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Topic Review
Dysregulated JNK Signaling Pathway in Human Diseases
JNK is named after c-Jun N-terminal kinase, as it is responsible for phosphorylating c-Jun. As a member of the mitogen-activated protein kinase (MAPK) family, JNK is also known as stress-activated kinase (SAPK) because it can be activated by extracellular stresses including growth factor, UV irradiation, and virus infection. Functionally, JNK regulates various cell behaviors such as cell differentiation, proliferation, survival, and metabolic reprogramming. Dysregulated JNK signaling contributes to several types of human diseases.
  • 852
  • 11 Mar 2024
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. 
  • 851
  • 22 Sep 2021
Topic Review
Aryl Hydrocarbon Receptor in Breast Cancer
The aryl hydrocarbon receptor (AhR) is expressed in breast cancer cells and tumors and in some studies, the AhR is a negative prognostic factor for patient survival. Structurally diverse AhR ligands have been extensively investigated as anticancer agents in breast cancer cells and tumors and show efficacy in both estrogen receptor (ER)-positive and ER -negative breast cancer cells. Moreover, synthetic AhR ligands are being developed and have been in clinical trials for treating breast cancer.
  • 851
  • 02 Dec 2022
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). 
  • 850
  • 07 Dec 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.
  • 850
  • 25 Jan 2022
Topic Review
Genomics and Transcriptomics of Myopia
Myopia is a globally emerging concern accompanied by multiple medical and socio-economic burdens with no well-established causal treatment to control thus far. The study of the genomics and transcriptomics of myopia treatment is crucial to delineate disease pathways and provide valuable insights for the design of precise and effective therapeutics. A strong understanding of altered biochemical pathways and underlying pathogenesis leading to myopia may facilitate early diagnosis and treatment of myopia, ultimately leading to the development of more effective preventive and therapeutic measures.
  • 850
  • 27 Mar 2023
Topic Review
Targeting Iron-Sulfur Clusters in Cancer
Iron dysregulation is a hallmark of cancer, characterized by an overexpression of genes involved in iron metabolism and iron-sulfur cluster (ISC) biogenesis. Dysregulated iron homeostasis increases intracellular labile iron, which may lead to the formation of excess cytotoxic radicals and make it vulnerable to various types of regulated cell death, including ferroptosis. The inhibition of ISC synthesis triggers the iron starvation response, increasing lipid peroxidation and ferroptosis in cancer cells treated with oxidative stress-inducing agents. Various methods, such as redox operations, iron chelation, and iron replacement with redox-inert metals, can destabilize or limit ISC formation and function, providing potential therapeutic strategies for cancer treatment. Targeting ISCs to induce ferroptosis represents a promising approach in cancer therapy.
  • 850
  • 01 Aug 2023
Topic Review
Aryl Hydrocarbon Receptor Biology and Signaling
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in regulating a wide range of biological responses. A diverse array of xenobiotics and endogenous small molecules bind to the receptor and drive unique phenotypic responses. Due in part to its role in mediating toxic responses to environmental pollutants, AhR activation has not been traditionally viewed as a viable therapeutic approach. Nonetheless, the expression and activation of AhR can inhibit the proliferation, migration, and survival of cancer cells, and many clinically approved drugs transcriptionally activate AhR. Identification of novel select modulators of AhR-regulated transcription that promote tumor suppression is an active area of investigation. The development of AhR-targeted anticancer agents requires a thorough understanding of the molecular mechanisms driving tumor suppression.
  • 849
  • 19 Apr 2023
Topic Review
DDX20
DEAD-box decapping enzyme 20 (DDX20) is a putative RNA-decapping enzyme that can be identified by the conserved motif Asp–Glu–Ala–Asp (DEAD). Cellular processes involve numerous RNA secondary structure alterations, including translation initiation, nuclear and mitochondrial splicing, and assembly of ribosomes and spliceosomes. DDX20 reportedly plays an important role in cellular transcription and post-transcriptional modifications. On the one hand, DDX20 can interact with various transcription factors and repress the transcriptional process. On the other hand, DDX20 forms the survival motor neuron complex and participates in the assembly of snRNP, ultimately affecting the RNA splicing process. Finally, DDX20 can potentially rely on its RNA-unwinding enzyme function to participate in microRNA (miRNA) maturation and act as a component of the RNA-induced silencing complex. 
  • 849
  • 26 Oct 2023
Topic Review
NRF2 in Chronic Kidney Disease
Nuclear factor erythroid 2 related factor 2 (NRF2) plays a central role in protecting cells from oxidative injury. As a transcription factor, NRF2 induces gene expression of enzymes that combat the effects of oxidative stress.
