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Topic Review
A Promiscuous Bacterial P450
CYP102A1 (BM3) is a catalytically self-sufficient flavocytochrome fusion protein isolated from Bacillus megaterium, which displays similar metabolic capabilities to many drug-metabolizing human P450 isoforms. BM3′s high catalytic efficiency, ease of production and malleable active site makes the enzyme a desirable tool in the production of small molecule metabolites, especially for compounds that exhibit drug-like chemical properties. The engineering of select key residues within the BM3 active site vastly expands the catalytic repertoire, generating variants which can perform a range of modifications. This provides an attractive alternative route to the production of valuable compounds that are often laborious to synthesize via traditional organic means. 
  • 938
  • 03 Nov 2021
Topic Review
Pyrophosphate in Vascular Calcification
In vertebrates, plasma and other extracellular fluids are supersaturated with phosphate and calcium, causing a tendency for spontaneous calcium-phosphate precipitation. Therefore, the synthesis of calcium phosphate deposition inhibitors is essential for survival, including pyrophosphate and several proteins.
  • 938
  • 21 Dec 2021
Topic Review
Implications of One-Carbon and Polyamine Metabolism for Cancer
Cancer metabolic reprogramming is essential for maintaining cancer cell survival and rapid replication. A common target of this metabolic reprogramming is one-carbon metabolism which is notable for its function in DNA synthesis, protein and DNA methylation, and antioxidant production. Polyamines are a key output of one-carbon metabolism with widespread effects on gene expression and signaling. One-carbon metabolism includes the methionine cycle, which is linked to the folate cycle, polyamine synthesis, and the trans-sulphuration pathway. 
  • 938
  • 17 Jan 2023
Topic Review
Maturation of Mitochondrial [4Fe-4S]-Containing Proteins
The importance of mitochondria in mammalian cells is widely known. Several biochemical reactions and pathways take place within mitochondria: among them, there are those involving the biogenesis of the iron–sulfur (Fe-S) clusters. The latter are evolutionarily conserved, ubiquitous inorganic cofactors, performing a variety of functions, such as electron transport, enzymatic catalysis, DNA maintenance, and gene expression regulation. The synthesis and distribution of Fe-S clusters are strictly controlled cellular processes that involve several mitochondrial proteins that specifically interact each other to form a complex machinery (Iron Sulfur Cluster assembly machinery, ISC machinery hereafter). This machinery ensures the correct assembly of both [2Fe-2S] and [4Fe-4S] clusters and their insertion in the mitochondrial target proteins. 
  • 937
  • 02 Aug 2022
Topic Review
PTMs and Mutations of Human Linker Histone Subtypes
Linker histones (LH) are a critical component of chromatin in addition to the canonical histones (H2A, H2B, H3, and H4). In humans, 11 subtypes (7 somatic and 4 germinal) of linker histones have been identified, and their diverse cellular functions in chromatin structure, DNA replication, DNA repair, transcription, and apoptosis have been explored, especially for the somatic subtypes. Delineating the unique role of human linker histone (hLH) and their subtypes is highly tedious given their high homology and overlapping expression patterns. However, advancements in mass spectrometry combined with HPLC have helped in identifying the post-translational modifications (PTMs) found on the different LH subtypes. However, while a number of PTMs have been identified and their potential nuclear and non-nuclear functions explored in cellular processes, there are very few studies delineating the direct relevance of these PTMs in diseases. In addition, whole-genome sequencing of clinical samples from cancer patients and individuals afflicted with Rahman syndrome have identified high-frequency mutations and therefore broadened the perspective of the linker histone mutations in diseases.
  • 937
  • 19 Jan 2023
Topic Review
RNAnalysis for Codeless RNAnalysing Sequencing of Data
In next-generation sequencing experiments, significant obstacles include conducting exploratory data analysis, deciphering trends, pinpointing potential targets/candidates, and presenting results in a clear and intuitive manner. These challenges become more pronounced for researchers lacking expertise in coding, as most analysis tools demand programming skills. Even for adept computational biologists, there is a need for an efficient and reproducible system to produce standardized results.
  • 937
  • 12 Dec 2023
Topic Review
Bacterial Pathogens Secretory System Components
Bacterial secretory systems are essential for virulence in human pathogens. The systems have become a target of alternative antibacterial strategies based on small molecules and antibodies. Strategies to use components of the systems to design prophylactics have been less publicized despite vaccines being the preferred solution to dealing with bacterial infections.
