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Journal articles on the topic 'Therapeutics, pharmacological'

Author: Grafiati

Published: 4 June 2021

Last updated: 29 January 2023

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1

Kim, Doyoung, and Sujin Park. "Pharmacological therapeutics in androgenetic alopecia." Journal of the Korean Medical Association 63, no. 5 (May 10, 2020): 277–85. http://dx.doi.org/10.5124/jkma.2020.63.5.277.

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Androgenetic alopecia (AGA) is the most common type of hair loss and affects both men and women. Male pattern hair loss shows characteristic frontal recession and vertex baldness, whereas female pattern hair loss produces diffuse alopecia over the mid-frontal scalp. AGA is mediated by increased androgen susceptibility in affected scalp hairs. 5α-Reductase converts testosterone into dihydrotestosterone, a potent androgen, in the scalp. Both androgen receptors and 5α-reductase have higher expression levels in the balding scalp than in non-affected regions. Increased androgen susceptibility induces hair follicle miniaturization, which leads to the progressive loss of thicker terminal hairs in the balding scalp. Currently, topical minoxidil and oral 5α-reductase inhibitors, such as finasteride and dutasteride, are approved options for the pharmacological treatment of AGA. Topical minoxidil remains the mainstay of therapy for mild to moderate AGA in both men and women. The daily intake of 1-mg finasteride or 0.5-mg dutasteride shows better efficacy than topical minoxidil in regard to hair regrowth in male AGA. Anti-androgens can be used in female AGA wit clinical and biochemical evidence of hyperandrogenism. Patients may be overwhelmed and confused by the variety of treatment options for AGA management, including over-the-count drugs with low evidence quality. Therefore, physicians must be aware of the current guidelines for the management of AGA based on evidence-based approaches to select better options for patients.

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2

McMahon, F. Gilbert. "The Pharmacological Basis of Therapeutics." American Journal of Tropical Medicine and Hygiene 35, no. 3 (May 1, 1986): 673. http://dx.doi.org/10.4269/ajtmh.1986.35.673.

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3

Davies, J. E. "The pharmacological basis of therapeutics." Occupational and Environmental Medicine 64, no. 8 (August 1, 2007): e2-e2. http://dx.doi.org/10.1136/oem.2007.033902.

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4

Elovic, Elie. "Pharmacological Therapeutics in Nutritional Management." Journal of Head Trauma Rehabilitation 15, no. 3 (June 2000): 962–64. http://dx.doi.org/10.1097/00001199-200006000-00009.

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5

Woog, J. J. "The Pharmacological Basis of Therapeutics." Archives of Ophthalmology 104, no. 3 (March 1, 1986): 342–43. http://dx.doi.org/10.1001/archopht.1986.01050150036019.

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6

Papageorgiou, Maria, and Emmanuel Biver. "Interactions of the microbiome with pharmacological and non-pharmacological approaches for the management of ageing-related musculoskeletal diseases." Therapeutic Advances in Musculoskeletal Disease 13 (January 2021): 1759720X2110090. http://dx.doi.org/10.1177/1759720x211009018.

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Despite major progress in the understanding of the pathophysiology and therapeutic options for common ageing-related musculoskeletal conditions (i.e. osteoporosis and associated fractures, sarcopenia and osteoarthritis), there is still a considerable proportion of patients who respond sub optimally to available treatments or experience adverse effects. Emerging microbiome research suggests that perturbations in microbial composition, functional and metabolic capacity (i.e. dysbiosis) are associated with intestinal and extra-intestinal disorders including musculoskeletal diseases. Besides its contributions to disease pathogenesis, the role of the microbiome is further extended to shaping individuals’ responses to disease therapeutics (i.e. pharmacomicrobiomics). In this review, we focus on the reciprocal interactions between the microbiome and therapeutics for osteoporosis, sarcopenia and osteoarthritis. Specifically, we identify the effects of therapeutics on microbiome’s configurations, functions and metabolic output, intestinal integrity and immune function, but also the effects of the microbiome on the metabolism of these therapeutics, which in turn, may influence their bioavailability, efficacy and side-effect profile contributing to variable treatment responses in clinical practice. We further discuss emerging strategies for microbiota manipulation as preventive or therapeutic (alone or complementary to available treatments) approaches for improving outcomes of musculoskeletal health and disease.

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7

Lee, Chris W., Arulmani Manavalan, and Dana Clausen. "Pharmacological chaperone therapeutics for Krabbe disease." Molecular Genetics and Metabolism 126, no. 2 (February 2019): S92. http://dx.doi.org/10.1016/j.ymgme.2018.12.229.

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8

Virgen, Celina G., Neil Kelkar, Aaron Tran, Christina M. Rosa, Diana Cruz-Topete, Shripa Amatya, Elyse M. Cornett, Ivan Urits, Omar Viswanath, and Alan David Kaye. "Pharmacological management of cancer pain: Novel therapeutics." Biomedicine & Pharmacotherapy 156 (December 2022): 113871. http://dx.doi.org/10.1016/j.biopha.2022.113871.

