scholarly journals Engineering Safer Psychedelics for Treating Addiction

2021 ◽  
Vol 16 ◽  
pp. 263310552110338
Author(s):  
Jamie Peters ◽  
David E Olson
Keyword(s):  
Executive Control ◽  
Neural Circuitry ◽  
Opioid Addiction ◽  
Adult Brain ◽  
Great Promise ◽  
Therapeutic Effects ◽  
Preclinical Models ◽  
Drug Seeking ◽  
Reward Circuitry

Addiction is best described as a disorder of maladaptive neuroplasticity involving the simultaneous strengthening of reward circuitry that drives compulsive drug seeking and weakening of circuits involved in executive control over harmful behaviors. Psychedelics have shown great promise for treating addiction, with many people attributing their therapeutic effects to insights gained while under the influence of the drug. However, psychedelics are also potent psychoplastogens—molecules capable of rapidly re-wiring the adult brain. The advent of non-hallucinogenic psychoplastogens with anti-addictive properties raises the intriguing possibility that hallucinations might not be necessary for all therapeutic effects of psychedelic-based medicines, so long as the underlying pathological neural circuitry can be remedied. One of these non-hallucinogenic psychoplastogens, tabernanthalog (TBG), appears to have long-lasting therapeutic effects in preclinical models relevant to alcohol and opioid addiction. Here, we discuss the implications of these results for the development of addiction treatments, as well as the next steps for advancing TBG and related non-hallucinogenic psychoplastogens as addiction therapeutics.

Stem cell application in neurorehabilitation

2020 ◽  
pp. 169-184
Author(s):  
Sebastian Jessberger ◽  
Armin Curt ◽  
Roger A. Barker
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Stem Cell ◽  
Adult Brain ◽  
Proper Function ◽  
Great Promise ◽  
Neuropsychiatric Diseases ◽  
Brain And Spinal Cord ◽  
The Brain

A number of diseases of the brain and spinal cord are associated with substantial neural cell death and/or disruption of correct and functional neural networks. In the past, a variety of therapeutic strategies to rescue these systems have been proposed along with agents to induce functional plasticity within the remaining central nervous system (CNS) structures. In the case of injury or neurodegenerative disease these approaches have only met with limited success, indicating the need for novel approaches to treat diseases of the adult CNS. Recently, the idea of recruiting endogenous or transplanting stem cells to replace lost structures within the adult brain or spinal cord has gained significant attention, along with in situ reprogramming, and opened up novel therapeutic avenues in the context of regenerative medicine. Here we review recent advances in our understanding of how endogenous stem cells may be a part of pathological processes in certain neuropsychiatric diseases and summarize recent clinical and preclinical data suggesting that stem cell-based therapies hold great promise as a future treatment option in a number of diseases disrupting the proper function of the adult CNS.

Antipsychotic efficacy: Relationship to optimal D2-receptor occupancy

2007 ◽  
Vol 22 (5) ◽  
pp. 267-275 ◽  
Author(s):  
Luca Pani ◽  
Luigi Pira ◽  
Giorgio Marchese
Keyword(s):  
Atypical Antipsychotics ◽  
D2 Receptor ◽  
Receptor Occupancy ◽  
Antipsychotic Agents ◽  
Therapeutic Window ◽  
Therapeutic Effects ◽  
Preclinical Models ◽  
Biochemical Interaction ◽  
The Relationship ◽  
The Brain

AbstractClinically important differences exist between antipsychotic agents and formulations in terms of safety and tolerability. Features of the biochemical interaction between the antipsychotic and the D2-receptor may underlie these differences. This article reviews current information on the relationship between antipsychotic receptor occupancy and clinical response. A literature search was performed using the keywords ‘antipsychotic or neuroleptic’, ‘receptor’ and ‘occupancy’ and ‘dopamine’ and ‘D2’ supplemented by the authors’ knowledge of the literature. Imaging and clinical data have generally supported the hypotheses that optimal D2-receptor occupancy in the striatum lies in a ‘therapeutic window’ between ∼65 and ∼80%, however, pharmacokinetic and pharmacodynamic properties of a drug should also be taken into account to fully evaluate its therapeutic effects. Additional research, perhaps in preclinical models, is needed to establish D2-receptor occupancy in various regions of the brain and the optimal duration of D2-receptor blockade in order to maximise efficacy and tolerability profiles of atypical antipsychotics and thereby improve treatment outcomes for patients with schizophrenia.

