International Journal of Molecular Sciences

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31 pages, 6666 KiB

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by Claire Coderch, Javier Arranz-Herrero, Estanislao Nistal-Villan, Beatriz de Pascual-Teresa and Sergio Rius-Rocabert

Int. J. Mol. Sci. 2023, 24(10), 9032; https://doi.org/10.3390/ijms24109032 - 20 May 2023

Cited by 3 | Viewed by 2462

Abstract

The stimulator of interferon genes (STING) is an adaptor protein involved in the activation of IFN-β and many other genes associated with the immune response activation in vertebrates. STING induction has gained attention from different angles such as the potential to trigger an [...] Read more.

The stimulator of interferon genes (STING) is an adaptor protein involved in the activation of IFN-β and many other genes associated with the immune response activation in vertebrates. STING induction has gained attention from different angles such as the potential to trigger an early immune response against different signs of infection and cell damage, or to be used as an adjuvant in cancer immune treatments. Pharmacological control of aberrant STING activation can be used to mitigate the pathology of some autoimmune diseases. The STING structure has a well-defined ligand binding site that can harbor natural ligands such as specific purine cyclic di-nucleotides (CDN). In addition to a canonical stimulation by CDNs, other non-canonical stimuli have also been described, whose exact mechanism has not been well defined. Understanding the molecular insights underlying the activation of STING is important to realize the different angles that need to be considered when designing new STING-binding molecules as therapeutic drugs since STING acts as a versatile platform for immune modulators. This review analyzes the different determinants of STING regulation from the structural, molecular, and cell biology points of view. Full article

(This article belongs to the Special Issue Latest Review Papers in Biochemistry 2023)

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20 pages, 4314 KiB

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Applications and Opportunities in Using Disulfides, Thiosulfinates, and Thiosulfonates as Antibacterials

by Lindsay Blume, Timothy E. Long and Edward Turos

Int. J. Mol. Sci. 2023, 24(10), 8659; https://doi.org/10.3390/ijms24108659 - 12 May 2023

Cited by 2 | Viewed by 1743

Abstract

Sulfur-containing molecules have a long history of bioactivity, especially as antibacterial agents in the fight against infectious pathogens. Organosulfur compounds from natural products have been used to treat infections throughout history. Many commercially available antibiotics also have sulfur-based moieties in their structural backbones. [...] Read more.

Sulfur-containing molecules have a long history of bioactivity, especially as antibacterial agents in the fight against infectious pathogens. Organosulfur compounds from natural products have been used to treat infections throughout history. Many commercially available antibiotics also have sulfur-based moieties in their structural backbones. In the following review, we summarize sulfur-containing antibacterial compounds, focusing on disulfides, thiosulfinates, and thiosulfonates, and opportunities for future developments in the field. Full article

(This article belongs to the Special Issue Latest Review Papers in Biochemistry 2023)

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24 pages, 1083 KiB

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Relevance of Sugar Transport across the Cell Membrane

by Roxana Carbó and Emma Rodríguez

Int. J. Mol. Sci. 2023, 24(7), 6085; https://doi.org/10.3390/ijms24076085 - 23 Mar 2023

Cited by 6 | Viewed by 3633

Abstract

Sugar transport through the plasma membrane is one of the most critical events in the cellular transport of nutrients; for example, glucose has a central role in cellular metabolism and homeostasis. The way sugars enter the cell involves complex systems. Diverse protein systems [...] Read more.

Sugar transport through the plasma membrane is one of the most critical events in the cellular transport of nutrients; for example, glucose has a central role in cellular metabolism and homeostasis. The way sugars enter the cell involves complex systems. Diverse protein systems participate in the membrane traffic of the sugars from the extracellular side to the cytoplasmic side. This diversity makes the phenomenon highly regulated and modulated to satisfy the different needs of each cell line. The beautiful thing about this process is how evolutionary processes have diversified a single function: to move glucose into the cell. The deregulation of these entrance systems causes some diseases. Hence, it is necessary to study them and search for a way to correct the alterations and utilize these mechanisms to promote health. This review will highlight the various mechanisms for importing the valuable sugars needed to create cellular homeostasis and survival in all kinds of cells. Full article