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9

Maynard, R. L. "The Pharmacological Basis of Therapeutics. 9th ed." Occupational and Environmental Medicine 54, no. 1 (January 1, 1997): 69. http://dx.doi.org/10.1136/oem.54.1.69.

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10

Ikegaya, Yuji, and Eiichi Hinoi. "Toward a New Era of Pharmacological Therapeutics." YAKUGAKU ZASSHI 133, no. 12 (December 1, 2013): 1335–36. http://dx.doi.org/10.1248/yakushi.13-00228-f.

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11

Leader, Benjamin, Quentin J. Baca, and David E. Golan. "Protein therapeutics: a summary and pharmacological classification." Nature Reviews Drug Discovery 7, no. 1 (January 2008): 21–39. http://dx.doi.org/10.1038/nrd2399.

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12

Cook, D. Ryan. "The Pharmacological Basis of Therapeutics (seventh edition)." Anesthesia & Analgesia 65, no. 11 (November 1986): 1253. http://dx.doi.org/10.1213/00000539-198611000-00041.

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13

Nahorski, S. R. "The Pharmacological Basis of Therapeutics, 8th Edition." Trends in Pharmacological Sciences 11, no. 12 (December 1990): 516. http://dx.doi.org/10.1016/0165-6147(90)90055-d.

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14

Egle, John L. "The Pharmacological Basis of Therapeutics, 7th ed." Journal of Pharmaceutical Sciences 75, no. 8 (August 1986): 829. http://dx.doi.org/10.1002/jps.2600750839.

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15

Landmesser, Ulf, Wolfgang Poller, Sotirios Tsimikas, Patrick Most, Francesco Paneni, and Thomas F. Lüscher. "From traditional pharmacological towards nucleic acid-based therapies for cardiovascular diseases." European Heart Journal 41, no. 40 (April 29, 2020): 3884–99. http://dx.doi.org/10.1093/eurheartj/ehaa229.

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Abstract Nucleic acid-based therapeutics are currently developed at large scale for prevention and management of cardiovascular diseases (CVDs), since: (i) genetic studies have highlighted novel therapeutic targets suggested to be causal for CVD; (ii) there is a substantial recent progress in delivery, efficacy, and safety of nucleic acid-based therapies; (iii) they enable effective modulation of therapeutic targets that cannot be sufficiently or optimally addressed using traditional small molecule drugs or antibodies. Nucleic acid-based therapeutics include (i) RNA-targeted therapeutics for gene silencing; (ii) microRNA-modulating and epigenetic therapies; (iii) gene therapies; and (iv) genome-editing approaches (e.g. CRISPR-Cas-based): (i) RNA-targeted therapeutics: several large-scale clinical development programmes, using antisense oligonucleotides (ASO) or short interfering RNA (siRNA) therapeutics for prevention and management of CVD have been initiated. These include ASO and/or siRNA molecules to lower apolipoprotein (a) [apo(a)], proprotein convertase subtilisin/kexin type 9 (PCSK9), apoCIII, ANGPTL3, or transthyretin (TTR) for prevention and treatment of patients with atherosclerotic CVD or TTR amyloidosis. (ii) MicroRNA-modulating and epigenetic therapies: novel potential therapeutic targets are continually arising from human non-coding genome and epigenetic research. First microRNA-based therapeutics or therapies targeting epigenetic regulatory pathways are in clinical studies. (iii) Gene therapies: EMA/FDA have approved gene therapies for non-cardiac monogenic diseases and LDL receptor gene therapy is currently being examined in patients with homozygous hypercholesterolaemia. In experimental studies, gene therapy has significantly improved cardiac function in heart failure animal models. (iv) Genome editing approaches: these technologies, such as using CRISPR-Cas, have proven powerful in stem cells, however, important challenges are remaining, e.g. low rates of homology-directed repair in somatic cells such as cardiomyocytes. In summary, RNA-targeted therapies (e.g. apo(a)-ASO and PCSK9-siRNA) are now in large-scale clinical outcome trials and will most likely become a novel effective and safe therapeutic option for CVD in the near future. MicroRNA-modulating, epigenetic, and gene therapies are tested in early clinical studies for CVD. CRISPR-Cas-mediated genome editing is highly effective in stem cells, but major challenges are remaining in somatic cells, however, this field is rapidly advancing.

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16

Ansari, Mohammad A., Khan F. Badrealam, Asrar Alam, Saba Tufail, Gulshan Khalique, Mohammad J. Equbal, Mohammad A. Alzohairy, Ahmad Almatroudi, Mohammad N. Alomary, and Faheem H. Pottoo. "Recent Nano-based Therapeutic Intervention of Bioactive Sesquiterpenes: Prospects in Cancer Therapeutics." Current Pharmaceutical Design 26, no. 11 (April 24, 2020): 1138–44. http://dx.doi.org/10.2174/1381612826666200116151522.

