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1.
Cell ; 186(4): 803-820.e25, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36738734

RESUMO

Complex diseases often involve the interplay between genetic and environmental factors. Charcot-Marie-Tooth type 2 neuropathies (CMT2) are a group of genetically heterogeneous disorders, in which similar peripheral neuropathology is inexplicably caused by various mutated genes. Their possible molecular links remain elusive. Here, we found that upon environmental stress, many CMT2-causing mutant proteins adopt similar properties by entering stress granules (SGs), where they aberrantly interact with G3BP and integrate into SG pathways. For example, glycyl-tRNA synthetase (GlyRS) is translocated from the cytoplasm into SGs upon stress, where the mutant GlyRS perturbs the G3BP-centric SG network by aberrantly binding to G3BP. This disrupts SG-mediated stress responses, leading to increased stress vulnerability in motoneurons. Disrupting this aberrant interaction rescues SG abnormalities and alleviates motor deficits in CMT2D mice. These findings reveal a stress-dependent molecular link across diverse CMT2 mutants and provide a conceptual framework for understanding genetic heterogeneity in light of environmental stress.


Assuntos
Doença de Charcot-Marie-Tooth , Proteínas com Motivo de Reconhecimento de RNA , Grânulos de Estresse , Animais , Camundongos , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/metabolismo , Doença de Charcot-Marie-Tooth/patologia , Citoplasma , Neurônios Motores , Proteínas com Motivo de Reconhecimento de RNA/metabolismo
2.
Calcif Tissue Int ; 115(2): 101-116, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38833001

RESUMO

Primary failure of eruption (PFE) is a rare disorder that is characterized by the inability of a molar tooth/teeth to erupt to the occlusal plane or to normally react to orthodontic force. This condition is related to hereditary factors and has been extensively researched over many years. However, the etiological mechanisms of pathogenesis are still not fully understood. Evidence from studies on PFE cases has shown that PFE patients may carry parathyroid hormone 1 receptor (PTH1R) gene mutations, and genetic detection can be used to diagnose PFE at an early stage. PTH1R variants can lead to altered protein structure, impaired protein function, and abnormal biological activities of the cells, which may ultimately impact the behavior of teeth, as observed in PFE. Dental follicle cells play a critical role in tooth eruption and root development and are regulated by parathyroid hormone-related peptide (PTHrP)-PTH1R signaling in their differentiation and other activities. PTHrP-PTH1R signaling also regulates the activity of osteoblasts, osteoclasts and odontoclasts during tooth development and eruption. When interference occurs in the PTHrP-PTH1R signaling pathway, the normal function of dental follicles and bone remodeling are impaired. This review provides an overview of PTH1R variants and their correlation with PFE, and highlights that a disruption of PTHrP-PTH1R signaling impairs the normal process of tooth development and eruption, thus providing insight into the underlying mechanisms related to PTH1R and its role in driving PFE.


Assuntos
Receptor Tipo 1 de Hormônio Paratireóideo , Erupção Dentária , Receptor Tipo 1 de Hormônio Paratireóideo/genética , Receptor Tipo 1 de Hormônio Paratireóideo/metabolismo , Humanos , Erupção Dentária/genética , Erupção Dentária/fisiologia , Mutação , Dente não Erupcionado/genética , Animais , Doenças Dentárias
3.
Int J Mol Sci ; 24(19)2023 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-37834427

