Indolamine

Although immunotherapy has achieved great success in the treatment of a variety of tumors, its efficacy for glioblastoma (GBM) is still limited. Both the immunosuppressive tumor microenvironment (TME) and poor penetration of immunotherapeutic agents into tumors contributed to the poor anti-glioma immunity. Herein, we develop an injectable prodrug-loaded hydrogel delivery system with sono-activatable properties for sonodynamic therapy (SDT)-triggered immunomodulation for GBM treatment. The prodrug alginate hydrogels (APN), which contain semiconducting polymer nanoparticles (SPNs) and the NLG919 prodrug linked by singlet oxygen (1 O2 )-cleavable linkers, are in situ formed via coordination of alginate solution with Ca2+ in the TME...

OBJECTIVE: This study examined (a) whether there are a subgroup of cancer patients experiencing the selected psycho-neurological symptoms as a cluster (depression, cognitive impairment, fatigue, sleep disturbance, and pain); (b) whether demographic and clinical characteristics and pro-inflammatory cytokines (IL-1α, IL-1β, IL-4, IL-6, TNF-alpha) are associated with subgroup membership; and (c) whether the activity of indolamine-2.3 dioxygenase(IDO) is associated with pro-inflammatory cytokine activity and psycho-neurological symptom cluster experience...

Pancreatic ductal adenocarcinoma (PDAC) is the most common exocrine tumor of the pancreas characterized by late diagnosis, adverse overall 5-year survival, a higher propensity for metastatic disease, and lack of efficacy of systemic therapy options. These adverse outcomes can be partly attributed to complex tumor microenvironment (TME). Over the past decade, immunotherapy has revolutionized the management of certain cancers; thus far, the immunologically 'non-inflamed' tumor microenvironment in PDACs has proven to be challenging...

Current pharmacological treatments against post-traumatic stress disorder (PTSD) lack adequate efficacy. As a result, intense research has focused on identifying other molecular pathways mediating the pathogenesis of this condition. One such pathway is neuroinflammation, which has demonstrated a role in PTSD pathogenesis by causing synaptic dysfunction, neuronal death, and functional impairment in the hippocampus. Phosphodiesterase (PDE) inhibitors (PDEIs) have emerged as promising therapeutic agents against neuroinflammation in other neurological conditions...

Pregnancy establishment in bovines requires maternal immune cell modulation. Present study investigated possible role of immunosuppressive indolamine-2, 3-dioxygenase 1 (IDO1) enzyme in the alteration of neutrophil (NEUT) and peripheral blood mononuclear cells (PBMCs) functionality of crossbred cows. Blood was collected from non-pregnant (NP) and pregnant (P) cows, followed by isolation of NEUT and PBMCs. Plasma pro-inflammatory (IFNγ and TNFα) and anti-inflammatory cytokines (IL-4 and IL-10) were estimated by ELISA and analysis of IDO1 gene in NEUT and PBMCs by RT-qPCR...

Melatonin, a pineal hormone, has potential role on steroidogenesis, growth and maturation of sperm and ovum during gametogenesis. The possible use of this indolamine as an antioxidant in the production of good quality gametes opens up a new area of current research. Nowadays, a large number of reproductive dysfunctions like infertility, failure in fertilization due to gametic malformations are major concern worldwide. So, understanding molecular mechanisms including interacting genes and their action is a prerequisite to the therapeutic approach against these issues...

Recent research has focused mostly on understanding and combating the neurodegenerative mechanisms and symptoms of Parkinson's disease (PD). Moreover, developing novel therapeutic targets to halt the progression of PD remains a key focus for researchers. As yet, no agents have been found to have unambiguous evidence of disease-modifying actions in PD. The primary objective of this review is to summarize the promising targets that have recently been uncovered which include histamine 4 receptors, beta2 adrenergic receptor, phosphodiesterase 4, sphingosine-1-phosphate receptor subtype 1, angiotensin receptors, high-mobility group box 1, rabphilin-3A, purinergic 2Y type 12 receptor, colony-stimulating factor-1 receptor, transient receptor potential vanilloid 4, alanine-serine-cysteine transporter 2, G protein-coupled oestrogen receptor, a mitochondrial antiviral signalling protein, glucocerebrosidase, indolamine-2,3-dioxygenase-1, soluble epoxy hydroxylase and dual specificity phosphatase 6...

