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1.
BMC Med Imaging ; 24(1): 93, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649991

RESUMO

BACKGROUND: The vestibular aqueduct (VA) serves an essential role in homeostasis of the inner ear and pathogenesis of Ménière's disease (MD). The bony VA can be clearly depicted by high-resolution computed tomography (HRCT), whereas the optimal sequences and parameters for magnetic resonance imaging (MRI) are not yet established. We investigated VA characteristics and potential factors influencing MRI-VA visibility in unilateral MD patients. METHODS: One hundred patients with unilateral MD underwent MRI with three-dimensional sampling perfection with application optimized contrasts using different flip angle evolutions (3D-SPACE) sequence and HRCT evaluation. The imaging variables included MRI-VA and CT-VA visibility, CT-VA morphology and CT-peri-VA pneumatization. RESULTS: The most frequent type of MRI-VA and CT-VA visualization was invisible VA and continuous VA, respectively. The MRI-VA visibility was significantly lower than CT-VA visibility. MRI-VA visibility had a weak positive correlation with ipsilateral CT-VA visualization. For the affected side, the MRI-VA visualization was negatively correlated with the incidence of obliterated-shaped CT-VA and positively with that of tubular-shaped CT-VA. MRI-VA visualization was not affected by CT-peri-VA pneumatization. CONCLUSION: In patients with MD, the VA visualization on 3D-SPACE MRI is poorer than that observed on CT and may be affected by its osseous configuration. These findings may provide a basis for further characterization of VA demonstrated by MRI and its clinical significance.


Assuntos
Imageamento por Ressonância Magnética , Doença de Meniere , Tomografia Computadorizada por Raios X , Aqueduto Vestibular , Humanos , Doença de Meniere/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Aqueduto Vestibular/diagnóstico por imagem , Feminino , Masculino , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Adulto , Idoso , Imageamento Tridimensional/métodos , Adulto Jovem
2.
Sci Rep ; 14(1): 9032, 2024 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641704

RESUMO

CSF1R is a receptor tyrosine kinase responsible for the growth/survival/polarization of macrophages and overexpressed in some AML patients. We hypothesized that a novel multi-kinase inhibitor (TKi), narazaciclib (HX301/ON123300), with high potency against CSF1R (IC50 ~ 0.285 nM), would have anti-AML effects. We tested this by confirming HX301's high potency against CSF1R (IC50 ~ 0.285 nM), as well as other kinases, e.g. FLT3 (IC50 of ~ 19.77 nM) and CDK6 (0.53 nM). An in vitro proliferation assay showed that narazaciclib has a high growth inhibitory effect in cell cultures where CSF1R or mutant FLT3-ITD variants that may be proliferation drivers, including primary macrophages (IC50 of 72.5 nM) and a subset of AML lines (IC50 < 1.5 µM). In vivo pharmacology modeling of narazaciclib using five AML xenografts resulted in: inhibition of MV4-11 (FLT3-ITD) subcutaneous tumor growth and complete suppression of AM7577-PDX (FLT3-ITD/CSF1Rmed) systemic growth, likely due to the suppression of FLT3-ITD activity; complete suppression of AM8096-PDX (CSF1Rhi/wild-type FLT3) growth, likely due to the inhibition of CSF1R ("a putative driver"); and nonresponse of both AM5512-PDX and AM7407-PDX (wild-type FLT3/CSF1Rlo). Significant leukemia load reductions in bone marrow, where disease originated, were also achieved in both responders (AM7577/AM8096), implicating that HX301 might be a potentially more effective therapy than those only affecting peripheral leukemic cells. Altogether, narazaciclib can potentially be a candidate treatment for a subset of AML with CSF1Rhi and/or mutant FLT3-ITD variants, particularly second generation FLT3 inhibitor resistant variants.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/patologia , Receptores Proteína Tirosina Quinases , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Receptores de Fator Estimulador de Colônias , Tirosina Quinase 3 Semelhante a fms/genética , Linhagem Celular Tumoral , Mutação , Apoptose , Quinase 6 Dependente de Ciclina
3.
Carbohydr Polym ; 332: 121923, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38431418

