
  • 08 Jun 2022
Topic Review
L–Tryptophan Derivatives as Essential Compounds for Serotonin Synthesis
L–Tryptophan (Trp) and its derivatives, such as 5-hydroxy–L–tryptophan (5-OH-L-Trp), and tryptamine, are related to biochemical reactions that lead to serotonin synthesis in the brain’s neurotransmitters, lower levels of which are observed in clinically depressed patients.
  • 720
  • 10 Apr 2023
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