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Immunotherapy for depression: Recent insights and future targets Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-03-03 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
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Chemical inhibitors targeting histone methylation readers Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-02-22 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
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Nanotechnology and nano-sized tools: Newer approaches to circumvent oncolytic adenovirus limitations Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-02-20 Maryam Mashhadi Abolghasem Shirazi, Tayebeh Azam Saedi, Zahra Samadi Moghaddam, Mahnaz Nemati, Reza Shiri, Babak Negahdari, Nasser Hashemi Goradel
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Uric acid in health and disease: From physiological functions to pathogenic mechanisms Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-02-19 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
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Mechanistic and therapeutic relationships of traumatic brain injury and γ-amino-butyric acid (GABA) Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-02-16 Jeffrey M. Witkin, Hana Shafique, Rok Cerne, Jodi L. Smith, Ann M. Marini, Robert H. Lipsky, Elizabeth Delery
Traumatic brain injury 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
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Pathological and pharmacological functions of the metabolites of polyunsaturated fatty acids mediated by cyclooxygenases, lipoxygenases, and cytochrome P450s in cancers Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-02-16 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
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Harnessing and delivering microbial metabolites as therapeutics via advanced pharmaceutical approaches Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-02-16 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
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Immunotherapy in melanoma: Can we predict response to treatment with circulating biomarkers? Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-02-16 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
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The therapeutic potential of targeting the CHD protein family in cancer Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-02-15 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
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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 Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-02-13 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
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The role of microglia heterogeneity in synaptic plasticity and brain disorders: Will sequencing shed light on the discovery of new therapeutic targets? Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-02-10 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
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Olea europaea L-derived secoiridoids: Beneficial health effects and potential therapeutic approaches Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-01-30 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
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A novel therapeutic target for kidney diseases: Lessons learned from starvation response Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-01-28 Kosuke Yamahara, Mako Yasuda-Yamahara, Shinji Kume
The prevalence of chronic kidney disease (CKD) is increasing worldwide, making the disease an urgent clinical challenge. Caloric restriction has various anti-aging and organ-protective effects, and unraveling its molecular mechanisms may provide insight into the pathophysiology of CKD. In response to changes in nutritional status, intracellular nutrient signaling pathways show adaptive changes. When
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Multi-omics approaches for biomarker discovery in predicting the response of esophageal cancer to neoadjuvant therapy: A multidimensional perspective Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-01-28 Zhi Yang, Fada Guan, Lawrence Bronk, Lina Zhao
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Berberine prevents NAFLD and HCC by modulating metabolic disorders Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-02-01 Xinyue Lin, Juanhong Zhang, Yajun Chu, Qiuying Nie, Junmin Zhang
Non-alcoholic fatty liver disease (NAFLD) is a global metabolic disease with high prevalence in both adults and children. Importantly, NAFLD is becoming the main cause of hepatocellular carcinoma (HCC). Berberine (BBR), a naturally occurring plant component, has been demonstrated to have advantageous effects on a number of metabolic pathways as well as the ability to kill liver tumor cells by causing
