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Topic Review
SARS-CoV-2 Infection and Autophagy
The coronavirus disease pandemic, which profoundly reshaped the world in 2019 (COVID-19), has affected over 200 countries, caused over 500 million cumulative cases, and claimed the lives of over 6.4 million people worldwide as of August 2022. The causative agent is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Depicting this virus’ life cycle and pathogenic mechanisms, as well as the cellular host factors and pathways involved during infection, has great relevance for the development of therapeutic strategies. Autophagy is a catabolic process that sequesters damaged cell organelles, proteins, and external invading microbes, and delivers them to the lysosomes for degradation. Autophagy would be involved in the entry, endo, and release, as well as the transcription and translation, of the viral particles in the host cell.
  • 878
  • 01 Aug 2023
Topic Review
PRMT5
PRMT5 is the predominant Type II arginine methyltransferase, indicating that it confers both MMA and SDMA marks on target substrates in a distributive manner.
  • 877
  • 21 Jan 2021
Topic Review
Diseases Associated with Fli1 Deficiency
Being initially described as a factor of virally induced leukemias, Fli1 (Friend leukemia integration 1) lately has attracted considerable interest due to its role in both healthy physiology and a variety of pathological conditions. Over the past years Fli1 was found to be one of the crucial regulators of normal hematopoiesis, vasculogenesis and immune responses. However, abnormal expression of Fli1 due to genetic predisposition, epigenetic reprogramming (modifications) or environmental factors is associated with a few diseases of different etiology. Fli1 hyperexpression leads to malignant transformation of cells and progression of cancers such as Ewing’s sarcoma. The deficiency of Fli1 implicates in development of systemic sclerosis and hypertensive disorders, which are often accompanied by pronounced fibrosis in different organs. 
  • 877
  • 02 Feb 2023
Topic Review
Parkinson's Disease and COVID-19: Role of TLR4
Parkinson’s disease (PD) is the most common neurodegenerative motor disorder characterized by selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the midbrain, depletion of dopamine (DA), and impaired nigrostriatal pathway. The pathological hallmark of PD includes the aggregation and accumulation α-synuclein (α-SYN). Although the precise mechanisms underlying the pathogenesis of PD are still unknown, the activation of toll-like receptors (TLRs), mainly TLR4 and subsequent neuroinflammatory immune response, seem to play a significant role. Mounting evidence suggests that viral infection can concur in precipitation of PD or parkinsonism. The recently identified coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of ongoing pandemic coronavirus disease 2019 (COVID-19), responsible for 160 million cases that led to the death of more than three million individuals worldwide. Studies have reported that many patients with COVID-19 display several neurological manifestations, including acute cerebrovascular diseases, conscious disturbance, and typical motor and non-motor symptoms accompanying PD. The involvement of the TLR4 signaling pathway in mediating the virus entry, and the consequent massive immune and inflammatory response in COVID-19 patients has been recently explored. The strong binding of SARS-CoV-2 spike (S) protein to TLR4 and the possible interaction between SARS-CoV-2 and α-SYN suggest a potential contribute to the acceleration of neuronal death.
  • 876
  • 08 Oct 2021
Topic Review
Cancer-Associated Fibroblasts in Cholangiocarcinoma
Cholangiocarcinoma (CCA) is an aggressive neoplasia with an increasing incidence and mortality. It is characterized by a strong desmoplastic stroma surrounding cancer cells. Cancer-associated fibroblasts (CAFs) are the main cell type of CCA stroma and they have an important role in modulating cancer microenvironments. CAFs originate from multiple lines of cells and mainly consist of fibroblasts and alpha-smooth muscle actin (α-SMA) positive myofibroblast-like cells. The continuous cross-talking between CCA cells and desmoplastic stroma is permitted by CAF biochemical signals, which modulate a number of pathways. Stromal cell-derived factor-1 expression increases CAF recruitment to the tumor reactive stroma and influences apoptotic pathways. The Bcl-2 family protein enhances susceptibility to CAF apoptosis and PDGFRβ induces fibroblast migration and stimulates tumor lymphangiogenesis. Many factors related to CAFs may influence CCA prognosis.
