Eicosanoid signaling in neuroinflammation associated with Alzheimer's disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative condition affecting a substantial portion of the global population. It is marked by a complex interplay of factors, including the accumulation of amyloid plaques and tau tangles within the brain, leading to neuroinflammation and neuronal damage. Recent studies have underscored the role of free lipids and their derivatives in the initiation and progression of AD.

Mangiferin, A Naturally Occurring Glucosylxanthone, Induces Apoptosis in Caco-2 Cells and Exerts Protective Effects on Acetic Acid-Induced Ulcerative Colitis in Mice through the Regulation of NLRP3.

Inflammatory bowel diseases (IBD), an inflammatory disease, include Crohn's disease and ulcerative colitis. Dysregulated autoimmune response to gut dysbiosis is mainly involved in the pathogenesis of IBD and is triggered by various inciting environmental factors. With its rising prevalence in every continent, IBD has evolved into a global disease, which is on the rise, affecting people of all ages.

Design, synthesis and evaluation of 2-aryl quinoline derivatives against 12R-lipoxygenase (12R-LOX): Discovery of first inhibitor of 12R-LOX.

The 12R-lipoxygenase (12R-LOX), a (non-heme) iron-containing metalloenzyme belonging to the lipoxygenase (LOX) family catalyzes the conversion of arachidonic acid (AA) to its key metabolites. Studies suggested that 12R-LOX plays a critical role in immune modulation for the maintenance of skin homeostasis and therefore can be considered as a potential drug target for psoriasis and other skin related inflammatory diseases. However, unlike 12-LOX (or 12S-LOX) the enzyme 12R-LOX did not receive much attention till date.

Comprehensive Analysis of Serum Small Extracellular Vesicles-Derived Coding and Non-Coding RNAs from Retinoblastoma Patients for Identifying Regulatory Interactions.

The present study employed nanoparticle tracking analysis, transmission electron microscopy, immunoblotting, RNA sequencing, and quantitative real-time PCR validation to characterize serum-derived small extracellular vesicles (sEVs) from RB patients and age-matched controls. Bioinformatics methods were used to analyze functions, and regulatory interactions between coding and non-coding (nc) sEVs RNAs. The results revealed that the isolated sEVs are round-shaped with a size < 150 nm, 5.

Managing SARS-CoV2 Infections Through Resolution of Inflammation by Eicosanoids: A Review.

Severe Corona Virus Disease is characterized by angiocentric inflammation of lungs and cytokine storm leading to potentially fatal multiple organ failure. Several studies have shown the high levels of pro-inflammatory cytokines, indicative of a poor prognosis in COVID-19. Eicosanoids play an important role in the induction of inflammation and cytokine production, while anti-inflammatory and pro-resolving properties of some eicosanoic acid derivatives enable inflamed tissues to return to homeostasis through the resolution of inflammation by aiding the clearance of cell debris and downregulation of pro-inflammatory stimulants.

Milk exosomes elicit a potent anti-viral activity against dengue virus.

Background: Exosomes are nano-sized vesicles secreted by various cells into the intra and extracellular space and hence is an integral part of biological fluids including milk. In the last few decades, many research groups have proved the potential of milk exosomes as a sustainable, economical and non-immunogenic drug delivery and therapeutic agent against different pathological conditions. However, its anti-viral properties still remain to be unearthed.

Drug Loading and Functional Efficacy of Cow, Buffalo, and Goat Milk-Derived Exosomes: A Comparative Study.

Quite recently, milk exosomes have been recognized as efficient drug delivery systems owing to their biocompatibility and easy availability for scale-up technologies. However, there are no reports of comparative studies with regards to drug delivery by milk exosomes derived from different species. In this study, we isolated and characterized milk exosomes of cow, buffalo, and goat by various techniques and tried to understand their drug loading capacity and functional efficiency in HepG2, HCT116, and A549 cells by using doxorubicin.

Knock-In Mice Expressing a 15-Lipoxygenating Alox5 Mutant Respond Differently to Experimental Inflammation Than Reported Mice.

Arachidonic acid 5-lipoxygenase (ALOX5) is the key enzyme in the biosynthesis of pro-inflammatory leukotrienes. We recently created knock-in mice (-KI) which express an arachidonic acid 15-lipoxygenating Alox5 mutant instead of the 5-lipoxygenating wildtype enzyme. These mice were leukotriene deficient but exhibited an elevated linoleic acid oxygenase activity.