RESUMO

Timber, the most prevalent organic material on this planet, is the result of a secondary xylem emerging from vascular cambium. Yet, the intricate processes governing its seasonal generation are largely a mystery. To better understand the cyclic growth of vascular tissues in elm, we undertook an extensive study examining the anatomy, physiology, and genetic expressions in Ulmus pumila. We chose three robust 15-year-old elm trees for our study. The cultivars used in this study were collected from the Inner Mongolia Autonomous Region in China and nurtured in the tree farm of Shandong Normal University. Monthly samples of 2-year-old elm branches were taken from the tree from February to September. Marked seasonal shifts in elm branch vascular tissues were observed by phenotypic observation: In February, the cambium of the branch emerged from dormancy, spurring growth. By May, elms began generating secondary xylem, or latewood, recognized by its tiny pores and dense cell structure. From June to August, there was a marked increase in the thickness of the secondary xylem. Transcriptome sequencing provides a potential molecular mechanism for the thickening of elm branches and their response to stress. In February, the tree enhanced its genetic responses to cold and drought stress. The amplified expression of CDKB, CYCB, WOX4, and ARF5 in the months of February and March reinforced their essential role in the development of the vascular cambium in elm. Starting in May, the elm deployed carbohydrates as a carbon resource to synthesize the abundant cellulose and lignin necessary for the formation of the secondary wall. Major genes participating in cellulose (SUC and CESA homologs), xylan (UGD, UXS, IRX9, IRX10, and IRX14), and lignin (PAL, C4H, 4CL, HCT, C3H, COMT, and CAD) biosynthetic pathways for secondary wall formation were up-regulated by May or/and June. In conclusion, our findings provided a foundation for an in-depth exploration of the molecular processes dictating the seasonal growth of elm timber.


Assuntos
Lignina , Ulmus , Humanos , Adolescente , Pré-Escolar , Lignina/química , Ulmus/química , Transcriptoma , Estações do Ano , Celulose
4.
Macromol Rapid Commun ; 43(4): e2100663, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34822206

RESUMO

3D printing of conductive polymers is an attractive technique for achieving high flexibility, wearability, and sensing characteristics without geometrical limitations. However, there is an urgent need to integrate printability, conductivity, and sensing capability. Herein, a conductive polymer ink for 3D printing that combines the desirable features of high electrical conductivity, flexible stretchability, and strain-sensing monitoring is prepared. The ink matrix is polydimethylsiloxane and synergistically enhanced by acetylene carbon black (ACB) and multi-walled carbon nanotubes (MWCNTs) (silane or un-silane-modified). The inks are screened step-by-step to explore their printability, rheology, mechanical properties, and electrical performance upon loading. The formation of an electrically conductive network, electrical properties upon tensile load, and strain sensing stability under cyclic stretching are investigated intensively. It is demonstrated that conductive polymers filled by ACB and silane-modified, MWCNTs (MWCNTs-MTES) possess superior printability, stretchability, conductivity, and strain sensing behaviors. Finally, a flexible wearable strain-sensing skin patch is printed, and it successfully records joint motion signals on human fingers, wrists, and elbows with good stability and repeatability. Those results show the extent of potential applications in healthcare and motion monitoring fields. This work provides an efficient and simple route to achieve comfortably wearable and high-performance strain sensors.


Assuntos
Nanotubos de Carbono , Dispositivos Eletrônicos Vestíveis , Condutividade Elétrica , Humanos , Polímeros , Silanos
5.
BMC Neurol ; 21(1): 402, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34666706

RESUMO

BACKGROUND: Charcot-Marie-Tooth (CMT) disease is a group of inherited peripheral neuropathies, which are subdivided into demyelinating and axonal forms. Biallelic mutations in POLR3B are the well-established cause of hypomyelinating leukodystrophy, which is characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. To date, only one study has reported the demyelinating peripheral neuropathy phenotype caused by heterozygous POLR3B variants. CASE PRESENTATION: A 19-year-old male patient was referred to our hospital for progressive muscle weakness of the lower extremities. Physical examination showed muscle atrophy, sensory loss and deformities of the extremities. Nerve conduction studies and electromyography tests revealed sensorimotor demyelinating polyneuropathy with secondary axonal loss. Trio whole-exome sequencing revealed a de novo variant in POLR3B (c.3137G > A). CONCLUSIONS: In this study, we report the case of a Chinese patient with a de novo variant in POLR3B (c.3137G > A), who manifested demyelinating CMT phenotype without additional neurological or extra-neurological involvement. This work is the second report on POLR3B-related CMT.


