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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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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 13.5) 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
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Anticancer drug delivery by focused ultrasound-mediated blood-brain/tumor barrier disruption for glioma therapy: From benchside to bedside Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-08-22 Charlotte Bérard, Charles Truillet, Benoit Larrat, Frédéric Dhermain, Marie-Anne Estève, Florian Correard, Anthony Novell
The therapeutic management of gliomas remains particularly challenging. Brain tumors present multiple obstacles that make therapeutic innovation complex, mainly due to the presence of blood-tumor and blood-brain barriers (BTB and BBB, respectively) which prevent penetration of anticancer agents into the brain parenchyma. Focused ultrasound-mediated BBB disruption (FUS-BBBD) provides a physical method
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Antithrombotic therapy following transcatheter aortic valve intervention Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-08-11 Harish Sharma, Shazia Afzal, Jürgen Leick, Nikos Werner, Sagar N. Doshi, M. Adnan Nadir
Transcatheter aortic valve replacement (TAVR) is increasingly being performed to treat symptomatic patients with aortic stenosis and annual procedure volume has overtaken surgical aortic valve replacement in the United States. However, current international guidelines were written prior to the publication of several important recent studies. Furthermore, European and American guidelines differ in their
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Beyond statins: New pharmacological targets to decrease LDL-cholesterol and cardiovascular events Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-08-09 Emanuel Raschi, Manuela Casula, Arrigo F.G. Cicero, Alberto Corsini, Claudio Borghi, Alberico Catapano
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Therapeutic targeting of the pituitary tumor microenvironment Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-08-09 Mirela-Diana Ilie, Dario De Alcubierre, Anna Lucia Carretti, Emmanuel Jouanneau, Gérald Raverot
The tumor microenvironment (TME), the complex environment in which tumors develop, has been increasingly targeted for cancer treatment in recent years. Aggressive pituitary tumors and pituitary carcinomas have been so far targeted with immune-checkpoint inhibitors (28 cases, including a large cohort), and anti-angiogenic drugs (34 cases), specifically bevacizumab (30 cases), sunitinib (three cases)
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The role of DNA methylation in personalized medicine for immune-related diseases Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-08-09 Manoj Kumar Gupta, He Peng, Yang Li, Cheng-Jian Xu
Epigenetics functions as a bridge between host genetic & environmental factors, aiding in human health and diseases. Many immune-related diseases, including infectious and allergic diseases, have been linked to epigenetic mechanisms, particularly DNA methylation. In this review, we summarized an updated overview of DNA methylation and its importance in personalized medicine, and demonstrated that DNA
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GABAergic modulation of sleep-wake states Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-08-03 Yo Oishi, Yuki C. Saito, Takeshi Sakurai
Benzodiazepine, a classical medication utilized in the treatment of insomnia, operates by augmenting the activity of the GABAA receptor. This underscores the significance of GABAergic neurotransmission in both the initiation and maintenance of sleep. Nevertheless, an increasing body of evidence substantiates the notion that GABA-mediated neurotransmission also assumes a vital role in promoting wakefulness
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The Triple Crown: NO, CO, and H2S in cancer cell biology Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-07-28 Palak P. Oza, Khosrow Kashfi
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Vasospastic angina: Past, present, and future Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-07-22 Zuowen He, Xin Xu, Qu Zhao, Hu Ding, Dao Wen Wang
Vasospastic angina (VSA) is characterized by episodes of rest angina that are responsive to short-acting nitrates and are attributable to coronary artery vasospasm. The condition is underdiagnosed as the provocation test is rarely performed. VSA, the most important component of non-obstructive coronary artery disease, can present with angina, be asymptomatic, or can even present with fatal arrhythmias