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Gene and stem cell therapy for inherited cardiac arrhythmias Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-01-30 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
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Non-canonical G protein signaling Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-01-29 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
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CDNF and ER stress: Pharmacology and therapeutic possibilities Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-01-28 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
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Transformation or replacement - Effects of hormone therapy on cardiovascular risk Pharmacol. Therapeut. (IF 12.0) Pub Date : 2024-01-28 Julia Kielb, Süreyya Saffak, Jessica Weber, Leonard Baensch, Khatereh Shahjerdi, Aylin Celik, Nora Farahat, Sally Riek, Oscar Chavez-Talavera, Maria Grandoch, Amin Polzin, Malte Kelm, Lisa Dannenberg
Hormone therapy (HT) is important and frequently used both regarding replacement therapy (HRT) and gender affirming therapy (GAHT). While HRT has been effective in addressing symptoms related to hormone shortage, several side effects have been described. In this context, there are some studies that show increased cardiovascular risk. However, there are also studies reporting protective aspects of HT
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Recent drug design strategies and identification of key heterocyclic scaffolds for promising anticancer targets Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-12-30 Alia Mushtaq, Peng Wu, Muhammad Moazzam Naseer
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TAAR1 as an emerging target for the treatment of psychiatric disorders Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-12-22 Jianfeng Liu, Ruyan Wu, Jun-Xu Li
Trace amines, a group of amines expressed at the nanomolar level in the mammalian brain, can modulate monoamine transmission. The discovery of and the functional research on the trace amine-associated receptors (TAARs), especially the most well-characterized TAAR1, have largely facilitated our understanding of the function of the trace amine system in the brain. TAAR1 is expressed in the mammalian
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Therapeutic strategies to target connective tissue growth factor in fibrotic lung diseases Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-12-15 Takuma Isshiki, Safaa Naiel, Megan Vierhout, Kohei Otsubo, Pareesa Ali, Kazuya Tsubouchi, Parichehr Yazdanshenas, Vaishnavi Kumaran, Anna Dvorkin-Gheva, Martin R.J. Kolb, Kjetil Ask
The treatment of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), remains challenging as current available antifibrotic agents are not effective in halting disease progression. Connective tissue growth factor (CTGF), also known as cellular communication factor 2 (CCN2), is a member of the CCN family of proteins that regulates cell signaling through cell surface receptors such
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Clinical advances in TNC delivery vectors and their conjugate agents Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-12-09 Wujun Chen, Yudong Wu, Jie Wang, Wanpeng Yu, Xin Shen, Kai Zhao, Bing Liang, Xiaokun Hu, Shuai Wang, Hongfei Jiang, Xinlin Liu, Miao Zhang, Xiaohui Xing, Chao Wang, Dongming Xing
Tenascin C (TNC), a glycoprotein that is abundant in the tumor extracellular matrix (ECM), is strongly overexpressed in tumor tissues but virtually undetectable in most normal tissues. Many TNC antibodies, peptides, aptamers, and nanobodies have been investigated as delivery vectors, including 20A1, α-A2, α-A3, α-IIIB, α-D, BC-2, BC-4 BC-8, 81C6, ch81C6, F16, FHK, Ft, Ft-NP, G11, G11-iRGD, GBI-10,
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Organic cation transporters in psychiatric and substance use disorders Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-12-09 Lauren E. Honan, Rheaclare Fraser-Spears, Lynette C. Daws
Psychiatric and substance use disorders inflict major public health burdens worldwide. Their widespread burden is compounded by a dearth of effective treatments, underscoring a dire need to uncover novel therapeutic targets. In this review, we summarize the literature implicating organic cation transporters (OCTs), including three subtypes of OCTs (OCT1, OCT2, and OCT3) and the plasma membrane monoamine
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Emerging roles of RNA ac4C modification and NAT10 in mammalian development and human diseases Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-12-07 Yigan Zhang, Yumei Lei, Yanbin Dong, Shuwen Chen, Siyuan Sun, Fange Zhou, Zhiwen Zhao, Bonan Chen, Lv Wei, Juan Chen, Zhongji Meng
RNA ac4C modification is a novel and rare chemical modification observed in mRNA. Traditional biochemical studies had primarily associated ac4C modification with tRNA and rRNA until in 2018, Arango D et al. first reported the presence of ac4C modification on mRNA and demonstrated its critical role in mRNA stability and translation regulation. Furthermore, they established that the ac4C modification
