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Topic Review
Therapeutic Efficacy of Cucurbitacin
Cucurbitacins are a class of secondary metabolites initially isolated from the Cucurbitaceae family. They are important for their analgesic, anti-inflammatory, antimicrobial, antiviral, and anticancer biological actions.
  • 906
  • 07 Nov 2022
Topic Review
Crosstalk of ADP-Ribosylation with Other Protein Post-Translational Modifications
ADP-ribosylation is a post-translational modification of proteins that plays a key role in various cellular processes, including DNA repair. ADP-ribosylation can regulate the recruitment and activity of DNA repair proteins by facilitating protein–protein interactions and regulating protein conformations. Moreover, ADP-ribosylation can influence additional post-translational modifications (PTMs) of proteins involved in DNA repair, such as ubiquitination, methylation, acetylation, phosphorylation, and SUMOylation. The interaction between ADP-ribosylation and these additional PTMs can fine-tune the activity of DNA repair proteins and ensure the proper execution of the DNA repair process.
  • 906
  • 19 Oct 2023
Topic Review
Presenilin-2
Presenilin-2 (PS2) is one of the three proteins that are dominantly mutated in familial Alzheimer’s disease (FAD). It forms the catalytic core of the γ-secretase complex—a function shared with its homolog presenilin-1 (PS1)—the enzyme ultimately responsible of amyloid-β  (Aβ) formation. PS2 is also involved in several functions, also independently of γ-secretase activity, ranging from Ca2+ signalling to inter-organelle communication and autophagy. FAD-linked PS2 mutations impact on multiple aspects of cell and tissue physiology, including bioenergetics and brain network excitability.
  • 906
  • 05 Nov 2020
Topic Review
Various Adeno-Associated Viruses Serotypes in Gene Therapy
Depending on their serotype, adeno-associated viruses (AAVs) can have specific tropism for specific organs and tissues of the body. There are different AAV serotypes that vary in many aspects. A variety of AAV features have made it an appealing viral vector candidate to be used in gene therapy applications. 
  • 905
  • 06 May 2023
Topic Review
Delivery of Nitric Oxide in the Cardiovascular System
Nitric oxide (NO) is a key molecule in cardiovascular homeostasis and its abnormal delivery is highly associated with the occurrence and development of cardiovascular disease (CVD). The assessment and manipulation of NO delivery is crucial to the diagnosis and therapy of CVD, such as endothelial dysfunction, atherosclerotic progression, pulmonary hypertension, and cardiovascular manifestations of coronavirus (COVID-19). 
  • 904
  • 18 Nov 2021
Topic Review
Oxidative Stress-Induced Cellular Senescence
Cellular senescence, a cell state characterized by a generally irreversible cell cycle arrest, is implicated in various physiological processes and a wide range of age-related pathologies. Oxidative stress, a condition caused by an imbalance between the production and the elimination of reactive oxygen species (ROS) in cells and tissues, is a common driver of cellular senescence. ROS encompass free radicals and other molecules formed as byproducts of oxygen metabolism, which exhibit varying chemical reactivity. 
  • 904
  • 28 Jun 2023
Topic Review
Castration and Male Peripheral Neurons
This entry deals with the influence of androgens (testosterone) on pelvic autonomic pathways in male mammals. The vast majority of the relevant information has been gained in experiments involving castration (testosterone deprivation) performed in male rats, and recently, in male pigs. In both species, testosterone significantly affects the biology of the pathway components, including the pelvic neurons. However, there are great differences between rats and pigs in this respect. The most significant alteration is that testosterone deprivation accomplished a few days after birth results some months later in the excessive loss (approximately 90%) of pelvic and urinary bladder trigone intramural neurons in the male pig, while no changes in the number of pelvic neurons are observed in male rats (rats do not have the intramural ganglia). In the castrated pigs, much greater numbers of pelvic neurons than in the non-castrated animals express CGRP, GAL, VIP (peptides known to have neuroprotective properties), and caspase 3, suggesting that neurons die due to apoptosis triggered by androgen deprivation. In contrast, only some morpho-electrophysiological changes affecting neurons following castration are found in male rats. Certain clinicopathological consequences of testosterone deprivation for the functioning of urogenital organs are also discussed. 
  • 903
  • 18 Sep 2021
Topic Review
Mitotropic Substances
Mitotropic substances, or so-called mitoceuticals, describe substances whose mode of action is directed at the bioenergetic processes of the mitochondria and are, in part, essential for their function. The term mitoceuticals, created by Dr. Franz Enzmann, encompasses several groups of mitotropic substances, which have a versatile potential and form the basis for a preventive and therapeutic approach in mitochondrial medicine. They act non-specifically and reach all mitochondria in the organism. The best-known substances include electron and proton carriers, such as ubiquinol/ubiquinone (coenzyme Q10; CoQ10), vitamins, minerals, and micronutrients. Mitoceuticals are substances that are part of the natural metabolic system of a cell anyway. They are used both preventively and therapeutically for accompanying treatment. In both cases, the aim is to compensate for an existing mitochondrial dysfunction. In the meantime, there are a large number of mitotropic substances and even more studies on them.