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: In the recent scenario, nanotechnology-based therapeutics intervention has gained tremendous impetus all across the globe. Nano-based pharmacological intervention of various bioactive compounds has been explored on an increasing scale. Sesquiterpenes are major constituents of essential oils (EOs) present in various plant species which possess intriguing therapeutic potentials. However, owing to their poor physicochemical properties; they have pharmacological limitations. Recent advances in nano-based therapeutic interventions offer various avenues to improve their therapeutic applicability. Reckoning with these, the present review collates various nano-based therapeutic intervention of sesquiterpenes with prospective potential against various debilitating diseases especially cancer. In our viewpoint, considering the burgeoning advancement in the field of nanomedicine; in the near future, the clinical applicability of these nano-formulated sesquiterpenes can be foreseen with great enthusiasm.

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17

Pal, Mrinalini, Vaibhav Sharan Pandey, Ajay Dhawal, Prachi Upadhyay, Prachi Upadhyay, ,. Vartika, Ratanajay Sharma, Brahmanand Singh, Ishwar Das, and Vashist Narayan Pandey. "The Pharmacological and Therapeutic Activities of Canavalia gladiata (Jacq.) DC." Journal of Drug Delivery and Therapeutics 12, no. 5-S (October 15, 2022): 208–16. http://dx.doi.org/10.22270/jddt.v12i5-s.5729.

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Canavalia gladiata is a perennial ethnomedicinal climber food plant found throughout the World. It shows many therapeutic properties which can be utilized for the treatment against many human diseases. In this review, we surveyed the recent findings on the pharmacological and therapeutic properties of Canavalia gladiata. The objective of this is to provide detail analysis on active compounds present in this species and to provide information regarding its pharmacological activities on human diseases and safety. Its bioactive compounds possess outstanding pharmacological properties like hemagglutianting activity, HIV-I inhibition, antimicrobial, antiproliferative, hepatoprotective, ROS- inhibitor, anti-cancer and anti-diabetic properties has been studied. The chemical constituents, pharmacological activities and therapeutic studies of C. gladiata showed a promising medicinal plant with various chemical compounds and numerous pharmacological activities. Keywords: Pharmacological activities, Therapeutics, Bioactive compounds, Canavalia gladiata.

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18

Jain, Ritik S., Irfan Sayyed, Girish Y. Pawar, Paresh A. Patil, and Dipesh R. Karnavat. "Review on Pharmacological and Therapeutics uses of Miswak." Asian Journal of Pharmacy and Technology 10, no. 2 (2020): 90. http://dx.doi.org/10.5958/2231-5713.2020.00017.3.

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19

Abujarour, Ramzey, Bahram Valamehr, Monica Bennett, Megan Robinson, and Peter Flynn. "Pharmacological modulators of stem cells as novel therapeutics." Qatar Foundation Annual Research Forum Proceedings, no. 2012 (October 2012): AESNP14. http://dx.doi.org/10.5339/qfarf.2012.aesnp14.

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20

DiStefano, Victor. "Goodman and Gilman's, The Pharmacological Basis of Therapeutics." Journal of Pediatric Ophthalmology & Strabismus 23, no. 3 (May 1986): 155–56. http://dx.doi.org/10.3928/0191-3913-19860501-17.

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21

Abe, Tatsuya, Yoshikazu Hachiro, Kei Ohara, Mitsuhiro Inagaki, Houhei Hishiyama, Masao Kunimoto, and Masanori Murakami. "Current Developments in Pharmacological Therapeutics for Chronic Constipation." Nippon Daicho Komonbyo Gakkai Zasshi 72, no. 10 (2019): 600–608. http://dx.doi.org/10.3862/jcoloproctology.72.600.

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22

alkhawaldeh, ahmad. "Potential pharmacological Therapeutics options for COVID-19: Review." International Journal of Engineering and Artificial Intelligence 2, no. 2 (July 1, 2021): 9–22. http://dx.doi.org/10.55923/jo.ijeal.2.21.406.

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Unusual pneumonia result from unknown pathogen was emerged in December 2019 in a seafood market of Wuhan city in China. The pathogen was soon identified as a novel coronavirus (2019-nCoV), which is closely related to sever acute respiratory syndrome CoV (SARS-CoV) which has taken the world to the edge of health emergency. On 11th March 2020, COVID-19 was declared a pandemic by the World Health Organization. SARS-CoV-2 belongs to the family of Coronaviridae. Corona virus has been reported to cause similar morbific impacts on the lower respiratory system. Transmits occurs when people breathe in air contaminated by droplets and small airborne particles. Transmission can also occur if sprayed with contaminated fluids, in the eyes, nose or mouth. People remain contagious for up to 20 days, and can spread the virus even if they do not develop any symptoms. Although this disease primarily targets lungs, damages in other organs, such as heart, kidney, liver, and testis, may occur.

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23

Henter, Ioline D., Rafael T. de Sousa, Philip W. Gold, Andre R. Brunoni, Carlos A. Zarate, and Rodrigo Machado-Vieira. "Mood Therapeutics: Novel Pharmacological Approaches for Treating Depression." Expert Review of Clinical Pharmacology 10, no. 2 (January 16, 2017): 153–66. http://dx.doi.org/10.1080/17512433.2017.1253472.