Assuntos
Doença de Charcot-Marie-Tooth , Adulto , Doença de Charcot-Marie-Tooth/genética , China , Heterozigoto , Humanos , Masculino , Mutação/genética , Fenótipo , RNA Polimerase III , Adulto Jovem
6.
J Peripher Nerv Syst ; 25(2): 107-111, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32319184

RESUMO

Mutations in MCM3AP have recently been reported to cause autosomal recessive Charcot-Marie-Tooth disease (CMT). However, only nine CMT families with MCM3AP mutations have been reported and genotype-phenotype correlation remains unclear. This study aimed to investigate the genetic spectrum of MCM3AP and its relationship with phenotype of CMT. Whole-exome sequencing (WES) was performed in the family and variants were validated by Sanger sequencing. Reverse transcription-PCR (RT-PCR) were performed in splicing analysis. We reported a novel splicing variant (c.5634-1G>T) and a known missense variant (c.2633G>A, p.Arg878His). Functional studies showed that c.5634-1G>T led to splicing defect and aberrant transcript eliminated by nonsense-mediated mRNA decay. The symptom of the patient was less severe and slowly progressed with axonal peripheral neuropathy compared to the reported CMT patients. Genotype-phenotype correlation analysis indicated that affected individuals with null mutations presented with delayed independent walking. The percentage of intellectual disability and loss of ambulation in the null group tended to be greater, although this failed to reach statistical significance. Our findings expand the genetic spectrum of MCM3AP and suggest that genotype-phenotype correlation would help genetic counseling of MCM3AP in CMT patients.


Assuntos
Acetiltransferases/genética , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/fisiopatologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Criança , Feminino , Humanos , Linhagem , Fenótipo
7.
Clin Genet ; 96(5): 439-448, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31372974

RESUMO

Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited sensorimotor neuropathies. To clarify the genetic spectrum and clinical profiles in Chinese CMT patients, we enrolled 150 unrelated CMT patients from southeast China. We performed multiplex ligation-dependent probe amplification (MLPA) testing in all patients and next-generation sequencing (NGS) among those patients without PMP22 rearrangements. We identified PMP22 duplications in 40 patients and deletions in 12 patients. In addition, we found 19 novel variants and 36 known mutations in 57 patients. Among these 55 variants, 45 pathogenic or likely pathogenic variants were identified in 48 cases, and 10 variants with uncertain significance were identified in 9 cases. Therefore, we obtained a genetic diagnosis in 63.8% (88/138) of CMT patients and 66.7% (100/150) of all included patients. PMP22, GJB1, and MFN2 are the most common causative genes in CMT1 (demyelinated form), intermediate CMT, and CMT2 (axonal form), respectively. In this study, we identified a higher proportion of intermediate CMT, a relatively high frequency of NDRG1 mutations and clinical features of later onset age in CMT1A patients. Our results broaden the genetic and clinical spectrum of CMT patients, which can help optimize the genetic and clinical diagnosis.


Assuntos
Doença de Charcot-Marie-Tooth/genética , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas da Mielina/genética , Adolescente , Adulto , Idade de Início , Doença de Charcot-Marie-Tooth/epidemiologia , Doença de Charcot-Marie-Tooth/patologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Rearranjo Gênico/genética , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação/genética , Deleção de Sequência/genética , Adulto Jovem
9.
BMC Oral Health ; 19(1): 164, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345197

RESUMO

BACKGROUND: Otodental syndrome is an exceptionally rare autosomal dominant condition characterized by a delayed eruption of posterior teeth, globodontia, lisping, and sensorineural hearing loss. In this case report, we reported a 3-year-old Chinese boy with the otodental syndrome. CASE PRESENTATION: A 3-year-old Chinese boy was referred to our hospital with complaint of no eruption of primary canines and molars. Three years follow-up showed lately erupted bulbous primary canines with hypoplastic enamel spot, globe-shaped primary molars and sensorineural hearing loss at 4 and a half-year-old age. We diagnosed otodental syndrome in the patient's mother with hearing loss at 16-year-old age. Gene sequencing and analysis of deafness-related genes GJB2, GJB3, SLC26A4, and mtDNA did not reveal any mutation or SNPs in the patient and his mother. CONCLUSIONS: This case report highlights the importance of detailed medical, dental, and family history examination, as well as multi-disciplinary teamwork for diagnosis and treatment of otodental syndrome.


