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Topic Review
NF-κB as CRC Promising Biomarkers
From the Centers for Disease Control and Prevention (CDC), colorectal cancer (CRC), also known as bowel cancer, refers to cancers that originate in the colon or rectum. This is further defined by the positioning of the cancer, dictating whether it is termed colon cancer or rectum cancer. Biomarkers play an important role in the early diagnosis and targeted treatment of CRC. Biomarkers of CRC can be widely characterized into two major groups: diagnostic and clinical biomarkers. NF-κB comprises a family of five transcription factors that regulate the expression of a variety of genes involved in several biological processes. These processes include inflammation, cellular development and differentiation, cell cycle progression, cell migration and so on. As a major nexus of inflammation and cancer, NF-κB signaling has been reported to be extensively implicated in CRC progression. From the formation of polyps to the development of an invasive adenocarcinoma, NF-κB has been shown to play a role in multiple stages of malignancy development in the colon.
  • 870
  • 19 Jul 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. 
  • 870
  • 17 Dec 2021
Topic Review
LonP1 in the Oral and Maxillofacial Regions
Recent studies have indicated a central role for LonP1 in mitochondrial function. Its physiological functions include proteolysis, acting as a molecular chaperone, binding mitochondrial DNA, and being involved in cellular respiration, cellular metabolism, and oxidative stress. Given its vital role in energy metabolism, LonP1 has been suggested to be associated with multi-system neoplasms and developmental disorders. 
  • 870
  • 21 Nov 2022
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.
  • 870
  • 28 Nov 2022
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.
  • 870
  • 01 Aug 2023
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.
  • 869
  • 10 Nov 2022
Topic Review
TRPV3 Ion Channel
Transient receptor potential vanilloid subtype 3 (TRPV3) is an ion channel with a sensory function that is most abundantly expressed in keratinocytes and peripheral neurons. TRPV3 plays a role in Ca2+ homeostasis due to non-selective ionic conductivity and participates in signaling pathways associated with itch, dermatitis, hair growth, and skin regeneration. TRPV3 is a marker of pathological dysfunctions, and its expression is increased in conditions of injury and inflammation.
  • 869
  • 24 May 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. 
  • 868
  • 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.
  • 867
  • 24 Sep 2020
Topic Review
Heparan Sulfate
White adipose tissues are major endocrine organs that release factors, termed adipokines, which affect other major organ systems. The development and functions of adipose tissues depend largely upon the glycosaminoglycan heparan sulfate. Heparan sulfate proteoglycans (HSPGs) surround both adipocytes and vascular structures and facilitate the communication between these two components. This communication mediates the continued export of adipokines from adipose tissues. Heparan sulfates regulate cellular physiology and communication through a sulfation code that ionically interacts with heparan-binding regions on a select set of proteins. Many of these proteins are growth factors and chemokines that regulate tissue function and inflammation. Cells regulate heparan sulfate sulfation through the release of heparanases and sulfatases. It is now possible to tissue engineer vascularized adipose tissues that express heparan sulfate proteoglycans. This makes it possible to use these tissue constructs to study the role of heparan sulfates in the regulation of adipokine production and release. It is possible to regulate the production of heparanases and sulfatases in order to fine-tune experimental studies.
  • 867
  • 09 Sep 2022
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
  • 867
  • 23 Aug 2023
Topic Review
Estrogen Receptor Beta
The discovery of the Estrogen Receptor Beta (ERβ) in 1996 opened new perspectives in the diagnostics and therapy of different types of cancer. 
  • 866
  • 19 Feb 2021
Topic Review
Ultrastructural Features of the Blood-Brain Barrier
The blood-brain barrier (BBB) is a dynamic barrier separating neurocytes and brain tissues from blood that is extremely sealed and strictly regulated by transporters such as aquaporin-4 (AQP-4), glucose transporter (GLUT), and specialized tight junctional complexes (TJCs) including tight junctions (TJs), adherens junctions (AJs), and Zonulae occludens (ZOs). With specifically selective transcellular and paracellular permeability, the BBB maintains a homeostatic microenvironment to protect the central nervous system (CNS).
  • 866
  • 27 Jul 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.
  • 865
  • 20 Feb 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.
  • 865
  • 10 May 2023
Topic Review
Epidrugs in Therapy of Central Nervous System Disorders
The polygenic nature of neurological and psychiatric syndromes and the significant impact of environmental factors on the underlying developmental, homeostatic, and neuroplastic mechanisms suggest that an efficient therapy for these disorders should be a complex one. Pharmacological interventions with drugs selectively influencing the epigenetic landscape (epidrugs) allow one to hit multiple targets, therefore, assumably addressing a wide spectrum of genetic and environmental mechanisms of central nervous system (CNS) disorders. 
  • 865
  • 28 Nov 2023
Topic Review
Microglia and Hypothalamic Inflammation
Hypothalamic inflammation is a condition frequently observed in experimental models of diet-induced obesity (DIO) and obese humans. This inflammatory response is mainly triggered by excessive saturated fatty acids (SFAs) from the diet, which reach the neural tissue mainly through the median eminence (ME), where fenestrated vascular endothelium lacks a blood–brain barrier (BBB). Brain perivascular macrophages (PVMs) also react to excessive free fatty acids (FFAs) circulating in the blood vessels, with a consequent increase in BBB permeability. Glial cells, such as astrocytes and microglia, quickly sense and react to the presence of those SFAs in the hypothalamic parenchyma, releasing pro-inflammatory cytokines, chemokines, and reactive oxygen species (ROS). If the stimulus persists, the hypothalamic neuronal network may be damaged, resulting in neuro-inflammation, which eventually leads to energy balance disruption, and finally, to neuronal dysfunction/apoptosis.
  • 865
  • 11 Mar 2021
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.
  • 864
  • 08 Oct 2021
Topic Review
miR-23b-3p, miR-124-3p, and miR-218-5p Regulate Cervical Cancer Progression
In cervical cancer (CC), miR-23b-3p, miR-124-3p, and miR-218-5p have been found to act as tumor suppressors by regulating cellular processes related to progression and metastasis.
  • 864
  • 28 Nov 2022
Topic Review
Role of miRs in Polyphenol-Mediated Anticancer
The anticancer effects of daily consumption of polyphenols. These dietary polyphenols include chlorogenic acid, curcumin, epigallocatechin-3-O-gallate, genistein, quercetin, and resveratrol. These polyphenols have similar chemical and biological properties in that they can act as antioxidants and exert the anticancer effects via cell signaling pathways involving their reactive oxygen species (ROS)-scavenging activity. These polyphenols may also act as pro-oxidants under certain conditions, especially at high concentrations. Epigenetic modifications, including dysregulation of noncoding RNAs (ncRNAs) such as microRNAs, long noncoding RNAs, and circular RNAs are now known to be involved in the anticancer effects of polyphenols. These polyphenols can modulate the expression/activity of the component molecules in ROS-scavenger-triggered anticancer pathways (RSTAPs) by increasing the expression of tumor-suppressive ncRNAs and decreasing the expression of oncogenic ncRNAs in general. Multiple ncRNAs are similarly modulated by multiple polyphenols. Many of the targets of ncRNAs affected by these polyphenols are components of RSTAPs. Therefore, ncRNA modulation may enhance the anticancer effects of polyphenols via RSTAPs in an additive or synergistic manner, although other mechanisms may be operating as well.
  • 863
  • 19 Dec 2022
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