RESUMO

Bacterial cellulose (BC) produced by Acetobacter xylinum has great advantages in wound dressing. However, the structural limitation under static culture, and lack of antibacterial properties restrict its application, especially for infectious wound healing. The present study reported an original wound dressing, which was composed of a Janus BC membrane with antibacterial nano-sized copper oxide (CuO) through polydopamine (PDA) conjugation to promote wound healing under infectious condition. The finished product (CuO/PDA/BC membrane) exhibited favorable air permeability, high hydrophilicity and good mechanical properties, as well as strong antibacterial effects by the sustained release of CuO and photothermal effect of CuO/PDA. Furthermore, CuO/PDA/BC membrane inhibited inflammatory response and promoted wound healing in an infectious wound model in vivo. These results suggested that our CuO/PDA/BC membrane had great potential as wound dressing for infectious wound healing.


Assuntos
Celulose , Indóis , Polímeros , Infecção dos Ferimentos , Humanos , Celulose/farmacologia , Celulose/química , Cobre/farmacologia , Cobre/química , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Óxidos/farmacologia
4.
J Pain ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38417595

RESUMO

Chronic overlapping pain conditions (COPCs) by definition, frequently co-occur, perhaps reflecting their shared etiologies. Their overlapping nature presents a methodological challenge, possibly masking associations between COPCs and health outcomes attributable to either general or specific processes. To address this challenge, we used population-based cohort data to evaluate the predictive validity of a bifactor model of 9 self-reported COPCs by assessing its association with incident pain-related clinical diagnoses; pain-relevant pharmacotherapy; and other health outcomes. We obtained data from a 2005 to 2006 study of Swedish adult twins linked with health data from nationwide registers through 2016 (N = 25,418). We then fit a bifactor model comprising a general COPC factor and 2 independent specific factors measuring pain-related somatic symptoms and neck and shoulder pain. Accounting for age, biological sex, and cancer, the general factor was associated with increased risk of all pain-related outcomes (eg, COPC diagnosis adjusted odds ratio [aOR], 1.71; 95% confidence interval [1.62, 1.81]), most mental health-related outcomes (eg, depression aOR, 1.72 [1.60, 1.85]), and overdose and mortality (eg, all-cause mortality aOR, 1.25 [1.09, 1.43]). The somatic symptoms specific factor was associated with pain-relevant pharmacotherapy (eg, prescribed opioids aOR, 1.25 [1.15, 1.36]), most mental health-related outcomes (eg, depression aOR, 1.95 [1.70, 2.23]), and overdose (eg, nonfatal overdose aOR, 1.66 [1.31, 2.10]). The neck and shoulder pain-specific factor was weakly and inconsistently associated with the outcomes. Findings provide initial support for the validity and utility of a general-factor model of COPCs as a tool to strengthen understanding of co-occurrence, etiology, and consequences of chronic pain. PERSPECTIVE: This article presents associations between a novel measurement model of COPCs and various health outcomes. Findings provide support for measuring pain across multiple domains rather than only measuring pain specific to one physical location in both research and clinical contexts.

5.
Am J Psychiatry ; : appiajp20220951, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38263878

RESUMO

OBJECTIVE: Most mental disorders, when examined individually, are associated with an increased risk of cardiometabolic complications. However, these associations might be attributed to a general liability to psychopathology or confounded by unmeasured familial factors. The authors investigated the association between psychiatric conditions in young adulthood and the risk of cardiometabolic complications in middle adulthood, up to 40 years later. METHODS: This cohort study (N=672,823) identified all individuals and their siblings born in Sweden between 1955 and 1962 and followed the cohort through 2013. Logistic regression models were used to estimate the bivariate associations between 10 psychiatric conditions or criminal convictions and five cardiometabolic complications in individuals. A general factor model was used to identify general, internalizing, externalizing, and psychotic factors based on the comorbidity among psychiatric conditions and criminal convictions. The cardiometabolic complications were then regressed on the latent general factor and three uncorrelated specific factors within a structural equation modeling framework in individuals and across sibling pairs. RESULTS: Each psychiatric condition significantly increased the risk of cardiometabolic complications. These associations appeared nonspecific, as multivariate models indicated that most were attributable to the general factor of psychopathology, rather than to specific psychiatric conditions. There were no or only small associations between individuals' general psychopathology and their siblings' cardiometabolic complications. The same pattern was evident for the specific internalizing and psychotic factors. CONCLUSIONS: Associations between mental disorders in early life and later long-term risk of cardiometabolic complications appeared to be attributable to a general liability to psychopathology. Familial coaggregation analyses suggested that the elevated risk could not be attributed to confounders shared within families. One possibility is that lifestyle-based interventions may reduce the risk of later cardiometabolic complications for patients with several mental disorders.