Assuntos
Transtornos Cromossômicos/diagnóstico , Coloboma/diagnóstico , Perda Auditiva Neurossensorial/diagnóstico , Anormalidades Dentárias/diagnóstico , Anormalidades Múltiplas/genética , Adolescente , Povo Asiático , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 11 , Coloboma/genética , Perda Auditiva Neurossensorial/genética , Humanos , Masculino , Mutação , Odontoma/diagnóstico , Odontoma/genética , Anormalidades Dentárias/genética
10.
Zhonghua Nan Ke Xue ; 25(9): 802-810, 2019 Sep.
Artigo em Zh | MEDLINE | ID: mdl-32233207

RESUMO

OBJECTIVE: To investigate the status quo of the diagnosis and treatment of male urethritis (MU) in urology and andrology. METHODS: According to The Guidelines for Clinical Diagnosis and Treatment of Sexually Transmitted Diseases (2017), we designed 27 questions on the prevalence, diagnosis, treatment, and prognosis of MU. Using these questions, we conducted a questionnaire investigation among urological, andrological and other relevant clinicians with different professional titles, followed by an analysis of the compliance of the doctors to the Guidelines. RESULTS: Totally, 116 valid questionnaires were collected from 86 urological, 28 andrological and 2 other relevant doctors, including 22 professors, 36 associate professors, 40 attending doctors and 16 resident doctors. MU was found mostly in those aged 20-40 years and more than half of the patients had a history of unclean sex, gonococcal urethritis significantly less prevalent than non-gonococcal, with Ureaplasma urealyticum as the most common pathogen of non-gonococcal urethritis. As for the compliance to the Guidelines in the diagnosis of MU, 22.73% of the professors, 16.67% of the associate professors, 15.00% of the attending doctors and 12.50% of the resident doctors examined the eyes, mouth and perianus (P > 0.05), 40.91% of the professors, 58.33% of the associate professors, 40.00% of the attending doctors and 37.50% of the resident doctors conducted HIV and syphilis screening (P > 0.05), and 86.36% of the professors, 77.78% of the associate professors, 70.00% of the attending doctors and 75.00% of the resident doctors performed genital mycoplasma screening (P > 0.05). Concerning the treatment of MU, 50.00% of the professors, 47.22% of the associate professors, 22.50% of the attending doctors and 43.75% of the resident doctors used anti-Chlamydia trachomatis drugs for gonococcal urethritis (P > 0.05), 0.00% of the professors, 11.11% of the associate professors, 5.00% of the attending doctors and 31.25% of the resident doctors prescribed 1g single-dose oral azithromycin for non-gonococcal urethritis (P < 0.05), 13.64% of the professors, 33.33% of the associate professors, 17.50% of the attending doctors and 6.25% of the resident doctors medicated persistent or recurrent non-gonococcal urethritis for >4 weeks (P > 0.05), 63.64% of the professors, 83.33% of the associate professors, 57.50% of the attending doctors and 62.50% of the resident doctors treated asymptomatic trachomatis and mycoplasma infections according to the proposed medication in the Guidelines (P > 0.05). As regards the results of treatment, the cure rate of gonococcal urethritis was 100.00% by professors, 97.22% by associate professors, 95.00% by attending doctors and 81.25% by resident doctors (P > 0.05), and that of non-gonococcal urethritis was 86.36% by professors, 61.11% by associate professors, 62.50% by attending doctors and 37.50% by resident doctors (P < 0.05). CONCLUSIONS: Urological and andrological clinicians do not strictly follow the Guidelines in the diagnosis and treatment of male urethritis. There are significant differences in the dosing of azithromycin and results of treatment of non-gonococcal urethritis among doctors with different professional titles, but not in the other aspects.


