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MicroRNAs as potential biomarkers for diagnosis of attention deficit hyperactivity disorder

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Neural Regeneration Research 2024年第3期19卷 557-562页

作者： Bridget Martinez Philip V.Peplow department of pharmacology University of Nevada-RenoRenoUSA department of Medicine University of Nevada-RenoRenoUSA department of Anatomy University of OtagoDunedinNew Zealand

Inappropriate levels of hyperactivity,impulsivity,and inattention characterize attention deficit hyperactivity disorder,a common childhood-onset neuropsychiatric disorder.The cognitive function and learning ability of children with attention deficit hyperactivity disorder are affected,and these symptoms may persist to adulthood if they are not treated.The diagnosis of attention deficit hyperactivity disorder is only based on symptoms and objective tests for attention deficit hyperactivity disorder are missing.Treatments for attention deficit hyperactivity disorder in children include medications,behavior therapy,counseling,and education services which can relieve many of the symptoms of attention deficit hyperactivity disorder but cannot cure it.There is a need for a molecular biomarker to distinguish attention deficit hyperactivity disorder from healthy subjects and other neurological conditions,which would allow for an earlier and more accurate diagnosis and appropriate treatment to be initiated.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of attention deficit hyperactivity disorder.The recent studies reviewed had performed microRNA profiling in whole blood,white blood cells,blood plasma,and blood serum of children with attention deficit hyperactivity disorder.A large number of microRNAs were dysregulated when compared to healthy controls and with some overlap between individual studies.From the studies that had included a validation set of patients and controls,potential candidate biomarkers for attention deficit hyperactivity disorder in children could be miR-140-3p,let-7g-5p,-30e-5p,-223-3p,-142-5p,-486-5p,-151a-3p,-151a-5p,and-126-5p in total white blood cells,and miR-4516,-6090,-4763-3p,-4281,-4466,-101-3p,-130a-3p,-138-5p,-195-5p,and-106b-5p in blood serum.Further studies are warranted with children and adults with attention deficit hyperactivity disorder,and consideration should be given to utilizing rat

关键词： adults attention deficit hyperactivity disorder biomarkers blood plasma blood serum children microRNA total white blood cells whole blood

Role of N-formyl peptide receptor 2 in germinal matrix hemorrhage:an intrinsic review of a hematoma resolving pathway

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Neural Regeneration Research 2024年第2期19卷 350-354页

作者： Jerry Flores Jiping Tang department of Physiology&pharmacology Loma Linda University School of MedicineLoma LindaCAUSA

Germinal matrix hemorrhage is one of the leading causes of morbidity,mortality,and acquired infantile hydrocephalus in preterm infants in the United States,with little progress made in its clinical management.Blood clots have been shown to elicit secondary brain injury after germinal matrix hemorrhage,by disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage causing post-hemorrhagic hydrocephalus development.Current evidence suggests that rapid hematoma resolution is necessary to improve neurological outcomes after hemorrhagic stroke.Various articles have demonstrated the beneficial effects of stimulating the polarization of microglia cells into the M2 phenotype,as it has been suggested that they play an essential role in the rapid phagocytosis of the blood clot after hemorrhagic models of stroke.N-formyl peptide receptor 2(FPR2),a G-protein-coupled receptor,has been shown to be neuroprotective after stroke.FPR2 activation has been associated with the upregulation of phagocytic macrophage clearance,yet its mechanism has not been fully explored.Recent literature suggests that FPR2 may play a role in the stimulation of scavenger receptor CD36.Scavenger receptor CD36 plays a vital role in microglia phagocytic blood clot clearance after germinal matrix hemorrhage.FPR2 has been shown to phosphorylate extracellular-signal-regulated kinase 1/2(ERK1/2),which then promotes the transcription of the dual-specificity protein phosphatase 1(DUSP1)gene.In this review,we present an intrinsic outline of the main components involved in FPR2 stimulation and hematoma resolution after germinal matrix hemorrhage.

关键词： AnxA1 FPR2 GMH hematoma resolution hemorrhagic stroke M1 M2 microglia polarization microglia phagocytosis

MicroRNAs as potential biomarkers for diagnosis of schizophrenia and influence of antipsychotic treatment

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Neural Regeneration Research 2024年第7期19卷 1523-1531页

作者： Bridget Martinez Philip V.Peplow department of pharmacology University of Nevada-RenoRenoNVUSA department of Medicine University of Nevada-RenoRenoNVUSA department of Anatomy University of OtagoDunedinNew Zealand

Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizophrenia is a chro nic,severe,and disabling mental disorder with late adolescence or early adulthood onset,Antipsychotics are the most commonly used drugs to treat schizophrenia,but those currently in use do not fully reverse all three types of symptoms characte rizing this condition.Schizophrenia is frequently misdiagnosed,resulting in a delay of or inappropriate treatment.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of schizophrenia.The recent studies reviewed included microRNA profiling in blood-and urine-based materials and nervous tissue mate rials.From the studies that had validated the preliminary findings,potential candidate biomarkers for schizophrenia in adults could be miR-22-3p,-30e-5p,-92a-3p,-148b-5p,-181a-3p,-181a-5p,-181b-5p,-199 b-5p,-137 in whole blood,and miR-130b,-193a-3p in blood plasma.Antipsychotic treatment of schizophrenia patients was found to modulate the expression of certain microRNAs including miR-130b,-193a-3p,-132,-195,-30e,-432 in blood plasma.Further studies are warranted with adolescents and young adults having schizophrenia and consideration should be given to using animal models of the disorder to investigate the effect of suppressing or overexpressing specific microRNAs.