6.
Int J Biol Macromol ; 258(Pt 1): 128837, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128800

RESUMO

Foot-and-mouth disease virus (FMDV) is a highly contagious pathogen that has caused significant economic losses in the livestock industry. Peptide vaccines engineered with the protective epitopes of FMDV have provided a safer alternative for disease prevention than the traditional inactivated vaccines. However, the immunogenicity of the peptide is usually poor and therefore an adjuvant is required. Here, we showed that recombinant T4 phages displaying the B-cell epitope of the FMDV VP1 protein (VP1130-158), without additional adjuvants, induced similar levels of antigen-specific IgG1 but higher levels of IgG2a compared to the peptide vaccine. Incorporation of a CD4+ T cell epitope, either 3A21-35 of FMDV 3A protein or P2830-844 of tetanus toxoid, further enhanced the immunogenicity of VP1-T4 phage nanoparticles. Interestingly, the extrinsic adjuvant cannot enhance the immunogenicity of the nanoparticles, indicating the intrinsic adjuvant activities of T4 phage. Furthermore, the recombinant T4 phage can be produced on a large scale within a short period of time at a relatively low-cost using Escherichia coli, heralding its potential in the development of a safe and effective FMDV vaccine.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Vacinas Virais , Animais , Bacteriófago T4 , Febre Aftosa/prevenção & controle , 60547 , Anticorpos Antivirais , Epitopos de Linfócito B , Adjuvantes Imunológicos , Proteínas do Capsídeo
7.
Front Immunol ; 14: 1274027, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38098490

RESUMO

Background: Emerging infectious diseases pose a significant threat to both human and animal populations. Rapid de novo identification of protective antigens from a clinical isolate and development of an antigen-matched vaccine is a golden strategy to prevent the spread of emerging novel pathogens. Methods: Here, we focused on Actinobacillus pleuropneumoniae, which poses a serious threat to the pig industry, and developed a general workflow by integrating proteosurfaceomics, secretomics, and BacScan technologies for the rapid de novo identification of bacterial protective proteins from a clinical isolate. Results: As a proof of concept, we identified 3 novel protective proteins of A. pleuropneumoniae. Using the protective protein HBS1_14 and toxin proteins, we have developed a promising multivalent subunit vaccine against A. pleuropneumoniae. Discussion: We believe that our strategy can be applied to any bacterial pathogen and has the potential to significantly accelerate the development of antigen-matched vaccines to prevent the spread of an emerging novel bacterial pathogen.


Assuntos
Actinobacillus pleuropneumoniae , Pleuropneumonia , Animais , Humanos , Suínos , Antígenos de Bactérias , Vacinas Bacterianas , Proteínas de Bactérias , Pleuropneumonia/microbiologia , Pleuropneumonia/prevenção & controle
8.
Med Sci Monit ; 29: e940948, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37721931