  • 936
  • 09 Jul 2021
Topic Review
Targeting Fatty Acid Metabolism in Gynaecological Cancers
Fatty acid (FA) metabolism plays a vital role in promoting the development and progression of gynaecological cancers. Therefore, enzymes involved in FA metabolism are attractive targets in treating these cancer types. Moreover, inhibiting these enzymes can synergistically augment the antitumour effects of chemotherapeutic agents targeting the oestradiol pathway (e.g., selective ER modulators (SERM) and aromatase inhibitors) or to overcome chemotherapeutic resistance against these agents in gynaecological cancers. In addition to the developing pharmacological inhibitors specifically targeting FA metabolism enzymes, interest is also growing in implementing diet-based intervention to supplement conventional chemotherapeutic regime.
  • 936
  • 12 May 2022
Topic Review
Anticancer Effects of Glyceollins
Glyceollins are a group of phytoalexins that are isolated from soybeans. They have attracted attention because they exert numerous effects on human functions and diseases, notably anticancer effects.
  • 935
  • 28 Oct 2021
Topic Review
Vitamin D in Cognitive Dysfunction
Vitamin D is necessary for all vertebrates, including humans, to maintain adequate phosphate and calcium levels in the blood, thereby helping to develop normal bone, optimal maintenance of muscle contractions, and cellular functions in different parts of the body. The developmental disabilities induced by vitamin D deficiency (VDD) include neurological disorders (e.g., attention deficit hyperactivity disorder, autism spectrum disorder, schizophrenia) characterized by cognitive dysfunction. 
  • 935
  • 28 Jul 2022
Topic Review
Natural Polyphenols and Cervical Cancer
From all types of cancer, cervical cancer manages to be in top four most frequent types, with a 6.5% rate of occurrence. The infectious vector that induces the disease, the high-risk Human papillomavirus (HPV), which is a sexually transmitted virus, is capable of transforming the host cell by modulating some of the principal signaling pathways responsible for cell cycle arrest, proliferation, and survival. Fortunately, like other cancer types, cervical cancer can be treated by chirurgical interventions or chemoradiotherapy, but these methods are not exactly the lucky clover of modern medicine because of the adverse effects they have. That is the reason why in the last years the emphasis has been on alternative medicine, more specifically on phytochemicals, as a substantial number of studies showed that diet contributes to cancer prevention and treatment. All these studies are trying to find new chemopreventive agents with less toxicity but high effectiveness both in vitro and in vivo. Polyphenols have great potential in cervical cancer prevention, with strong effects on gene modulation.
  • 934
  • 23 Sep 2021
Topic Review
Small-Molecule Inhibitors Targeting Proteasome-Associated Deubiquitinases
The 26S proteasome is the principal protease for regulated intracellular proteolysis. This multi-subunit complex is also pivotal for clearance of harmful proteins that are produced throughout the lifetime of eukaryotes. Recent structural and kinetic studies have revealed a multitude of conformational states of the proteasome in substrate-free and substrate-engaged forms. These conformational transitions demonstrate that proteasome is a highly dynamic machinery during substrate processing that can be also controlled by a number of proteasome-associated factors. Essentially, three distinct family of deubiquitinases–USP14, RPN11, and UCH37–are associated with the 19S regulatory particle of human proteasome. USP14 and UCH37 are capable of editing ubiquitin conjugates during the process of their dynamic engagement into the proteasome prior to the catalytic commitment. In contrast, RPN11-mediated deubiquitination is directly coupled to substrate degradation by sensing the proteasome’s conformational switch into the commitment steps. 
  • 934
  • 23 Jun 2021
Topic Review
Transforming Growth Factor-Beta in Skeletal Muscle Wasting
Transforming growth factor (TGF)-β is the name for a superfamily of proteins, including myostatin, that functions in the body to affect growth and to stimulate the inflammatory response along with other functions covered elsewhere. TGF-β in skeletal muscle not only contributed to muscle fibrosis in Duchenne Muscular Dystrophy (DMD) disease, but also promoted skeletal muscle atrophy by decreasing muscle fiber diameter and amounts of heavy chain myosin (MHC) in muscle tissue. 
  • 933
  • 28 Mar 2022
Topic Review
Counteracting Immunosuppression in the Tumor Microenvironment
An apparent paradox exists between the evidence for spontaneous systemic T cell- mediated anti-tumor immune responses in cancer patients, observed particularly in their bone marrow, and local tumor growth in the periphery. This phenomenon, known as “concomitant immunity” suggests that the local tumor and its tumor microenvironment (TME) prevent systemic antitumor immunity to become effective. Oncolytic Newcastle disease virus (NDV), an agent with inherent anti-neoplastic and immune stimulatory properties, is capable of breaking therapy resistance and immunosuppression.
  • 933
  • 16 Nov 2022
Topic Review
RNA Interference Past and Future Applications in Plants
Antisense RNA was observed to elicit plant disease resistance and post-translational gene silencing (PTGS). The universal mechanism of RNA interference (RNAi) was shown to be induced by double-stranded RNA (dsRNA), an intermediate produced during virus replication. Plant viruses with a single-stranded positive-sense RNA genome have been instrumental in the discovery and characterization of systemic RNA silencing and suppression.  Application of exogenously applied dsRNA is proving to be a potent strategy for delivery to improve crop performance.