scholarly journals TNF-α Pretreatment Improves the Survival and Function of Transplanted Human Neural Progenitor Cells Following Hypoxic-Ischemic Brain Injury

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1195
Author(s):  
Miri Kim ◽  
Kwangsoo Jung ◽  
Younhee Ko ◽  
Il-Sun Kim ◽  
Kyujin Hwang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Infarct Volume ◽  
Fetal Brain ◽  
Neural Progenitor ◽  
Great Promise ◽  
Therapeutic Effects ◽  
Ischemic Brain ◽  
Tnf Α

Neural progenitor cells (NPCs) therapy offers great promise in hypoxic-ischemic (HI) brain injury. However, the poor survival of implanted NPCs in the HI host environment limits their therapeutic effects. Tumor necrosis factor-alpha (TNF-α) is a pleiotropic cytokine that is induced in response to a variety of pathological processes including inflammation and immunity. On the other hand, TNF-α has protective effects on cell apoptosis and death and affects the differentiation, proliferation, and survival of neural stem/progenitor cells in the brain. The present study investigated whether TNF-α pretreatment on human NPCs (hNPCs) enhances the effectiveness of cell transplantation therapy under ischemic brain. Fetal brain tissue-derived hNPCs were pretreated with TNF-α before being used in vitro experiments or transplantation. TNF-α significantly increased expression of cIAP2, and the use of short hairpin RNA-mediated knockdown of cIAP2 demonstrated that cIAP2 protected hNPCs against HI-induced cytotoxicity. In addition, pretreatment of hNPCs with TNF-α mediated neuroprotection by altering microglia polarization via increased expression of CX3CL1 and by enhancing expression of neurotrophic factors. Furthermore, transplantation of TNF-α-treated hNPCs reduced infarct volume and improved neurological functions in comparison with non-pretreated hNPCs or vehicle. These findings show that TNF-α pretreatment, which protects hNPCs from HI-injured brain-induced apoptosis and increases neuroprotection, is a simple and safe approach to improve the survival of transplanted hNPCs and the therapeutic efficacy of hNPCs in HI brain injury.

Recent Research Trends on Bismuth Compounds in Cancer Chemoand Radiotherapy

2019 ◽  
Vol 26 (4) ◽  
pp. 729-759 ◽  
Author(s):  
Mateusz Kowalik ◽  
Joanna Masternak ◽  
Barbara Barszcz
Keyword(s):  
American Chemical Society ◽  
Chemical Society ◽  
Research Field ◽  
Research Trends ◽  
Future Research ◽  
Great Promise ◽  
Therapeutic Effects ◽  
Bismuth Compounds ◽  
Research On Application ◽  
Almost All

Background:Application of coordination chemistry in nanotechnology is a rapidly developing research field in medicine. Bismuth complexes have been widely used in biomedicine with satisfactory therapeutic effects, mostly in Helicobacter pylori eradication, but also as potential antimicrobial and anti-leishmanial agents. Additionally, in recent years, application of bismuth-based compounds as potent anticancer drugs has been studied extensively.Methods:Search for data connected with recent trends on bismuth compounds in cancer chemo- and radiotherapy was carried out using web-based literature searching tools such as ScienceDirect, Springer, Royal Society of Chemistry, American Chemical Society and Wiley. Pertinent literature is covered up to 2016.Results:In this review, based on 213 papers, we highlighted a number of current problems connected with: (i) characterization of bismuth complexes with selected thiosemicarbazone, hydrazone, and dithiocarbamate classes of ligands as potential chemotherapeutics. Literature results derived from 50 papers show that almost all bismuth compounds inhibit growth and proliferation of breast, colon, ovarian, lung, and other tumours; (ii) pioneering research on application of bismuth-based nanoparticles and nanodots for radiosensitization. Results show great promise for improvement in therapeutic efficacy of ionizing radiation in advanced radiotherapy (described in 36 papers); and (iii) research challenges in using bismuth radionuclides in targeted radioimmunotherapy, connected with choice of adequate radionuclide, targeting vector, proper bifunctional ligand and problems with 213Bi recoil daughters toxicity (derived from 92 papers).Conclusion:This review presents recent research trends on bismuth compounds in cancer chemo- and radiotherapy, suggesting directions for future research.

