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MicroRNAs as potential biomarkers for diagnosis of attention deficit hyperactivity disorder

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 *** 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 *** diagnosis of attention deficit hyperactivity disorder is only based on symptoms and objective tests for attention deficit hyperactivity disorder are *** 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 *** 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 *** expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of attention deficit hyperactivity *** 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 *** 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 *** studies are warranted with children and adults with attention deficit hyperactivity disorder,and

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

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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 *** is frequently misdiagnosed,resulting in a delay of or inappropriate *** expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of *** recent studies reviewed included microRNA profiling in blood-and urine-based materials and nervous tissue mate *** 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 *** treatment of schizophrenia patients was found to modulate the expression of certain microRNAs including miR-130b,-193a-3p,-132,-195,-30e,-432 in blood *** 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

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MicroRNAs as potential diagnostic biomarkers for bipolar disorder

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Neural Regeneration Research 2025年第6期20卷 1681-1695页

Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed i

关键词： biomarker bipolar disorder blood leukocytes blood plasma blood plasma extracellular vesicles/exosomes blood serum brain tissue brain tissue extracellular vesicles/exosomes lymphoblastoid cell lines microRNA neural progenitor cells whole blood

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MicroRNAs as potential biomarkers for diagnosis of post-traumatic stress disorder

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Neural Regeneration Research 2025年第7期20卷 1957-1970页

Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life ***,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress *** addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate *** suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress *** performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December *** included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum *** of these studies had also used whole *** studies were excluded as they did not involve microRNA *** of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult *** measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString *** six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to *** miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/

关键词： biomarker diagnosis microRNA peripheral blood mononuclear cells plasma extracellular vesicles/exosomes post-traumatic stress disorder serum exosomes whole blood whole plasma

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pH对铜冶炼烟尘中重金属浸出行为的影响及其矿物学控制机理

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Journal of Central South University 2024年第4期31卷 1121-1135页

作者：王小燕肖细元郭朝晖彭驰 RICHMOND Anaman 薛生国 bridget Ataa School of Metallurgy and Environment Central South UniversityChangsha 410083China

以某废弃铜冶炼厂收集的铜冶炼烟尘作为样本,采用TCLP毒性浸出和宽溶液pH(3~13)范围浸出实验,研究了铜冶炼烟尘中重金属的释放行为及其矿物学控制机制。结果表明,TCLP浸出液中As、Cd、Cu、Pb和Zn浓度分别是我国《危险废物鉴别标准浸出... 详细信息

以某废弃铜冶炼厂收集的铜冶炼烟尘作为样本,采用TCLP毒性浸出和宽溶液pH(3~13)范围浸出实验,研究了铜冶炼烟尘中重金属的释放行为及其矿物学控制机制。结果表明,TCLP浸出液中As、Cd、Cu、Pb和Zn浓度分别是我国《危险废物鉴别标准浸出毒性鉴别》(GB 5085.3—2007)中相应元素限值的704倍、82.7倍、2.08倍、3.1倍和3.26倍。在整个溶液pH处理范围内,As的释放率高达26.0%~28.1%。在酸性条件下Cd、Cu和Zn的浸出率明显较高,而Pb在pH 13.0时释放率较高。地球化学分析表明,在pH 5.5~11.5的溶液处理下,As的溶解度部分受新形成的Ca、Cu、Pb和Zn砷酸盐控制,而Cd、Cu、Pb和Zn的溶解度主要受碱性条件下氢氧化物沉淀形成控制。BCR顺序提取和XRD分析表明,浸出液中Cd和Zn浓度较高与其在灰尘中赋存活性态比例高一致。研究结果为烟尘处理或处置防止重金属污染提供科学指导。

关键词：烟尘形态溶解度化学形态释放重金属

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Malignant melanoma in the pediatric population

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World Journal of Surgical Procedures 2015年第3期5卷 229-234页

作者： John Psaltis Eric Reintgen Ali Antar Mark Giori Leah Alvin Alyssa Benjamin bridget budny Taylor Gianangelo Aaron Gruman Anna Stamas Michael Reintgen Rosemary Giuliano Jeff Smith Douglas Reintgen Department of Surgery Morsani School of Medicine University of South Florida Department of Pathology Florida Hospital-N Pinellas

Controversial pigmented lesions in children are a problem for pathologist, clinicians and families that are confronted with this dilemma. Some skin lesions in this population defy diagnosis with pathologists split between a benign diagnosis and a cancer diagnosis. Three cases of controversial pigmented lesions in the pediatric population are presented. Three patients underwent radical resection of the controversial pigmented lesion, intra-operative lymphatic mapping and sentinel lymph node(SLN) biopsy. Due to the low morbidity of the SLN procedure a case is made to perform lymphatic mapping in this clinical scenario. If the SLNs are negative, not much is lost except for the scar and this becomes another line of evidence that perhaps the original lesion was benign. If the SLN shows metastatic cells, then the original skin lesion must be malignant and the patient is offered stage Ⅲ recommendations that would include complete node dissections and adjuvant Interferon therapy. This strategy provides for adequate treatment of the worse-case scenario, that the skin lesion is malignant. The cost to the patient is a low morbidity procedure, the SLN biopsy.