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Repurposing of pexidartinib for microglia depletion and renewal Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-12-03 Marc-Philipp Weyer, Jenny Strehle, Michael K.E. Schäfer, Irmgard Tegeder
Pexidartinib (PLX3397) is a small molecule receptor tyrosine kinase inhibitor of colony stimulating factor 1 receptor (CSF1R) with moderate selectivity over other members of the platelet derived growth factor receptor family. It is approved for treatment of tenosynovial giant cell tumors (TGCT). CSF1R is highly expressed by microglia, which are macrophages of the central nervous system (CNS) that defend
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Hypertension & dementia: Pathophysiology & potential utility of antihypertensives in reducing disease burden Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-12-03 Mara Lyon, Josie L. Fullerton, Simon Kennedy, Lorraine M. Work
Dementia is a common cause of disability and dependency among the elderly due to its progressive neurodegenerative nature. As there is currently no curative therapy, it is of major importance to identify new ways to reduce its prevalence. Hypertension is recognised as a modifiable risk factor for dementia, particularly for the two most common subtypes; vascular dementia (VaD) and Alzheimer's disease
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Therapeutic potential of stem cells in regeneration of liver in chronic liver diseases: Current perspectives and future challenges Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-11-25 Poonam Yadav, Sumeet Kumar Singh, Sonu Rajput, Prince Allawadhi, Amit Khurana, Ralf Weiskirchen, Umashanker Navik
The deposition of extracellular matrix and hyperplasia of connective tissue characterizes chronic liver disease called hepatic fibrosis. Progression of hepatic fibrosis may lead to hepatocellular carcinoma. At this stage, only liver transplantation is a viable option. However, the number of possible liver donors is less than the number of patients needing transplantation. Consequently, alternative
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Retracing our steps: A review on autism research in children, its limitation and impending pharmacological interventions Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-11-24 Salam Salloum-Asfar, Nasser Zawia, Sara A. Abdulla
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by three core impairments: impaired communication, impaired reciprocal social interaction, and restricted, repetitive, and stereotypical behavior patterns. Spectrum refers to the heterogeneity of presentation, severity of symptoms, and medical comorbidities associated with ASD. Among the most common underlying medical conditions
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From exploring cancer and virus targets to discovering active peptides through mRNA display Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-11-10 José Brango-Vanegas, Michel Lopes Leite, Kamila Botelho Sampaio de Oliveira, Nicolau Brito da Cunha, Octávio Luiz Franco
During carcinogenesis, neoplastic cells accumulate mutations in genes important for cellular homeostasis, producing defective proteins. Viral infections occur when viral capsid proteins bind to the host cell receptor, allowing the virus to enter the cells. In both cases, proteins play important roles in cancer development and viral infection, so these targets can be exploited to develop alternative
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What matters in aging is signaling for responsiveness Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-11-10 Sang Chul Park, Young-Sam Lee, Kyung A Cho, Sung Young Kim, Yun-Il Lee, Seung-Rock Lee, In Kyoung Lim
Biological responsiveness refers to the capacity of living organisms to adapt to changes in both their internal and external environments through physiological and behavioral mechanisms. One of the prominent aspects of aging is the decline in this responsiveness, which can lead to a deterioration in the processes required for maintenance, survival, and growth. The vital link between physiological responsiveness
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Retinoid X Receptor agonists as selective modulators of the immune system for the treatment of cancer Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-11-10 Ana S. Leal, Pei-Yu Hung, Afrin Sultana Chowdhury, Karen T. Liby
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Emerging role of immune cells as drivers of pulmonary fibrosis Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-11-10 Steven E. Mutsaers, Tylah Miles, Cecilia M. Prêle, Gerard F. Hoyne
The pathogenesis of pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF) and other forms of interstitial lung disease, involves a complex interplay of various factors including host genetics, environmental pollutants, infection, aberrant repair and dysregulated immune responses. Highly variable clinical outcomes of some ILDs, in particular IPF, have made it difficult to identify the precise
