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Topic Review
LCA, DCA, and Their Derivatives from Gut Microbiota
A wide variety and large number of bacterial species live in the gut, forming the gut microbiota. Gut microbiota not only coexist harmoniously with their hosts, but they also induce significant effects on each other. The composition of the gut microbiota can be changed due to environmental factors such as diet and antibiotic intake. In contrast, alterations in the composition of the gut microbiota have been reported in a variety of diseases, including intestinal, allergic, and autoimmune diseases and cancer. The gut microbiota metabolize exogenous dietary components ingested from outside the body to produce short-chain fatty acids (SCFAs) and amino acid metabolites. Unlike SCFAs and amino acid metabolites, the source of bile acids (BAs) produced by the gut microbiota is endogenous BAs from the liver. The gut microbiota metabolize BAs to generate secondary bile acids, such as lithocholic acid (LCA), deoxycholic acid (DCA), and their derivatives, which have recently been shown to play important roles in immune cells. 
  • 968
  • 22 Nov 2023
Topic Review
Quercetin in Age-Related Diseases
Polyphenols are the known group of phytochemicals that essentially consists of phenolic rings. These are the plant product present in varied fruits and vegetables. These secondary metabolites perform a protective function in plants from environmental and biological stress. When consumed as a human diet these are also known to prevent various age-associated diseases. Polyphenols are known to possess antioxidant properties and protect against oxidative stress. Quercetin is among the widely occurring polyphenol, found abundantly in nature. It is commonly present in different plant products. Onion is known to have the highest quantity of quercetin. This plant compound is possessed antioxidant properties and is considered to have a protective function against aging. It is known to be present in both free and conjugated forms. Quercetin has anti-oxidative, anti-inflammatory, anti-proliferative, anti-carcinogenic, anti-diabetic, and anti-viral properties.
  • 966
  • 11 May 2022
Topic Review
Mechanism of TGF-β Functions in mCRC
Colorectal cancer (CRC) is a serious public health issue, and it has the leading incidence and mortality among malignant tumors worldwide. CRC patients with metastasis in the liver, lung or other distant sites always have poor prognosis. CRC metastasis is a dynamic, multistep and multifactorial process, which includes the following successive steps: detachment from the primary CRC site, infiltration into adjacent tissues, invasion into blood/lymphatic circulation, transportation through the circulatory system, intravasation from vasculature and formation of CRC colonies in distant sites. Three critical factors contribute to CRC cells migration (pivotal for early metastasis): regulating the epithelial–mesenchymal transition (EMT) process, stemness and the microenvironment of CRC cells. Additionally, angiogenesis facilitates CRC cell transportation to distal locations. TGF-β signaling contributes to mCRC mainly through the following four mechanisms: promoting EMT, facilitating angiogenesis, creating an immunosuppressive microenvironment and regulating the stemness of mCRC .
  • 966
  • 01 Dec 2022
Topic Review
Pathological Role of Mitochondrial Reactive Oxygen Species
Mitochondrial reactive oxygen species (mtROS)  are cellular messengers instrumental in maintaining cellular homeostasis. As cellular messengers, they are produced in specific places at specific times, and the intensity and duration of the ROS signal determine the downstream effects of mitochondrial redox signalling.
  • 966
  • 12 Apr 2023
Topic Review
Network Regulation of microRNA Biogenesis and Target Interaction
MicroRNAs (miRNAs) are versatile, post-transcriptional regulators of gene expression. Canonical miRNAs are generated through the two-step DROSHA- and DICER-mediated processing of primary miRNA (pri-miRNA) transcripts with optimal or suboptimal features for DROSHA and DICER cleavage and loading into Argonaute (AGO) proteins, whereas multiple hairpin-structured RNAs are encoded in the genome and could be a source of non-canonical miRNAs. Advances in miRNA biogenesis research have revealed details of the structural basis of miRNA processing and cluster assistance mechanisms that facilitate the processing of suboptimal hairpins encoded together with optimal hairpins in polycistronic pri-miRNAs. In addition, a deeper investigation of miRNA–target interaction has provided insights into the complexity of target recognition with distinct outcomes, including target-mediated miRNA degradation (TDMD) and cooperation in target regulation by multiple miRNAs.
  • 965
  • 20 Feb 2023
Topic Review
Amyloid-β Proteins and Pericytes
This review provides an updated overview of the interaction between Aβ proteins with pericytes, one the most significant and often forgotten cellular components of the BBB and the inner blood retinal barrier (IBRB).
  • 964
  • 24 May 2020
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.