Assuntos
Infecções por Ureaplasma/tratamento farmacológico , Uretrite/tratamento farmacológico , Uretrite/terapia , Adulto , Andrologia , Azitromicina/administração & dosagem , Fidelidade a Diretrizes , Humanos , Masculino , Mycoplasma genitalium , Inquéritos e Questionários , Uretrite/microbiologia , Urologia , Adulto Jovem
11.
Anal Bioanal Chem ; 410(11): 2665-2669, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29556736

RESUMO

On-site rapid monitoring of nitrite as an assessment indicator of the environment, food, and physiological systems has drawn extensive attention. Here, electrokinetic stacking (ES) was combined with colorimetric reaction on a paper-based device (PAD) to achieve colorless nitrite detection with smartphone. In this paper, nitrite was stacked on the paper fluidic channel as a narrow band by electrokinetic stacking. Then, Griess reagent was introduced to visualize the stacking band. Under optimal conditions, the sensitivity of nitrite was 160-fold increased within 5 min. A linear response in the range of 0.075 to 1.0 µg mL-1 (R2 = 0.99) and a limit of detection (LOD) of 73 ng mL-1 (0.86 µM) were obtained. The LOD was 10 times lower than the reported PAD, and close to that achieved by a desktop spectrophotometer. The applicability was demonstrated by nitrite detection from saliva and water with good selectivity, adding 100 times more concentrated co-ions. High recovery (91.0~108.7%) and reasonable intra-day and inter-day reproducibility (RSD < 9%) were obtained. This work shows that the sensitivity of colorless analyte detection-based colorimetric reaction can be effectively enhanced by integration of ES on a PAD. Graphical abstract Schematic of the experimental setups (left) and the corresponding images (right) of the actual portable device.


Assuntos
Colorimetria/instrumentação , Nitritos/análise , Papel , Saliva/química , Poluentes Químicos da Água/análise , Água/análise , Colorimetria/economia , Desenho de Equipamento , Humanos , Limite de Detecção , Reprodutibilidade dos Testes , Smartphone , Fatores de Tempo
12.
Hum Mutat ; 38(11): 1569-1578, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28776325

RESUMO

Charcot-Marie-Tooth disease type 4D (CMT4D) is an autosomal-recessive demyelinating form of CMT characterized by a severe distal motor and sensory neuropathy. NDRG1 is the causative gene for CMT4D. To date, only four mutations in NDRG1 -c.442C>T (p.Arg148*), c.739delC (p.His247Thrfs*74), c.538-1G>A, and duplication of exons 6-8-have been described in CMT4D patients. Here, using targeted next-generation sequencing examination, we identified for the first time two homozygous missense variants in NDRG1, c.437T>C (p.Leu146Pro) and c.701G>A (p.Arg234Gln), in two Chinese CMT families with consanguineous histories. Further functional studies were performed to characterize the biological effects of these variants. Cell culture transfection studies showed that mutant NDRG1 carrying p.Leu146Pro, p.Arg148*, or p.Arg234Gln variant degraded faster than wild-type NDRG1, resulting in lower protein levels. Live cell confocal microscopy and coimmunoprecipitation analysis indicated that these variants did not disrupt the interaction between NDRG1 and Rab4a protein. However, NDRG1-knockdown cells expressing mutant NDRG1 displayed enlarged Rab4a-positive compartments. Moreover, mutant NDRG1 could not enhance the uptake of DiI-LDL or increase the fraction of low-density lipoprotein receptor on the cell surface. Taken together, our study described two missense mutations in NDRG1 and emphasized the important role of NDRG1 in intracellular protein trafficking.


Assuntos
Proteínas de Ciclo Celular/genética , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Estudos de Associação Genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação de Sentido Incorreto , Doença de Refsum/diagnóstico , Doença de Refsum/genética , Adolescente , Adulto , Alelos , Substituição de Aminoácidos , Proteínas de Ciclo Celular/metabolismo , Doença de Charcot-Marie-Tooth/metabolismo , Feminino , Duplicação Gênica , Técnicas de Silenciamento de Genes , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Fenótipo , Ligação Proteica , Receptores de LDL/genética , Receptores de LDL/metabolismo , Doença de Refsum/metabolismo , Análise de Sequência de DNA , Deleção de Sequência , Adulto Jovem , Proteínas rab4 de Ligação ao GTP/metabolismo
13.
Yao Xue Xue Bao ; 50(1): 15-20, 2015 Jan.
Artigo em Zh | MEDLINE | ID: mdl-25924469

