Article
Psychology, Clinical
Renee D. Goodwin, Scott J. Moeller, Jiaqi Zhu, Jeremy Yarden, Sarah Ganzhorn, Jill M. Williams
Summary: The use of cocaine without heroin declined overall from 2002 to 2017, but showed an increasing trend from 2011. In contrast, the co-use of heroin and cocaine, as well as heroin use without cocaine, showed a linear increase during the same period. It is important for screening, outreach, clinical treatment, and first responders to be aware of the increasing trends in polysubstance use and the potential impact of co-use of heroin and cocaine on intervention and overdose outcomes in the US.
ADDICTIVE BEHAVIORS
(2021)
Article
Environmental Sciences
Hongmei Ning, Chong Li, Zhihong Yin, Dongfang Hu, Yaming Ge, Lingli Chen
Summary: The study revealed that high concentrations of fluoride (1.5, 2, and 2.5 mM) exerted significant toxic effects on the cellular morphologies and neural formation of primary cultured cortical neurons.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2021)
Article
Toxicology
Mariana Sayuri Berto Udo, Mariana Aguilera Alencar da Silva, Sara de Souza Prates, Leandro Ferreira Dal'Jovem, Stephanie de Oliveira Duro, Fernanda Faiao-Flores, Raphael Caio Tamborelli Garcia, Silvya Stuchi Maria-Engler, Tania Marcourakis
Summary: The study found that cocaine alone caused dysfunction in the autophagic process and activated the extrinsic apoptotic pathway, while AEME directly activated caspase-9 and caspase-8, inducing early stage apoptosis. The combination of C + A was more neurotoxic, causing cell damage and activating both apoptotic pathways.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Environmental Sciences
Yongjie Xu, Tao Peng, Yang Xiang, Gengze Liao, Fei Zou, Xiaojing Meng
Summary: This study found that exposure to manganese increases mortality and malformation rates in zebrafish larvae, and significantly reduces swim distance and velocity. Manganese exposure also leads to apoptosis of dopaminergic neurons and decreased expression of tyrosine hydroxylase. Transcriptome sequencing results showed upregulation of genes associated with apoptosis and DNA damage repair.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Chemistry, Analytical
Robert G. Ewing, Megan K. Nims, Kelsey A. Morrison, Garret L. Hart, Nancy M. Avalos, Elizabeth H. Denis
Summary: There is a need for non-contact, real-time vapor detection of drugs, such as fentanyl, to combat illicit transportation and the opioid epidemic. This study used atmospheric flow tube-mass spectrometry (AFT-MS) to measure the vapor pressures of fentanyl and demonstrated its non-contact, real-time vapor detection capabilities. The results showed that AFT-MS is a viable method for screening packages and cargo for fentanyl and other drugs.
Article
Biochemistry & Molecular Biology
Shuheng Wen, Kana Unuma, Takeshi Funakoshi, Toshihiko Aki, Koichi Uemura
Summary: This study investigated the effects of cocaine on cardiac Cx43 and found a negative correlation between CBN and dephosphorylated cardiac Cx43. Additionally, increased levels of apoptosis, necroptosis, and adiponectin were observed in the myocardium after cocaine exposure. These findings provide insights into the cardiotoxicity of cocaine and the potential protective role of adiponectin in the heart.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Environmental Sciences
Tran Thi Thanh Hue, Qiuda Zheng, Nguyen Thi Kieu Anh, Vu Ngan Binh, Ngo Quang Trung, Hoang Thu Trang, Pham Quoc Chinh, Luu Quang Minh, Phong K. Thai
Summary: Illicit drug use is a significant issue in Vietnam, but there is limited information available. This study utilized wastewater-based epidemiology to assess the prevalence of illicit drug use in an urban population of Vietnam. The findings reveal that methamphetamine has become the most commonly used drug, surpassing heroin.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Biochemistry & Molecular Biology
Elena G. Varlamova, Nina I. Uspalenko, Natalia V. Khmil, Maria I. Shigaeva, Mikhail R. Stepanov, Mikhail A. Ananyan, Maria A. Timchenko, Maxim V. Molchanov, Galina D. Mironova, Egor A. Turovsky
Summary: Cerebral ischemia affects up to 15 million people worldwide every year, making the development of effective preventive programs and therapy methods crucial. This study compared the cytoprotective mechanisms of taxifolin (TAX) and its new water-soluble form, aqua taxifolin (aqTAX), on cultured brain cells under ischemic conditions. The results showed that aqTAX exhibited better protective effects by inhibiting cell death and reducing the increase in intracellular calcium levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Food Science & Technology
Damijana Mojca Juric, Klara Bulc Rozman, Metoda Lipnik-Stangelj, Dusan Suput, Miran Brvar
Summary: The influence of cannabidiol (CBD) on brain development is not well understood, but it may interfere with the endogenous cannabinoid system during critical periods, leading to apoptosis and necroptosis in neurons and astrocytes.