Nutraceuticals Role in Stress, Aging, and Neurodegenerative Disorders

2019 ◽  
pp. 288-306
Author(s):  
Manisha Choudhary ◽  
Sandeep Tripathi ◽  
Rajesh Kumar Kesharwani
Keyword(s):  
Neurodegenerative Disorders ◽  
Functional Food ◽  
Functional Foods ◽  
Value Added ◽  
Food Supplements ◽  
Great Promise ◽  
Therapeutic Effects ◽  
Collective Effort ◽  
Soft Gels ◽  
Lifestyle Diseases

Nutraceuticals and functional foods have attracted considerable interest recently because of their well-known safety and potential nutritional and therapeutic effects. Nutraceuticals include food supplements, dietary supplements, value-added processed foods, as well as non-food supplements such as tablets, soft gels, and capsules etc. which are packed with bioactive components. Life expectancy continues to rise and along with a rise in the lifestyle diseases (i.e., obesity, diabetes, hypertension, cardiovascular diseases, and neurodegenerative disorders). Functional foods and nutraceuticals constitute a great promise to improve health, neurodegenerative disorders, and aging-related chronic diseases. A collective effort by the academia, industry, government, and research organization must keep on promoting nutraceutical and functional food to contain the menace of lifestyle diseases.

Stem cell application in neurorehabilitation

2015 ◽  
pp. 148-160
Author(s):  
Sebastian Jessberger ◽  
Armin Curt ◽  
Roger Barker
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Stem Cell ◽  
Adult Brain ◽  
Proper Function ◽  
Great Promise ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Significant Attention ◽  
Future Treatment Option

Several diseases of the brain and spinal cord are associated with substantial neural cell death and/or disruption of neural networks. A�variety of therapeutic strategies to rescue these systems has been proposed along with agents to induce functional plasticity within the remaining central nervous system (CNS) structures. In the case of injury or neurodegenerative disease these approaches have only met with limited success, indicating the need for novel approaches to treat diseases of the adult CNS. Recently, the idea of recruiting stem cells to replace lost structures within the adult brain or spinal cord has gained significant attention and opened up novel therapeutic avenues. Here, recent advances in our understanding of endogenous stem cells are reviewed and new clinical and preclinical data suggesting that stem cell-based therapies hold great promise as a future treatment option in a number of diseases disrupting the proper function of the adult CNS are summarized.

scholarly journals Quantitative Analysis of HER2 Amplification by Droplet Digital PCR in the Follow-Up of Gastric Cancer Patients Being Treated with Trastuzumab after Surgery

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Yanzhuo Liu ◽  
Maozhu Yang ◽  
Tao Jiang ◽  
Chunbin Lan ◽  
Hao Yuan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor Receptor ◽  
Elongation Factor ◽  
Progression Free Survival ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Great Promise ◽  
Therapeutic Effects ◽  
Her2 Amplification

Background. Circulating tumor DNA (ctDNA) derived from tumors is a promising biomarker for monitoring tumor status and evaluating therapeutic effects and prognosis. We studied the plasma human epidermal growth factor receptor 2 (HER2) amplification in gastric cancer (GC) patients by droplet digital PCR (ddPCR) during therapy with trastuzumab. Methods. A total of 12 patients were recruited after surgery. All patients received FOLFOX chemotherapy combined with trastuzumab as a treatment regimen. During the 12 months of the follow-up period, using elongation factor Tu GTP binding domain containing 2 (EFTUD2) as a reference gene, plasma HER2 to EFTUD2 ratios (the HER2 ratio) were determined for each patient every 2 months by ddPCR. Results. The concordance rate of HER2 amplification examined in plasma and formalin-fixed paraffin-embedded (FFPE) samples with ddPCR was 81.4%, with a sensitivity of 76.5% and a specificity of 83.8%. Plasma HER2 ratios were correlated with the primary tumor size (p<0.01). A significant decrease in the plasma HER2 ratio was found after two months of treatment (p<0.0001). Nine patients experienced partial response, and three patients had stable disease. Seven patients had progressive disease (PD) during follow-up, and four of them had died. The median progression-free survival (PFS) was 9.8 months. For each patient who developed PD, the plasma HER2 ratio was approximately 2.3-4.1 times higher than the cut-off value at the time of PD, which was the highest during the whole follow-up period. Conclusion. Longitudinal monitoring for the plasma HER2 ratio by ddPCR in the clinical courses of GC patients holds great promise for use as an indicator of tumor progression and treatment efficacy.