关键词： Pediatric pigmented skin lesions Sentinel lymph node biopsy Melanoma

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MicroRNA biomarkers in frontotemporal dementia and to distinguish from Alzheimer's disease and amyotrophic lateral sclerosis

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Neural Regeneration Research 2022年第7期17卷 1412-1422页

作者： bridget Martinez Philip V.Peplow Department of Medicine St.Georges University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

Frontotemporal lobar degeneration describes a group of progressive brain disorders that primarily are associated with atrophy of the prefrontal and anterior temporal *** lobar degeneration is considered to be equivalent to frontotemporal *** dementia is characterized by progressive impairments in behavior,executive function,and *** are two main clinical subtypes:behavioral-variant frontotemporal dementia and primary progressive *** early diagnosis of frontotemporal dementia is critical for developing management strategies and interventions for these *** validated biomarkers,the clinical diagnosis depends on recognizing all the core or necessary neuropsychiatric features,but misdiagnosis often occurs due to overlap with a range of neurologic and psychiatric *** the studies reviewed a very large number of microRNAs were found to be dysregulated but with limited overlap between individual *** of specific miRNAs singly or in combination,or as miRNA pairs(as a ratio)in blood plasma,serum,or cerebrospinal fluid enabled frontotemporal dementia to be discriminated from healthy controls,Alzheimer’s disease,and amyotrophic lateral ***,upregulation of miR-223-3p and downregulation of miR-15a-5p,which occurred both in blood serum and cerebrospinal fluid,distinguished behavioral-variant frontotemporal dementia from healthy *** of miR-132-3p in frontal and temporal cortical tissue distinguished frontotemporal lobar degeneration and frontotemporal dementia,respectively,from healthy *** strong miRNA biofluid biomarker contenders for behavioral-variant frontotemporal dementia are miR-223-3p,miR-15a-5p,miR-22-3p in blood serum and cerebrospinal fluid,and miR-124 in cerebrospinal *** miRNAs were identified able to distinguish between behavioral-variant frontotemporal dementia and primary progressive aphasia *** studies are

关键词： Alzheimer’s disease amyotrophic lateral sclerosis behavioral variant biomarker blood plasma blood serum brain cerebrospinal fluid cortical tissue frontotemporal dementia frontotemporal lobar degeneration microRNA primary progressive aphasia

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Biomaterial and tissue-engineering strategies for the treatment of brain neurodegeneration

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Neural Regeneration Research 2022年第10期17卷 2108-2116页

作者： bridget Martinez Philip V.Peplow Department of Medicine St.Georges University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

The incidence of neurodegenerative diseases is increasing due to changing age demographics and the incidence of sports-related traumatic brain injury is tending to increase over *** approved medicines for neurodegenerative diseases only temporarily reduce the symptoms but cannot cure or delay disease *** transplantation strategies offer an alternative approach to facilitating central nervous system repair,but efficacy is limited by low in vivo survival rates of cells that are injected in *** cells that are attached to or encapsulated within a suitable biomaterial construct has the advantage of enhancing cell survival in vivo.A variety of biomaterials have been used to make constructs in different types that included nanoparticles,nanotubes,microspheres,microscale fibrous scaffolds,as well as scaffolds made of gels and in the form of *** these,Tween 80-methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid)nanoparticles loaded with rhynchophylline had higher transport across a blood-brain barrier model and decreased cell death in an in vitro model of Alzheimer’s disease than rhynchophylline or untreated nanoparticles with *** an in vitro model of Parkinson’s disease,trans-activating transcriptor bioconjugated with zwitterionic polymer poly(2-methacryoyloxyethyl phosphorylcholine)and protein-based nanoparticles loaded with non-Fe hemin had a similar protective ability as free non-Fe hemin.A positive effect on neuron survival in several in vivo models of Parkinson’s disease was associated with the use of biomaterial constructs such as trans-activating transcriptor bioconjugated with zwitterionic polymer poly(2-methacryoyloxyethyl phosphorylcholine)and protein-based nanoparticles loaded with non-Fe hemin,carbon nanotubes with olfactory bulb stem cells,poly(lactic-co-glycolic acid)microspheres with attached DI-MIAMI cells,ventral midbrain neurons mixed with short fibers of poly-(L-lactic acid