Article
Neurosciences
Faramarz Khosravi, Sepideh Mirzaei, Vida Hojati, Mehrdad Hashemi, Maliheh Entezari
Summary: Recent research has shown that Parkinson's disease (PD) patients have low serum levels of vitamins B12 and D. In this study, the effects of supplementation with both vitamins B12 and D on PD female mice and their fetuses were investigated. The results suggest that co-administration of vitamins B12 and D improves viability and reduces apoptosis and necrosis of cerebellar neurons in PD mice and their fetuses. These findings indicate that vitamins B12 and D have neuroprotective effects in PD, and they are recommended for supplementation during pregnancy in PD patients.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Cell Biology
Davide Warm, Davide Bassetti, Jonas Schroer, Heiko J. Luhmann, Anne Sinning
Summary: The early occurrence of calcium transients is strongly linked to neuronal survival, with silent neurons exhibiting a higher probability of cell death. Activity of neighboring neurons in local clusters exerts a pro-survival effect, while networks with a high modular topology are associated with lower cell death rates.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Analytical
Anna Zubrycka, Andrzej Kwasanica, Monika Haczkiewicz, Karolina Sipa, Konrad Rudnicki, Slawomira Skrzypek, Lukasz Poltorak
Summary: This study analyzed 5647 street samples and identified 53 illicit drugs, with Delta-9-tetrahydrocannabinol, amphetamine being the most common. Except for methadone, almost all samples were spiked with at least one cutting agent, with caffeine being the most frequently found adulterant.
Article
Medicine, Research & Experimental
Yubing Liang, Yu Huang, Rongge Shao, Fei Xiao, Fei Lin, Huijun Dai, Linghui Pan
Summary: This study investigated the mechanism of propofol on primary hippocampal neuron injury and found that propofol can cause damage to hippocampal neuron mitochondria, leading to neuronal apoptosis and neurotoxicity.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Giorgia Caspani, Viktoria Sebok, Nowshin Sultana, Jonathan R. Swann, Alexis Bailey
Summary: Metabolomics can elucidate the biochemical impact of substance abuse, understand the addiction cycle, and predict prognosis for recovery or relapse.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Elena G. Varlamova, Egor Y. Plotnikov, Egor A. Turovsky
Summary: A defect in brain blood circulation leads to ischemia, damage, and death of nerve cells. This study reveals the protective role of neuronal calcium sensor-1 (NCS-1) in ischemia/reoxygenation and hyperammonemia. Knockdown of NCS-1 increases cell death and exacerbates symptoms of network hyperexcitation, especially in GABAergic neurons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ligia Fao, Patricia Coelho, Luis Duarte, Rita Vilaca, Michael R. Hayden, Sandra I. Mota, Ana Cristina Rego
Summary: This study demonstrates that c-Src/Fyn proteins play an important role in controlling mitochondrial function and redox regulation in Huntington's disease (HD). Restoring c-Src/Fyn levels in HD improves mitochondrial morphology and function, reducing the levels of oxidant species and cell death. These findings suggest that c-Src/Fyn could be a potential therapeutic target for HD.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Review
Chemistry, Organic
Melford Chuka Egbujor, Jorge Garrido, Fernanda Borges, Luciano Saso
Summary: Sulfonamides are known for their diverse biological activities, including antioxidant activity. They have structural diversity and are suitable for drug discovery programs. Despite being extensively used as antibacterial agents, their therapeutic potential as antioxidants has been relatively underexplored. Some sulfonamide derivatives have been found to activate Nrf2, a key process in cellular response to oxidative stress.