  • 903
  • 23 May 2023
Topic Review
Role of SCAP/SREBP in Hepatic Steatosis
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a unique, multi-factorial condition with several phases of progression including steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Sterol element binding protein 1c (SREBP1c) is the main transcription factor involved in regulating hepatic de novo lipogenesis. This transcription factor is synthesized as an inactive precursor, and its proteolytic maturation is initiated in the membrane of the endoplasmic reticulum upon stimulation by insulin. SREBP cleavage activating protein (SCAP) is required as a chaperon protein to escort SREBP from the endoplasmic reticulum and to facilitate the proteolytic release of the N-terminal domain of SREBP into the Golgi. SCAP inhibition prevents activation of SREBP and inhibits the expression of genes involved in triglyceride and fatty acid synthesis, resulting in the inhibition of de novo lipogenesis.
  • 903
  • 24 Jan 2024
Topic Review
Glycoprotein Ib-IX-V Receptor Complex
The GPIb-IX-V complex is a profuse membrane receptor complex originating in megakaryocytes and exclusively functional on the surface of platelets. It primarily functions to mediate the first critical step in platelet adhesion, by facilitating binding to von Willebrand factor (VWF) on damaged sub-endothelium under conditions of high fluid shear stress. Although the primary ligand for the GPIb-V-IX receptor is VWF, it can also bind to a number of other ligands in the circulation such as thrombin, P-selectin, factor XI, factor XII, high molecular weight kininogen as well as bacteria. GPIb-IX-V offers a critical role in thrombosis, metastasis, and the life cycle of platelets, and is implicated in a number of thrombotic pathological processes such as stroke or myocardial infarction.
  • 901
  • 17 Oct 2022
Topic Review
Synthesis and Metabolism of H2S in Lung Cancer
Lung cancer is one of the 10 most common cancers in the world, which seriously affects the normal life and health of patients. The mechanisms of action of the occurrence and development of lung cancer have not been fully clarified. As a new type of gas signal molecule, hydrogen sulfide (H2S) has received great attention for its physiological and pathological roles in mammalian cells. It has been found that H2S is widely involved in the regulation of the respiratory system and digestive system, and plays an important role in the occurrence and development of lung cancer.
  • 901
  • 13 Jan 2023
Topic Review
Mechanisms of Circular RNAs and Cardiovascular Diseases
Circular RNAs (circRNAs) are a family of noncoding RNAs (ncRNAs) that are endogenous and widely distributed in different species, performing several functions, mainly their association with microRNAs (miRNAs) and RNA-binding proteins. Cardiovascular diseases (CVDs) remain the leading cause of death worldwide; therefore, the development of new therapies and strategies, such as gene therapies or nonpharmacological therapies, with low cost, such as physical exercise, to alleviate these diseases is of extreme importance for society.
  • 901
  • 02 Feb 2023
Topic Review
Mechanism of Action of the Plagiochilins
Plagiochilin A functions as an inhibitor of the termination phase of cytokinesis: the membrane abscission stage. This unique, innovative mechanism of action, coupled with its marked anticancer action, notably against prostate cancer cells, make plagiochilin A an interesting lead molecule for the development of novel anticancer agents. There are known options to increase its potency, as deduced from structure–activity relationships. The analysis shed light on this family of bryophyte species and the little-known group of bioactive terpenoid plagiochilins. Plagiochilin A and derivatives shall be further exploited for the design of novel anticancer targeting the cytokinesis pathway.
  • 901
  • 24 Mar 2023
Topic Review
Genista tridentata Phytochemical Characterization
Genista tridentata (L.) Willk., known as “prickled broom”, is a Leguminosae (Fabaceae) species native to the Iberian Peninsula, Morocco, Algeria, and Tunisia. It is used in folk medicine as an anti-inflammatory, for gastrointestinal and respiratory disorders, rheumatism, and headaches, to lower blood pressure, against hypercholesterolemia and hyperglycemia. 
  • 901
  • 08 Nov 2023
Topic Review
Proteases and Dry Eye Disease
Dry eye disease (DED) is a multifactorial disorder that leads to ocular discomfort, visual disturbance, and tear film instability. DED is accompanied by an increase in tear osmolarity and ocular surface inflammation. The diagnosis and treatment of DED still present significant challenges.