  • 964
  • 01 Aug 2023
Topic Review
Transforming Growth Factor-Beta in Skeletal Muscle Wasting
Transforming growth factor (TGF)-β is the name for a superfamily of proteins, including myostatin, that functions in the body to affect growth and to stimulate the inflammatory response along with other functions covered elsewhere. TGF-β in skeletal muscle not only contributed to muscle fibrosis in Duchenne Muscular Dystrophy (DMD) disease, but also promoted skeletal muscle atrophy by decreasing muscle fiber diameter and amounts of heavy chain myosin (MHC) in muscle tissue. 
  • 963
  • 28 Mar 2022
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.
  • 963
  • 07 Nov 2022
Topic Review
Tackling Chronic Inflammation with Withaferin
Chronic inflammatory diseases are considered to be one of the biggest threats to human health. Most prescribed pharmaceutical drugs aiming to treat these diseases are characterized by side-effects and negatively affect therapy adherence. Finding alternative treatment strategies to tackle chronic inflammation has therefore been gaining interest over the last few decades. In this context, Withaferin A (WA), a natural bioactive compound isolated from Withania somnifera, has been identified as a promising anti-cancer and anti-inflammatory compound. Although the majority of studies focus on the molecular mechanisms of WA in cancer models, recent evidence demonstrates that WA also holds promise as a new phytotherapeutic agent against chronic inflammatory diseases. By targeting crucial inflammatory pathways, including NF-kB and Nrf2 signaling, WA suppresses the inflammatory disease state in several in vitro and preclinical in vivo models of diabetes, obesity, neurodegenerative disorders, cystic fibrosis, and osteoarthritis. This review provides a concise overview of the molecular mechanisms by which WA orchestrates its anti-inflammatory effects to restore immune homeostasis. 
  • 963
  • 10 Aug 2021
Topic Review
Redox Homeostasis Regulation in Retinal Pigment Epithelium Cells
The retinal pigment epithelium (RPE) performs a range of necessary functions within the neural layers of the retina and helps ensure vision. The regulation of pro-oxidative and antioxidant processes is the basis for maintaining RPE homeostasis and preventing retinal degenerative processes. Long-term stable changes in the redox balance under the influence of endogenous or exogenous factors can lead to oxidative stress (OS) and the development of a number of retinal pathologies associated with RPE dysfunction, and can eventually lead to vision loss. Reparative autophagy, ubiquitin–proteasome utilization, the repair of damaged proteins, and the maintenance of their conformational structure are important interrelated mechanisms of the endogenous defense system that protects against oxidative damage. Antioxidant protection of RPE cells is realized as a result of the activity of specific transcription factors, a large group of enzymes, chaperone proteins, etc., which form many signaling pathways in the RPE and the retina.
  • 963
  • 04 Aug 2023
Topic Review
Breast Cancer Management and Extracellular Vesicle Research
Extracellular vesicles are lipid bilayer-enclosed particles released from all types of cells and found in biological fluids, which transport variable content and have crucial functions in cell–cell communication. The role of extracellular vesicles in cancer is a current hot topic, and no bibliometric study has ever analyzed research production regarding their role in breast cancer and indicated the trends in the field. In this way, the study aimed to investigate the trends in breast cancer management involved with extracellular vesicle research.
  • 962
  • 23 Nov 2021
Topic Review
Aptamer Applications in Neuroscience
Being the predominant cause of disability, neurological diseases have received much attention from the global health community. Over a billion people suffer from one of the following neurological disorders: dementia, epilepsy, stroke, migraine, meningitis, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, prion disease, or brain tumors. The diagnosis and treatment options are limited for many of these diseases. Aptamers, being small and non-immunogenic nucleic acid molecules that are easy to chemically modify, offer potential diagnostic and theragnostic applications to meet these needs.
  • 962
  • 20 Dec 2021
Topic Review
LRRFIP1 is a DAPK1 Interactor
Death-associated protein kinase 1 (DAPK1) is a pleiotropic hub of a number of networked distributed intracellular processes. Among them, DAPK1 is known to interact with the excitotoxicity driver NMDA receptor (NMDAR), and in sudden pathophysiological conditions of the brain, e.g., stroke, several lines of evidence link DAPK1 with the transduction of glutamate-induced events that determine neuronal fate. In turn, DAPK1 expression and activity are known to be affected by the redox status of the cell. To delineate specific and differential neuronal DAPK1 interactors in stroke-like conditions in vitro, we exposed primary cultures of rat cortical neurons to oxygen/glucose deprivation (OGD), a condition that increases reactive oxygen species (ROS) and lipid peroxides. OGD or control samples were co-immunoprecipitated separately, trypsin-digested, and proteins in the interactome identified by high-resolution LC-MS/MS. Data were processed and curated using bioinformatics tools. OGD increased total DAPK1 protein levels, cleavage into shorter isoforms, and dephosphorylation to render the active DAPK1 form. The DAPK1 interactome comprises some 600 proteins, mostly involving binding, catalytic and structural molecular functions. OGD up-regulated 190 and down-regulated 192 candidate DAPK1-interacting proteins. Some differentially up-regulated interactors related to NMDAR and specially the interaction of DAPK1 with the protein leucine-rich repeat of flightless interacting protein 1 (LRRFIP1), that we observed upregulated during OGD and ferroptosis , were validated by WB.