scholarly journals Exosome-based immunotherapy: a promising approach for cancer treatment

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhijie Xu ◽  
Shuangshuang Zeng ◽  
Zhicheng Gong ◽  
Yuanliang Yan
Keyword(s):  
Cancer Immunotherapy ◽  
Cancer Progression ◽  
Human Cancer ◽  
Rapid Development ◽  
Immune Therapy ◽  
Drug Carriers ◽  
Great Promise ◽  
Therapeutic Effects ◽  
Technological Advances ◽  
Novel Therapeutic Strategies

Abstract In the era of the rapid development of cancer immunotherapy, there is a high level of interest in the application of cell-released small vesicles that stimulate the immune system. As cell-derived nanovesicles, exosomes show great promise in cancer immunotherapy because of their immunogenicity and molecular transfer function. The cargoes carried on exosomes have been recently identified with improved technological advances and play functional roles in the regulation of immune responses. In particular, exosomes derived from tumor cells and immune cells exhibit unique composition profiles that are directly involved in anticancer immunotherapy. More importantly, exosomes can deliver their cargoes to targeted cells and thus influence the phenotype and immune-regulation functions of targeted cells. Accumulating evidence over the last decade has further revealed that exosomes can participate in multiple cellular processes contributing to cancer development and therapeutic effects, showing the dual characteristics of promoting and suppressing cancer. The potential of exosomes in the field of cancer immunotherapy is huge, and exosomes may become the most effective cancer vaccines, as well as targeted antigen/drug carriers. Understanding how exosomes can be utilized in immune therapy is important for controlling cancer progression; additionally, exosomes have implications for diagnostics and the development of novel therapeutic strategies. This review discusses the role of exosomes in immunotherapy as carriers to stimulate an anti-cancer immune response and as predictive markers for immune activation; furthermore, it summarizes the mechanism and clinical application prospects of exosome-based immunotherapy in human cancer.

scholarly journals Polyamine Metabolism as a Therapeutic Target in Hedgehog-Driven Basal Cell Carcinoma and Medulloblastoma

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 150 ◽  
Author(s):  
Sonia Coni ◽  
Laura Di Magno ◽  
Silvia Maria Serrao ◽  
Yuta Kanamori ◽  
Enzo Agostinelli ◽  
...  
Keyword(s):  
Hedgehog Signaling ◽  
Current Knowledge ◽  
Germline Mutations ◽  
Therapeutic Benefit ◽  
Polyamine Metabolism ◽  
Therapeutic Effects ◽  
Preclinical Models ◽  
Genes Encoding ◽  
Established Role ◽  
Potential Therapeutic Benefit

Hedgehog (Hh) signaling is a critical developmental regulator and its aberrant activation,due to somatic or germline mutations of genes encoding pathway components, causes Basal CellCarcinoma (BCC) and medulloblastoma (MB). A growing effort has been devoted at theidentification of druggable vulnerabilities of the Hedgehog signaling, leading to the identificationof various compounds with variable efficacy and/or safety. Emerging evidence shows that anaberrant polyamine metabolism is a hallmark of Hh-dependent tumors and that itspharmacological inhibition elicits relevant therapeutic effects in clinical or preclinical models ofBCC and MB. We discuss here the current knowledge of polyamine metabolism, its role in cancerand the available targeting strategies. We review the literature about the connection betweenpolyamines and the Hedgehog signaling, and the potential therapeutic benefit of targetingpolyamine metabolism in two malignancies where Hh pathways play a well-established role: BCCand MB.

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