  • 848
  • 24 Feb 2021
Topic Review
Exosomes for Diseases Prevention
Exosomes are nano-sized vesicles secreted by most cells that contain a variety of biological molecules, such as lipids, proteins and nucleic acids. They have been recognized as important mediators for long-distance cell-to-cell communication and are involved in a variety of biological processes. Exosomes have unique advantages, positioning them as highly effective drug delivery tools and providing a distinct means of delivering various therapeutic agents to target cells. In addition, as a new clinical diagnostic biomarker, exosomes play an important role in many aspects of human health and disease, including endocrinology, inflammation, cancer, and cardiovascular disease. 
  • 848
  • 29 Jul 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.  
  • 848
  • 24 Sep 2021
Topic Review
Therapeutic Implications for Pancreatic Ductal Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is a type of cancer that arises in the exocrine glands of the pancreas and comprises over 90% of pancreatic malignancies. Currently the 11th most common cancer worldwide, PDAC is the seventh leading cause of cancer-related deaths and is on track to move to second place by 2030. Despite the high prevalence, therapeutic options remain limited, with only modest improvements in overall survival (OS) occurring over the past 50 years.
  • 848
  • 12 Oct 2021
Topic Review
Epigenetic Biomarkers for Neurodegenerative Disorders
Epigenetics is the study of heritable changes in gene expression that occur without alterations to the DNA sequence, linking the genome to its surroundings. The accumulation of epigenetic alterations over the lifespan may contribute to neurodegeneration.
  • 848
  • 19 Jan 2022
Topic Review
CirDNA Metabolism and Biological Role
Circulating DNA has already proven itself as a valuable tool in translational medicine. However, one of the overlooked areas of circulating DNA research is its association with different proteins, despite considerable evidence that this association might impact DNA’s fate in circulation and its biological role. The colorful history of circulating DNA (cell-free DNA and cell surface bound DNA, which hereafter will be referred to as cirDNA) research and attempts of its use in the field of oncology went from being skeptically discarded to becoming a valuable tool in clinical oncology.
  • 847
  • 22 Jul 2022
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.
  • 846
  • 29 Mar 2022
Topic Review
Mesenchymal Stem Cell Viral Infection and Host Responses
Mesenchymal stem cells (MSCs) play a critical role in response to stress such as infection. They initiate the removal of cell debris, exert major immunoregulatory activities, control pathogens, and lead to a remodeling/scarring phase. Interestingly, many viruses and particularly those associated to chronic infection and inflammation may hijack and polarize MSC’s immune regulatory activities to their own advantages. Virus will remain in the MSC perivascular niche while being protected from immune attack. In the context of immunodepression (e.g. organ transplantation) the hidden viruses may rebound and causing tissue injuries. 
  • 846
  • 01 Aug 2022
Topic Review
Salivary Metabolomics for Oral Cancer Detection
The development of low- or non-invasive screening tests for cancer is crucial for early detection. Saliva is an ideal biofluid containing informative components for monitoring oral and systemic diseases. Metabolomics has frequently been used to identify and quantify numerous metabolites in saliva samples, serving as novel biomarkers associated with various conditions, including cancers. 
  • 845
  • 27 Jun 2022
Topic Review
Methoxyfuranocoumarins of Natural Origin
Plant secondary metabolites, including furanocoumarins, have attracted attention for decades as active molecules with therapeutic potential, especially those occurring in a limited number of species as evolutionarily specific and chemotaxonomically important. The most famous methoxyfuranocoumarins (MFCs), bergapten, xanthotoxin, isopimpinellin, phellopterin, byakangelicol, byakangelicin, isobergapten, pimpinellin, sphondin, as well as rare ones such as peucedanin and 8-methoxypeucedanin, apaensin, cnidilin, moellendorffiline and dahuribiethrins, have been investigated for their various biological activities.
  • 845
  • 24 Jan 2024
Topic Review
Oxidative Stress and Redox Enzymes in Neurodegenerative Diseases
Neurodegenerative diseases comprise a wide range of diseases with heterogeneous aetiologies and exhibit degenerative processes commonly accompanied by oxidative stress and mitochondrial dysfunction. Mitochondrial dysfunction is a major risk factor associated with aging and the initiation and progression of neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Neurodegenerative diseases are characterised by irreversible, progressive loss of neuronal cells, formation of protein aggregates, and a decline in cognitive or motor functions. Neurodegenerative diseases are induced by imbalanced redox homeostasis and impaired energy metabolism, as hypothesised by several aging theories, including the free radical theory, the mitochondrial dysfunction theory, the genetic theory, and the telomere shortening theory.
  • 844
  • 19 Jan 2022
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