PURPOSE: Melatonin (Mel) is an indolamine mainly synthesized by the pineal gland and many other organs. It plays an important role in scavenging free radicals and stimulating antioxidant enzymes. The goal of this study was to investigate the effect of Mel and/or insulin treatment on oxidative liver and pancreas injuries in diabetic rats. METHODS: Male Wistar albino rats were assigned into 5 groups. Group I: control animals. Group II: diabetes was induced via a single dose of STZ (60 mg/kg) administered intraperitoneally...

Melatonin is an endogenous indoleamine that has been shown to inhibit tumor growth in laboratory models of prostate cancer. Prostate cancer risk has additionally been associated with exogenous factors that interfere with normal pineal secretory activity, including aging, poor sleep, and artificial light at night. Therefore, we aim to expand on the important epidemiological evidence, and to review how melatonin can impede prostate cancer. More specifically, we describe the currently known mechanisms of melatonin-mediated oncostasis in prostate cancer, including those that relate to the indolamine's ability to modulate metabolic activity, cell cycle progression and proliferation, androgen signaling, angiogenesis, metastasis, immunity and oxidative cell status, apoptosis, genomic stability, neuroendocrine differentiation, and the circadian rhythm...

BACKGROUND: Uveal melanoma is the most common primary intraocular tumor in adults. In Sweden, at least 100 patients are diagnosed with the disease each year. Almost half of the patients develop metastases, with a median survival time of 1 year once metastases are detected. The primary ocular tumor is typically treated with either enucleation or brachytherapy, and no adjuvant treatment is added. Melatonin is an indolamine hormone that has improved survival in previous trials with patients diagnosed with various cancers, including advanced cutaneous melanoma...

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with serious mucosal inflammation mainly in the colon and rectum. Currently, there is no effective therapeutics for UC. Indoximod (IND) is a water-insoluble inhibitor for indolamine 2, 3-dioxygenase (IDO) and has been mainly reported in cancer therapy. Here, we prepared orally administrated IND nanoparticles (IND-NPs) for UC treatment and investigated their functions and mechanisms in cellular and animal inflammatory models. Confocal imaging demonstrated that IND-NPs maintained the expression level of ZO-1, Occludin and E-cadherin, thereby stabilizing of intercellular junction in Caco-2 cells...

Fatigue is a frequent symptom in hemodialysis (HD), and the indolamine-2,3-dioxygenase (IDO) metabolic trap has been hypothesized in the pathogenesis of fatigue. The association between IDO activity according to fatigue and its relationship with muscle mass and function in HD patients was verified. Chronic HD patients were considered, and fatigue was assessed. The plasma kynurenines and tryptophan ratio (Kyn/Trp), as surrogate of IDO activity, and interleukin (IL)-6 were measured. Muscularity was assessed by BIA and muscle strength by hand-grip dynamometer...

In DNA, electron excitation allows adjacent pyrimidine bases to dimerize by [2 + 2] cycloaddition, creating chemically stable but lethal and mutagenic cyclobutane pyrimidine dimers (CPDs). The usual cause is ultraviolet radiation. Alternatively, CPDs can be made in the dark (dCPDs) via chemically mediated electron excitation of the skin pigment melanin, after it is oxidized by peroxynitrite formed from the stress-induced radicals superoxide and nitric oxide. We now show that the dark process is not limited to the unusual structural molecule melanin: signaling biomolecules such as indolamine and catecholamine neurotransmitters and hormones can also be chemiexcited to energy levels high enough to form dCPDs...