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24

Stigelman, William H., and Pharm D. "Goodman and Gilman's the Pharmacological Basis of Therapeutics." Military Medicine 151, no. 7 (July 1, 1986): 386. http://dx.doi.org/10.1093/milmed/151.1.386.

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25

Boyd, Robert E., Gary Lee, Philip Rybczynski, Elfrida R. Benjamin, Richie Khanna, Brandon A. Wustman, and Kenneth J. Valenzano. "Pharmacological Chaperones as Therapeutics for Lysosomal Storage Diseases." Journal of Medicinal Chemistry 56, no. 7 (March 11, 2013): 2705–25. http://dx.doi.org/10.1021/jm301557k.

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26

Strawser, Cassandra, Kimberly Schadt, Lauren Hauser, Ashley McCormick, McKenzie Wells, Jane Larkindale, Hong Lin, and David R. Lynch. "Pharmacological therapeutics in Friedreich ataxia: the present state." Expert Review of Neurotherapeutics 17, no. 9 (July 26, 2017): 895–907. http://dx.doi.org/10.1080/14737175.2017.1356721.

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27

Thompson Coon, J. "Goodman and Gilman's the Pharmacological Basis of Therapeutics." Focus on Alternative and Complementary Therapies 7, no. 2 (June 14, 2010): 207. http://dx.doi.org/10.1111/j.2042-7166.2002.tb05480.x.

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28

van Wijngaarden, I., M. Th M. Tulp, and W. Soudijn. "Serotonin agonists and antagonists. Pharmacological tools and therapeutics." Recueil des Travaux Chimiques des Pays-Bas 112, no. 2 (September 2, 2010): 126–30. http://dx.doi.org/10.1002/recl.19931120209.

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29

Hastings, Robert C., and Gillis W. Long. "Goodman and Gilman's The Pharmacological Basis of Therapeutics." JAMA 265, no. 20 (May 22, 1991): 2734. http://dx.doi.org/10.1001/jama.1991.03460200114048.

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30

Bigby, Judy Ann. "Goodman and Gillman's The Pharmacological Basis of Therapeutics." Archives of Dermatology 128, no. 1 (January 1, 1992): 132. http://dx.doi.org/10.1001/archderm.1992.01680110146030.

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31

Lasagna, Louis. "Goodman and Gilman's the Pharmacological Basis of Therapeutics." JAMA: The Journal of the American Medical Association 255, no. 19 (May 16, 1986): 2678. http://dx.doi.org/10.1001/jama.1986.03370190162045.

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32

Jiang, Chunhuan, Qinglong Xu, Xiaoan Wen, and Hongbin Sun. "Current developments in pharmacological therapeutics for chronic constipation." Acta Pharmaceutica Sinica B 5, no. 4 (July 2015): 300–309. http://dx.doi.org/10.1016/j.apsb.2015.05.006.

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33

Hastings, Robert C. "Goodman and Gilman's The Pharmacological Basis of Therapeutics." JAMA: The Journal of the American Medical Association 276, no. 12 (September 25, 1996): 999. http://dx.doi.org/10.1001/jama.1996.03540120077042.

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34

Casavant, M. J. "Goodman and Gilman's The Pharmacological Basis of Therapeutics." JAMA: The Journal of the American Medical Association 288, no. 16 (October 23, 2002): 2052. http://dx.doi.org/10.1001/jama.288.16.2052.

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35

Yang, Waisley, Rohit Singla, Oshin Maheshwari, Christine J. Fontaine, and Joana Gil-Mohapel. "Alcohol Use Disorder: Neurobiology and Therapeutics." Biomedicines 10, no. 5 (May 21, 2022): 1192. http://dx.doi.org/10.3390/biomedicines10051192.

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Alcohol use disorder (AUD) encompasses the dysregulation of multiple brain circuits involved in executive function leading to excessive consumption of alcohol, despite negative health and social consequences and feelings of withdrawal when access to alcohol is prevented. Ethanol exerts its toxicity through changes to multiple neurotransmitter systems, including serotonin, dopamine, gamma-aminobutyric acid, glutamate, acetylcholine, and opioid systems. These neurotransmitter imbalances result in dysregulation of brain circuits responsible for reward, motivation, decision making, affect, and the stress response. Despite serious health and psychosocial consequences, this disorder still remains one of the leading causes of death globally. Treatment options include both psychological and pharmacological interventions, which are aimed at reducing alcohol consumption and/or promoting abstinence while also addressing dysfunctional behaviours and impaired functioning. However, stigma and social barriers to accessing care continue to impact many individuals. AUD treatment should focus not only on restoring the physiological and neurological impairment directly caused by alcohol toxicity but also on addressing psychosocial factors associated with AUD that often prevent access to treatment. This review summarizes the impact of alcohol toxicity on brain neurocircuitry in the context of AUD and discusses pharmacological and non-pharmacological therapies currently available to treat this addiction disorder.

