journal
https://read.qxmd.com/read/38521247/cyp2j2-mediated-metabolism-of-arachidonic-acid-in-heart-a-review-of-its-kinetics-inhibition-and-role-in-heart-rhythm-control
#1
REVIEW
Jacqueline Wen Hui Leow, Eric Chun Yong Chan
Cytochrome P450 2 J2 (CYP2J2) is primarily expressed extrahepatically and is the predominant epoxygenase in human cardiac tissues. This highlights its key role in the metabolism of endogenous substrates. Significant scientific interest lies in cardiac CYP2J2 metabolism of arachidonic acid (AA), an omega-6 polyunsaturated fatty acid, to regioisomeric bioactive epoxyeicosatrienoic acid (EET) metabolites that show cardioprotective effects including regulation of cardiac electrophysiology. From an in vitro perspective, the accurate characterization of the kinetics of CYP2J2 metabolism of AA including its inhibition and inactivation by drugs could be useful in facilitating in vitro-in vivo extrapolations to predict drug-AA interactions in drug discovery and development...
March 21, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38521246/characteristics-of-anticancer-activity-of-cbp-p300-inhibitors-features-of-their-classes-intracellular-targets-and-future-perspectives-of-their-application-in-cancer-treatment
#2
REVIEW
Magdalena Strachowska, Agnieszka Robaszkiewicz
Due to the contribution of highly homologous acetyltransferases CBP and p300 to transcription elevation of oncogenes and other cancer promoting factors, these enzymes emerge as possible epigenetic targets of anticancer therapy. Extensive efforts in search for small molecule inhibitors led to development of compounds targeting histone acetyltransferase catalytic domain or chromatin-interacting bromodomain of CBP/p300, as well as dual BET and CBP/p300 inhibitors. The promising anticancer efficacy in in vitro and mice models led CCS1477 and NEO2734 to clinical trials...
March 21, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38508342/musculoskeletal-crosstalk-in-chronic-obstructive-pulmonary-disease-and-comorbidities-emerging-roles-and-therapeutic-potentials
#3
REVIEW
Kevin Mou, Stanley M H Chan, Ross Vlahos
Chronic Obstructive Pulmonary Disease (COPD) is a multifaceted respiratory disorder characterized by progressive airflow limitation and systemic implications. It has become increasingly apparent that COPD exerts its influence far beyond the respiratory system, extending its impact to various organ systems. Among these, the musculoskeletal system emerges as a central player in both the pathogenesis and management of COPD and its associated comorbidities. Muscle dysfunction and osteoporosis are prevalent musculoskeletal disorders in COPD patients, leading to a substantial decline in exercise capacity and overall health...
March 18, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38499069/efficacy-and-safety-of-transarterial-chemoembolization-combined-with-lenvatinib-and-pd-1-inhibitor-in-the-treatment-of-advanced-hepatocellular-carcinoma-a-meta-analysis
#4
REVIEW
Lei Wang, Li Lin, Wei Zhou
The study aims to evaluate the benefits and potential adverse effects of transarterial chemoembolization (TACE) combined with lenvatinib and programmed cell death 1 (PD-1) protein inhibitors in the treatment of advanced hepatocellular carcinoma (HCC). A systematic literature search of several databases for relevant studies, published from inception up to May 2023, was performed. Clinical trials investigating TACE combined with lenvatinib and PD-1 inhibitors compared with other treatment regimens for advanced HCC were included...
March 16, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38467308/orthotopic-and-metastatic-tumour-models-in-preclinical-cancer-research
#5
REVIEW
Stephen M Stribbling, Callum Beach, Anderson J Ryan
Mouse models of disease play a pivotal role at all stages of cancer drug development. Cell-line derived subcutaneous tumour models are predominant in early drug discovery, but there is growing recognition of the importance of the more complex orthotopic and metastatic tumour models for understanding both target biology in the correct tissue context, and the impact of the tumour microenvironment and the immune system in responses to treatment. The aim of this review is to highlight the value that orthotopic and metastatic models bring to the study of tumour biology and drug development while pointing out those models that are most likely to be encountered in the literature...