RESUMO

BACKGROUND The aim of this study was to analyze the correlation and the accuracy of lower-extremity torsion deformities measured by physical examination, CT scan, and three-dimensional gait analysis in children with CP. MATERIAL AND METHODS The study group included 72 children with CP with lower-extremity torsion deformities. All subjects were assessed by: 1. physical examination: maximum internal rotation (MIR), maximum external rotation (MER) for hip joint torsion, and transmalleolar axis (TMA) for tibial torsion; 2. CT scanning: femoral anteversion (FAV) and tibial torsion (TT); 3. three-dimensional gait analysis kinematic parameters: single-support phase of femoral rotation, double-support phase of femoral rotation, swing phase of femoral rotation and single-support phase of tibial rotation, double-support phase of tibial rotation, and swing phase of tibial rotation. Statistical analysis was performed using the Pearson correlation test. A significance level of P<0.05 was set. RESULTS In femurs, MIR and MER were correlated with FAV, and the correlation of MER was higher, while physical examination and FAV were not correlated with any kinematic data in gait analysis. In tibias, there was no correlation between TMA and TT, but both TMA and TT were correlated with the gait analysis kinematic data, and the correlation of TT was higher. TMA was more correlated with tibial rotation during swing phase, while TT was more correlated with tibial rotation in single-support phase. CONCLUSIONS Three-dimensional gait analysis can analyze the tibial rotation of children with cerebral palsy, which is highly correlated with CT and physical examination. However, femoral rotation was not associated with CT and physical examination.


Assuntos
Paralisia Cerebral , Análise da Marcha , Criança , Humanos , Paralisia Cerebral/diagnóstico por imagem , Exame Físico , Tomografia Computadorizada por Raios X , Extremidade Inferior/diagnóstico por imagem
9.
BMJ Open ; 13(9): e075767, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37748853

RESUMO

INTRODUCTION: Depressive symptoms have surfaced as the principal mental health concern among patients with breast cancer, with surgical interventions potentially exacerbating these symptoms and adversely influencing clinical outcomes. This study protocol is designed to investigate the efficacy of low-dose esketamine administered perioperatively on depressive symptoms in patients with breast cancer. It also aims to illuminate the potential neurobiological underpinnings of this effect. METHODS AND ANALYSIS: This research represents a single-centre, prospective, randomised, double-blind, placebo-controlled study. The trial anticipates enrolling 108 female patients exhibiting mild-to-severe depressive symptoms who are slated for radical mastectomy. Through stratified randomisation, eligible patients will be systematically assigned to either the esketamine group (0.25 mg/kg) or placebo group (0.9% saline) in a 1:1 ratio. The primary outcome is the response rate at the third postoperative day. Secondary outcomes encompass the remission rate, depression-related scores, depression severity and safety-related endpoints. Tertiary (exploratory) outcomes involve alterations in brain-derived neurotrophic factor and resting-state functional brain connectivity. ETHICS AND DISSEMINATION: The Clinical Trial Ethics Committee at The First Affiliated Hospital of Anhui Medical University has conferred ethical approvals for this trial (approval number: PJ2023-05-25). Results from this trial will be disseminated in peer-reviewed journals and presented at professional symposiums. TRIAL REGISTRATION NUMBER: Chinese Clinical Trials Registry (ChiCTR2300071062).


Assuntos
Neoplasias da Mama , Depressão , Humanos , Feminino , Depressão/tratamento farmacológico , Depressão/etiologia , Depressão/diagnóstico , Neoplasias da Mama/cirurgia , Estudos Prospectivos , Resultado do Tratamento , Mastectomia/efeitos adversos , Método Duplo-Cego , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Antiviral Res ; 217: 105688, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37516153

RESUMO

Vaccines that trigger mucosal immune responses at the entry portals of pathogens are highly desired. Here, we showed that antigen-decorated nanoparticle generated through CRISPR engineering of T4 bacteriophage can serve as a universal platform for the rapid development of mucosal vaccines. Insertion of Flu viral M2e into phage T4 genome through fusion to Soc (Small Outer Capsid protein) generated a recombinant phage, and the Soc-M2e proteins self-assembled onto phage capsids to form 3M2e-T4 nanoparticles during propagation of T4 in E. coli. Intranasal administration of 3M2e-T4 nanoparticles maintains antigen persistence in the lungs, resulting in increased uptake and presentation by antigen-presenting cells. M2e-specific secretory IgA, effector (TEM), central (TCM), and tissue-resident memory CD4+ T cells (TRM) were efficiently induced in the local mucosal sites, which mediated protections against divergent influenza viruses. Our studies demonstrated the mechanisms of immune protection following 3M2e-T4 nanoparticles vaccination and provide a versatile T4 platform that can be customized to rapidly develop mucosal vaccines against future emerging epidemics.