RESUMO

Molecular imprinting technique (MIT) involves the synthesis of polymer in the presence of a template to produce complementary binding sites in terms of its size, shape and functional group orientation. Such kind of polymer possesses specific recognition ability towards its template molecule. Despite the rapid development of MIT over the years, the majority of the template molecules that have been studied are small molecules, while molecular imprinting of proteins remains a significant yet challenging task due to their large size, structural flexibility and complex conformation. This review, we summarized the research findings over the past years, and discussed the nano-reinforcing materials used to prepare molecular imprinting of proteins and the perspective of these nano-reinforcing materials.


Assuntos
Impressão Molecular , Nanoestruturas/química , Proteínas/química , Sítios de Ligação , Conformação Molecular , Polímeros/química
14.
Genes Genet Syst ; 992024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38556272

RESUMO

Primula secundiflora is an insect-pollinated, perennial herb belonging to the section Proliferae (Primulaceae) that exhibits considerable variation in its mating system, with predominantly outcrossing populations comprising long-styled and short-styled floral morphs and selfing populations comprising only homostyles. To facilitate future investigations of the population genetics and mating patterns of this species, we developed 25 microsatellite markers from P. secundiflora using next-generation sequencing and measured polymorphism and genetic diversity in a sample of 30 individuals from three natural populations. The markers displayed high polymorphism, with the number of observed alleles per locus ranging from three to 16 (mean = 8.36). The observed and expected heterozygosities ranged from 0.100 to 1.000 and 0.145 to 0.843, respectively. Twenty-one of the loci were also successfully amplified in P. denticulata. These microsatellite markers should provide powerful tools for investigating patterns of population genetic diversity and the evolutionary relationships between distyly and homostyly in P. secundiflora.


Assuntos
Repetições de Microssatélites , Polimorfismo Genético , Primula , Primula/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Alelos , Genética Populacional/métodos
15.
Adv Sci (Weinh) ; 11(24): e2306675, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38647399

RESUMO

The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane-coated nanoparticles derived from different cell types can mimic the surface properties and functionalities of the source cells, further enhancing their targeting precision and therapeutic efficacy. Neuroinflammation has been increasingly recognized as a critical factor in the pathogenesis of various NDs, especially Alzheimer's disease (AD). In this study, a novel cell membrane coating is designed by hybridizing the membrane from platelets and chemokine (C-C motif) receptor 2 (CCR2) cells are overexpressed to cross the BBB and target neuroinflammatory lesions. Past unsuccessful endeavors in AD drug development underscore the challenge of achieving favorable outcomes when utilizing single-mechanism drugs.Two drugs with different mechanisms of actions into liposomes are successfully loaded to realize multitargeting treatment. In a transgenic mouse model for familial AD (5xFAD), the administration of these drug-loaded hybrid cell membrane liposomes results in a significant reduction in amyloid plaque deposition, neuroinflammation, and cognitive impairments. Collectively, the hybrid cell membrane-coated nanomaterials offer new opportunities for precise drug delivery and disease-specific targeting, which represent a versatile platform for targeted therapy in AD.


Assuntos
Doença de Alzheimer , Barreira Hematoencefálica , Modelos Animais de Doenças , Lipossomos , Camundongos Transgênicos , Nanopartículas , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Camundongos , Nanopartículas/química , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Humanos
16.
Ann Transl Med ; 10(12): 670, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35845517