关键词： antipsychotics biomarkers blood exosomes blood plasma brain tissue exosomes brain tissues leukocytes microRNAs neural stem cells olfactory neuroepithelium schizophrenia whole blood

Modern View on Potentials of Forensic Pharmaceutical and Pharmacological Expertise

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Journal of Forensic Science and Medicine 2024年第1期10卷 62-67页

作者： Elena M.Vazhnichaya Nataliia M.Deviatkina department of pharmacology Clinical Pharmacology and PharmacyPoltava State Medical UniversityPoltavaUkraine

The great number of drugs and their variety have increased the potential of therapy but increased the risks of crimes related to the production,sale,and use of medicines.The prosecution of such crimes requires pharmaceutical or pharmacological expertise.The development of forensic pharmacy and forensic pharmacology is relevant and needs consideration of their modern capabilities.The purpose of the work is to analyze literature data on the scientific basis of forensic pharmaceutical and pharmacological expertise and their modern possibilities.The texts of articles,book chapters,and websites were studied using keywords relevant to the purpose of the review.It is shown,that modern forensic pharmaceutical expertise is a separate type of expertise that focuses on the study of drugs and documents that regulate the production,distribution,and quality of medicines.It uses the latest analytical methods of pharmacy.A pharmacologist analyzes body fluids and tissues and interprets the resulting data to help courts and investigators assess the role of a drug in the person’s behavior,illness,injury,or death.The range of issues included in the pharmacological examination is fully within the competence of the forensic medical examination,which can be appointed in civil cases or criminal proceedings connected with harm to health or death.Forensic pharmacology is not the same as forensic toxicology or pharmacovigilance and requires a separate approach based on purely pharmacological knowledge.

关键词： Drug expertise forensic pharmacology forensic pharmacy

Antitumor effects of a novel photosensitizer-mediated photodynamic therapy and its influence on the cell transcriptome

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Oncology Research 2024年第5期32卷 911-923页

作者： JINGJING CHEN DAN WANG ZEQUN WANG MENGYUAN HAN HOUQING YIN WENTING ZHOU RIBAI YAN YAN PAN department of pharmacology School of PharmacyChangzhi Medical CollegeChangzhiChina2 Department of PharmacologySchool of Basic Medical SciencesHealth Science CenterPeking UniversityBeijingChina3 Beijing Key Laboratory of Tumor Systems BiologyPeking UniversityBeijingChina4 Department of PharmacologyXinjiang Medical UniversityUrumqiChina5 School of Pharmaceutical SciencesPeking UniversityBeijingChina

Photodynamic therapy(PDT)is a promising cancer treatment.This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]−10,15,20-triphenyl-porphyrin(DTP)mediated PDT(DTP-PDT).Cell viability,reactive oxygen species(ROS),and apoptosis were measured with a Cell Counting Kit-8 assay,DCFH-DA fluorescent probe,and Hoechst staining,respectively.Cell apoptosis-and autophagy-related proteins were examined using western blotting.RNA sequencing was used to screen differentially expressed mRNAs(DERs),and bioinformatic analysis was performed to identify the major biological events after DTP-PDT.Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells.The ROS scavenger N-acetyl-L-cysteine(NAC)and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity.DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2,which could also be inhibited by NAC or SB203580.The level of LC3B-Ⅱ,a marker of autophagy,was increased by DTP-PDT.A total of 3496 DERs were obtained after DTP-PDT.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes,the nuclear lumen,protein binding,cell cycle,protein targeting to the endoplasmic reticulum,and ribosomal DNA replication.Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints.Protein-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting genes.Therefore,DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy,partly through ROS and the P38 MAPK signaling pathway.Genes associated with the cell cycle,ribosomes,DNA replication,and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.

关键词： Photodynamic therapy ROS Apoptosis Autophagy Bioinformatic analysis

Na^(+)/K^(+)-ATPase:ion pump,signal transducer,or cytoprotective protein,and novel biological functions

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Neural Regeneration Research 2024年第12期19卷 2684-2697页

作者： Songqiang Huang Wanting Dong Xiaoqian Lin Jinsong Bian department of pharmacology Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and DiseasesSchool of MedicineSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina department of pharmacology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.

