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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.
  • 901
  • 19 Jul 2021
Topic Review
ceRNA Regulate Alternative Splicing in Cervical Cancer
Cervical cancer (CC) is the primary cause of female cancer fatalities in low-middle-income countries (LMICs). Through their interaction with mRNA, non-coding RNAs form a network of competing endogenous RNAs (ceRNAs), which regulate gene expression and promote cervical cancer development and advancement. The dysregulated expression of non-coding RNAs is an understudied and tangled process that promotes cervical cancer development. The ceRNA network hypothesizes that RNA transcripts with miRNA response elements (MREs) can sequester from other targets, thus regulating their expression and cellular processes. CircRNA and lncRNA competitively bind to miRNAs and regulate downstream gene expression, forming the ceRNA regulatory axis.
  • 901
  • 08 Feb 2023
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.
  • 901
  • 11 Mar 2024
Topic Review
Chronic Muscle Disuse
Periods of muscle disuse promote diminished muscle quality along with muscle atrophy that is characterized by reductions in muscle fiber cross-sectional area (CSA). Skeletal muscle disuse may be brought about by chronic sedentarism, periods of immobilization due to injury, bed rest as result of illness, or even exposure to microgravity. Such inactivity elicits functional and metabolic derangements in the affected tissue including marked mitochondrial alterations that contribute to the impaired metabolic health and degree of atrophy in the muscle. These impairments within the tissue prompt a net increase in catabolic processes in conjunction with reductions in skeletal muscle protein synthesis. Skeletal muscle mitochondrial decline and atrophy are underlying features of many diseases and they exacerbate disease progression and reduced mobility with aging. Thus, understanding the molecular underpinnings of muscle mitochondrial deficits with prolonged inactivity is of considerable interest.
  • 901
  • 21 May 2021
Topic Review
Leptin in Inflammation
Leptin is an important regulator of basal metabolism and food intake, with a pivotal role in obesity. Leptin exerts many different actions on various tissues and systems, including cancer, and is considered as a linkage between metabolism and the immune system. 
  • 901
  • 05 Jul 2021
Topic Review
AMD and the Complement System
Wet age-related macular degeneration (wAMD) is characterized by choroidal neovascularization (CNV), and it is the leading cause of blindness affecting elderly in the Western world. AMD is a complex disease that has strong associations with the complement system. All three initiating complement pathways may be relevant in CNV formation, but most evidence indicates a major role for the alternative pathway (AP) and for the terminal complement complex, as well as certain complement peptides generated upon complement activation. Since the complement system is associated with AMD and CNV, a complement inhibitor may be a therapeutic option for patients with wAMD. The aim of the review is to (i) reflect on the possible complement targets in the context of wAMD pathology, (ii) investigate the results of prior clinical trials with complement inhibitors for wAMD patients, and (iii) outline important considerations when developing a future strategy for the treatment of wAMD.
  • 901
  • 22 Feb 2021
Topic Review
Function of Defensive Molecules Momilactones A and B
Labdane-related diterpenoids, momilactones A and B were isolated and identified in rice husks in 1973 and later found in rice leaves, straws, roots, root exudate, other several Poaceae species and the moss species Calohypnum plumiforme. Momilactones in rice plants suppressed the growth of fungal pathogens, indicating the defense function against pathogen attacks. Rice plants also inhibited the growth of adjacent competitive plants through the root secretion of momilactones into their rhizosphere due to the potent growth-inhibitory activity of momilactones, indicating a function in allelopathy.
  • 900
  • 30 Mar 2023
Topic Review
GNL3 and PA2G4 as Prostate Cancer Prognostic Biomarkers
Guanine nucleotide-binding protein-like 3 (GNL3) and proliferation-associated protein 2G4 (PA2G4) are molecules involved during metaphase-to-anaphase transition and growth regulation. GNL3 and PA2G4 have been found to be overexpressed in several human cancers, including prostate cancer. Clinical data suggest that GNL3 and PA2G4 could be developed as prognostic biomarkers of clinical significance in prostate cancer.