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Multitarget antibacterial drugs: An effective strategy to combat bacterial resistance Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-10-30 Jin Feng, Youle Zheng, Wanqing Ma, Awais Ihsan, Haihong Hao, Guyue Cheng, Xu Wang
The rise of antibiotic resistance and the decrease in the discovery of new antibiotics have caused a global health crisis. Of particular concern is the fact that despite efforts to develop new antibiotics, drug discovery is unable to keep up with the rapid development of resistance. This ongoing crisis highlights the fact that single-target drugs may not always exhibit satisfactory therapeutic effects
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Biologics for severe asthma and beyond Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-10-30 Carlo Mümmler, Katrin Milger
Advances in pathophysiological understanding and the elucidation of a type 2 inflammatory signature with interleukins 4, 5 and 13 at its center have led to the development of targeted antibody therapies that are now approved for the treatment of severe asthma. In suitable patients, these medications reduce asthma exacerbations and the necessity for oral corticosteroids, improve asthma control, quality
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Obesity and its comorbidities, current treatment options and future perspectives: Challenging bariatric surgery? Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-10-23 Simon Kloock, Christian G. Ziegler, Ulrich Dischinger
Obesity and its comorbidities, including type 2 diabetes mellitus, cardiovascular disease, heart failure and non-alcoholic liver disease are a major health and economic burden with steadily increasing numbers worldwide. The need for effective pharmacological treatment options is strong, but, until recently, only few drugs have proven sufficient efficacy and safety. This article provides a comprehensive
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NLRP3 and cancer: Pathogenesis and therapeutic opportunities Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-10-21 Isak W. Tengesdal, Charles A. Dinarello, Carlo Marchetti
More than a decade ago IL-1 blockade was suggested as an add-on therapy for the treatment of cancer. This proposal was based on the overall safety record of anti-IL-1 biologics and the anti-tumor properties of IL-1 blockade in animal models of cancer. Today, a new frontier in IL-1 activity regulation has developed with several orally active NLRP3 inhibitors currently in clinical trials, including cancer
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Post-translational modifications of histone and non-histone proteins in epigenetic regulation and translational applications in alcohol-associated liver disease: Challenges and research opportunities Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-10-13 Wiramon Rungratanawanich, Jacob W. Ballway, Xin Wang, Kyoung-Jae Won, James P. Hardwick, Byoung-Joon Song
Epigenetic regulation is a process that takes place through adaptive cellular pathways influenced by environmental factors and metabolic changes to modulate gene activity with heritable phenotypic variations without altering the DNA sequences of many target genes. Epigenetic regulation can be facilitated by diverse mechanisms: many different types of post-translational modifications (PTMs) of histone
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Boron in cancer therapeutics: An overview Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-10-17 Swanand Kulkarni, Dyuti Bhandary, Yogesh Singh, Vikramdeep Monga, Suresh Thareja
Boron has become a crucial weapon in anticancer research due to its significant intervention in cell proliferation. Being an excellent bio-isosteric replacement of carbon, it has modulated the anticancer efficacy of various molecules in the development pipeline. It has elicited promising results through interactions with various therapeutic targets such as HIF-1α, steroid sulfatase, arginase, proteasome
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Severe hypertriglyceridemia: Existing and emerging therapies Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-10-15 Waqas A. Malick, Ron Do, Robert S. Rosenson
Severe hypertriglyceridemia (sHTG), defined as a triglyceride (TG) concentration ≥ 500 mg/dL (≥ 5.7 mmol/L) is an important risk factor for acute pancreatitis. Although lifestyle, some medications, and certain conditions such as diabetes may lead to HTG, sHTG results from a combination of major and minor genetic defects in proteins that regulate TG lipolysis. Familial chylomicronemia syndrome (FCS)
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Neuropathic pain: From actual pharmacological treatments to new therapeutic horizons Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-10-11 Maxime Thouaye, Ipek Yalcin