Assuntos
Vacinas contra Influenza , Nanopartículas , Infecções por Orthomyxoviridae , Animais , Camundongos , Vacinas contra Influenza/genética , Bacteriófago T4/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Escherichia coli/genética , Infecções por Orthomyxoviridae/prevenção & controle , Camundongos Endogâmicos BALB C , Proteínas da Matriz Viral
11.
bioRxiv ; 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37205589

RESUMO

Chemically modified antisense oligonucleotides (ASO) currently in pre-clinical and clinical experiments mainly focus on the 2'-position derivatizations to enhance stability and targeting affinity. Considering the possible incompatibility of 2'-modifications with RNase H stimulation and activity, we have hypothesized that the atom specific modifications on nucleobases can retain the complex structure and RNase H activity, while enhancing ASO's binding affinity, specificity, and stability against nucleases. Herein we report a novel strategy to explore our hypothesis by synthesizing the deoxynucleoside phosphoramidite building block with the seleno-modification at 5-position of thymidine, as well as its Se-oligonucleotides. Via X-ray crystal structural study, we found that the Se-modification was located in the major groove of nucleic acid duplex and didn't cause the thermal and structural perturbations. Surprisingly, our nucleobase-modified Se-DNAs were exceptionally resistant to nuclease digestion, while compatible with RNase H activity. This affords a novel avenue for potential antisense modification in the form of Se-antisense oligonucleotides (Se-ASO).

12.
Sci Rep ; 13(1): 5419, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37012357

RESUMO

Both PD1/PD-L1 and CD47 blockades have demonstrated limited activity in most subtypes of NHL save NK/T-cell lymphoma. The hemotoxicity with anti-CD47 agents in the clinic has been speculated to account for their limitations. Herein we describe a first-in-class and rationally designed bispecific antibody (BsAb), HX009, targeting PD1 and CD47 but with weakened CD47 binding, which selectively hones the BsAb for tumor microenvironment through PD1 interaction, potentially reducing toxicity. In vitro characterization confirmed: (1) Both receptor binding/ligand blockade, with lowered CD47 affinity; (2) functional PD1/CD47 blockades by reporter assays; (3) T-cell activation in Staphylococcal-enterotoxin-B-pretreated PBMC and mixed-lymphocyte-reaction. In vivo modeling demonstrated antitumor activity in Raji-B and Karpass-229-T xenograft lymphomas. In the humanized mouse syngeneic A20 B-lymphoma (huCD47-A20) HuGEMM model, which has quadruple knocked-in hPD1xhPD-L1xhCD47xhSIRPα genes and an intact autologous immune-system, a contribution of effect is demonstrated for each targeted biologic (HX008 targeting PD1 and SIRPα-Fc targeting CD47), which is clearly augmented by the dual targeting with HX009. Lastly, the expression of the immune-checkpoints PD-L1/L2 and CD47 seemed co-regulated among a panel of lymphoma-derived-xenografts, where HX009 maybe more effective in those with upregulated CD47. Our data warrants HX009's further clinical development for treating NHLs.


Assuntos
Anticorpos Biespecíficos , Linfoma não Hodgkin , Neoplasias , Camundongos , Animais , Humanos , Antígeno B7-H1 , Leucócitos Mononucleares/metabolismo , Anticorpos Monoclonais/uso terapêutico , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Antígeno CD47 , Neoplasias/metabolismo , Microambiente Tumoral
14.
Regen Biomater ; 10: rbac094, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36683758

RESUMO

Three-dimensional printing technology with the rapid development of printing materials are widely recognized as a promising way to fabricate bioartificial bone tissues. In consideration of the disadvantages of bone substitutes, including poor mechanical properties, lack of vascularization and insufficient osteointegration, functional modification strategies can provide multiple functions and desired characteristics of printing materials, enhance their physicochemical and biological properties in bone tissue engineering. Thus, this review focuses on the advances of functional engineering strategies for 3D printed biomaterials in hard tissue replacement. It is structured as introducing 3D printing technologies, properties of printing materials (metals, ceramics and polymers) and typical functional engineering strategies utilized in the application of bone, cartilage and joint regeneration.