Tryptophan (TRP) is an essential amino acid catabolized mainly through the kynurenine pathway (KP), and part of it is catabolized in the brain. The abnormal depletion of TRP and production of kynurenine (KYN) by two enzymes, tryptophan 2, 3-dioxygenase (TDO) and indolamine 2, 3-dioxygenase (IDO), have been linked to various neurological diseases. The ratio of TRP/KYN in plasma is a valuable measure for IDO/TDO activity and the prognosis of disease conditions. The vinylphenyl boronic acid (4-VPBA) was evaluated as a novel stationary phase for OT-CEC-MS/MS...

Coffee is one of the most popular beverages in the world. Therefore, this study analyzed 49 coffee samples of Arabica and Robusta species of different geographical origins and the treatment of beans including three degrees of roasting with the use of LC-MS/MS. This is the first study to present a comprehensive analysis of Kopi Luwak coffee brew metabolites in comparison to fully washed coffees and the drying post-harvest treatment of Arabica or Robusta coffee brews. Kopi Luwak showed higher levels of caffeine and theophylline in comparison to the analyzed washed and unwashed Arabica coffees, as well as a different proportion of caffeoylquinic isomers...

Infertility is an increasing global public health concern with socio-psychological implications for affected couples. Remarkable advances in reproductive medicine have led to successful treatments such as assisted reproductive techniques (ART). However, the search for new therapeutic tools to improve ART success rates has become a research hotspot. In the last few years, pineal indolamine melatonin has been investigated for its powerful antioxidant properties and its role in reproductive physiology. It is considered a promising therapeutical agent to counteract the detrimental effects associated with oxidative stress in fertility treatments...

Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of somatic diseases. The pathophysiology of anxiety development is complex and involves alterations in stress hormone production, neurosignaling pathways or free radical production. The various manifestations of anxiety, its complex pathophysiological background and the side effects of available treatments underlie the quest for constantly seeking therapies for these conditions...

Melatonin (MEL) presents well-documented pleiotropic actions against oxidative stress (OS), acting indirectly through activation of transcription factors, e.g., FoxO3 and Nrf2. Thus, this study aimed to investigate the possible modulating effects of MEL on the redox signaling pathways PI3K/AKT/FoxO3 and Keap1/Nrf2/ARE in K562 erythroleukemic cells subjected to OS induction. For this, the viability, and transcript levels of genes involved in redox adaptation were evaluated in K562 cells in different periods of erythroid differentiation: under OS induction by hydrogen peroxide (100 µM H2 O2 ); treated with 1 nM (C1) and 1 mM (C2) MEL; and associated or not with stress induction...

In recent days, the hike in obesity mediated epidemic across the globe and prevalence of obesity induced cardiovascular disease (CVD) has become one of the chief grounds of morbidity and mortality. This epidemic driven detrimental events in the cardiac tissues starts with the altered distribution and metabolism pattern of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) leading to cholesterol (oxidized LDL) deposition on arterial wall and atherosclerotic plaque generation, followed by vascular spasm and infarction...

We studied suppressor potential of myeloid-derived suppressor cells (MDSC) in multiple myeloma patients, including before and after mobilization of hematopoietic stem cells (HSC), by evaluating the expression of arginase-1 (Arg1), indolamine-2,3-dioxygenase (IDO), and PD-L1 in MDSC subsets. The study included 20 multiple myeloma patients in remission, 5 patients with progression, as well as 10 sex-and age-matched healthy donors. The expression of Arg1, IDO, and PD-L1 in circulating granulocytic MDSC (G-MDSC, Lin- HLA-DR- CD33+ CD66b+ ), monocytic MDSC (M-MDSC, CD14+ HLA-DRlow/- ), and early-stage MDSC (E-MDSC, Lin- HLA-DR- CD33+ CD66b- ) was evaluated by flow cytometry...