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Pharmacological interventions targeting α-synuclein aggregation triggered REM sleep behavior disorder and early development of Parkinson's disease Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-07-25 Lida Du, Xiaoli He, Xiaonuo Fan, Xiaoya Wei, Linhao Xu, Tuo Liang, Chunbo Wang, Ya Ke, Wing-ho Yung
Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by elevated motor behaviors and dream enactments in REM sleep, often preceding the diagnosis of Parkinson's disease (PD). As RBD could serve as a biomarker for early PD developments, pharmacological interventions targeting α-synuclein aggregation triggered RBD could be applied toward early PD progression. However,
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A systematic review on renal effects of SGLT2 inhibitors in rodent models of diabetic nephropathy Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-07-24 Aqsa Ashfaq, Myriam Meineck, Andrea Pautz, Ebru Arioglu-Inan, Julia Weinmann-Menke, Martin C. Michel
We have performed a systematic review of studies reporting on the renal effects of SGLT2 inhibitors in rodent models of diabetes. In 105 studies, SGLT2 inhibitors improved not only the glycemic control but also various aspects of renal function in most cases. These nephroprotective effects were similarly reported whether treatment with the SGLT2 inhibitor started concomitant with the onset of diabetes
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Adenosine receptor signalling as a driver of pulmonary fibrosis Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-07-22 Emily Cash, Amanda T. Goodwin, Amanda L. Tatler
Pulmonary fibrosis is a debilitating and life-limiting lung condition in which the damage- response mechanisms of mixed-population cells within the lungs go awry. The tissue microenvironment is drastically remodelled by aberrantly activated fibroblasts which deposit ECM components into the surrounding lung tissue, detrimentally affecting lung function and capacity for gas exchange. Growing evidence
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Pathophysiological mechanisms of complications associated with propionic acidemia Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-07-22 Hannah Marchuk, You Wang, Zachary Alec Ladd, Xiaoxin Chen, Guo-Fang Zhang
Propionic acidemia (PA) is a genetic metabolic disorder caused by mutations in the mitochondrial enzyme, propionyl-CoA carboxylase (PCC), which is responsible for converting propionyl-CoA to methylmalonyl-CoA for further metabolism in the tricarboxylic acid cycle. When this process is disrupted, propionyl-CoA and its metabolites accumulate, leading to a variety of complications including life-threatening
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Preface to the Special Issue Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-07-20 Darryl C. Zeldin, Kenneth Honn, Caryn Volpe
Abstract not available
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Tyrosine kinase and immune checkpoints inhibitors in favorable risk metastatic renal cell carcinoma: Trick or treat? Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-07-20 Martina Catalano, Giuseppe Procopio, Pierangela Sepe, Matteo Santoni, Francesco Sessa, Donata Villari, Gabriella Nesi, Giandomenico Roviello
Over the past decade, the management of metastatic renal cell carcinoma (RCC) has undergone rapid evolution, culminating in a significant improvement in prognosis with frontline immunotherapy. RCC is a highly immunogenic and pro-angiogenic cancer, and mounting evidence has established the immunosuppressive effects of pro-angiogenic factors on the host's immune system. Anti-angiogenic agents such as
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Potassium homeostasis – Physiology and pharmacology in a clinical context Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-07-15 Ralph Kettritz, Johannes Loffing
Membrane voltage controls the function of excitable cells and is mainly a consequence of the ratio between the extra- and intracellular potassium concentration. Potassium homeostasis is safeguarded by balancing the extra−/intracellular distribution and systemic elimination of potassium to the dietary potassium intake. These processes adjust the plasma potassium concentration between 3.5 and 4.5 mmol/L
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Strategies to overcome cancer multidrug resistance (MDR) through targeting P-glycoprotein (ABCB1): An updated review Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-07-11
The emergence of multidrug resistance (MDR) in malignant tumors is one of the leading threats encountered currently in many chemotherapeutic agents. The overexpression of the ATP-binding cassette (ABC) transporters is involved in MDR. P-glycoprotein (P-gp)/ABCB1 is a member of the ABC transporter family that significantly increases the efflux of various anticancer drugs from tumor cells. Therefore