15.
Psychol Res Behav Manag ; 16: 71-83, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36643733

RESUMO

Purpose: Stress may relate to an increased risk of psychological and physical disorders. Thus, a brief and efficient measurement instrument for researchers to measure stress is essentially needed. Participants and Methods: To assess measurement properties of the validated Chinese version of the Perceived Stress Questionnaire-13 (PSQ-C-13), we conducted a two-wave longitudinal study from September to December, 2021 with a convenient sample of medical students. Results: A two-factor (constraint and imbalance) structure showed good fit indices (Comparative Fit Index [CFI] = 0.972, Tucker-Lewis Index [TLI] = 0.966, Root Mean Square Error of Approximation [RMSEA] = 0.062). Spearman correlations with the Chinese Perceived Stress Scale-10 illustrated that convergent validity of the PSQ-C-13 was relatively satisfactory (r = 0.678 [baseline], 0.753 [follow-up]). Measurement invariance was supported across subgroups (gender, age, home location, single-child status, monthly households' income, and part-time status) and time points. Internal consistency was sound (Cronbach's α = 0.908 [baseline], 0.922 [follow-up]; McDonald's ω = 0.909 [baseline], 0.923 [follow-up]). Stability between time points was good (Intraclass Correlation Coefficient = 0.834). Conclusion: The two factors of the PSQ-C-13 including constraint and imbalance may adequately measure the level of stress on participants. The PSQ-C-13 is a convenient and efficient instrument that contains valid and reliable psychometric properties.

16.
IEEE J Biomed Health Inform ; 27(2): 598-607, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35724285

RESUMO

Analysis of high dimensional biomedical data such as microarray gene expression data and mass spectrometry images, is crucial to provide better medical services including cancer subtyping, protein homology detection, etc. Clustering is a fundamental cognitive task which aims to group unlabeled data into multiple clusters based on their intrinsic similarities. However, for most clustering methods, including the most widely used K-means algorithm, all features of the high dimensional data are considered equally in relevance, which distorts the performance when clustering high-dimensional data where there exist many redundant variables and correlated variables. In this paper, we aim at addressing the problem of the high dimensional bioinformatics data clustering and propose a new correlation induced clustering, CoIn, to capture complex correlations among high dimensional data and guarantee the correlation consistency within each cluster. We evaluate the proposed method on a high dimensional mass spectrometry dataset of liver cancer tumor to explore the metabolic differences on tissues and discover the intra-tumor heterogeneity (ITH). By comparing the results of baselines and ours, it has been found that our method produces more explainable and understandable results for clinical analysis, which demonstrates the proposed clustering paradigm has the potential with application to knowledge discovery in high dimensional bioinformatics data.


Assuntos
Algoritmos , Neoplasias Hepáticas , Humanos , Biologia Computacional/métodos , Análise por Conglomerados , Cognição
17.
Biol Trace Elem Res ; 201(9): 4508-4517, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36567423

RESUMO

The objective of this study was to investigate the effects of iron nanoliposomes on iron supplementation and toxicity in SD rats induced by a low-iron diet. The size and infrared spectroscopy of a liposomal oral delivery system were investigated. The particle size of nanoliposomes embedded with chelates was increased. Infrared spectra proved that peptides-iron and blank nanoliposomes were bonded by interaction forces, including the fracture of hydrogen bonds, C = C bonds, hydrophobic interaction, and C-N bonds. We found that iron supplementation chelates had a certain protective effect on viscera after being embedded by nanoliposomes. After 10 days of treatment, the concentration of hemoglobin could be gradually increased. Nanoliposome encapsulated peptides-iron has a better effect than other groups. At the same time, SOD, MDA, and CAT reached normal levels after 20 days. Histological results showed that the sections of the nanoliposomes groups were clearer than those of the other groups. There was a little inflammation in the liver without obvious pathological changes, which also proved that the iron chelates embedded by nanoliposomes had no obvious side effects on iron supplementation in rats. Nanoliposome encapsulated peptides-iron has a small side effect and a significant curative effect of iron supplementation. It maybe has a good application prospect in the clinical medical field.