  • 876
  • 10 Nov 2022
Topic Review
Protein Phosphatases and Their Role in Spermatozoa Function
Male fertility relies on the ability of spermatozoa to fertilize the egg in the female reproductive tract (FRT). Spermatozoa acquire activated motility during epididymal maturation; however, to be capable of fertilization, they must achieve hyperactivated motility in the FRT. Extensive research found that three protein phosphatases (PPs) are crucial to sperm motility regulation, the sperm-specific protein phosphatase type 1 (PP1) isoform gamma 2 (PP1γ2), protein phosphatase type 2A (PP2A) and protein phosphatase type 2B (PP2B). 
  • 876
  • 09 Jan 2023
Topic Review
Presepsin as Sepsis Early Marker
The diagnosis and treatment of sepsis have always been a challenge for the physician, especially in critical care setting such as emergency department (ED), and currently sepsis remains one of the major causes of mortality. Although the traditional definition of sepsis based on systemic inflammatory response syndrome (SIRS) criteria changed in 2016, replaced by the new criteria of SEPSIS-3 based on organ failure evaluation, early identification and consequent early appropriated therapy remain the primary goal of sepsis treatment. Unfortunately, currently there is a lack of a foolproof system for making early sepsis diagnosis because conventional diagnostic tools like cultures take a long time and are often burdened with false negatives, while molecular techniques require specific equipment and have high costs. In this context, biomarkers, such as C-Reactive Protein (CRP) and Procalcitonin (PCT), are very useful tools to distinguish between normal and pathological conditions, graduate the disease severity, guide treatment, monitor therapeutic responses and predict prognosis. 
  • 876
  • 12 Aug 2021
Topic Review
Progress in Research on CYC-like Genes in Fabaceae
CYCLOIDEA (CYC)-like genes belong to the TCP transcription factor family and play important roles associated with flower development. The CYC-like genes in the CYC1, CYC2, and CYC3 clades resulted from gene duplication events. The CYC2 clade includes the largest number of members that are crucial regulators of floral symmetry. To date, studies on CYC-like genes have mainly focused on plants with actinomorphic and zygomorphic flowers, such as Fabaceae species, and the effects of CYC-like gene duplication events and diverse spatiotemporal expression patterns on flower development. The Fabaceae species are diverse in floral symmetry and are suitable for exploring the evolution and underlying mechanism of floral symmetry. 
  • 876
  • 09 Mar 2023
Topic Review
Diamond Electrodes for Neurochemical Sensing
Carbon-based electrodes combined with fast-scan cyclic voltammetry (FSCV) enable neurochemical sensing with high spatiotemporal resolution and sensitivity. While their attractive electrochemical and conductive properties have established a long history of use in the detection of neurotransmitters both in vitro and in vivo, carbon fiber microelectrodes (CFMEs) also have limitations in their fabrication, flexibility, and chronic stability. Diamond is a form of carbon with a more rigid bonding structure (sp3-hybridized) which can become conductive when boron-doped. Boron-doped diamond (BDD) is characterized by an extremely wide potential window, low background current, and good biocompatibility. Additionally, methods for processing and patterning diamond allow for high-throughput batch fabrication and customization of electrode arrays with unique architectures.