(This article belongs to the Special Issue Latest Review Papers in Biochemistry 2023)

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18 pages, 2366 KiB

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Role of GARP Vesicle Tethering Complex in Golgi Physiology

by Amrita Khakurel and Vladimir V. Lupashin

Int. J. Mol. Sci. 2023, 24(7), 6069; https://doi.org/10.3390/ijms24076069 - 23 Mar 2023

Cited by 3 | Viewed by 2136

Abstract

The Golgi associated retrograde protein complex (GARP) is an evolutionarily conserved component of Golgi membrane trafficking machinery that belongs to the Complexes Associated with Tethering Containing Helical Rods (CATCHR) family. Like other multisubunit tethering complexes such as COG, Dsl1, and Exocyst, the GARP [...] Read more.

The Golgi associated retrograde protein complex (GARP) is an evolutionarily conserved component of Golgi membrane trafficking machinery that belongs to the Complexes Associated with Tethering Containing Helical Rods (CATCHR) family. Like other multisubunit tethering complexes such as COG, Dsl1, and Exocyst, the GARP is believed to function by tethering and promoting fusion of the endosome-derived small trafficking intermediate. However, even twenty years after its discovery, the exact structure and the functions of GARP are still an enigma. Recent studies revealed novel roles for GARP in Golgi physiology and identified human patients with mutations in GARP subunits. In this review, we summarized our knowledge of the structure of the GARP complex, its protein partners, GARP functions related to Golgi physiology, as well as cellular defects associated with the dysfunction of GARP subunits. Full article

(This article belongs to the Special Issue Latest Review Papers in Biochemistry 2023)

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11 pages, 298 KiB

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The State of the Art of Molecular Fecal Investigations for Helicobacter pylori (H. pylori) Antibiotic Resistances

by Francesca Celiberto, Giuseppe Losurdo, Maria Pricci, Bruna Girardi, Angela Marotti, Alfredo Di Leo and Enzo Ierardi

Int. J. Mol. Sci. 2023, 24(5), 4361; https://doi.org/10.3390/ijms24054361 - 22 Feb 2023

Cited by 4 | Viewed by 1897

Abstract

A new paradigm shift for the treatment of Helicobacter pylori (H. pylori) infection would be timely due to a progressive increase in antibiotic resistance. Such a shift in the perspective of the H. pylori approach should include the preliminary assessment of [...] Read more.

A new paradigm shift for the treatment of Helicobacter pylori (H. pylori) infection would be timely due to a progressive increase in antibiotic resistance. Such a shift in the perspective of the H. pylori approach should include the preliminary assessment of antibiotic resistance. However, the availability of sensitivity tests is not widespread and the guidelines have always indicated empirical treatments without taking into account the need to make sensitivity tests accessible, i.e., the necessary starting point for improving results in different geographical areas. Currently, the traditional tools for this purpose (culture) are based on performing an invasive investigation (endoscopy) and often involve technical difficulties; thus, they were only confined to the settings where multiple attempts at eradication have failed. In contrast, genotypic resistance testing of fecal samples using molecular biology methods is much less invasive and more acceptable to patients. The purpose of this review is to update the state of the art of molecular fecal susceptibility testing for the management of this infection and to extensively discuss the potential benefits of their large-scale deployment, i.e., novel pharmacological opportunities. Full article

(This article belongs to the Special Issue Latest Review Papers in Biochemistry 2023)

26 pages, 2457 KiB

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PPARs and the Kynurenine Pathway in Melanoma—Potential Biological Interactions

by Katarzyna Walczak, Agnieszka Gerkowicz and Dorota Krasowska

Int. J. Mol. Sci. 2023, 24(4), 3114; https://doi.org/10.3390/ijms24043114 - 04 Feb 2023

