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Topic Review
Studying the Human Microbiota
Biological clocks are systems in living organisms that allow them to respond to the passage of time, anticipate environmental changes, and regulate and coordinate various physiological processes.
  • 861
  • 21 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.
  • 860
  • 11 Mar 2021
Topic Review
Myelin Basic Protein Interaction Landscape
Intrinsically disordered myelin basic protein (MBP) is one of the key autoantigens in autoimmune neurodegeneration and multiple sclerosis particularly. MBP is highly positively charged and lacks a distinct structure in solution, and therefore its intracellular partners are still mostly enigmatic. Here authors used combination of formaldehyde-induced cross-linking followed by immunoprecipitation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to elucidate the interaction network of MBP in mammalian cells and provide the list of potential MBP interacting proteins.
  • 860
  • 15 Nov 2021
Topic Review
Transthyretin Misfolding
Transthyretin (TTR) is an essential transporter of a thyroid hormone and a holo-retinol binding protein, found abundantly in human plasma and cerebrospinal fluid. In addition, this protein is infamous for its amyloidogenic propensity, causing various amyloidoses in humans, such as senile systemic amyloidosis, familial amyloid polyneuropathy, and familial amyloid cardiomyopathy. Decreased stability of the native tetrameric conformation and subsequent misfolding of TTR is the main cause of these diseases.
  • 859
  • 18 May 2021
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.
  • 859
  • 19 Jul 2021
Topic Review
Cancer-Associated DNA/RNA Binding Proteins
DNA and RNA binding proteins (DRBPs) are a broad class of molecules that regulate numerous cellular processes across all living organisms, creating intricate dynamic multilevel networks to control nucleotide metabolism and gene expression. These interactions are highly regulated, and dysregulation contributes to the development of a variety of diseases, including cancer. 
  • 859
  • 31 Aug 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). 
  • 859
  • 09 Jan 2023
Topic Review
Nanoparticles in the Food Industry
Nanoparticles (NPs) are clusters of atoms in the nano-scale. The use of inorganic NPs has expanded into various industries including food manufacturing, agriculture, cosmetics, and construction. This has allowed NPs access to the human gastrointestinal tract, yet little is known about their impact on human health. As the gut microbiome continues to be increasingly implicated in various gut diseases of unknown etiology, researchers have begun studying the potentially toxic effects of NPs on the gut microbiome and gut barrier. This research has been invaluable in determining the impact of NPs on the intestinal tract ultimately showing that NPs have the potential to contribute to diseases including inflammatory bowel disease and colorectal cancer. With a focus on inorganic nanoparticles, this review presents a discussion of these studies while highlighting NP characteristics, study design, and techniques. Additionally, NP-induced changes to microbial composition are compared with disease-associated alterations in order to elucidate a potential link.
  • 858
  • 11 Mar 2021
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). 
  • 858
  • 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. 
  • 858
  • 13 Jan 2022
Topic Review
ncRNA Subtypes, Biogenesis, and Turnover
Epigenetics investigates modifications in the expression of genes that do not depend on the underlying DNA sequence. Some studies have confirmed that environmental factors, such as toxicants, may promote a phenotype or a disease in an individual or even in the subsequent progeny through epigenetic alterations. Several epigenetic mechanisms, including modifications in DNA (e.g., methylation), histones, and non-protein coding RNAs (ncRNAs) can change genome expression under the exogenous influenc. The latent interest in epigenetics has resulted in breakthroughs in seminal concepts in diseases ranging from autoimmune conditions to cancer, congenital diseases, mental retardation, endocrine diseases, pediatric diseases, neuropsychiatric disorders, and many others.
  • 858
  • 20 Apr 2022
Topic Review
Ovarian Aging
Ovarian aging has a genetic basis that conditions the ovarian activity via a plethora of cell-signaling pathways that control the functions of different types of cells in the ovary. There are various factors that can influence these pathways so as to reduce their efficiency. Oxidative stress, often related to mitochondrial dysfunction, leading to the apoptosis of ovarian cells, can be at the origin of vicious circles in which the primary cause feeds back other abnormalities, resulting in an overall decline in the ovarian activity and in the quantity and quality of oocytes.
  • 857
  • 27 Feb 2021
Topic Review
Therapy for Sickle Cell Disease
Sickle cell disease (SCD) is a severe hereditary form of anemia that results from a single mutation in the sixth codon of the gene encoding the β-globin chain (from glutamic acid to valine) of the adult Hb tetramer (α2β2), which is prone to polymerization at low oxygen levels.