Overview on the Discovery and Development of Anti-Inflammatory Drugs: Should the Focus Be on Synthesis or Degradation of PGE?

Inflammation is a protective response that develops against tissue injury and infection. Chronic inflammation, on the other hand, is the key player in the pathogenesis of many inflammatory disorders including cancer. The cytokine storm, an inflammatory response flaring out of control, is mostly responsible for the mortality in COVID-19 patients.

Exosomes: The protagonists in the tale of colorectal cancer?

Exosomes, which facilitate intercellular communication, antigen presentation and shuttling of biological agents, were initially thought as the cell's garbage cargo but today, after about 40 years of their discovery, we are now beginning to understand their potential role in diagnosis and therapy of several diseases including cancers. Various studies over the decades have signified the role of exosomes in different stages of cancer. Exosomes play a key role in colorectal cancer initiation (CRC), promotion of anti- apoptotic signaling pathways, regulating tumor microenvironment, enhancing tumorigenicity, promotion of angiogenesis, stem cell proliferation and endothelial cell migration, establishment of immune suppressive environment, formation of pre- metastatic niche and metastasis.

Bedd. root-derived flavonoids as prominent antiviral agents against Newcastle disease virus.

The discovery and development of novel antiviral drugs from natural sources is continuously increasing due to limitations of currently available drugs such as toxic side effects, drug residue risk factors, high costs, and poor therapeutic strategies. Also, there are very few known antiviral drugs that are effective against only specific viruses. Hence, the present study is intended to isolate and characterize potent antiviral compounds from the methanolic root extract of Bedd.

Performance Evaluation of Docking Programs- Glide, GOLD, AutoDock & SurflexDock, Using Free Energy Perturbation Reference Data: A Case Study of Fructose-1, 6-bisphosphatase-AMP Analogs.

Background: The accurate ranking of analogs of lead molecules with respect to their estimated binding free energies to drug targets remains highly challenging in molecular docking due to small relative differences in their free energy values.

Methods: Free energy perturbation (FEP) method, which provides the most accurate relative binding free energy values were earlier used to calculate free energies of many ligands for several important drug targets including Fructose-1,6-BisphosPhatase (FBPase). The availability of abundant structural and experimental binding affinity data for FBPase inhibitors provided an ideal system to evaluate four widely used docking programs, AutoDock, Glide, GOLD and SurflexDock, distinct from earlier comparative evaluation studies.

Role of Prostaglandins in Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune demyelinating disorder with chronic inflammation in the central nervous system, manifested by both physical and cognitive disability. Neuroinflammation and neurodegeneration are the phenomena that appear in the central nervous system associated with various neurodegenerative disorders, including MS, Alzheimer's diseases, amyotrophic lateral sclerosis and Parkinson's disease. Prostaglandins are one of the major mediators of inflammation that exhibit an important function in enhancing neuroinflammatory and neurodegenerative processes.

Potential Therapeutic Applications of C-Phycocyanin.

Background: Cancer and other disorders such as inflammation, autoimmune diseases and diabetes are the major health problems observed all over the world. Therefore, identifying a therapeutic target molecule for the treatment of these diseases is urgently needed to benefit public health. C-Phycocyanin (C-PC) is an important light yielding pigment intermittently systematized in the cyanobacterial species along with other algal species.

Tumor microenvironment determines drug efficacy in vitro - apoptotic and anti-inflammatory effects of 15-lipoxygenase metabolite, 13-HpOTrE.

Recent studies using 3D scaffolds have emphasized the importance of the surrounding stroma on chemoresistance in drug efficacy screenings. Since 15-lipoxygenase (15-LOX) metabolites reduced growth of breast, colon, prostate, lung and leukemia cancer cells in 2D cell culture, we were intrigued by the direct comparison of 15-LOX metabolite efficacy in 2D and 3D culture including a stroma equivalent. Herein, we studied the effects of 15-LOX metabolites 13-HpOTrE, 13-HpODE, and 15-HpETE on cutaneous squamous cell carcinoma cells.

Evaluation of anti-inflammatory and immunomodulatory effects of Premna integrifolia extracts and assay-guided isolation of a COX-2/5-LOX dual inhibitor.