  • 899
  • 03 Jul 2023
Topic Review
The V-ATPase a3 Subunit
This entry focuses on one of the 16 proteins composing the V-ATPase complex responsible for resorbing bone: the a3 subunit. The rationale for focusing on this biomolecule is that mutations in this one protein account for over 50% of osteopetrosis cases, highlighting its critical role in bone physiology. Despite its essential role in bone remodeling and its involvement in bone diseases, little is known about the way in which this subunit is targeted and regulated within osteoclasts. To this end, this review is broadened to include the three other mammalian paralogues (a1, a2 and a4) and the two yeast orthologs (Vph1p and Stv1p). By examining the literature on all of the paralogues/orthologs of the V-ATPase a subunit, we hope to provide insight into the molecular mechanisms and future research directions specific to a3. This review starts with an overview on bone, highlighting the role of V-ATPases in osteoclastic bone resorption. We then cover V-ATPases in other location/functions, highlighting the roles which the four mammalian a subunit paralogues might play in differential targeting and/or regulation. Author review the ways in which the energy of ATP hydrolysis is converted into proton translocation, and go in depth into the diverse role of the a subunit, not only in proton translocation but also in lipid binding, cell signaling and human diseases. Finally, the therapeutic implication of targeting a3 specifically for bone diseases and cancer is discussed, with concluding remarks on future directions.
  • 898
  • 21 Jul 2021
Topic Review
EVs–PEG–cECMH Product
The combination of cardiosphere-derived extracellular vesciles (EVs), polyethylene glycol (PEG), and cardiac extracellular matrix hydrogel (cECMH), EVs–PEG–cECMH, is a potential multipronged product with improved gelation time and mechanical properties, increased on-site retention, and maintained bioactivity that, all together, may translate into boosted therapeutic efficacy.
  • 898
  • 14 Sep 2021
Topic Review
Skeletal Muscle Pathogenesis in Polyglutamine Diseases
Polyglutamine diseases are characterized by selective dysfunction and degeneration of specific types of neurons in the central nervous system. In addition, nonneuronal cells can also be affected as a consequence of primary degeneration or due to neuronal dysfunction. Skeletal muscle is a primary site of toxicity of polyglutamine-expanded androgen receptor, but it is also affected in other polyglutamine diseases, more likely due to neuronal dysfunction and death. Nonetheless, pathological processes occurring in skeletal muscle atrophy impact the entire body metabolism, thus actively contributing to the inexorable progression towards the late and final stages of disease. 
  • 898
  • 28 Jul 2022
Topic Review
AR and PI3K/AKT in Prostate Cancer
The androgen receptor (AR) has a pivotal role in the pathogenesis and progression of PCa. Many therapies targeting AR signaling have been developed over the years. AR signaling inhibitors (ARSIs), including androgen synthesis inhibitors and AR antagonists, have proven to be effective in castration-sensitive PCa (CSPC) and improve survival, but men with castration-resistant PCa (CRPC) continue to have a poor prognosis. Despite a good initial response, drug resistance develops in almost all patients with metastatic CRPC, and ARSIs are no longer effective. Several mechanisms confer resistance to ARSI and include AR mutations but also hyperactivation of other pathways, such as PI3K/AKT/mTOR. This pathway controls key cellular processes, including proliferation and tumor progression, and it is the most frequently deregulated pathway in human cancers.
  • 898
  • 02 Feb 2023
Topic Review
Chaperone-Like Activity of HSPB5
Small heat-shock proteins (sHSPs) are ATP-independent molecular chaperones that interact with partially unfolded proteins, preventing their aberrant aggregation, thereby exhibiting a chaperone-like activity. Dynamics of the quaternary structure plays an important role in the chaperone-like activity of sHSPs. However, relationship between the dynamic structure of sHSPs and their chaperone-like activity remains insufficiently characterized. Many factors (temperature, ions, a target protein, crowding etc.) affect the structure and activity of sHSPs. The least studied is an effect of crowding on sHSPs activity. In this work the chaperone-like activity of HSPB5 was quantitatively characterized by dynamic light scattering using two test systems, namely test systems based on heat-induced aggregation of muscle glycogen phosphorylase b (Phb) at 48 °C and dithiothreitol-induced aggregation of α-lactalbumin at 37 °C. Analytical ultracentrifugation was used to control the oligomeric state of HSPB5 and target proteins. The possible anti-aggregation functioning of suboligomeric forms of HSPB5 is discussed. The effect of crowding on HSPB5 anti-aggregation activity was characterized using Phb as a target protein. The duration of the nucleation stage was shown to decrease with simultaneous increase in the relative rate of aggregation of Phb in the presence of HSPB5 under crowded conditions. Crowding may subtly modulate sHSPs activity.