MINI-REVIEWS IN ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Joana Reis, Carlos Fernandes, Hoda Salem, Marta Maia, Claudia Tome, Sofia Benfeito, Jose Teixeira, Paulo J. Oliveira, Eugenio Uriarte, Francesco Ortuso, Stefano Alcaro, Donatella Bagetta, Fernando Cagide, Fernanda Borges
Summary: The absence of disease modifying drugs in Parkinson's disease therapy has led to the development of new chemical compounds targeting relevant biological targets. In this study, a small library of chromone derivatives was synthesized and screened to find potent inhibitors of monoamine oxidases, with modifications leading to compounds that showed desirable drug-like properties. Two specific compounds were identified as reversible, potent, selective, and non-cytotoxic MAO-B inhibitors, and displayed cytoprotective effects.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Carlos Fernandes, Fernando Cagide, Jorge Simoes, Carlos Pita, Eurico Pereira, Afonso J. C. Videira, Pedro Soares, Jose F. S. Duarte, Antonio M. S. Santos, Paulo J. Oliveira, Fernanda Borges, Filomena S. G. Silva
Summary: Targeting mitochondria with antioxidants is a promising strategy to prevent cellular senescence and skin ageing. This study investigates the potential use of mitochondria-targeted antioxidants (MitoBENs) as active ingredients to prevent senescence in skin cells. Among the tested compounds, the pyrogallol derivative MB2 showed the least toxicity and had a potent antioxidant protective effect against hydrogen peroxide cytotoxicity. It also decreased transcripts related to senescence in a 3D skin cell model. These findings suggest that MB2 could be a good candidate for further development as an active ingredient in skin anti-ageing products.
Review
Cell Biology
Pedro Soares, Catia Silva, Daniel Chavarria, Filomena S. G. Silva, Paulo J. Oliveira, Fernanda Borges
Summary: Amyotrophic lateral sclerosis (ALS) is a progressive disease that leads to paralysis and death due to respiratory failure. Current ALS drugs only provide mild relief to patients. Recent advances in understanding ALS biology have identified potential targets for drug development, including mitochondria and oxidative stress, iron metabolism and ferroptosis, and regulators of hypoxia and inflammation. This review focuses on discussing the latest advances in ALS drug development and proposes the rational design of multi-target ligands as a potential effective therapy for ALS.
AGEING RESEARCH REVIEWS
(2023)
Article
Chemistry, Medicinal
Maria J. Matos, Paula Novo, Lucia Mayan, Iria Torres, Eugenio Uriarte, Matilde Yanez, Jose Angel Fontenla, Francesco Ortuso, Stefano Alcaro, Francesca Procopio, Maria Isabel Rodriguez-Franco, Cristina Val, Maria I. Loza, Jose Brea, Fernanda Borges, Dolores Vina
Summary: Psychiatric and neurological disorders affect millions of people worldwide, and current treatments are limited in their effectiveness. New therapeutic solutions are urgently needed to improve the lives of patients.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Mariana Pires, Ana Cristina Rego
Summary: APOE epsilon 4 allele (ApoE4) is the primary genetic risk factor for sporadic Alzheimer's disease (AD), associated with cognitive impairment and neurodegeneration. ApoE4 impacts mitochondrial function, increases reactive oxygen species (ROS) and calcium levels, affects mitochondrial dynamics and translocates to the nucleus to regulate gene expression related to aging, amyloid-beta production, inflammation and apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ildete L. Ferreira, Solange Costa, Bruno J. Moraes, Ana Costa, Olga Fokt, Daniela Marinho, Vera Alves, Isabel P. Baptista, A. Cristina Rego
Summary: Periodontitis (PDT) and type 2 diabetes (T2D) have a bidirectional relationship and are associated with imbalanced oxidative stress and mitochondrial dysfunction. This study investigated the mitochondrial and redox (de)regulation in peripheral blood mononuclear cells (PBMCs) of T2D-PDT, PDT, T2D patients, and control individuals. The results showed that PBMCs from T2D-PDT patients exhibited significant redox changes, while PBMCs from PDT patients showed mitochondrial deregulation and reduced expression of Nrf2-target genes.