Cited by 1 | Viewed by 2910

Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors involved in various physiological and pathological processes within the skin. PPARs regulate several processes in one of the most aggressive skin cancers, melanoma, including proliferation, cell cycle, metabolic homeostasis, cell death, and metastasis. In this [...] Read more.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors involved in various physiological and pathological processes within the skin. PPARs regulate several processes in one of the most aggressive skin cancers, melanoma, including proliferation, cell cycle, metabolic homeostasis, cell death, and metastasis. In this review, we focused not only on the biological activity of PPAR isoforms in melanoma initiation, progression, and metastasis but also on potential biological interactions between the PPAR signaling and the kynurenine pathways. The kynurenine pathway is a major pathway of tryptophan metabolism leading to nicotinamide adenine dinucleotide (NAD+) production. Importantly, various tryptophan metabolites exert biological activity toward cancer cells, including melanoma. Previous studies confirmed the functional relationship between PPAR and the kynurenine pathway in skeletal muscles. Despite the fact this interaction has not been reported in melanoma to date, some bioinformatics data and biological activity of PPAR ligands and tryptophan metabolites may suggest a potential involvement of these metabolic and signaling pathways in melanoma initiation, progression, and metastasis. Importantly, the possible relationship between the PPAR signaling pathway and the kynurenine pathway may relate not only to the direct biological effect on melanoma cells but also to the tumor microenvironment and the immune system. Full article

(This article belongs to the Special Issue Latest Review Papers in Biochemistry 2023)

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13 pages, 530 KiB

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Coenzyme Q10 Metabolism: A Review of Unresolved Issues

by David Mantle, Guillermo Lopez-Lluch and Iain Parry Hargreaves

Int. J. Mol. Sci. 2023, 24(3), 2585; https://doi.org/10.3390/ijms24032585 - 30 Jan 2023

Cited by 15 | Viewed by 5348

Abstract

The variable success in the outcome of randomised controlled trials supplementing coenzyme Q10 (CoQ10) may in turn be associated with a number of currently unresolved issues relating to CoQ10 metabolism. In this article, we have reviewed what is currently known about these factors [...] Read more.

The variable success in the outcome of randomised controlled trials supplementing coenzyme Q10 (CoQ10) may in turn be associated with a number of currently unresolved issues relating to CoQ10 metabolism. In this article, we have reviewed what is currently known about these factors and where gaps in knowledge exist that need to be further elucidated. Issues addressed include (i) whether the bioavailability of CoQ10 could be improved; (ii) whether CoQ10 could be administered intravenously; (iii) whether CoQ10 could be administered via alternative routes; (iv) whether CoQ10 can cross the blood-brain barrier; (v) how CoQ10 is transported into and within target cells; (vi) why some clinical trials supplementing CoQ10 may have been unsuccessful; and (vii) which is the most appropriate tissue for the clinical assessment of CoQ10 status. Full article

(This article belongs to the Special Issue Latest Review Papers in Biochemistry 2023)

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21 pages, 3756 KiB

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Top Selling (2026) Small Molecule Orphan Drugs: A Journey into Their Chemistry

by Davide Benedetto Tiz, Luana Bagnoli, Ornelio Rosati, Francesca Marini, Luca Sancineto and Claudio Santi

Int. J. Mol. Sci. 2023, 24(2), 930; https://doi.org/10.3390/ijms24020930 - 04 Jan 2023

Cited by 2 | Viewed by 3482

Abstract

This review describes, from a chemical point of view, the top “blockbuster” small molecule orphan drugs according to their forecasted sales in 2026. Orphan drugs are intended for the treatment, prevention, or diagnosis of a rare disease or condition. These molecules are mostly [...] Read more.

This review describes, from a chemical point of view, the top “blockbuster” small molecule orphan drugs according to their forecasted sales in 2026. Orphan drugs are intended for the treatment, prevention, or diagnosis of a rare disease or condition. These molecules are mostly addressed to the treatment of rare forms of cancer. The respiratory and central nervous systems represent other common therapeutic subcategories. This work will show how the orphan drugs market has significantly grown and will account for a consistent part of prescriptions by 2026. Full article

(This article belongs to the Special Issue Latest Review Papers in Biochemistry 2023)

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