  • 875
  • 20 Feb 2021
Topic Review
Phytochemicals Modulate lncRNAs and Carbonic Anhydrases in Cancer
Long non-coding RNAs (lncRNAs) are classified as a group of transcripts that regulate various biological processes, such as RNA processing, epigenetic control, and signaling pathways. According to recent studies, lncRNAs are dysregulated in cancer and play an important role in cancer incidence and spreading. There is also an association between lncRNAs and the overexpression of some tumor-associated proteins, including carbonic anhydrases II, IX, and XII (CA II, CA IX, and CA XII). Therefore, not only CA inhibition but also lncRNA modulation, could represent an attractive strategy for cancer prevention and therapy. Experimental studies have suggested that herbal compounds regulate the expression of many lncRNAs involved in cancer, such as HOTAIR (HOX transcript antisense RNA), H19, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), PCGEM1 (Prostate cancer gene expression marker 1), PVT1, etc. These plant-derived drugs or phytochemicals include resveratrol, curcumin, genistein, quercetin, epigallocatechin-3-galate, camptothecin, and 3,3'-diindolylmethane. More comprehensive information about lncRNA modulation via phytochemicals would be helpful for the administration of new herbal derivatives in cancer therapy.
  • 875
  • 01 Dec 2021
Topic Review
α-Synuclein Epigenetic Regulation
Synucleinopathies are a group of neurodegenerative diseases with common pathological lesions associated with the excessive accumulation and abnormal intracellular deposition of toxic species of α-synuclein. The shared clinical features are chronic progressive decline of motor, cognitive, and behavioral functions. These disorders include Parkinson’s disease, dementia with Lewy body, and multiple system atrophy. Vigorous research in the mechanisms of pathology of these illnesses is currently under way to find disease-modifying treatment and molecular markers for early diagnosis. α-Synuclein is a prone-to-aggregate, small amyloidogenic protein with multiple roles in synaptic vesicle trafficking, neurotransmitter release, and intracellular signaling events. Its expression is controlled by several mechanisms, one of which is epigenetic regulation.
  • 875
  • 10 May 2023
Topic Review
Mitochondrial Regulation of Ferroptosis in Cancer Therapy
Ferroptosis, characterized by glutamate overload, glutathione depletion, and cysteine/cystine deprivation during iron- and oxidative-damage-dependent cell death, is a particular mode of regulated cell death. It is expected to effectively treat cancer through its tumor-suppressor function, as mitochondria are the intracellular energy factory and a binding site of reactive oxygen species production, closely related to ferroptosis. 
  • 875
  • 25 Jun 2023
Topic Review
NUB1 and FAT10 Proteins
The upregulated expression of both NUB1 and FAT10 has been observed in various cancers. NUB1 protein binds to FAT10 non-covalently to promote FAT10 degradation. An overexpressed FAT10 stimulates nuclear factor-kappa β, activates the inflammatory pathways, and induces the proliferation of cancer. The FAT10 protein interacts with the mitotic arrest deficient 2 protein, causing chromosomal instability and breast tumourigenesis. FAT10 binds to the proliferating cell nuclear antigen protein and inhibits the DNA damage repair response. In addition, FAT10 involves epithelial–mesenchymal transition, invasion, apoptosis, and multiplication in hepatocellular carcinoma. 
  • 874
  • 12 Sep 2021
Topic Review
Making Bioactive Peptides Druggable
International Journal of Molecular Sciences Special Issue on the topic "Making Bioactive Peptides Druggable: Challenges and Prospects" is open for submissions. The Editorial Board of IJMS, and Guest Editors Paula Gomes and Cátia Teixeira are honored to invite all those devoted to the field of peptide-focused research to contribute to this special issue. This issue is intended to be an up-to-date collection of works, either original or literature reviews, focused on the current challenges, approaches, and prospects towards the improvement of peptide pharmacokinetics. Submissions are open till the 30th of March, 2021. For detailed information, please, use this link.
  • 873
  • 24 Sep 2020
Topic Review
Telomere Abnormalities Regulate Neuroblastoma
Telomere maintenance is a powerful prognostic marker of HRNB thereby representing an attractive target for the development of novel therapeutic treatments.