  • 857
  • 22 Jun 2021
Topic Review
Post-Acute Sequela of SARS-CoV-2
The COVID-19 pandemic has paralleled the great Spanish flu pandemic of 1918–1919 in the United States. Previous historical accounts have strongly suggested a post-viral syndrome and, currently, a post-COVID-19 viral syndrome is unquestionable, which shares many of the characteristics of myalgic encephalomyelitis/chronic fatigue syndrome that is present globally. The original term for this post-acute sequela of SARS-CoV-2 (PASC) was termed long haulers by those who were affected with this syndrome and it is now termed long COVID (LC) or PASC. International researchers and clinicians are desperately trying to better understand the pathobiological mechanisms possibly involved in this syndrome. This review aims to summarize many of the cumulated findings associated with LC/PASC and provides supportive and representative illustrations and transmission electron micrographic remodeling changes within brain tissues associated with a stress type of injury as occurs in the classic db/db and novel BTBR ob/ob obesity and diabetes mellitus mice models. These models are utilized to merely provide a response to metabolic stress injury wound healing mechanisms that are also present in humans. This review posits that neuroglial activation and chronic neuroinflammation may be a common denominator for the development of the complex LC/PASC syndrome following acute COVID-19 due to SARS-CoV-2.  This review was written with the intent of describing the mounting problem of Long COVID or PASC referred to by patients as Long-Haulers and the authors' personal experience with treating patients with the post-viral syndrome of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) due to HSV-1 encephalitis and a cluster of patients with human cytomegalic virus (hCMV) infections who were suffering from what is now termed Long COVID- Post-Acute Sequela of Coronavirus-2 or PASC.  
  • 857
  • 24 Sep 2021
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.
  • 856
  • 25 Jan 2022
Topic Review
Retinal Amyloid-β
Amyloid-β (Aβ) is a 39–43 amino acid protein peptide that originates from the amyloidogenic pathway with cleavage of a transmembrane glycoprotein, amyloid precursor protein (APP), by β- and γ-secretase. Retinal Aβ accumulations in neurodegeneration-associated disorders like Alzheimer's disease, glaucoma, and age-related macular degeneration have been extensively studied and regarded as an overlapping pathological feature between these disorders with no successful cure. 
  • 855
  • 22 Sep 2021
Topic Review
SH003 as a Therapeutic Anticancer Agent
SH003, a novel herbal medicine containing Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii, showed the potential to act as an anticancer agent in previous research studies.
  • 855
  • 29 Mar 2022
Topic Review
m6A Modification and Glucose Metabolism
The highly conserved and dynamically reversible N6-methyladenine (m6A) modification has emerged as a critical gene expression regulator by affecting RNA splicing, translation efficiency, and stability at the post-transcriptional level, which has been established to be involved in various physiological and pathological processes, including glycolipid metabolism and the development of glycolipid metabolic disease (GLMD). Hence, accumulating studies have focused on the effects and regulatory mechanisms of m6A modification on glucose metabolism, lipid metabolism, and GLMD. Glucose metabolism involves a very complex regulatory network, including anaerobic glycolysis, aerobic oxidation, pentose phosphate pathway, glycogen synthesis, and gluconeogenesis. An increasing number of studies have reported that m6A modification is an important regulatory mechanism of glucose homeostasis and downstream effects.
  • 855
  • 14 Feb 2023
Topic Review
Extracellular Vesicles Application as Drug Delivery Carriers
Extracellular vesicles (EVs) are membrane vesicles released into the extracellular milieu by cells of various origins. They contain different biological cargoes, protecting them from degradation by environmental factors. There is an opinion that EVs have a number of advantages over synthetic carriers, creating new opportunities for drug delivery. There are minimal requirements for carriers used for therapeutic nucleic acids (tNAs) delivery in the clinic. Briefly, they should provide for long circulation, low immunogenicity, and high intracellular accumulation of tNAs, simultaneously. In addition, the tNA delivery system must be biodegradable and act in a specific manner. A number of reviews have already discussed the use of EVs as a delivery system in various aspects: the EV surface molecules potentially involved in their interaction with recipient cells, the doses of EVs used for preclinical studies, strategies for engineering EVs with specific targeting ligands, approaches used for increasing the EV stability in the bloodstream. 
  • 855
  • 05 May 2023
Topic Review
TATDN2
Replicative DNA polymerases are blocked by nearly all types of DNA damage. The resulting DNA replication stress threatens genome stability. DNA replication stress is also caused by depletion of nucleotide pools, DNA polymerase inhibitors, and DNA sequences or structures that are difficult to replicate. Replication stress triggers complex cellular responses that include cell cycle arrest, replication fork collapse to one-ended DNA double-strand breaks, induction of DNA repair, and programmed cell death after excessive damage. Replication stress caused by specific structures (e.g., G-rich sequences that form G-quadruplexes) is localized but occurs during the S phase of every cell division.
  • 855
  • 06 Dec 2023
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