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36

Akter, Sumaya, Akhi Moni, Golam Mahbub Faisal, Muhammad Ramiz Uddin, Nourin Jahan, Md Abdul Hannan, Asadur Rahman, and Md Jamal Uddin. "Renoprotective Effects of Mangiferin: Pharmacological Advances and Future Perspectives." International Journal of Environmental Research and Public Health 19, no. 3 (February 7, 2022): 1864. http://dx.doi.org/10.3390/ijerph19031864.

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Both acute and chronic kidney diseases substantially contribute to the morbidities and mortality of patients worldwide. The existing therapeutics, which are mostly developed from synthetic sources, present some unexpected effects in patients, provoking researchers to explore potential novel alternatives. Natural products that have protective effects against various renal pathologies could be potential drug candidates for kidney diseases. Mangiferin is a natural polyphenol predominantly isolated from Mangifera indica and possesses multiple health benefits against various human ailments, including kidney disease. The main objective of this review is to update the renoprotective potentials of mangiferin with underlying molecular pharmacology and to highlight the recent development of mangiferin-based therapeutics toward kidney problems. Literature published over the past decade suggests that treatment with mangiferin attenuates renal inflammation and oxidative stress, improves interstitial fibrosis and renal dysfunction, and ameliorates structural alteration in the kidney. Therefore, mangiferin could be used as a multi-target therapeutic candidate to treat renal diseases. Although mangiferin-loaded nanoparticles have shown therapeutic promise against various human diseases, there is limited information on the targeted delivery of mangiferin in the kidney. Further research is required to gain insight into the molecular pharmacology of mangiferin targeting kidney diseases and translate the preclinical results into clinical use.

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37

Berei, Joseph, Adam Eckburg, Edward Miliavski, Austin D. Anderson, Rachel J. Miller, Joshua Dein, Allison M. Giuffre, et al. "Potential Telomere-Related Pharmacological Targets." Current Topics in Medicinal Chemistry 20, no. 6 (April 13, 2020): 458–84. http://dx.doi.org/10.2174/1568026620666200109114339.

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Telomeres function as protective caps at the terminal portion of chromosomes, containing non-coding nucleotide sequence repeats. As part of their protective function, telomeres preserve genomic integrity and minimize chromosomal exposure, thus limiting DNA damage responses. With continued mitotic divisions in normal cells, telomeres progressively shorten until they reach a threshold at a point where they activate senescence or cell death pathways. However, the presence of the enzyme telomerase can provide functional immortality to the cells that have reached or progressed past senescence. In senescent cells that amass several oncogenic mutations, cancer formation can occur due to genomic instability and the induction of telomerase activity. Telomerase has been found to be expressed in over 85% of human tumors and is labeled as a near-universal marker for cancer. Due to this feature being present in a majority of tumors but absent in most somatic cells, telomerase and telomeres have become promising targets for the development of new and effective anticancer therapeutics. In this review, we evaluate novel anticancer targets in development which aim to alter telomerase or telomere function. Additionally, we analyze the progress that has been made, including preclinical studies and clinical trials, with therapeutics directed at telomere-related targets. Furthermore, we review the potential telomere-related therapeutics that are used in combination therapy with more traditional cancer treatments. Throughout the review, topics related to medicinal chemistry are discussed, including drug bioavailability and delivery, chemical structure-activity relationships of select therapies, and the development of a unique telomere assay to analyze compounds affecting telomere elongation.

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38

Fechner, Henry, Sandra Pinkert, Anja Geisler, Wolfgang Poller, and Jens Kurreck. "Pharmacological and Biological Antiviral Therapeutics for Cardiac Coxsackievirus Infections." Molecules 16, no. 10 (October 11, 2011): 8475–503. http://dx.doi.org/10.3390/molecules16108475.

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39

Robinson, Samuel D., and Helena Safavi-Hemami. "Venom peptides as pharmacological tools and therapeutics for diabetes." Neuropharmacology 127 (December 2017): 79–86. http://dx.doi.org/10.1016/j.neuropharm.2017.07.001.

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40

Nomura, Yasuyuki. "Pharmacological approaches to novel therapeutics for ischemic brain strokes." Japanese Journal of Pharmacology 76 (1998): 39. http://dx.doi.org/10.1016/s0021-5198(19)40287-4.

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41

Muther, Thomas F. "Book ReviewGoodman and Gilman's The Pharmacological Basis of Therapeutics." New England Journal of Medicine 314, no. 21 (May 22, 1986): 1394. http://dx.doi.org/10.1056/nejm198605223142121.

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42

Li, Yang, Maryam B. Lustberg, and Shuiying Hu. "Emerging Pharmacological and Non-Pharmacological Therapeutics for Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy." Cancers 13, no. 4 (February 12, 2021): 766. http://dx.doi.org/10.3390/cancers13040766.

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Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event of several first-line chemotherapeutic agents, including platinum compounds, taxanes, vinca alkaloids, thalidomide, and bortezomib, which negatively affects the quality of life and clinical outcome. Given the dearth of effective established agents for preventing or treating CIPN, and the increasing number of cancer survivors, there is an urgent need for the identification and development of new, effective intervention strategies that can prevent or mitigate this debilitating side effect. Prior failures in the development of effective interventions have been due, at least in part, to a lack of mechanistic understanding of CIPN and problems in translating this mechanistic understanding into testable hypotheses in rationally-designed clinical trials. Recent progress has been made, however, in the pathogenesis of CIPN and has provided new targets and pathways for the development of emerging therapeutics that can be explored clinically to improve the management of this debilitating toxicity. This review focuses on the emerging therapeutics for the prevention and treatment of CIPN, including pharmacological and non-pharmacological strategies, and calls for fostering collaboration between basic and clinical researchers to improve the development of effective strategies.

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43

Nizam, Nuder Nower, Sohel Mahmud, Mohammad Kamruzzaman, and Md Kamrul Hasan. "Bakuchiol and its pharmacological benefits." F1000Research 12 (January 9, 2023): 29. http://dx.doi.org/10.12688/f1000research.129072.1.

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Background and aims: Natural compounds extracted from medicinal plants have recently gained attention in therapeutics as they are considered to have lower toxicity and higher tolerability relative to chemically synthesized compounds. Bakuchiol is one such compound; it is a type of meroterpene derived from the leaves and seeds of Psoralea corylifolia plants. Natural sources of bakuchiol have been used in traditional Chinese and Indian medicine for centuries due to its preventive benefits against tumors and inflammation. It plays a strong potential role as an antioxidant with impressive abilities to remove Reactive Oxygen Species (ROS). This review has focused on bakuchiol's extraction, therapeutic applications, and pharmacological benefits. Methods: A search strategy has been followed to retrieve the relevant newly published literature on the pharmacological benefits of bakuchiol. After an extensive study of the retrieved articles and maintaining the inclusion and exclusion criteria, 106 articles were finally selected for this review. Results: Strong support of primary research on the protective effects via antitumorigenic, anti-inflammatory, antioxidative, antimicrobial, and antiviral activities are delineated. Conclusions: From ancient to modern life, medicinal plants have always been drawing the attention of human beings to alleviate ailments for a healthy and balanced lifestyle. This review is a comprehensive approach to highlighting bona fide essential pharmacological benefits and mechanism of action of therapeutic implications.

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44

Jo, Seong Jun, Soon Uk Chae, Chae Bin Lee, and Soo Kyung Bae. "Clinical Pharmacokinetics of Approved RNA Therapeutics." International Journal of Molecular Sciences 24, no. 1 (January 1, 2023): 746. http://dx.doi.org/10.3390/ijms24010746.

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RNA-mediated drugs are a rapidly growing class of therapeutics. Over the last five years, the list of FDA-approved RNA therapeutics has expanded owing to their unique targets and prolonged pharmacological effects. Their absorption, distribution, metabolism, and excretion (ADME) have important clinical im-plications, but their pharmacokinetic properties have not been fully understood. Most RNA therapeutics have structural modifications to prevent rapid elimination from the plasma and are administered intravenously or subcutaneously, with some exceptions, for effective distribution to target organs. Distribution of drugs into tissues depends on the addition of a moiety that can be transported to the target and RNA therapeutics show a low volume of distribution because of their molecular size and negatively-charged backbone. Nucleases metabolize RNA therapeutics to a shortened chain, but their metabolic ratio is relatively low. Therefore, most RNA therapeutics are excreted in their intact form. This review covers not only ADME features but also clinical pharmacology data of the RNA therapeutics such as drug–drug interaction or population pharmacokinetic analyses. As the market of RNA therapeutics is expected to rapidly expand, comprehensive knowledge will contribute to interpreting and evaluating the pharmacological properties.

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45

Stokum, Jesse A., Volodymyr Gerzanich, Kevin N. Sheth, W. Taylor Kimberly, and J. Marc Simard. "Emerging Pharmacological Treatments for Cerebral Edema: Evidence from Clinical Studies." Annual Review of Pharmacology and Toxicology 60, no. 1 (January 6, 2020): 291–309. http://dx.doi.org/10.1146/annurev-pharmtox-010919-023429.

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Cerebral edema, a common and often fatal companion to most forms of acute central nervous system disease, has been recognized since the time of ancient Egypt. Unfortunately, our therapeutic armamentarium remains limited, in part due to historic limitations in our understanding of cerebral edema pathophysiology. Recent advancements have led to a number of clinical trials for novel therapeutics that could fundamentally alter the treatment of cerebral edema. In this review, we discuss these agents, their targets, and the data supporting their use, with a focus on agents that have progressed to clinical trials.

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Tzelepis, Konstantinos, Etienne De Braekeleer, Eliza Yankova, Justyna Rak, Demetrios Aspris, Ana Filipa Domingues, Richard Fosbeary, et al. "Pharmacological Inhibition of the RNA m6a Writer METTL3 As a Novel Therapeutic Strategy for Acute Myeloid Leukemia." Blood 134, Supplement_1 (November 13, 2019): 403. http://dx.doi.org/10.1182/blood-2019-127962.

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Acute myeloid leukemia (AML) is an aggressive cancer with a poor prognosis, for which the therapeutic landscape has changed little for decades. New evidence has revealed an important role for RNA modifications in cancer development and maintenance via the catalytic function of RNA-modifying enzymes. We and others have recently shown that METTL3, the RNA methyltransferase responsible for the deposition of N-6-methyl groups on adenosine (m6A) in mRNA, is a promising therapeutic target for AML1,2. Here we present the in vitro and in vivo characterization of novel small molecule inhibitors of METTL3 as an effective therapeutic strategy in AML. Recently, we generated a comprehensive catalogue of RNA-modifying enzymes that are essential for AML cells using CRISPR-Cas9 recessive screens and characterised METTL3 as a novel therapeutic candidate through its effects on mRNA translational efficiency of key leukemia oncogenes1. Using a structure-guided medicinal chemistry platform we developed and optimised small molecule inhibitors of METTL3 from 2 distinct chemical series. Here we demonstrate that compounds 1 and 2 show biochemical inhibition of METTL3 enzyme with single digit nanomolar potency, while direct binding to METTL3 was confirmed by Surface Plasmon Resonance (SPR) analysis with comparable potency between compounds. Additionally, we developed compound 3 as an inactive analog which was confirmed inactive in enzyme assays (>50 µM IC50). Importantly, we verified that compounds 1 and 2 are selective for METTL3 and do not inhibit a panel of other RNA, DNA or protein methyltransferases tested (>10 µM IC50). Cellular target engagement was confirmed by demonstrating that compounds 1 and 2 reduced m6A levels and inhibited the protein expression of METTL3-dependent m6A substrates in mouse and human AML models, including SP1, with nanomolar potency. Furthermore, treatment of MOLM13 cells with compounds 1 and 2 inhibited their proliferation with comparable potency to SP1 inhibition. The same anti-proliferative effect was observed using a large panel of human AML cell lines. In addition, polyribosome profiling in MOLM13 cells treated with compounds 1 and 2 revealed enhanced blocking of mRNA translation, mirroring the effects derived from the genetic inhibition of METTL3. Notably, all of the above effects were not observed when the inactive analog (compound 3) was used, further highlighting the specificity and sensitivity of our active candidates. We subsequently performed in vivo characterisation of compound 1. This compound exhibited excellent bioavailability after oral or intraperitoneal administration with good dose-proportional exposure in mice and a half-life of 3.5 hours. It also appeared to be well-tolerated with no body weight loss or clinical signs of toxicity. We also evaluated its anti-tumor effects in patient derived xenotransplantation experiments (PDX) as well as transplantation experiments using an MLL-AF9 driven primary murine AML model. Daily dosing of 30 mg/kg significantly inhibited AML expansion and reduced spleen weight compared to vehicle control, indicating a pronounced anti-tumor effect in vivo. Target engagement was confirmed in bone marrow and spleen as measured by the reduction of METTL3-dependent m6A targets. Importantly, we went on to demonstrate that, while the pharmacological inhibition of METTL3 is required for AML cell survival, it was dispensable for normal hematopoiesis. Collectively, we describe the detailed characterization of potent and selective inhibitors of the METTL3 RNA methyltransferase, and demonstrate their activity and utility using biochemical, cellular and in vivo systems. We show that inhibition of METTL3 by small molecules in vivo leads to strong anti-tumor effects in physiologically and clinically relevant models of AML. To our knowledge, this is the first study demonstrating in vivo activity of inhibitors of an RNA methyltransferase, hence providing proof of concept that RNA modifying enzymes represent a new target class for anti-cancer therapeutics. References Barbieri, I. et al. Promoter-bound METTL3 maintains myeloid leukaemia by m(6)A-dependent translation control. Nature552, 126-131, doi:10.1038/nature24678 (2017). Vu, L. P. et al. The N(6)-methyladenosine (m(6)A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nat Med23, 1369-1376, doi:10.1038/nm.4416 (2017). Disclosures Yankova: STORM THERAPEUTICS: Employment. Fosbeary:STORM THERAPEUTICS: Employment. Hendrick:STORM THERAPEUTICS: Employment. Leggate:STORM THERAPEUTICS: Employment. Ofir-Rosenfeld:STORM THERAPEUTICS: Employment. Sapetschnig:STORM THERAPEUTICS: Employment. Albertella:STORM THERAPEUTICS: Employment. Blackaby:STORM THERAPEUTICS: Employment. Rausch:STORM THERAPEUTICS: Employment. Vassiliou:Kymab Ltd: Consultancy, Other: Minor Stockholder; Oxstem Ltd: Consultancy; Celgene: Research Funding. Kouzarides:STORM THERAPEUTICS: Equity Ownership.