March 9, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38442780/immunotherapy-for-depression-recent-insights-and-future-targets
#6
REVIEW
Ying Bai, Yang Cai, Di Chang, Daxing Li, Xinchen Huo, Tianhao Zhu
Depression stands as a prominent contributor to global disability, entailing an elevated risk of suicide. Substantial evidence supports the notion that immune dysregulation may play a role in the development of depression and impede responses to antidepressant treatments. Immune dysregulation may cause depression in susceptible individuals through raising inflammatory responses. Differences in immune cell types and the release of pro-inflammatory mediators are observed in the blood and cerebrospinal fluid of patients with major depressive disorder, which is associated with neuroimmune dysfunction...
March 3, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38401773/chemical-inhibitors-targeting-histone-methylation-readers
#7
REVIEW
Xiaolei Huang, Yichang Chen, Qin Xiao, Xinci Shang, Yanli Liu
Histone methylation reader domains are protein modules that recognize specific histone methylation marks, such as methylated or unmethylated lysine or arginine residues on histones. These reader proteins play crucial roles in the epigenetic regulation of gene expression, chromatin structure, and DNA damage repair. Dysregulation of these proteins has been linked to various diseases, including cancer, neurodegenerative diseases, and developmental disorders. Therefore, targeting these proteins with chemical inhibitors has emerged as an attractive approach for therapeutic intervention, and significant progress has been made in this area...
February 22, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38387653/nanotechnology-and-nano-sized-tools-newer-approaches-to-circumvent-oncolytic-adenovirus-limitations
#8
REVIEW
Maryam Mashhadi Abolghasem Shirazi, Tayebeh Azam Saedi, Zahra Samadi Moghaddam, Mahnaz Nemati, Reza Shiri, Babak Negahdari, Nasser Hashemi Goradel
Oncolytic adenoviruses (OAds), engineered Ads preferentially infect and lyse tumor cells, have attracted remarkable attention as immunotherapy weapons for the treatment of various malignancies. Despite hopeful successes in preclinical investigations and translation into clinical phases, they face some challenges that thwart their therapeutic effectiveness, including low infectivity of cancer cells, liver sequestration, pre-existing neutralizing antibodies, physical barriers to the spread of Ads, and immunosuppressive TME...
February 20, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38382882/uric-acid-in-health-and-disease-from-physiological-function-to-pathogenic-mechanism
#9
REVIEW
Shijie Wen, Hiroshi Arakawa, Ikumi Tamai
Owing to renal reabsorption and the loss of uricase activity, uric acid (UA) is strictly maintained at a higher physiological level in humans than in other mammals, which provides a survival advantage during evolution but increases susceptibility to certain diseases such as gout. Although monosodium urate (MSU) crystal precipitation has been detected in different tissues of patients as a trigger for disease, the pathological role of soluble UA remains controversial due to the lack of causality in the clinical setting...
February 19, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38369063/pathological-and-pharmacological-functions-of-the-metabolites-of-polyunsaturated-fatty-acids-mediated-by-cyclooxygenases-lipoxygenases-and-cytochrome-p450s-in-cancers
#10
REVIEW
Yi-Wen Meng, Jun-Yan Liu
Oxylipins have garnered increasing attention because they were consistently shown to play pathological and/or pharmacological roles in the development of multiple cancers. Oxylipins are the metabolites of polyunsaturated fatty acids via both enzymatic and nonenzymatic pathways. The enzymes mediating the metabolism of PUFAs include but not limited to lipoxygenases (LOXs), cyclooxygenases (COXs), and cytochrome P450s (CYPs) pathways, as well as the down-stream enzymes. Here, we systematically summarized the pleiotropic effects of oxylipins in different cancers through pathological and pharmacological aspects, with specific reference to the enzyme-mediated oxylipins...