Neuropathic pain, caused by a lesion or disease affecting the somatosensory system, affects between 3 and 17% of the general population. The treatment of neuropathic pain is challenging due to its heterogeneous etiologies, lack of objective diagnostic tools and resistance to classical analgesic drugs. First-line treatments recommended by the Special Interest Group on Neuropathic Pain (NeuPSIG) and
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Signaling pathways in brain ischemia: Mechanisms and therapeutic implications Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-10-01 Wen Lin, Xiang-Yu Zhao, Jia-wen Cheng, Li-tao Li, Quan Jiang, Yi-Xuan Zhang, Feng Han
Ischemic stroke occurs when the arteries supplying blood to the brain are narrowed or blocked, inducing damage to brain tissue due to a lack of blood supply. One effective way to reduce brain damage and alleviate symptoms is to reopen blocked blood vessels in a timely manner and reduce neuronal damage. To achieve this, researchers have focused on identifying key cellular signaling pathways that can
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Presynaptic glutamate receptors in nociception Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-09-30 Rou-Gang Xie, Guang-Yin Xu, Sheng-Xi Wu, Ceng Luo
Chronic pain is a frequent, distressing and poorly understood health problem. Plasticity of synaptic transmission in the nociceptive pathways after inflammation or injury is assumed to be an important cellular basis for chronic, pathological pain. Glutamate serves as the main excitatory neurotransmitter at key synapses in the somatosensory nociceptive pathways, in which it acts on both ionotropic and
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Sulfoconjugation of protein peptides and glycoproteins in physiology and diseases Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-09-28 Pengfei Xu, Xinran Cai, Xiuchen Guan, Wen Xie
Protein sulfoconjugation, or sulfation, represents a critical post-translational modification (PTM) process that involves the attachment of sulfate groups to various positions of substrates within the protein peptides or glycoproteins. This process plays a dynamic and complex role in many physiological and pathological processes. Here, we summarize the importance of sulfation in the fields of oncology
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Therapeutic implications of impaired nuclear receptor function and dysregulated metabolism in Wilson's disease Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-09-22 Clavia Ruth Wooton-Kee
Copper is an essential trace element that is required for the activity of many enzymes and cellular processes, including energy homeostasis and neurotransmitter biosynthesis; however, excess copper accumulation results in significant cellular toxicity. The liver is the major organ for maintaining copper homeostasis. Inactivating mutations of the copper-transporting P-type ATPase, ATP7B, result in Wilson's
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Medulloblastoma targeted therapy: From signaling pathways heterogeneity and current treatment dilemma to the recent advances in development of therapeutic strategies Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-09-12 Qiyue Wang, Xiaofei Xin, Qihao Dai, Mengjuan Sun, Jinhua Chen, Ebrahim Mostafavi, Yan Shen, Xueming Li
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Modulating glucocorticoid receptor actions in physiology and pathology: Insights from coregulators Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-09-16 Lina Fadel, Marija Dacic, Vlera Fonda, Baila A. Sokolsky, Fabiana Quagliarini, Inez Rogatsky, N. Henriette Uhlenhaut
Glucocorticoids (GCs) are a class of steroid hormones that regulate key physiological processes such as metabolism, immune function, and stress responses. The effects of GCs are mediated by the glucocorticoid receptor (GR), a ligand-dependent transcription factor that activates or represses the expression of hundreds to thousands of genes in a tissue- and physiological state-specific manner. The activity
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Glyoxalase I is a novel target for the prevention of metabolic derangement Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-09-16 Edwin R. Miranda, Jacob M. Haus
Obesity prevalence in the US has nearly tripled since 1975 and a parallel increase in prevalence of type 2 diabetes (T2D). Obesity promotes a myriad of metabolic derangements with insulin resistance (IR) being perhaps the most responsible for the development of T2D and other related diseases such as cardiovascular disease. The precarious nature of IR development is such that it provides a valuable
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Novel approaches to target fibroblast mechanotransduction in fibroproliferative diseases Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-09-12 Maya Ezzo, Boris Hinz