  • 933
  • 29 Jun 2023
Topic Review
ROS and Antioxidants in Halophytes
Reactive oxygen species (ROS) are excited or partially reduced forms of atmospheric oxygen, which are continuously produced during aerobic metabolism like many physiochemical processes operating throughout seed life. Previously, it was believed that ROS are merely cytotoxic molecules, however, now it has been established that they perform numerous beneficial functions in plants including many critical roles in seed physiology. ROS facilitate seed germination via cell wall loosening, endosperm weakening, signaling, and decreasing abscisic acid (ABA) levels. Most of the existing knowledge about ROS homeostasis and functions is based on the seeds of common plants or model ones.
  • 933
  • 30 Aug 2023
Topic Review
Ion Mobility–Mass Spectrometry for Bioanalysis
This study aims to cover the main strategies based on ion mobility spectrometry (IMS) for the analysis of biological samples. The determination of endogenous and exogenous compounds in such samples is important for the understanding of the health status of individuals. For this reason, the development of new approaches that can be complementary to the ones already established (mainly based on liquid chromatography coupled to mass spectrometry) is welcomed. In this regard, ion mobility spectrometry has appeared in the analytical scenario as a powerful technique for the separation and characterization of compounds based on their mobility. IMS has been used in several areas taking advantage of its orthogonality with other analytical separation techniques, such as liquid chromatography, gas chromatography, capillary electrophoresis, or supercritical fluid chromatography. Bioanalysis is not one of the areas where IMS has been more extensively applied. However, over the last years, the interest in using this approach for the analysis of biological samples has clearly increased.
  • 932
  • 31 Mar 2021
Topic Review
Unfolded Protein Response and CD
Endoplasmic reticulum (ER) stress triggers a series of signaling and transcriptional events termed the unfolded protein response (UPR). Severe ER stress is associated with the development of fibrosis in different organs, including lung, liver, kidney, heart, and intestine. ER stress is an essential response of epithelial and immune cells in the pathogenesis of Inflammatory Bowel Disease (IBD), including Crohn’s disease (CD). Intestinal epithelial cells are susceptible to ER stress-mediated damage due to secretion of a large amount of proteins that are involved in mucosal defense. In other cells, ER stress is linked to myofibroblast activation, extracellular matrix production, macrophage polarization, and immune cell differentiation.
  • 932
  • 07 May 2021
Topic Review
Oxidative Stress-Mediated Inflammation in T2DM-Induced Diabetic Nephropathy
Diabetic nephropathy is manifested in more than 10% of people with diabetes. It is a common cause of kidney failure and end-stage kidney disease. Understanding of mechanisms underlying the initiation and development of diabetes-induced kidney injuries will allow for the development of more effective methods of prevention and treatment of the disease. Diabetic nephropathy is a wide-ranging complication of diabetes, and it is necessary to discuss the “weight” of pro-inflammatory pathways and molecules in the progress of renal injuries during the development of the disease. A large spectrum of pro-inflammatory molecules and pathways participate in different stages of the pathophysiological progression of diabetic nephropathy, including pro-inflammatory cytokines, chemokines, their receptors, adhesion molecules, and transcription factors. On the other hand, it is known that one of the consequences of hyperglycemia-induced ROS generation is the up-regulation of pro-inflammatory cascades, which, in turn, activate the transcription of genes encoding cytokines-chemokines, growth factors, and extracellular matrix proteins.
  • 932
  • 27 Dec 2022
Topic Review
Impact of Ultraviolet Radiation on Cyanobacteria
Ultraviolet radiation (UVR) tends to damage key cellular machinery. Cells may adapt by developing several defence mechanisms as a response to such damage; otherwise, their destiny is cell death. Since cyanobacteria are primary biotic components and also important biomass producers, any drastic effects caused by UVR may imbalance the entire ecosystem. Cyanobacteria are exposed to UVR in their natural habitats. This exposure can cause oxidative stress which affects cellular morphology and vital processes such as cell growth and differentiation, pigmentation, photosynthesis, nitrogen metabolism, and enzyme activity, as well as alterations in the native structure of biomolecules such as proteins and DNA. The high resilience and several mitigation strategies adopted by a cyanobacterial community in the face of UV stress are attributed to the activation of several photo/dark repair mechanisms, avoidance, scavenging, screening, antioxidant systems, and the biosynthesis of UV photoprotectants, such as mycosporine-like amino acids (MAAs), scytonemin (Scy), carotenoids, and polyamines.
  • 932
  • 08 Aug 2023
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