Premna integrifolia (Agnimantha brihat) is a traditional medicinal plant with a prominent place in Ayurveda, Siddha and Unani systems of medicine. In this study we have evaluated the anti-inflammatory and immunomodulatory properties of the Premna integrifolia root extracts employing cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX) enzyme-based assays, lymphocyte proliferation assay, pro-and anti-inflammatory cytokines measurement. Petroleum ether extract (PEE) of Premna integrifolia showed potent inhibition of COX-2 and 5-LOX with IC values of 6.

Synthesis, Characterization, and Biodistribution of Quantum Dot-Celecoxib Conjugate in Mouse Paw Edema Model.

Increased risk of cardiovascular side effects has been reported with many of the drugs in the market, including nonsteroidal anti-inflammatory drugs (NSAIDs). Hence, it is critical to thoroughly evaluate the biodistribution and pharmacokinetic properties of the drugs. Presently nanotechnology in combination with noninvasive imaging techniques such as magnetic resonance imaging (MRI), computed axial tomography (CAT), and positron emission tomography (PET) provides a better estimate of the spatio-temporal distribution of therapeutic molecules.

Anti-inflammatory profile of Aegle marmelos (L) Correa (Bilva) with special reference to young roots grown in different parts of India.

Background: Aegle marmelos (Bilva) is being used in Ayurveda for the treatment of several inflammatory disorders. The plant is a member of a fixed dose combination of Dashamoola in Ayurveda. However, the usage of roots/root bark or stems is associated with sustainability concerns.

Current insights into functions of phospholipase A2 receptor in normal and cancer cells: More questions than answers.

Lipid signaling network was proposed as a potential target for cancer prevention and treatment. Several recent studies revealed that phospholipid metabolising enzyme, phospholipase A2 (PLA), is a critical regulator of cancer accelerating pathologies and apoptosis in several types of cancers. In addition to functioning as an enzyme, PLA can activate a phospholipase A2 receptor (PLA2R1) in plasma membrane.

Benzoylsalicylic acid derivatives as defense activators in tobacco and Arabidopsis.

Systemic acquired resistance (SAR) is a long lasting inducible whole plant immunity often induced by either pathogens or chemical elicitors. Salicylic acid (SA) is a known SAR signal against a broad spectrum of pathogens in plants. In a recent study, we have reported that benzoylsalicylic acid (BzSA) is a SAR inducer in tobacco and Arabidopsis plants.

Evaluation of Anti-Inflammatory Properties of Isoorientin Isolated from Tubers of .

Inflammation is the major causative factor of different diseases such as cardiovascular disease, diabetes, obesity, osteoporosis, rheumatoid arthritis, inflammatory bowel disease, and cancer. Anti-inflammatory drugs are often the first step of treatment in many of these diseases. The present study is aimed at evaluating the anti-inflammatory properties of isoorientin, a selective cyclooxygenase-2 (COX-2) inhibitor isolated from the tubers of , in vitro on mouse macrophage cell line (RAW 264.

15-Lipoxygenase metabolites of α-linolenic acid, [13-(S)-HPOTrE and 13-(S)-HOTrE], mediate anti-inflammatory effects by inactivating NLRP3 inflammasome.

The ratio of ω-6 to ω-3 polyunsaturated fatty acids (PUFAs) appears to be critical in the regulation of various pathophysiological processes and to maintain cellular homeostasis. While a high proportion of dietary intake of ω-6 PUFAs is associated with various inflammatory disorders, higher intake of ω-3 PUFAs is known to offer protection. It is now well established that beneficial effects of ω-3 PUFAs are mediated in part by their oxygenated metabolites mainly via the lipoxygenase (LOX) and cyclooxygenase (COX) pathways.

Benzoylsalicylic acid isolated from seed coats of Givotia rottleriformis induces systemic acquired resistance in tobacco and Arabidopsis.

Systemic acquired resistance (SAR), a whole plant defense response to a broad spectrum of pathogens, is characterized by a coordinated expression of a large number of defense genes. Plants synthesize a variety of secondary metabolites to protect themselves from the invading microbial pathogens. Several studies have shown that salicylic acid (SA) is a key endogenous component of local and systemic disease resistance in plants.

Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase As (PLAs), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles.