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Social Psychopharmacology: Novel Approaches to Treat Deficits in Social Motivation in Schizophrenia.Schizophrenia Bulletin Sep 2023Diminished social motivation is a negative symptom of schizophrenia and leads to severe functional consequences for many patients suffering from the illness. However,... (Review)
Review
BACKGROUND AND HYPOTHESIS
Diminished social motivation is a negative symptom of schizophrenia and leads to severe functional consequences for many patients suffering from the illness. However, there are no effective medications available to treat this symptom. Despite the lack of approved treatments for patients, there is a growing body of literature on the effects of several classes of drugs on social motivation in healthy volunteers that may be relevant to patients. The aim of this review is to synthesize these results in an effort to identify novel directions for the development of medications to treat reduced social motivation in schizophrenia.
STUDY DESIGN
In this article, we review pharmacologic challenge studies addressing the acute effects of psychoactive drugs on social motivation in healthy volunteers and consider how these findings may be applied to deficits in social motivation in schizophrenia. We include studies testing amphetamines and 3,4-methylenedioxymethamphetamine (MDMA), opioids, cannabis, serotonergic psychedelics, antidepressants, benzodiazepines, and neuropeptides.
STUDY RESULTS
We report that amphetamines, MDMA, and some opioid medications enhance social motivation in healthy adults and may represent promising avenues of investigation in schizophrenia.
CONCLUSIONS
Given the acute effects of these drugs on behavioral and performance-based measures of social motivation in healthy volunteers, they may be particularly beneficial as an adjunct to psychosocial training programs in patient populations. It remains to be determined how these medications affect patients with deficits in social motivation, and in which contexts they may be most effectively administered.
Topics: Adult; Humans; Schizophrenia; Motivation; Psychopharmacology; N-Methyl-3,4-methylenedioxyamphetamine; Apathy
PubMed: 37358825
DOI: 10.1093/schbul/sbad094 -
Journal of Materials Science. Materials... Nov 2023Half a million different plant species are occurring worldwide, of which only 1% has been phytochemically considered. Thus, there is great potential for discovering... (Review)
Review
Half a million different plant species are occurring worldwide, of which only 1% has been phytochemically considered. Thus, there is great potential for discovering novel bioactive compounds. In dentistry, herbal extracts have been used as antimicrobial agents, analgesics, and intracanal medicaments. Glass-ionomer cement (GIC) and bioactive glass (BAG) are attractive materials in dentistry due to their bioactivity, adhesion, and remineralisation capabilities. Thus, this review summarizes the evidence around the use of phytotherapeutics in dental glass-based materials. This review article covers the structure, properties, and clinical uses of GIC and BAG materials within dentistry, with an emphasis on all the attempts that have been made in the last 20 years to enhance their properties naturally using the wisdom of traditional medicines. An extensive electronic search was performed across four databases to include published articles in the last 20 years and the search was concerned only with the English language publications. Publications that involved the use of plant extracts, and their active compounds for the green synthesis of nanoparticles and the modification of GIC and BAG were included up to May 2023. Plant extracts are a potential and effective candidate for modification of different properties of GIC and BAG, particularly their antimicrobial activities. Moreover, natural plant extracts have shown to be very effective in the green synthesis of metal ion nanoparticles in an ecological, and easy way with the additional advantage of a synergistic effect between metal ions and the phytotherapeutic agents. Medicinal plants are considered an abundant, cheap source of biologically active compounds and many of these phytotherapeutics have been the base for the development of new lead pharmaceuticals. Further research is required to assess the safety and the importance of regulation of phytotherapeutics to expand their use in medicine.
Topics: Herbal Medicine; Plant Extracts; Glass Ionomer Cements; Metal Nanoparticles; Dentistry
PubMed: 37962680
DOI: 10.1007/s10856-023-06764-w -
Cancer Research Nov 2023Proteomics is a powerful approach that can rapidly enhance our understanding of cancer development. Detailed characterization of the genetic, pharmacogenomic, and immune...
UNLABELLED
Proteomics is a powerful approach that can rapidly enhance our understanding of cancer development. Detailed characterization of the genetic, pharmacogenomic, and immune landscape in relation to protein expression in patients with cancer could provide new insights into the functional roles of proteins in cancer. By taking advantage of the genotype data from The Cancer Genome Atlas and protein expression data from The Cancer Proteome Atlas, we characterized the effects of genetic variants on protein expression across 31 cancer types and identified approximately 100,000 protein quantitative trait loci (pQTL). Among these, over 8000 pQTLs were associated with patient overall survival. Furthermore, characterization of the impact of protein expression on more than 350 imputed anticancer drug responses in patients revealed nearly 230,000 significant associations. In addition, approximately 21,000 significant associations were identified between protein expression and immune cell abundance. Finally, a user-friendly data portal, GPIP (https://hanlaboratory.com/GPIP), was developed featuring multiple modules that enable researchers to explore, visualize, and browse multidimensional data. This detailed analysis reveals the associations between the proteomic landscape and genetic variation, patient outcome, the immune microenvironment, and drug response across cancer types, providing a resource that may offer valuable clinical insights and encourage further functional investigations of proteins in cancer.
SIGNIFICANCE
Comprehensive characterization of the relationship between protein expression and the genetic, pharmacogenomic, and immune landscape of tumors across cancer types provides a foundation for investigating the role of protein expression in cancer development and treatment.
Topics: Humans; Proteomics; Pharmacogenetics; Proteome; Genotype; Neoplasms; Tumor Microenvironment
PubMed: 37548539
DOI: 10.1158/0008-5472.CAN-23-0758 -
Pharmacology Research & Perspectives Dec 2023
Topics: Precision Medicine; Pharmacogenetics; Drug Discovery
PubMed: 37885364
DOI: 10.1002/prp2.1147 -
SLAS Discovery : Advancing Life... Sep 2023The Department of Medicinal Chemistry, together with the Institute for Structural Biology, Drug Discovery and Development, at Virginia Commonwealth University (VCU) has... (Review)
Review
Merging cultures and disciplines to create a drug discovery ecosystem at Virginia commonwealth university: Medicinal chemistry, structural biology, molecular and behavioral pharmacology and computational chemistry.
The Department of Medicinal Chemistry, together with the Institute for Structural Biology, Drug Discovery and Development, at Virginia Commonwealth University (VCU) has evolved, organically with quite a bit of bootstrapping, into a unique drug discovery ecosystem in response to the environment and culture of the university and the wider research enterprise. Each faculty member that joined the department and/or institute added a layer of expertise, technology and most importantly, innovation, that fertilized numerous collaborations within the University and with outside partners. Despite moderate institutional support with respect to a typical drug discovery enterprise, the VCU drug discovery ecosystem has built and maintained an impressive array of facilities and instrumentation for drug synthesis, drug characterization, biomolecular structural analysis and biophysical analysis, and pharmacological studies. Altogether, this ecosystem has had major impacts on numerous therapeutic areas, such as neurology, psychiatry, drugs of abuse, cancer, sickle cell disease, coagulopathy, inflammation, aging disorders and others. Novel tools and strategies for drug discovery, design and development have been developed at VCU in the last five decades; e.g., fundamental rational structure-activity relationship (SAR)-based drug design, structure-based drug design, orthosteric and allosteric drug design, design of multi-functional agents towards polypharmacy outcomes, principles on designing glycosaminoglycans as drugs, and computational tools and algorithms for quantitative SAR (QSAR) and understanding the roles of water and the hydrophobic effect.
Topics: Humans; Chemistry, Pharmaceutical; Computational Chemistry; Ecosystem; Universities; Virginia; Drug Discovery; Quantitative Structure-Activity Relationship; Molecular Biology
PubMed: 36863508
DOI: 10.1016/j.slasd.2023.02.006 -
EBioMedicine Mar 2024Pharmacogenomics (PGx) holds promise to revolutionize modern healthcare. Although there are several prospective clinical studies in oncology and cardiology,...
BACKGROUND
Pharmacogenomics (PGx) holds promise to revolutionize modern healthcare. Although there are several prospective clinical studies in oncology and cardiology, demonstrating a beneficial effect of PGx-guided treatment in reducing adverse drug reactions, there are very few such studies in psychiatry, none of which spans across all main psychiatric indications, namely schizophrenia, major depressive disorder and bipolar disorder. In this study we aim to investigate the clinical effectiveness of PGx-guided treatment (occurrence of adverse drug reactions, hospitalisations and re-admissions, polypharmacy) and perform a cost analysis of the intervention.
METHODS
We report our findings from a multicenter, large-scale, prospective study of pre-emptive genome-guided treatment named as PREemptive Pharmacogenomic testing for preventing Adverse drug REactions (PREPARE) in a large cohort of psychiatric patients (n = 1076) suffering from schizophrenia, major depressive disorder and bipolar disorder.
FINDINGS
We show that patients with an actionable phenotype belonging to the PGx-guided arm (n = 25) present with 34.1% less adverse drug reactions compared to patients belonging to the control arm (n = 36), 41.2% less hospitalisations (n = 110 in the PGx-guided arm versus n = 187 in the control arm) and 40.5% less re-admissions (n = 19 in the PGx-guided arm versus n = 32 in the control arm), less duration of initial hospitalisations (n = 3305 total days of hospitalisation in the PGx-guided arm from 110 patients, versus n = 6517 in the control arm from 187 patients) and duration of hospitalisation upon readmission (n = 579 total days of hospitalisation upon readmission in the PGx-guided arm, derived from 19 patients, versus n = 928 in the control arm, from 32 patients respectively). It was also shown that in the vast majority of the cases, there was less drug dose administrated per drug in the PGx-guided arm compared to the control arm and less polypharmacy (n = 124 patients prescribed with at least 4 psychiatric drugs in the PGx-guided arm versus n = 143 in the control arm) and smaller average number of co-administered psychiatric drugs (2.19 in the PGx-guided arm versus 2.48 in the control arm. Furthermore, less deaths were reported in the PGx-guided arm (n = 1) compared with the control arm (n = 9). Most importantly, we observed a 48.5% reduction of treatment costs in the PGx-guided arm with a reciprocal slight increase of the quality of life of patients suffering from major depressive disorder (0.935 versus 0.925 QALYs in the PGx-guided and control arm, respectively).
INTERPRETATION
While only a small proportion (∼25%) of the entire study sample had an actionable genotype, PGx-guided treatment can have a beneficial effect in psychiatric patients with a reciprocal reduction of treatment costs. Although some of these findings did not remain significant when all patients were considered, our data indicate that genome-guided psychiatric treatment may be successfully integrated in mainstream healthcare.
FUNDING
European Union Horizon 2020.
Topics: Humans; Pharmacogenetics; Prospective Studies; Depressive Disorder, Major; Quality of Life; Psychiatry; Drug-Related Side Effects and Adverse Reactions
PubMed: 38364700
DOI: 10.1016/j.ebiom.2024.105009 -
Pharmacology Research & Perspectives Aug 2023Ethnopharmacology seeks to investigate humankind's use of natural materials, such as plants, fungi, microorganisms, animals, and minerals, for medicinal purposes. In... (Review)
Review
Ethnopharmacology seeks to investigate humankind's use of natural materials, such as plants, fungi, microorganisms, animals, and minerals, for medicinal purposes. In this highly interdisciplinary field, which can be described as a bridge between the natural/medical and socio-cultural sciences, pharmacological, anthropological, and socio-cultural research methods are often applied, along with methods from other branches of science. When entering the field of ethnopharmacology as a newcomer, student, or early career researcher today, the tremendous amount of scientific publications, and even classical books from this field and related scientific disciplines, can be overwhelming. Ethnopharmacology has evolved over the past decades, and new key topics, such as the decolonization of the field, issues on intellectual property and benefit-sharing, species conservation, the preservation of traditional knowledge, the protection of indigenous communities, science outreach, and climate change, have become important and urgent aspects of the field that must not be disregarded by today's ethnopharmacologists. One of the questions of newcomers will be, "Where to begin?" This review article offers a brief (and certainly not comprehensive) introduction to the science of ethnopharmacology, highlighting some of its past most notable achievements and future prospects. In addition, this article provides an example for newcomers to the field of how to address different stages that may be involved in conducting ethnopharmacological field and lab studies, including early-stage drug discovery and community work. The example presented summarizes a series of studies conducted in the remote Greater Mpigi region of Uganda, located in East Africa. Stages of ethnopharmacological research described include ethnobotanical surveying and fieldwork, the pharmacological assessment of activity with diverse targets in the laboratory, and the transfer of results back to indigenous communities, that is, non-financial benefit sharing as a potential best practice example. As a result of this research example, a total of six original research articles have been published on the medicinal application and ethnopharmacology of 16 plant species from the Ugandan study site, offering a large quantity of results. These six publications reflect the multifaceted nature of the interdisciplinary science of ethnopharmacology, which may serve as a reference point and inspiration for newcomers to design and conduct their own independent ethnopharmacological research endeavors at other study sites. Major bottlenecks and solutions are provided, and the current social media channels with educational ethnopharmacological content are briefly introduced.
Topics: Animals; Ethnopharmacology; Plants, Medicinal; Ethnobotany; Surveys and Questionnaires; Research Design
PubMed: 37497567
DOI: 10.1002/prp2.1109 -
Cell Reports. Medicine Feb 2024Despite considerable efforts to identify human liver cancer genomic alterations that might unveil druggable targets, the systematic translation of multiomics data...
Despite considerable efforts to identify human liver cancer genomic alterations that might unveil druggable targets, the systematic translation of multiomics data remains challenging. Here, we report success in long-term culture of 64 patient-derived hepatobiliary tumor organoids (PDHOs) from a Chinese population. A divergent response to 265 metabolism- and epigenetics-related chemicals and 36 anti-cancer drugs is observed. Integration of the whole genome, transcriptome, chromatin accessibility profiles, and drug sensitivity results of 64 clinically relevant drugs defines over 32,000 genome-drug interactions. RUNX1 promoter mutation is associated with an increase in chromatin accessibility and a concomitant gene expression increase, promoting a cluster of drugs preferentially sensitive in hepatobiliary tumors. These results not only provide an annotated PDHO biobank of human liver cancer but also suggest a systematic approach for obtaining a comprehensive understanding of the gene-regulatory network of liver cancer, advancing the applications of potential personalized medicine.
Topics: Humans; Pharmacogenetics; Antineoplastic Agents; Liver Neoplasms; Organoids; Chromatin
PubMed: 38278146
DOI: 10.1016/j.xcrm.2023.101375 -
JAMA Network Open May 2024Disparities in outcomes exist between Black and White patients with acute myeloid leukemia (AML), with Black patients experiencing poorer prognosis compared with their... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Disparities in outcomes exist between Black and White patients with acute myeloid leukemia (AML), with Black patients experiencing poorer prognosis compared with their White counterparts.
OBJECTIVE
To assess whether varying intensity of induction therapy to treat pediatric AML is associated with reduced disparities in treatment outcome by race.
DESIGN, SETTING, AND PARTICIPANTS
A comparative effectiveness analysis was conducted of 86 Black and 359 White patients with newly diagnosed AML who were enrolled in the AML02 trial from 2002 to 2008 or the AML08 trial from 2008 to 2017. Statistical analysis was conducted from July 2023 through January 2024.
INTERVENTIONS
Patients in AML02 were randomly assigned to receive standard low-dose cytarabine-based induction therapy or augmented high-dose cytarabine-based induction therapy, whereas patients in AML08 received high-dose cytarabine-based therapy.
MAIN OUTCOMES AND MEASURES
Cytarabine pharmacogenomic 10-single-nucleotide variant (ACS10) scores were evaluated for association with outcome according to race and treatment arm.
RESULTS
This analysis included 86 Black patients (mean [SD] age, 8.8 [6.5] years; 54 boys [62.8%]; mean [SD] leukocyte count, 52 600 [74 000] cells/µL) and 359 White patients (mean [SD] age, 9.1 [6.2] years; 189 boys [52.6%]; mean [SD] leukocyte count, 54 500 [91 800] cells/µL); 70 individuals with other or unknown racial and ethnic backgrounds were not included. Among all patients without core binding factor AML who received standard induction therapy, Black patients had significantly worse outcomes compared with White patients (5-year event-free survival rate, 25% [95% CI, 9%-67%] compared with 56% [95% CI, 46%-70%]; P = .03). By contrast, among all patients who received augmented induction therapy, there were no differences in outcome according to race (5-year event-free survival rate, Black patients, 50% [95% CI, 38%-67%]; White patients, 48% [95% CI, 42%-55%]; P = .78). Among patients who received standard induction therapy, those with low ACS10 scores had a significantly worse 5-year event-free survival rate compared with those with high scores (42.4% [95% CI, 25.6%-59.3%] and 70.0% [95% CI, 56.6%-83.1%]; P = .004); however, among patients who received augmented induction therapy, there were no differences in 5-year event-free survival rates according to ACS10 score (low score, 60.6% [95% CI, 50.9%-70.2%] and high score, 54.8% [95% CI, 47.1%-62.5%]; P = .43).
CONCLUSIONS AND RELEVANCE
In this comparative effectiveness study of pediatric patients with AML treated in 2 consecutive clinical trials, Black patients had worse outcomes compared with White patients after treatment with standard induction therapy, but this disparity was eliminated by treatment with augmented induction therapy. When accounting for ACS10 scores, no outcome disparities were seen between Black and White patients. Our results suggest that using pharmacogenomics parameters to tailor induction regimens for both Black and White patients may narrow the racial disparity gap in patients with AML.
Topics: Humans; Leukemia, Myeloid, Acute; Male; Child; Female; Cytarabine; Treatment Outcome; Child, Preschool; White People; Pharmacogenetics; Adolescent; Antimetabolites, Antineoplastic; Black or African American; Induction Chemotherapy
PubMed: 38753328
DOI: 10.1001/jamanetworkopen.2024.11726 -
Zhongguo Ying Yong Sheng Li Xue Za Zhi... Dec 2023In the United States, cancer is one of the major causes of death. In 2010 alone, over 1.5 million fresh instances were recorded and over 0.5 billion died. After the... (Review)
Review
In the United States, cancer is one of the major causes of death. In 2010 alone, over 1.5 million fresh instances were recorded and over 0.5 billion died. After the completion of human genome sequence, significant progress in characterizing human epigenomes, proteomes and metabolomes has been made; a stronger knowledge of pharmacogenomics has been established and the capacity for individual personalization of health care has grown considerably. Personalized medicine has recently been primarily used to systematically select or optimize the prevention and therapeutic care of the patient through genetic or other data about the particular patient. Molecular profiling in healthy samples and cancer patients can allow for more personalized medications than is currently available. Patient protein, genetic and metabolic information may be used for adapting medical attention to the needs of that individual. The development of complementary diagnostics is a key attribute of this medicinal model. Molecular tests measuring the level of proteins, genes or specific mutations are used to provide a specific treatment for a particular individual by stratify the status of a disease, selecting the right drugs and tailoring dosages to the particular needs of the patient. These methods are also available for assessing risk factors for a patient for a number of conditions and for tailoring individual preventive therapies. Recent advances of personalized cancer medicine, challenges and futures perspectives are discussed.
Topics: Precision Medicine; Humans; Neoplasms; Rare Diseases; Pharmacogenetics
PubMed: 38830754
DOI: 10.62958/j.cjap.2023.008