February 16, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38369062/mechanistic-and-therapeutic-relationships-of-traumatic-brain-injury-and-%C3%AE-amino-butyric-acid-gaba
#11
REVIEW
Jeffrey M Witkin, Hana Shafique, Rok Cerne, Jodi L Smith, Ann M Marini, Robert H Lipsky, Elizabeth Delery
Traumatic brain injury (TBI) is a highly prevalent medical condition for which no medications specific for the prophylaxis or treatment of the condition as a whole exist. The spectrum of symptoms includes coma, headache, seizures, cognitive impairment, depression, and anxiety. Although it has been known for years that the inhibitory neurotransmitter γ-amino-butyric acid (GABA) is involved in TBI, no novel therapeutics based upon this mechanism have been introduced into clinical practice. We review the neuroanatomical, neurophysiological, neurochemical, and neuropharmacological relationships of GABA neurotransmission to TBI with a view toward new potential GABA-based medicines...
February 16, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38367868/the-therapeutic-potential-of-targeting-the-chd-protein-family-in-cancer
#12
REVIEW
Min Zhang, Kaiyuan Wu, Weijie Zhang, Xia Lin, Qi Cao, Lili Zhang, Kaifu Chen
Accumulating evidence indicates that epigenetic events undergo deregulation in various cancer types, playing crucial roles in tumor development. Among the epigenetic factors involved in the epigenetic remodeling of chromatin, the chromodomain helicase DNA-binding protein (CHD) family frequently exhibits gain- or loss-of-function mutations in distinct cancer types. Therefore, targeting CHD remodelers holds the potential for antitumor treatment. In this review, we discuss epigenetic regulations of cancer development...
February 15, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38367867/immunotherapy-in-melanoma-can-we-predict-response-to-treatment-with-circulating-biomarkers
#13
REVIEW
Elena Splendiani, Zein Mersini Besharat, Alessia Covre, Michele Maio, Anna Maria Di Giacomo, Elisabetta Ferretti
Melanoma is the most aggressive form of skin cancer, representing approximately 4% of all cutaneous neoplasms it accounts for up to 80% of deaths. Advanced stages of melanoma involve metastatic processes and are associated with high mortality and morbidity, mainly due to the rapid dissemination and heterogeneous responses to current therapies including immunotherapy. Indeed, immune checkpoints inhibitors (ICIs), either alone or in combination with other therapies are currently used in metastatic melanoma (MM) and linked to an increase in patient survival...
February 15, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38367866/harnessing-and-delivering-microbial-metabolites-as-therapeutics-via-advanced-pharmaceutical-approaches
#14
REVIEW
Lindsey M Williams, Shijie Cao
Microbial metabolites have emerged as key players in the interplay between diet, the gut microbiome, and host health. Two major classes, short-chain fatty acids (SCFAs) and tryptophan (Trp) metabolites, are recognized to regulate inflammatory, immune, and metabolic responses within the host. Given that many human diseases are associated with dysbiosis of the gut microbiome and consequent reductions in microbial metabolite production, the administration of these metabolites represents a direct, multi-targeted treatment...
February 15, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38360205/protein-rich-foods-sea-foods-and-gut-microbiota-amplify-immune-responses-in-chronic-diseases-and-cancers-targeting-perk-as-a-novel-therapeutic-strategy-for-chronic-inflammatory-diseases-neurodegenerative-disorders-and-cancer
#15
REVIEW
Fatma Saaoud, Yifan Lu, Keman Xu, Ying Shao, Domenico Praticò, Roberto I Vazquez-Padron, Hong Wang, Xiaofeng Yang
The endoplasmic reticulum (ER) is a cellular organelle that is physiologically responsible for protein folding, calcium homeostasis, and lipid biosynthesis. Pathological stimuli such as oxidative stress, ischemia, disruptions in calcium homeostasis, and increased production of normal and/or folding-defective proteins all contribute to the accumulation of misfolded proteins in the ER, causing ER stress. The adaptive response to ER stress is the activation of unfolded protein response (UPR), which affect a wide variety of cellular functions to maintain ER homeostasis or lead to apoptosis...