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Chilamakuri, Rameswari, and Saurabh Agarwal. "COVID-19: Characteristics and Therapeutics." Cells 10, no. 2 (January 21, 2021): 206. http://dx.doi.org/10.3390/cells10020206.

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Novel coronavirus (COVID-19 or 2019-nCoV or SARS-CoV-2), which suddenly emerged in December 2019 is still haunting the entire human race and has affected not only the healthcare system but also the global socioeconomic balances. COVID-19 was quickly designated as a global pandemic by the World Health Organization as there have been about 98.0 million confirmed cases and about 2.0 million confirmed deaths, as of January 2021. Although, our understanding of COVID-19 has significantly increased since its outbreak, and multiple treatment approaches and pharmacological interventions have been tested or are currently under development to mitigate its risk-factors. Recently, some vaccine candidates showed around 95% clinical efficacy, and now receiving emergency use approvals in different countries. US FDA recently approved BNT162 and mRNA-1273 vaccines developed by Pfizer/BioNTech and Moderna Inc. for emergency use and vaccination in the USA. In this review, we present a succinct overview of the SARS-CoV-2 virus structure, molecular mechanisms of infection, COVID-19 epidemiology, diagnosis, and clinical manifestations. We also systematize different treatment strategies and clinical trials initiated after the pandemic outbreak, based on viral infection and replication mechanisms. Additionally, we reviewed the novel pharmacological intervention approaches and vaccine development strategies against COVID-19. We speculate that the current pandemic emergency will trigger detailed studies of coronaviruses, their mechanism of infection, development of systematic drug repurposing approaches, and novel drug discoveries for current and future pandemic outbreaks.

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Jawad, Atteqa, Richa Kaushal, Muhammad Sohail, and Amna Yaqoob. "Histamine receptors as drug target: Current and future therapeutics." Journal of Shifa Tameer-e-Millat University 2, no. 1 (July 21, 2019): 31–35. http://dx.doi.org/10.32593/jstmu/vol2.iss1.25.

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Histamine is a neurotransmitter responsible for central regulation of inflammatory reactions. Initial studies were done by Sir Henry Dale in 1993. Histamine acts on its four type of receptors. H1 and H2 are well-established with pharmacological status. H1 receptors are mainly linked with inflammatory responses and developed to mitigate the inflammatory symptoms. While H2 antagonists are established with their role in decreasing basal gastric secretions by decreasing the cyclic adenylyl mono phosphate (cAMP), thus used as therapy line for gastric ulcers. H3 being located centrally imparts its central effects in cognitive functions that are pain, sleep, and memory modulation of neurotransmitters release including, dopamine, acetylcholine, noradrenalin and serotonin. H4 is discovered recently during cloning of H3 and found on immune related cells as, mast cells, T cells and dendrites. Experimental studies are helping in development of more pharmacologically worth drugs that can increase the quality of life.

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Loi, Samantha M., Dhamidhu Eratne, Wendy Kelso, Dennis Velakoulis, and Jeffrey CL Looi. "Alzheimer disease: Non-pharmacological and pharmacological management of cognition and neuropsychiatric symptoms." Australasian Psychiatry 26, no. 4 (April 19, 2018): 358–65. http://dx.doi.org/10.1177/1039856218766123.

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Objectives: This clinical update review focuses on the management of cognition and the neuropsychiatric features of Alzheimer’s disease (AD) and highlights current issues regarding pharmacological and non-pharmacological treatment, putative therapeutics and recent relevant research findings in this area. Conclusions: AD is a neurodegenerative progressive condition characterised by cognitive impairment and functional decline. Most people with AD will demonstrate neuropsychiatric features, better known as behavioural and psychological symptoms of dementia (BPSD). Early recognition and treatment of BPSD are essential, as these cause considerable distress and carer burden. While there are many disease-modifying therapies for the cognitive symptoms still in the research stage, only symptomatic treatments are currently available for these and the BPSD.

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Petit, Robert Gironés, Amanda Cano, Alba Ortiz, Marta Espina, Josefina Prat, Montserrat Muñoz, Patrícia Severino, et al. "Psoriasis: From Pathogenesis to Pharmacological and Nano-Technological-Based Therapeutics." International Journal of Molecular Sciences 22, no. 9 (May 7, 2021): 4983. http://dx.doi.org/10.3390/ijms22094983.

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Research in the pathogenesis of inflammatory skin diseases, such as skin dermatitis and psoriasis, has experienced some relevant breakthroughs in recent years. The understanding of age-related factors, gender, and genetic predisposition of these multifactorial diseases has been instrumental for the development of new pharmacological and technological treatment approaches. In this review, we discuss the molecular mechanisms behind the pathological features of psoriasis, also addressing the currently available treatments and novel therapies that are under clinical trials. Innovative therapies developed over the last 10 years have been researched. In this area, advantages of nanotechnological approaches to provide an effective drug concentration in the disease site are highlighted, together with microneedles as innovative candidates for drug delivery systems in psoriasis and other inflammatory chronic skin diseases.

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