Assuntos
Ferro , Lipossomos , Ratos , Animais , Ratos Sprague-Dawley , Lipossomos/química , Peptídeos/química , Quelantes de Ferro , Suplementos Nutricionais
18.
Res Sq ; 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38196584

RESUMO

Many efforts have sought to apply laboratory in vitro evolution (LIVE) to natural nucleic acid (NA) scaffolds to directly evolve functional molecules. However, synthetic biology can move beyond natural NA scaffolds to create molecular systems whose libraries are far richer reservoirs of functionality than natural NAs. For example, "artificially expanded genetic information systems" (AEGIS) add up to eight nucleotides to the four found in standard NA. Even in its simplest 6-letter versions, AEGIS adds functional groups, information density, and folding motifs that natural NA libraries lack. To complete this vision, however, tools are needed to sequence molecules that are created by AEGIS LIVE. Previous sequencing approaches, including approaches from our laboratories, exhibited limited performance and lost many sequences in diverse library mixtures. Here, we present a new approach that enzymatically transforms the target AEGIS DNA. With higher transliteration efficiency and fidelity, this Enzyme-Assisted Sequencing of Expanded Genetic Alphabet (ESEGA) approach produces substantially better sequences of 6-letter (AGCTZP) DNA than previous transliteration approaches. Therefore, ESEGA facilitates precise analysis of libraries, allowing 'next-generation deep sequencing' to accurately quantify the sequences of 6-letter DNA molecules at single base resolution. We then applied ESEGA to three tasks: (a) defining optimal conditions to perform 6-nucleotide PCR (b) evaluating the fidelity of 6-nucleotide PCR with various DNA polymerases, and (c) extending that evaluation to AEGIS components functionalized with alkynyl and aromatic groups. No other approach at present has this scope, allowing this work to be the next step towards exploiting the potential of expanded DNA alphabets in biotechnology.

19.
Molecules ; 27(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36500495

RESUMO

Tellurium was successfully incorporated into proteins and applied to protein structure determination through X-ray crystallography. However, studies on tellurium modification of DNA and RNA are limited. This review highlights the recent development of Te-modified nucleosides, nucleotides, and nucleic acids, and summarizes the main synthetic approaches for the preparation of 5-PhTe, 2'-MeTe, and 2'-PhTe modifications. Those modifications are compatible with solid-phase synthesis and stable during Te-oligonucleotide purification. Moreover, the ideal electronic and atomic properties of tellurium for generating clear isomorphous signals give Te-modified DNA and RNA great potential applications in 3D crystal structure determination through X-ray diffraction. STM study also shows that Te-modified DNA has strong topographic and current peaks, which immediately suggests potential applications in nucleic acid direct imaging, nanomaterials, molecular electronics, and diagnostics. Theoretical studies indicate the potential application of Te-modified nucleosides in cancer therapy.


Assuntos
Ácidos Nucleicos , Telúrio , Telúrio/química , Nucleotídeos , Nucleosídeos , DNA/química , RNA/química
20.
RSC Adv ; 12(40): 26372-26381, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36275107

RESUMO

Promoting a senescent phenotype to suppress tumour progression may present an alternative strategy for treating cancer and encourages the development of positron emission tomography (PET) imaging biomarkers for assessing response to treatment. The accumulation of lipofuscin deposits in senescent cells is visualised using the pathology stain Sudan Black B (SBB) which is an emerging biomarker of senescence. We describe the design, synthesis and evaluation of [18F]fluoroethyltriazole-SBB ([18F]FET-SBB), a fluorine-18 radiolabelled derivative of SBB. The in vitro uptake of [18F]FET-SBB in a senescent cell line corelated with lipofuscin deposits; in vivo PET imaging and metabolite analysis confirm a favourable pharmacokinetic and metabolic profile for further studies of in vivo models of senescence.

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