关键词： Alzheimer’s disease biomaterial cell transplantation neurodegeneration neurodegenerative disease Parkinson’s disease tissue-engineering traumatic brain injury

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MicroRNA expression in animal models of amyotrophic lateral sclerosis and potential therapeutic approaches

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Neural Regeneration Research 2022年第4期17卷 728-740页

作者： bridget Martinez Philip V.Peplow Physical Chemistry and Applied Spectroscopy Chemistry DivisionLos Alamos National LaboratoryLos AlamosNMUSA Department of Medicine St.Georges University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

A review of recent animal models of amyotrophic lateral sclerosis showed a large number of mi RNAs had altered levels of expression in the brain and spinal cord,motor neurons of spinal cord and brainstem,and hypoglossal,facial,and red motor nuclei and were mostly *** the mi RNAs found to be upregulated in two of the studies were mi R-21,mi R-155,mi R-125 b,mi R-146 a,mi R-124,mi R-9,and mi R-19 b,while those downregulated in two of the studies included mi R-146 a,mi R-29,mi R-9,and mi R-125 b.A change of direction in mi RNA expression occurred in some tissues when compared(e.g.,mi R-29 b-3 p in cerebellum and spinal cord of wobbler mice at 40 days),or at different disease stages(e.g.,mi R-200 a in spinal cord of SOD1(G93 A)mice at 95 days vs.108 and 112 days).In the animal models,suppression of mi R-129-5 p resulted in increased lifespan,improved muscle strength,reduced neuromuscular junction degeneration,and tended to improve motor neuron survival in the SOD1(G93 A)mouse *** of mi R-155 was also associated with increased lifespan,while lowering of mi R-29 a tended to improve lifespan in males and increase muscle strength in SOD1(G93 A)*** of members of mi R-17~92 cluster improved motor neuron survival in SOD1(G93 A)*** with an artificial mi RNA designed to target h SOD1 increased lifespan and improved muscle strength in SOD1(G93 A)*** studies with animal models of amyotrophic lateral sclerosis are warranted to validate these findings and identify specific mi RNAs whose suppression or directed against h SOD1 results in increased lifespan,improved muscle strength,reduced neuromuscular junction degeneration,and improved motor neuron survival in SOD1(G93 A)animals.

关键词： amyotrophic lateral sclerosis animal model brain brainstem microRNA motor neuron degeneration spinal cord therapeutic approaches

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Protective effects of pharmacological therapies in animal models of multiple sclerosis: a review of studies 2014–2019

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Neural Regeneration Research 2020年第7期15卷 1220-1234页

作者： bridget Martinez Philip V.Peplow Physical Chemistry and Applied Spectroscopy Chemistry DivisionLos Alamos National LaboratoryLos AlamosNMUSA Department of Medicine St.Georges University School of MedicineTrue BlueGrenada Department of Anatomy University of OtagoDunedinNew Zealand

Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous *** disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is *** there is considerable loss of axons,MS patients enter a secondary progressive ***-modifying drugs currently in use for MS suppress the immune system and reduce relapse rates but are not effective in the progressive *** animal models of MS(mostly mouse and rat)have been established and proved useful in studying the disease process and response to *** experimental autoimmune encephalomyelitis animal studies reviewed here showed that a chronic progressive disease can be induced by immunization with appropriate amounts of myelin oligodendrocyte glycoprotein together with mycobacterium tuberculosis and pertussis toxin in Freund's *** clinical manifestations of autoimmune encephalomyelitis disease were prevented or reduced by treatment with certain pharmacological agents given prior to,at,or after peak disease,and the agents had protective effects as shown by inhibiting demyelination and damage to neurons,axons and *** the cuprizone-induced toxicity animal studies,the pharmacological agents tested were able to promote remyelination and increase the number of oligodendrocytes when administered therapeutically or prophylactically.A monoclonal IgM antibody protected axons in the spinal cord and preserved motor function in animals inoculated with Theiler's murine encephalomyelitis *** all these studies the pharmacological agents were administered singly.A combination therapy may be more effective,especially using agents that target neuroinflammation and neurodegeneration,as they may exert synergistic actions.

关键词： animal models autoimmune encephalomyelitis disease cuprizone-induced toxicity multiple sclerosis neurodegeneration neuroinflammation neuroprotection pharmacological agents progressive disease Theiler's murine encephalomyelitis virus

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