February 13, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38346477/the-role-of-microglia-heterogeneity-in-synaptic-plasticity-and-brain-disorders-will-sequencing-shed-light-on-the-discovery-of-new-therapeutic-targets
#16
REVIEW
Yi You, Zhong Chen, Wei-Wei Hu
Microglia play a crucial role in interacting with neuronal synapses and modulating synaptic plasticity. This function is particularly significant during postnatal development, as microglia are responsible for removing excessive synapses to prevent neurodevelopmental deficits. Dysregulation of microglial synaptic function has been well-documented in various pathological conditions, notably Alzheimer's disease and multiple sclerosis. The recent application of RNA sequencing has provided a powerful and unbiased means to decipher spatial and temporal microglial heterogeneity...
February 10, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38301770/gene-and-stem-cell-therapy-for-inherited-cardiac-arrhythmias
#17
REVIEW
Zhong-He Zhang, Hector Barajas-Martinez, Hong Jiang, Cong-Xin Huang, Charles Antzelevitch, Hao Xia, Dan Hu
Inherited cardiac arrhythmias are a group of genetic diseases predisposing to sudden cardiac arrest, mainly resulting from variants in genes encoding cardiac ion channels or proteins involved in their regulation. Currently available therapeutic options (pharmacotherapy, ablative therapy and device-based therapy) can not preclude the occurrence of arrhythmia events and/or provide complete protection. With growing understanding of the genetic background and molecular mechanisms of inherited cardiac arrhythmias, advancing insight of stem cell technology, and development of vectors and delivery strategies, gene therapy and stem cell therapy may be promising approaches for treatment of inherited cardiac arrhythmias...
January 30, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38301769/olea-europaea-l-derived-secoiridoids-beneficial-health-effects-and-potential-therapeutic-approaches
#18
REVIEW
Simone Filardo, Mattioli Roberto, Daniel Di Risola, Luciana Mosca, Marisa Di Pietro, Rosa Sessa
Over the years, health challenges have become increasingly complex and global and, at the beginning of the 21st century, chronic diseases, including cardiovascular, neurological, and chronic respiratory diseases, as well as cancer and diabetes, have been identified by World Health Organization as one of the biggest threats to human health. Recently, antimicrobial resistance has also emerged as a growing problem of public health for the management of infectious diseases. In this scenario, the exploration of natural products as supplementation or alternative therapeutic options is acquiring great importance, and, among them, the olive tree, Olea europaea L, specifically leaves, fruits, and oil, has been increasingly investigated for its health promoting properties...
January 30, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38295906/non-canonical-g-protein-signaling
#19
REVIEW
Bernd Nürnberg, Sandra Beer-Hammer, Ellen Reisinger, Veronika Leiss
The original paradigm of classical - also referred to as canonical - cellular signal transduction of heterotrimeric G proteins (G protein) is defined by a hierarchical, orthograde interaction of three players: the agonist-activated G protein-coupled receptor (GPCR), which activates the transducing G protein, that in turn regulates its intracellular effectors. This receptor-transducer-effector concept was extended by the identification of regulators and adapters such as the regulators of G protein signaling (RGS), receptor kinases like βARK, or GPCR-interacting arrestin adapters that are integrated into this canonical signaling process at different levels to enable fine-tuning...
January 29, 2024: Pharmacology & Therapeutics
https://read.qxmd.com/read/38290651/cdnf-and-er-stress-pharmacology-and-therapeutic-possibilities
#20
REVIEW
Helike Lõhelaid, Mart Saarma, Mikko Airavaara
Cerebral dopamine neurotrophic factor (CDNF) is an endogenous protein in humans and other vertebrates, and it has been shown to have protective and restorative effects on cells in various disease models. Although it is named as a neurotrophic factor, its actions are drastically different from classical neurotrophic factors such as neurotrophins or the glial cell line-derived neurotrophic family of proteins. Like all secreted proteins, CDNF has a signal sequence at the N-terminus, but unlike common growth factors it has a KDEL-receptor retrieval sequence at the C-terminus...
January 28, 2024: Pharmacology & Therapeutics
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