  • 873
  • 29 Mar 2022
Topic Review
Novel Heterocyclic Derivatives against SARS-CoV-2
The heterocyclic ring derivatives were evaluated for their therapeutic potentials against SARS-CoV-2 Mpro, Spro, and RdRp. All the compounds reported showed excellent binding affinities with the various target proteins. Among the derivatives, compound C13 exhibits the highest binding affinity for the drug targets Spro (−10.6 kcal/mol) and RdRp (−9.5 kcal/mol), respectively. At a binding affinity of −8.8kcal/mol, the compound C15 exhibits the highest binding affinity for Mpro. The compounds interacted with the LEU A:271, LEU A:287, ASP A:289, and LEU A:272 of Mpro and the HIS A:540, PRO A:415, PHE A:486, and LEU A:370 of the Spro receptor binding motif and some active site amino acids of RdRp. The compounds also possess a favourable ADMET profile and showed no tendency towards hERG inhibition, hepatotoxicity, carcinogenicity, mutagenicity, or drug-liver injury. 
  • 873
  • 17 Dec 2021
Biography
Alexander O. Shpakov
Alexander O. Shpakov is a Professor of Biochemistry at the I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry (IEPB), Russian Academy of Sciences, in Saint-Petersburg, Russia. He was born in 1963 at Leningrad in Russia. He received his Master of Science degree in Bioorganic Chemistry in 1987 from the Leningrad State University, Russia, and his PhD degree in Biochemistry in 1996
  • 872
  • 23 Aug 2023
Topic Review
The Importance of Krüppel-Like Factors in Cardiovascular Diseases
Krüppel-like factors (KLFs) are a set of DNA-binding proteins belonging to a family of zinc-finger transcription factors, which have been associated with many biological processes related to the activation or repression of genes, inducing cell growth, differentiation, and death, and the development and maintenance of tissues. In response to metabolic alterations caused by disease and stress, the heart will undergo cardiac remodeling, leading to cardiovascular diseases (CVDs). KLFs are among the transcriptional factors that take control of many physiological and, in this case, pathophysiological processes of CVD. KLFs seem to be associated with congenital heart disease-linked syndromes, malformations because of autosomal diseases, mutations that relate to protein instability, and/or loss of functions such as atheroprotective activities. Ischemic damage also relates to KLF dysregulation because of the differentiation of cardiac myofibroblasts or a modified fatty acid oxidation related to the formation of a dilated cardiomyopathy, myocardial infarctions, left ventricular hypertrophy, and diabetic cardiomyopathies.
  • 871
  • 09 Feb 2023
Topic Review
Auxin's Role in Nitrate-Regulated Plant Growth and Development
As a major component of vital macromolecules such as nucleic acids, amino acids, and chlorophyll, nitrogen is an essential macronutrient for plants. Although nitrogen is one of the most abundant elements in nature, accounting for about 70% of atmospheric gasses, its availability for plant uptake in the soil varies temporally and spatially. Therefore, modern agriculture relies heavily on nitrogen fertilization to maximize crop quality and yield. Auxins are a group of naturally occurring molecules derived from tryptophan, with indole-3-acetic acid (IAA) being the major form of auxin. The biosynthesis of IAA is defined by a two-step metabolic pathway, in which the TAA family of aminotransferases converts tryptophan (Trp) to indole-3-pyruvate (IPA), followed by a YUC flavin monooxygenases-mediated conversion of IPA to IAA. Auxin has extensive regulatory functions in plant development. 
  • 871
  • 10 Jul 2023
Topic Review
Enoxacin as a Small-Molecule Enhancer of microRNA
Enoxacin is a second-generation quinolone with promising anticancer activity. In contrast to other members of the quinolone group, it exhibits an extraordinary cytotoxic mechanism of action. Enoxacin enhances RNA interference and promotes microRNA processing, as well as the production of free radicals. Interestingly, apart from its proapoptotic, cell cycle arresting and cytostatic effects, enoxacin manifests a limitation of cancer invasiveness. The underlying mechanisms are the competitive inhibition of vacuolar H+-ATPase subunits and c-Jun N-terminal kinase signaling pathway suppression. The mentioned mechanisms seem to contribute to a safer, more selective and more effective anticancer therapy.
  • 870
  • 08 Jul 2022
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