关键词： antibody biological functions cellular communication electrochemical gradient ion balance ion channels Na^(+)/K^(+)-ATPase neurological diseases neurotransmitter release signal transduction

SIRT2 as a potential new therapeutic target for Alzheimer's disease

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Neural Regeneration Research 2024年第1期19卷 124-131页

作者： Noemi Sola-Sevilla Elena Puerta department of pharmacology and Toxicology Faculty of PharmacyUniversity of NavarraNavarra Institute for Health Research(IdiSNA)PamplonaSpain

Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective treatment.In this context,sirtuin 2,the sirtuin with the highest expression in the brain,has emerged as a potential therapeutic target for neurodegenerative diseases.This review summarizes and discusses the complex roles of sirtuin 2 in different molecular mechanisms involved in Alzheimer's disease such as amyloid and tau pathology,microtubule stability,neuroinflammation,myelin formation,autophagy,and oxidative stress.The role of sirtuin 2 in all these processes highlights its potential implication in the etiology and development of Alzheimer's disease.However,its presence in different cell types and its enormous variety of substrates leads to apparently contra dictory conclusions when it comes to understanding its specific functions.Further studies in sirtuin 2 research with selective sirtuin2 modulators targeting specific sirtuin 2 substrates are necessary to clarify its specific functions under different conditions and to validate it as a novel pharmacological target.This will contribute to the development of new treatment strategies,not only for Alzheimer's disease but also for other neurodegenerative diseases.

关键词： Alzheimer's disease amyloid autophagy memory neurodegenerative diseases neuroinflammation sirtuin 2 tau

CuInS_(2)quantum-dot-modified g-C_(3)N_(4)S-scheme heterojunction photocatalyst for hydrogen production and tetracycline degradation

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Journal of Materials Science & Technology 2024年第5期172卷 145-155页

作者： Jingjing Zhang Yue Zhao Kezhen Qi Shu-yuan Liu College of Pharmacy Dali UniversityDali 671000China department of pharmacology Shenyang Medical CollegeShenyang 110034China

CuInS_(2)quantum-dot(CIS QD)-modified g-C_(3)N_(4)(CN)catalysts(CIS/CN)were prepared with the aid of an in-situ growth process.The as-obtained photocatalysts were explored by measuring their crystallinity,surface morphology,binding energy and light absorption activity.The photocatalytic efficiency of the pho-tocatalysts was evaluated through photocatalytic water splitting for hydrogen production and tetracycline(TC)antibiotic degradation under the simulated solar light and visible light respectively.The optimized sample(10CIS/CN)showed the best photocatalytic activity:producing 102.4μmol g^(-1)h^(-1)of hydrogen in 1 h,or degrading 52.16%of TC in 120 min,which were respectively 48 or 3.4 times higher than the photocatalytic activity of CN itself.The enhancement in the efficiency of the composite system was prin-cipally accredited to the enlargement of light absorption,the more effective in charge transfer and the dropping of the charge carrier pair recombination through a formed S-scheme heterojunctional interface.This work is an effort to adjust CN-based polysulfide QD for speedy photocatalysis.The enriched photo-catalytic activity grants a new sense for adjusting the optical properties of CN.

关键词： CuInS_(2)QDs g-C_(3)N_(4) Photocatalysis Hydrogen production S-scheme heterojunction

Metabolic dysfunction-associated steatotic liver disease:Navigating terminological evolution,diagnostic frontiers and therapeutic horizon-an editorial exploration

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World Journal of Gastroenterology 2024年第18期30卷 2387-2390页

作者： Aleksandra Boldys Lukasz Buldak department of Internal Medicine and Clinical pharmacology School of Medicine in KatowiceMedical University of SilesiaKatowice 40-752Poland

Metabolic dysfunction-associated steatotic liver disease(MASLD),once known as non-alcoholic fatty liver disease(NAFLD),represents a spectrum of liver disorders characterized by lipid accumulation within hepatocytes.The redefinition of NAFLD in 2023 marked a significant reposition in terminology,emphasizing a broader understanding of liver steatosis and its associated risks.MASLD is now recognized as a major risk factor for liver cirrhosis,hepatocellular carcinoma,and systemic complications such as cardiovascular diseases or systemic inflammation.Diagnostic challenges arise,particularly in identifying MASLD in lean individuals,necessitating updated diagnostic protocols and investing in non-invasive diagnostic tools.Therapeutically,there is an urgent need for effective treatments targeting MASLD,with emerging pharmacological options focusing on,among others,carbohydrate and lipid metabolism.Additionally,understanding the roles of bile acid metabolism,the microbiome,and dietary interventions in MASLD pathogenesis and management holds promise for innovative therapeutic approaches.There is a strong need to emphasize the importance of collaborative efforts in understanding,diagnosing,and managing MASLD to improve physicians’approaches and patient outcomes.

关键词： Metabolic dysfunction-associated steatotic liver disease Diagnostics Pathophysiology of metabolic dysfunction-associated steatotic liver disease Therapy of metabolic dysfunction-associated steatotic liver disease Therapeutic innovations