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Autophagy inhibitors for cancer therapy: Small molecules and nanomedicines Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-07-03 Jian-Li Chen, Xuan Wu, Dan Yin, Xiao-Hui Jia, Xu Chen, Ze-Yun Gu, Xiao-Ming Zhu
Autophagy is a conserved process in which the cytosolic materials are degraded and eventually recycled for cellular metabolism to maintain homeostasis. The dichotomous role of autophagy in pathogenesis is complicated. Accumulating reports have suggested that cytoprotective autophagy is responsible for tumor growth and progression. Autophagy inhibitors, such as chloroquine (CQ) and hydroxychloroquine
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Protoporphyrin IX-induced phototoxicity: Mechanisms and therapeutics Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-06-29 Zahir Hussain, Qian Qi, Junjie Zhu, Karl E. Anderson, Xiaochao Ma
Protoporphyrin IX (PPIX) is an intermediate in the heme biosynthesis pathway. Abnormal accumulation of PPIX due to certain pathological conditions such as erythropoietic protoporphyria and X-linked protoporphyria causes painful phototoxic reactions of the skin, which can significantly impact daily life. Endothelial cells in the skin have been proposed as the primary target for PPIX-induced phototoxicity
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The shared role of cholesterol in neuronal and peripheral inflammation Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-06-29 Scott B. Hansen, Hao Wang
Neurodegeneration and its loss of cognitive function is associated with inflammation and an accumulation of lipids. In the periphery, cholesterol's uptake drives a major component of chronic inflammation. In this perspective, we describe the cellular and molecular roles of cholesterol in neuroinflammation and contrast them with those in the periphery. Incorporating shared mechanisms from the periphery
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An erythrocyte-centric view on the MFSD2B sphingosine-1-phosphate transporter Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-06-28 Shahrooz Ghaderi, Bodo Levkau
MFSD2B has been identified as the exclusive sphingosine-1-phosphate (S1P) transporter in red blood cells (RBC) and platelets. MFSD2B-mediated S1P export from platelets is required for aggregation and thrombus formation, whereas RBC MFSD2B maintains plasma S1P levels in concert with SPNS2, the vascular and lymphatic endothelial cell S1P exporter, to control endothelial permeability and ensure normal
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Stabilizing the neural barrier – A novel approach in pain therapy Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-06-28 Ann-Kristin Reinhold, Beate Hartmannsberger, Malgorzata Burek, Heike L. Rittner
Chronic and neuropathic pain are a widespread burden. Incomplete understanding of underlying pathomechanisms is one crucial factor for insufficient treatment. Recently, impairment of the blood nerve barrier (BNB) has emerged as one key aspect of pain initiation and maintenance. In this narrative review, we discuss several mechanisms and putative targets for novel treatment strategies. Cells such as
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Retina and RPE lipid profile changes linked with ABCA4 associated Stargardt's maculopathy Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-06-27 Mitra Farnoodian, Devika Bose, Francesca Barone, Luke Mathew Nelson, Marisa Boyle, Bokkyoo Jun, Khanh Do, William Gordon, Marie-Audrey Kautzmann Guerin, Rasangi Perera, Tiziana Cogliati, Ruchi Sharma, Brian P. Books, Nicolas Bazan, Kapil Bharti
Stargardt maculopathy, caused predominantly by mutations in the ABCA4 gene, is characterized by an accumulation of non-degradable visual pigment derivative, lipofuscin, in the retinal pigment epithelium (RPE) - resulting in RPE atrophy. RPE is a monolayer tissue located adjacent to retinal photoreceptors and regulates their health and functioning; RPE atrophy triggers photoreceptor cell death and vision
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Vitamin A and retinoid signaling in the kidneys Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-06-17 Krysta M. DiKun, Lorraine J. Gudas
Vitamin A (VA, retinol) and its metabolites (commonly called retinoids) are required for the proper development of the kidney during embryogenesis, but retinoids also play key roles in the function and repair of the kidney in adults. Kidneys filter 180-200 liters of blood per day and each kidney contains approximately 1 million nephrons, which are often referred to as the ‘functional units’ of the