  • 961
  • 04 Dec 2020
Topic Review
The Galaninergic System
Peptidergic systems play an important role in cancer progression. The galaninergic system (the peptide galanin and its receptors: galanin 1, 2 and 3) is involved in tumorigenesis, the invasion and migration of tumor cells and angiogenesis and it has been correlated with tumor stage/subtypes, metastasis and recurrence rate in many types of cancer. Galanin exerts a dual action in tumor cells: a proliferative or an antiproliferative effect depending on the galanin receptor involved in these mechanisms. Galanin receptors could be used in certain tumors as therapeutic targets and diagnostic markers for treatment, prognosis and surgical outcome. 
  • 961
  • 27 Oct 2022
Topic Review
Ferroptosis in H9c2 Cardioblasts: Metabolome Analysis
Ferroptosis is a newly discovered iron-dependent non-apoptotic programmed cell death pathway. It is characterized by the accumulation of oxidized phospholipids due to the excessive oxygenation of polyunsaturated fatty acid (FA) residues of phospholipids by lipoxygenases and the limited capability of glutathione peroxidase 4 (GPX4) to neutralize oxidized phospholipids. Mitochondria play a central role in the pathogenesis of human diseases. They contain the main components and enzymes of the ferroptotic machinery, such as lipoxygenase, GPX4, GSH, glutamate, and iron. Mitochondria do not synthesize GSH and are therefore dependent on the synthesis of cytosolic GSH.  The effects of ferroptosis on the metabolome in H9c2 cardioblasts by gas chromatography-mass spectrophotometry (GC-MS) are described here.
  • 960
  • 29 Mar 2022
Topic Review
Counteracting Immunosuppression in the Tumor Microenvironment
An apparent paradox exists between the evidence for spontaneous systemic T cell- mediated anti-tumor immune responses in cancer patients, observed particularly in their bone marrow, and local tumor growth in the periphery. This phenomenon, known as “concomitant immunity” suggests that the local tumor and its tumor microenvironment (TME) prevent systemic antitumor immunity to become effective. Oncolytic Newcastle disease virus (NDV), an agent with inherent anti-neoplastic and immune stimulatory properties, is capable of breaking therapy resistance and immunosuppression.
  • 960
  • 16 Nov 2022
Topic Review
Laser Capture Microdissection
The advancement in molecular techniques has been attributed to the quality and significance of cancer research. Pancreatic cancer (PC) is one of the rare cancers with aggressive behavior and a high mortality rate. The asymptomatic nature of the disease until its advanced stage has resulted in late diagnosis as well as poor prognosis. The heterogeneous character of PC has complicated cancer development and progression studies. The analysis of bulk tissues of the disease was insufficient to understand the disease, hence, the introduction of the single-cell separating technique aided researchers to decipher more about the specific cell population of tumors. 
  • 960
  • 01 Dec 2022
Topic Review Peer Reviewed
Tissue Integrity and COVID-19
Tissue integrity depends on biological tissue stiffness. Tissue integrity can protect both against age-related diseases and against severity of COVID-19. The disruption of tight junctions and increase of tissue permeability with advancing age can be related with age-related diseases as well as with age-dependent COVID-19. Release of tightly bound water from collagen fibrils leads to the increase of extracellular matrix stiffness and to the associated with matrix stiffness increased tissue permeability. The link between arterial stiffness and oxidative stress has been reported and is expected to be studied in more detail in the future. Trehalose can be suggested for retardation of tightly bound water release and subsequent extracellular matrix crosslinking by advanced glycation end products. Increase in tissue permeability can be blocked by polyphenols that inhibit ICAM-1 expression and mitigate cytoskeleton reorganization. NF-κB activation as a result of increased stiffness and cytoskeleton reorganization can cause both cardiovascular pathologies and COVID-19. Increased cholesterol content in cell membrane leads to increased virus entry into cell and increase of cholesterol is linked with cardiovascular diseases. Statins and chitosan are known as cholesterol-lowering substances. Nrf2 inhibits NF-κB activation and NF-κB inhibits Nrf2 pathway.
  • 960
  • 13 Apr 2022
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.
  • 959
  • 13 Sep 2022
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