RESUMO

Background: The development of personalized and high-precision dental treatment is inseparable from the accurate measurement and analysis of the model. Compared with traditional plaster models, digital models allow dentists to obtain richer and more detailed inspection results. However, the measurement of digital models in clinical practice usually ignores the influence of the overall three-dimensional (3D) structure of teeth and tooth arrangement on the measurement results. The purpose of this study was to evaluate the effect of calibrated tooth axis and tooth arrangement on tooth width and arch length. Methods: A total of 110 digital models from 80 participants were used to measure teeth width and dental arch length using the following methods: Method A, simple positioning of the proximal and distal of teeth; Method B: calibration of the clinical crown axis; and Method C: calibration of the overall 3D axis of the teeth. The Measurand model included pre- and post-orthodontic models of the same patients to assess the impact of tooth alignment on outcomes. Results: In the aligned dentition, whether the tooth axis was calibrated had no effect on the measurement results. On unaligned dentitions, calibrating the pinion allowed for more accurate measurements, with Method C the closest to the true size. Furthermore, the arrangement of teeth affected the measurement, but there was no continuous linear correlation with arch length discrepancy (ALD). Conclusions: Clinicians should choose appropriate measurement methods according to actual needs when performing model measurement, and should pay attention to the influence of tooth axis, tooth shape, and arrangement on the measurement results.

17.
Nanomedicine (Lond) ; 17(30): 2215-2229, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36927097

RESUMO

Aim: To explore how to transform cocrystals of the anticancer drug 5-fluorouracil (FL) with caffeic acid (CF; FL-CF-2H2O) into a nanoformulation, a self-assembly strategy of cocrystal-loaded micelles is proposed. Methods: Nanomicelles were assembled to deliver cocrystal FL-CF-2H2O with synergistic activity, and their in vitro/vivo properties were evaluated by combining theoretical and experimental methods. Result: More cocrystal was packed into the polymers due to the stronger interaction energy during micellar assembly, producing excellent cytotoxicity and pharmacokinetic behavior, especially synergistic abilities and long-term therapy. Conclusion: This case exemplifies the particular benefits of the self-assembly strategy of cocrystal-loaded micelles in keeping a delicate balance between long-term effects and high efficiency for FL, and offers a feasible technical scheme for cocrystal delivery agents for antitumor drugs.


To exemplify the feasibility of the cocrystal conversion of anticancer drug 5-fluorouracil (FL) with phenolic acid nutrient caffeic acid (CF) into a nanomicelle formulation, and further provide new options for the development of slowed-release cocrystal formulations with long-acting and synergistic antitumor effects, in this study, a cocrystalline complex of FL and CF (cocrystal FL-CF-2H2O) was loaded into polymer PEG-PCL to successfully assemble the cocrystal nanomicelles by a self-assembly strategy. The morphology of the cocrystal nanomicelles was characterized, and in vitro/vivo properties were evaluated by combining theoretical with experimental methods. The results showed that the cocrystal nanomicelles with regular sphericity and homogeneous particle size had greater drug loading and entrapment efficiency than FL nanomicelles, which is also supported by theoretical predictions of the interaction energy between the cocrystal FL-CF-2H2O and polymer PEG-PCL. The excellent encapsulation effects give rise to more potent cytotoxicity, better absorption and prolonged retention time in vivo. Relative to FL nanomicelles, the present cocrystal nanomicelles with synergistic antitumor abilities exhibited prominent slowed-release behavior that was more conducive to the long-term maintenance of therapeutic concentrations in vivo. The present case offers a feasible technical scheme for successful nanoformulation research on synergistic antitumor pharmaceutical cocrystals.


Assuntos
Antineoplásicos , Micelas , Fluoruracila/farmacologia , Polímeros/química , Antineoplásicos/farmacologia , Portadores de Fármacos
18.
J Pers Med ; 12(2)2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35207701

RESUMO

In the population of individuals with a disability, mental illness patients can be uncooperative during dental treatment; thus, general anesthesia has been widely applied during dental procedures. This study aims to investigate the association between general anesthesia and the outcomes of root canal treatment in patients with disability. Teeth treatment records of patients with disability from Kaohsiung Medical University Hospital Research Database and electronic database from January 2005 to December 2018 were used in this retrospective cohort study. The authors conducted analysis comparing root canal treatment outcomes under general anesthesia and non-general anesthesia, indicated by endodontic re-treatment or post-treatment teeth extraction. Over the 9-year follow-up period, root canal treatment outcomes representing a cumulative survival rate of 87.68% and 74.51% in the general anesthesia group and non-general anesthesia group, respectively, were found. After adjustment for potential confounders, the teeth with general anesthesia showed a substantially and significantly reduced HR of root canal treatment failure at 0.24 (95% confidence interval, 0.12 to 0.49). Our study supported the notion that root canal treatment with general anesthesia may entail substantial reduction of treatment failure in patients with disability.