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Targeting PCSK9 to tackle cardiovascular disease Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-06-17 Sandra Hummelgaard, Joachim Pold Vilstrup, Camilla Gustafsen, Simon Glerup, Kathrin Weyer
Lowering blood cholesterol levels efficiently reduces the risk of developing atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease (CAD), which is the main cause of death worldwide. CAD is caused by plaque formation, comprising cholesterol deposits in the coronary arteries. Proprotein convertase subtilisin kexin/type 9 (PCSK9) was discovered in the early 2000s and later
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Signaling pathways driving ocular malignancies and their targeting by bioactive phytochemicals Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-06-15 Courtney R. Croley, Joshua Pumarol, Blake E. Delgadillo, Andrew C. Cook, Faith Day, Tea Kaceli, Caroline C. Ward, Imran Husain, Ali Husain, Sabyasachi Banerjee, Anupam Bishayee
Ocular cancers represent a rare pathology. The American Cancer Society estimates that 3,360 cases of ocular cancer occur annually in the United States. The major types of cancers of the eye include ocular melanoma (also known as uveal melanoma), ocular lymphoma, retinoblastoma, and squamous cell carcinoma. While uveal melanoma is one of the primary intraocular cancers with the highest occurrence in
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Phosphorylation of nuclear receptors: Novelty and therapeutic implications Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-06-15 Sawako Shindo, Satoru Kakizaki, Toshiyuki Sakaki, Yuki Kawasaki, Tsutomu Sakuma, Masahiko Negishi, Ryota Shizu
Nuclear receptors (NR) collectively regulate several biological functions in various organs. While NRs can be characterized by activation of the transcription of their signature genes, they also have other diverse roles. Although most NRs are directly activated by ligand binding, which induces cascades of events leading to gene transcription, some NRs are also phosphorylated. Despite extensive investigations
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Preparing to strike: Acute events in signaling by the serpentine receptor for thromboxane A2 Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-06-13 Anthony W. Ashton
Over the last two decades, awareness of the (patho)physiological roles of thromboxane A2 signaling has been greatly extended. From humble beginnings as a short-lived stimulus that activates platelets and causes vasoconstriction to a dichotomous receptor system involving multiple endogenous ligands capable of modifying tissue homeostasis and disease generation in almost every tissue of the body. Thromboxane
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Inflammation, lipids, and pain in vulvar disease Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-06-05 Megan L. Falsetta, Krishna Rao Maddipati, Kenneth V. Honn
Localized provoked vulvodynia (LPV) affects ∼14 million people in the US (9% of women), destroying lives and relationships. LPV is characterized by chronic pain (>3 months) upon touch to the vulvar vestibule, which surrounds the vaginal opening. Many patients go months or years without a diagnosis. Once diagnosed, the treatments available only manage the symptoms of disease and do not correct the underlying
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The multifaceted landscape behind imatinib resistance in gastrointestinal stromal tumors (GISTs): A lesson from ripretinib Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-06-10 Aldo Di Vito, Gloria Ravegnini, Francesca Gorini, Trond Aasen, César Serrano, Eva Benuzzi, Emma Coschina, Sarah Monesmith, Fabiana Morroni, Sabrina Angelini, Patrizia Hrelia
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal sarcomas and the gold-standard treatment is represented by tyrosine kinase inhibitors (TKIs). Unfortunately, first-line treatment with the TKI imatinib usually promotes partial response or stable disease rather than a complete response, and resistance appears in most patients. Adaptive mechanisms are immediately relevant at the beginning
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Immunotherapies in chronic pain through modulation of neuroimmune interactions Pharmacol. Therapeut. (IF 13.5) Pub Date : 2023-06-10 Junli Zhao, Yul Huh, Andrey Bortsov, Luda Diatchenko, Ru-Rong Ji
It is generally believed that immune activation can elicit pain through production of inflammatory mediators that can activate nociceptive sensory neurons. Emerging evidence suggests that immune activation may also contribute to the resolution of pain by producing distinct pro-resolution/anti-inflammatory mediators. Recent research into the connection between the immune and nervous systems has opened