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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.
  • 874
  • 01 Dec 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. 
  • 874
  • 09 Mar 2023
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.
  • 874
  • 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. 
  • 874
  • 25 Jun 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.
  • 873
  • 21 Jan 2021
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
Topic Review
Application of CRISPR/CAS9 in Basic Gastric Cancer Research
Gastric cancer is the subject of clinical and basic studies due to its high incidence and mortality rates worldwide. Due to the diagnosis occurring in advanced stages and the classic treatment methodologies such as gastrectomy and chemotherapy, they are extremely aggressive and limit the quality of life of these patients. CRISPR/Cas9 is a tool that allows gene editing and has been used to explore the functions of genes related to gastric cancer, in addition to being used in the treatment of this neoplasm, greatly increasing our understanding of cancer genomics.
  • 873
  • 28 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). 
  • 873
  • 09 Jan 2023
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.
  • 872
  • 24 Sep 2020
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. 
  • 872
  • 12 Aug 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. 
  • 872
  • 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.
  • 871
  • 08 Oct 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
  • 871
  • 23 Aug 2023
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.
  • 869
  • 29 Mar 2022
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. 
  • 868
  • 10 Jul 2023
Topic Review
Iron-Binding Catecholato Chelators
Siderophores are iron-complexing compounds synthesized by bacteria and fungi. They are low molecular weight compounds (500-1500 Daltons) possessing high affinity for iron(III). This entry reports an integrated computational/synthetic approach towards a rational development of peptide-based siderophores.
  • 867
  • 16 Oct 2020
Topic Review
Parkin Downregulation in TDP-43 Proteinopathies
Parkin and PINK1 are key regulators of mitophagy, an autophagic pathway for selective elimination of dysfunctional mitochondria. To this date, parkin depletion has been associated with recessive early onset Parkinson’s disease (PD) caused by loss-of-function mutations in the PARK2 gene, while, in sporadic PD, the activity and abundance of this protein can be compromised by stress-related modifications. Intriguingly, research in recent years has shown that parkin depletion is not limited to PD but is also observed in other neurodegenerative diseases—especially those characterized by TDP-43 proteinopathies, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). 
  • 867
  • 07 Dec 2021
Topic Review
Inorganic SOD1 Inhibitors with Anti-Cancer Prospects
For eukaryotic cells, reactive oxygen species (ROS) encompass a group of molecules derived from oxygen. Due to the well-established role of ROS in cell signaling, cancer cells always have higher levels of endogenous ROS to enhance rapid cell growth and proliferation through the mitogen-activated protein kinase (MAPK)/extracellular-regulated kinase 1/2 (ERK1/2), phosphoinositide-3-kinase (PI3K)/Akt, nuclear factor-κB (NF-κB), and hypoxia-sensitive α (HIF1α) pathways. Evaluated ROS have frequently been observed in various cancers, which activate multiple pro-tumourigenic signaling, and induce survival and proliferation of cancer cells. Hydrogen peroxide and superoxide anion are the most important redox signaling agents in cancer cells, whose homeostasis is maintained by dozens of growth factors, cytokines and antioxidant enzymes. Therefore, antioxidant enzymes, especially Cu/Zn superoxide dismutase (SOD1), tend to have higher activities to maintain the homeostasis of ROS in cancer cells. We can inhibit the activity of SOD1 using copper chelators to kill cancer cells. 
  • 867
  • 13 Jan 2022
Topic Review
Triterpenoids in Momordica charantia
The vines and leaves of Momordica charantia L. are used as herbal medicines to treat inflammation-related disorders. However, their safety profile remains uncharacterized, and the constituents in their extracts that exert anti-inflammatory and adverse effects remain unclear. This study isolated the characteristic cucurbitane-type triterpenoid species in the vines and leaves of M. charantia L. and analyzed their cytotoxicity, anti-inflammatory effects, and underlying mechanisms. Four structurally related triterpenoids—momordicines I, II, IV, and (23E) 3β,7β,25-trihydroxycucurbita-5,23-dien-19-al (TCD)—were isolated from the triterpenoid-rich fractions of extracts from the vines and leaves of M. charantia. Momordicine I was cytotoxic on normal cells, momordicine II exerted milder cytotoxicity, and momordicine IV and TCD had no obvious adverse effects on cell growth. TCD had anti-inflammatory activity both in vivo and in vitro. In lipopolysaccharide-stimulated RAW 264.7 cells, TCD inhibited the inhibitor kappa B kinase/nuclear factor-κB pathway and enhanced the expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, and glutamate-cysteine ligase modifier subunit through the extracellular signal-regulated kinase1/2 and p38. Thus, the vines and leaves of M. charantia should be used with caution. An extraction protocol that can enrich TCD but remove momordicine I would likely enhance the safety of the extract.
  • 867
  • 25 Jan 2022
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.
  • 867
  • 09 Feb 2023
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