The ability of cells to sense and respond to changes in mechanical environment is vital in conditions of organ injury when the architecture of normal tissues is disturbed or lost. Among the various cellular players that respond to injury, fibroblasts take center stage in re-establishing tissue integrity by secreting and organizing extracellular matrix into stabilizing scar tissue. Activation, activity
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Use of big data and machine learning algorithms to extract possible treatment targets in neurodevelopmental disorders Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-09-12 Muhammad Ammar Malik, Stephen V. Faraone, Tom Michoel, Jan Haavik
Neurodevelopmental disorders (NDDs) impact multiple aspects of an individual's functioning, including social interactions, communication, and behaviors. The underlying biological mechanisms of NDDs are not yet fully understood, and pharmacological treatments have been limited in their effectiveness, in part due to the complex nature of these disorders and the heterogeneity of symptoms across individuals
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The role and participation of immune cells in the endometrial tumor microenvironment Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-09-09 Debasish Kumar Dey, Danielle Krause, Rajani Rai, Swati Choudhary, Lauren E. Dockery, Vishal Chandra
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Target protein degradation by protacs: A budding cancer treatment strategy Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-09-09 Diksha Choudhary, Amritpal Kaur, Pargat Singh, Gaurav Chaudhary, Rajwinder Kaur, Mohammad F. Bayan, Balakumar Chandrasekaran, Saeed M. Marji, Reema Ayman
Cancer is one of the most common causes of death. So, its lethal effect increases with time. Near about hundreds of cancers are known in humans. Cancer treatment is done to cure or prolonged remission, and shrinkage of the tumor. Cytotoxic agents, biological agents/targeted drugs, hormonal drugs, surgery, radiotherapy/proton therapy, chemotherapy, immunotherapy, and gene therapy are currently used
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Cancer metastasis: Molecular mechanisms and clinical perspectives Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-09-01 Sameer Ullah Khan, Kaneez Fatima, Fayaz Malik, Halime Kalkavan, Abubakar Wani
Metastatic progression combined with non-responsiveness towards systemic therapy often shapes the course of disease for cancer patients and commonly determines its lethal outcome. The complex molecular events that promote metastasis are a combination of both, the acquired pro-metastatic properties of cancer cells and a metastasis-permissive or -supportive tumor micro-environment (TME). Yet, dissemination
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Towards precision medicine in migraine: Recent therapeutic advances and potential biomarkers to understand heterogeneity and treatment response Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-08-30 Gabriella Juhasz, Kinga Gecse, Daniel Baksa
After 35 years since the introduction of the International Classification of Headache Disorders (ICHD), we are living in the era of the second great revolution in migraine therapies. First, discoveries of triptans provided a breakthrough in acute migraine treatment utilizing bench-to-bedside research results on the role of serotonin in migraine. Next, the discovery of the role of neuropeptides, more
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Potential targeting of the tumor microenvironment to improve cancer virotherapy Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-08-30 Zi-Xian Liao, Shan-hui Hsu, Shiue-Cheng Tang, Ivan Kempson, Pan-Chyr Yang, S. Ja Tseng
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Lactate acidosis and simultaneous recruitment of TGF-β leads to alter plasticity of hypoxic cancer cells in tumor microenvironment Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-08-23 Saumya Rastogi, Shashank Shekher Mishra, Mandeep Kumar Arora, Gaurav Kaithwas, Sugato Banerjee, Velayutham Ravichandiran, Subhadeep Roy, Lakhveer Singh
Lactate acidosis is often observed in the tumor microenvironment (TME) of solid tumors. This is because glucose breaks down quickly via glycolysis, causing lactate acidity. Lactate is harmful to healthy cells, but is a major oncometabolite for solid cancer cells that do not receive sufficient oxygen. As an oncometabolite, it helps tumor cells perform different functions, which helps solid hypoxic tumor
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Repurposing of antiangiogenic agents for treatment of vascular anomalies Pharmacol. Therapeut. (IF 12.0) Pub Date : 2023-08-23 Julie Blatt, Jennifer E. Brondon, Elizabeth L. Nieman, Kynlon Phillips, Arti Pandya
Vascular anomalies (VA) are developmental anomalies of veins, arteries, lymphatics or capillaries thought to be caused by mutations in genes that drive angiogenesis. Treatments targeting these genes are limited. We review the literature for conventional medications and products from traditional medicine cultures that have been found to have antiangiogenic activity. Fewer than 50 drugs with credible