  • 900
  • 13 Sep 2022
Topic Review
Endoplasmic Reticulum Stress in Diseases Pathogenesis
The endoplasmic reticulum (ER) is a dynamic structure, playing multiple roles including calcium storage, protein synthesis and lipid metabolism. During cellular stress, variations in ER homeostasis and its functioning occur. This condition is referred as ER stress and generates a cascade of signaling events termed unfolded protein response (UPR), activated as adaptative response to mitigate the ER stress condition. UPR is activated in several disorders, including inflammation, diabetes, metabolic and neurodegenerative diseases, as well as in cancer. 
  • 900
  • 27 Dec 2022
Topic Review
Association between Microplastics and Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) has emerged as the predominant cause of chronic liver injury; however, the mechanisms underlying its progression have not been fully elucidated. Pathophysiological studies have stated that NAFLD is significantly influenced by dietary and environmental factors that could participate in the development of NAFLD through different mechanisms. “Plastic pollution” is one of the most challenging environmental problems worldwide since several plastics have potential toxic or endocrine disputing properties. Specifically, the intake of microplastics (MPs) and nanoplastics (NPs) in water or diet and/or the inhalation from suspended particles is well established, and these particles have been found in human samples. Laboratory animals exposed to MPs develop inflammation, immunological responses, endocrine disruptions, and alterations in lipid and energy metabolism, among other disorders. MPs additives also demonstrated adverse reactions.  Adequate mitigation strategies worldwide, reducing environmental pollution and human exposure levels of MPs, could reduce the risk of NAFLD.
  • 900
  • 26 May 2023
Biography
Prof. Nilesh Kumar Sharma
Dr. Nilesh Kumar Sharma, an Ideator and scholar with a Ph.D. degree (2009) from IIT Roorkee, India, focusing on Health Science. He subsequently pursued post-doctoral research in DNA repair and Cancer genetics at prominent institutions including the National Institute of Environmental Health Sciences (NIEHS), (NIH), and Rutgers University, New Jersey Medical School (USA) between 2013-2016. Curren
  • 900
  • 04 Nov 2024
Topic Review
SMUG1 in rRNA Quality Control
RNA modifications are essential for proper RNA processing, quality control, and maturation steps. In the last decade, some eukaryotic DNA repair enzymes have been shown to have an ability to recognize and process modified RNA substrates and thereby contribute to RNA surveillance. Single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1) is a base excision repair enzyme that not only recognizes and removes uracil and oxidized pyrimidines from DNA but is also able to process modified RNA substrates. SMUG1 interacts with the pseudouridine synthase dyskerin (DKC1), an enzyme essential for the correct assembly of small nucleolar ribonucleoproteins (snRNPs) and ribosomal RNA (rRNA) processing. Here, we review rRNA modifications and RNA quality control mechanisms in general and discuss the specific function of SMUG1 in rRNA metabolism. Cells lacking SMUG1 have elevated levels of immature rRNA molecules and accumulation of 5-hydroxymethyluridine (5hmU) in mature rRNA. SMUG1 may be required for post-transcriptional regulation and quality control of rRNAs, partly by regulating rRNA and stability.
  • 899
  • 28 Jan 2021
Topic Review
Atopic Dermatitis-Associated Alopecia Areata
Alopecia areata (AA) is regarded as a tissue-specific and cell-mediated autoimmune disorder. Regarding the cytokine balance, AA has been considered a type 1 inflammatory disease. On the other hand, AA often complicates atopic dermatitis (AD) and AD is regarded as type 2 inflammatory disease. However, the immunological aspects of AA in relation to AD are still poorly understood. Therefore, we aim to clarify the immunological properties of AD-associated AA. In this study, we performed comparative analysis of the expression of intracytoplasmic cytokines (IFN-γ, IL-4, and IL-13), chemokine receptors (CXCR3 and CCR4) in peripheral blood which were taken from healthy controls, non-atopic AA patients, AA patients with extrinsic AD, and AA patients with intrinsic AD by flowcytometric analysis. We also compared the scalp skin samples taken from AA patients with extrinsic AD before and after treatment with dupilumab. In non-atopic AA patients, the ratios of CD4+IFN-γ+ cells to CD4+IL-4+ cells and CD4+IFN-γ+ cells to CD4+IL-13+ cells were higher than those in AA patients with extrinsic AD. Meanwhile, the ratio of CD8+IFN-γ+ cells to CD8+IL-13+ cells was significantly higher in the non-atopic AA than in the healthy controls. In AA patients with extrinsic AD, the skin AA lesion showed dense infiltration of not only CXCR3+ cells but also CCR4+ cells around hair bulb before dupilumab treatment. However, after the treatment, the number of CXCR3+ cells had no remarkable change while the number of CCR4+ cells significantly decreased. These results indicate that the immunological condition of AA may be different between atopic and non-atopic patients and between extrinsic and intrinsic AD patients. Our study provides an important notion that type 2 immunity may participate in the development of AA in extrinsic AD patients. It may be considered that the immunological state of non-atopic AA is different from that of atopic AA.
  • 898
  • 10 Mar 2021
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