  • 898
  • 20 Jul 2020
Topic Review
Inflammasome in Neurodegenerative Diseases
Neurodegenerative diseases are chronic, progressive disorders that occur in the central nervous system (CNS). They are characterized by the loss of neuronal structure and function and are associated with inflammation. Inflammation of the CNS is called neuroinflammation, which has been implicated in most neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Much evidence indicates that these different conditions share a common inflammatory mechanism: the activation of the inflammasome complex in peripheral monocytes and in microglia, with the consequent production of high quantities of the pro-inflammatory cytokines IL-1β and IL-18. Inflammasomes are a group of multimeric signaling complexes that include a sensor Nod-like receptor (NLR) molecule, the adaptor protein ASC, and caspase-1. The NLRP3 inflammasome is currently the best-characterized inflammasome. Multiple signals, which are potentially provided in combination and include endogenous danger signals and pathogens, trigger the formation of an active inflammasome, which, in turn, will stimulate the cleavage and the release of bioactive cytokines including IL-1β and IL-18.
  • 896
  • 03 Mar 2021
Topic Review
Molecular Techniques for Infectious Diseases
Infectious diseases significantly impact the health status of developing countries. Historically, infectious diseases of the tropics especially have received insufficient attention in worldwide public health initiatives, resulting in poor preventive and treatment options. Many molecular tests for human infections have been established since the 1980s, when polymerase chain reaction (PCR) testing was introduced. In spite of the substantial innovative advancements in PCR technology, which currently has found wide application in most viral pathogens of global concern, the development and application of molecular diagnostics, particularly in resource-limited settings, poses potential constraints.
  • 896
  • 14 Oct 2022
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.
  • 895
  • 18 May 2021
Topic Review
Human FoxP Transcription Factors
Although the Fox family of transcription factors has been described as monomers even in the presence of their cognate DNA, suggesting their full functionality without requiring oligomerization, members of the FoxP subfamily show both monomers and 3D-DS dimers (B). This novel ability in a well-known monomeric family has been largely attributed to a single replacement of a conserved proline by alanine (Pro39Ala) in the hinge region that connects helices H2 and H4 (B). Additionally, the ability to adopt intertwined dimers has been a focus of interest in terms of the possibility to bind different DNA loci within a given chromosome or even in physically mediating interchromosomal contacts, suggesting that the emergence of the 3D-DS could impact their mechanism of action and the complexity of the gene regulation networks in which they participate.
  • 895
  • 27 Oct 2021
Topic Review
C1q in Neurodegenerative Diseases
Complement Component 1q (C1q), an initiating recognition molecule of the classical complement pathway, can interact with a variety of ligands and perform a range of functions in physiological and pathophysiological conditions of the central nervous system (CNS). Beyond its established roles in CNS growth, development, and bodily immunization, a novel facet of C1q’s functionality has been freshly unveiled within the intricate tapestry of neuropathological pathways that underpin neurodegenerative disorders and traumatic brain injury (TBI). This revelation has cast a spotlight on C1q as a prospective therapeutic avenue for safeguarding neuronal well-being or for retarding the progression of neurodegenerative maladies.
  • 895
  • 13 Oct 2023
Topic Review
Rheumatoid Arthritis(RA)
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, which affects approximately 1% of the global population and occurs preferably in females, with a female-to-male ratio of 3:1. The disease can begin slowly and gradually with mainly non-specific symptoms such as fatigue, low-grade fever, general malaise, and joint pain; later, more defined symptoms such as intense pain, morning stiffness, and swelling of the joints have been described. In general, the joints most frequently affected are those of the hands and wrists, followed by those of the feet, knees, elbows, ankles, up to involving the wider joints of the shoulders, hips, jaws, and cervical spine. With overt disease, joint swelling occurs, caused by synovial effusion being associated to joint deformities and ankylosis. For this reason, RA is associated with a lower quality of life, a partial and/or total incapacity to work, a form of progressive disability and a higher probability of developing other co-morbidities.   
  • 894
  • 10 Feb 2021
Topic Review
FABP in α-Synuclein-Induced Mitochondrial Injury
Synucleinopathies are diverse diseases with motor and cognitive dysfunction due to progressive neuronal loss or demyelination, due to oligodendrocyte loss in the brain. While the etiology of neurodegenerative disorders (NDDs) is likely multifactorial, mitochondrial injury is one of the most vital factors in neuronal loss and oligodendrocyte dysfunction, especially in Parkinson’s disease, dementia with Lewy body, multiple system atrophy, and Krabbe disease. In recent years, the abnormal accumulation of highly neurotoxic α-synuclein in the mitochondrial membrane, which leads to mitochondrial dysfunction, was well studied. Furthermore, fatty acid-binding proteins (FABPs), which are members of a superfamily and are essential in fatty acid trafficking, were reported to trigger α-synuclein oligomerization in neurons and glial cells and to target the mitochondrial outer membrane, thereby causing mitochondrial loss.
  • 894
  • 02 Jun 2021
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