Article
Biochemistry & Molecular Biology
David Vicente-Zurdo, Leonardo Brunetti, Luca Piemontese, Beatriz Guedes, Sandra M. Cardoso, Daniel Chavarria, Fernanda Borges, Yolanda Madrid, Silvia Chaves, M. Amelia Santos
Summary: A series of Rivastigmine-Benzimidazole (RIV-BIM) hybrids were found to have multitarget effects in combating Alzheimer's disease (AD). They exhibited antioxidant activity, acted as cholinesterase inhibitors, inhibited amyloid-beta aggregation, and chelated redox-active biometal ions. Furthermore, they showed remarkable inhibitory activity against monoamine oxidases and neuroprotective effects in human neuroblastoma cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Ines Costa, Daniel Jose Barbosa, Vera Silva, Sofia Benfeito, Fernanda Borges, Fernando Remiao, Renata Silva
Summary: Ferroptosis is regulated cell death caused by oxidative perturbations controlled by Glutathione Peroxidase 4 (GPX4). It involves the increased production of reactive oxygen species, intracellular iron accumulation, lipid peroxidation, inhibition of system Xc-, glutathione depletion, and decreased GPX4 activity. In vitro and in vivo models have been used to study the pathophysiological mechanisms of neurodegenerative diseases involving ferroptosis. These models can also aid in the development of potential ferroptosis inhibitors for disease-modifying therapies. This review discusses the main in vitro and in vivo models used to evaluate ferroptosis and explore new drug targets and candidates.
Article
Biochemistry & Molecular Biology
Sonia A. Pinho, Sandra I. Anjo, Teresa Cunha-Oliveira
Summary: Theragnostics is a promising strategy that combines diagnostics and therapeutics in a personalized manner. This review emphasizes the significance of redox homeostasis and mitochondrial function in personalized theragnostics. Disruption of redox homeostasis can lead to oxidative stress and cellular damage, which are associated with various diseases. Developing models of oxidative stress and mitochondrial dysfunction in metabolically conditioned cells allows for studying disease mechanisms and developing new therapies. By selecting appropriate cellular models, optimizing cell culture conditions, and validating the models, it is possible to identify the most promising therapeutic options and tailor treatments to individual patients. Overall, this review highlights the importance of precise and individualized approaches in theragnostics and the need for accurate in vitro models reflecting in vivo conditions.
Review
Biology
Ricardo Amorim, Carina C. Magalhaes, Fernanda Borges, Paulo J. Oliveira, Jose Teixeira
Summary: Non-alcoholic fatty liver disease (NAFLD) is a global pandemic affecting 25% of the world's population and is a serious health and economic concern worldwide. NAFLD is mainly the result of unhealthy dietary habits combined with a sedentary lifestyle, although some genetic contributions to NAFLD have been documented. This review examines the role of mitochondrial dysfunction in the progression of NAFLD and suggests that targeting hepatocytes' mitochondrial physiology could be a potential therapy for this disease. However, further research is needed to explore the specific roles of different mitochondrial sub-populations and their communication with other subcellular organelles in NAFLD progression.
Article
Cell Biology
Daniela Marinho, Ildete Luisa Ferreira, Ricardo Lorenzoni, Sandra M. Cardoso, Isabel Santana, A. Cristina Rego
Summary: This study evaluates the efficacy of inhibiting or reducing histone deacetylases (HDACs) in Alzheimer's disease (AD) models by modifying gene transcription. The results show that inhibiting class I HDACs can ameliorate ER-mitochondria cross-talk in AD by normalizing calcium signaling between the two organelles. The selective HDAC inhibitor, Tacedinaline (Tac), counteracted the impaired ER-mitochondria communication and reduced amyloid beta levels in AD cells and animal models. These findings suggest that transcriptional regulation of ER-mitochondria communication could be a promising target for innovative therapeutics in AD.
Article
Chemistry, Medicinal
Daniel Martins, Eva Gil-Martins, Fernando Cagide, Catarina da Fonseca, Sofia Benfeito, Carlos Fernandes, Daniel Chavarria, Fernando Remiao, Renata Silva, Fernanda Borges
Summary: The introduction of an NBOMe moiety significantly increases the lipophilicity, brain permeability, and cytotoxic effects of the parent drugs, with disruption of GSH and ATP homeostasis. Inhibition of CYP3A4 and CYP2D6 suggests a role of CYP-mediated metabolism in impacting the toxicity of these drugs.
Review
Chemistry, Medicinal
Aitor Carneiro, Eugenio Uriarte, Fernanda Borges, Maria Joao Matos
Summary: Propargylamine is widely used in medicinal chemistry and chemical biology due to its unique reactivity. This review discusses the applications and potential of propargylamine-based compounds in drug discovery, highlighting their impact in various therapeutic fields.
FUTURE MEDICINAL CHEMISTRY
(2023)