19.
J Dent ; 117: 103925, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34929339

RESUMO

OBJECTIVES: The aim of this in-vitro study was to compare the virtual techniques for registering single-implant position to the physical gold standard using a universal-coordinate system. MATERIALS AND METHODS: Thirty dentate maxillary resin models with a dental implant inserted in the incisor region were prepared. On each model, a tooth-supported acrylic stent with a 1 cm x 1 cm x 1 cm cubic-corner (CC) was prepared. The Cartesian x,y,z-coordinate of the implant neck and apex were measured physically by a coordinate-measuring machine (CMM) with reference to this CC and served as the gold-standard. The resin models were scanned by a benchtop scanner (Group BS), cone-beam computed tomography (Group CBCT), and intraoral scanner (Group IOS). Stone casts, poured from open-tray polyether impression of the resin models, were scanned by the benchtop scanner (Group BS-cast). The implant neck and apex coordinates with reference to the CC were measured and the differences in the coordinates (∆x, ∆y, ∆z) and distance r from the gold standard were calculated. The data were analyzed by one-sample t-test and one-way ANOVA/Kruskal-Wallis test with the level of significance set at 0.05. RESULTS: The implant neck and apex positions of Group BS were statistically different from that of the CMM, r>0 (p<0.001). Group IOS showed a significant less ∆z and r at the implant neck than Group BS-cast (p = 0.006). No significant difference was found in the coordinates and distance at implant apex among Groups BS, CBCT, IOS and BS-cast. CONCLUSIONS: The physical measurements could be adopted as the gold standard in assessing the single-implant positions. The IOS was more accurate in registering the single-implant neck positions than scanning of the cast. CLINICAL SIGNIFICANCE: A universal-coordinate system defined by the cubic-corner allows comparing the virtual techniques in registering single-implant positions to the physical gold standard.


Assuntos
Implantes Dentários , Técnica de Moldagem Odontológica , Materiais para Moldagem Odontológica , Prótese Dentária Fixada por Implante , Modelos Dentários
20.
Zhongguo Gu Shang ; 35(8): 732-5, 2022 Aug 25.
Artigo em Zh | MEDLINE | ID: mdl-35979765

RESUMO

OBJECTIVE: To explore the risk factors of hidden blood loss in osteoporosis vertebral compression fractures during percutaneous vertebral augmentation. METHODS: From October 2018 to December 2019, 360 patients with osteoporosis vertebral compression fractures who received percutaneous vertebral augmentation were enrolled in this study. The factors analyzed included gender, age, surgical methods, disease course, height, weight, the operative segment, bone mineral density, amount of bone cement, operative time, percentage of height loss, percentage of vertebral height restoration, cement leakage, blood clotting function, preoperative and postoperative hemoglobin and hematocrit and other internal diseases. Total blood loss was calculated by Gross's formula, influential factors of the hidden blood loss were further analyzed by t-test, multivariate linear regression and one-way ANOVA analysis. RESULTS: Surgical methods, the operative segment, disease course, cement leakage, preoperative hemoglobin, cement leakage via the basivertebral and segmental vein were significantly correlated with hidden blood loss(P<0.05). CONCLUSION: Patients with percutaneous kyphoplasty, two-level and multi-level surgery, the course of the disease beyond 6 weeks, cement leakage via the basivertebral and segmental vein, and lower preoperative hemoglobin had more perioperative hidden blood loss.


Assuntos
Fraturas por Compressão , Cifoplastia , Osteoporose , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Cimentos Ósseos/efeitos adversos , Fraturas por Compressão/etiologia , Humanos , Cifoplastia/efeitos adversos , Cifoplastia/métodos , Osteoporose/complicações , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos , Fatores de Risco , Fraturas da Coluna Vertebral/etiologia , Resultado do Tratamento , Vertebroplastia/efeitos adversos
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