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1.
Sci Rep ; 14(1): 8964, 2024 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637563

RESUMO

Previous studies suggested odor stimulation may influence feeding of premature neonates. Therefore, this systematic review and meta-analysis of randomized controlled trials was conducted to assess the effect of human milk odor stimulation on feeding of premature infants. All randomized controlled trials related to human milk odor stimulation on feeding in premature infants published in PubMed, Cochrane, Library, Medline, Embase, Web of science databases and Chinese biomedical literature databases, China National Knowledge Infrastructure, China Science and Technology Journal Database (VIP) and Wanfang Chinese databases were searched, and The Cochrane Handbook 5.1.0 was used to evaluate the quality and authenticity of the literature. Relevant information of the included studies was extracted and summarized, and the evaluation indexes were analyzed using ReviewManager5.3. The retrieval time was from the establishment of the database to July 28, 2022.12 articles were assessed for eligibility, and six randomized controlled studies were eventually included in the meta-analysis (PRISMA). A total of 6 randomized controlled studies with 763 patients were finally included in the study, and the quality evaluation of literatures were all grade B. Human milk odor stimulation reduced the transition time to oral feeding in premature infants [SMD = - 0.48, 95% CI (- 0.69, - 0.27), Z = 4.54, P < 0.00001] and shortened the duration of parenteral nutrition [MD = - 1.01, 95% CI (- 1.70, - 0.32), Z = 2.88, P = 0.004]. However, it did not change the length of hospitalization for premature infants [MD = - 0.03, 95% CI (- 0.41, 0.35), Z = 0.17, P = 0.86]. The implementation of human milk odor stimulation can reduce the transition time to oral feeding and the duration of parenteral nutrition in premature infants, but further studies are needed to determine whether it can reduce the length of hospital stay in premature infants. More high-quality, large-sample studies are needed to investigate the effect of human milk odor stimulation on the feeding process and other outcomes in premature infants.


Assuntos
Leite Humano , Odorantes , Humanos , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Tempo de Internação , Aumento de Peso , Ingestão de Alimentos
2.
Angew Chem Int Ed Engl ; : e202402139, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563765

RESUMO

The development of artificial receptors that combine ultrahigh-affinity binding and controllable release for active guests holds significant importance in biomedical applications. On one hand, a complex with an exceedingly high binding affinity can resist unwanted dissociation induced by dilution effect and complex interferents within physiological environments. On the other hand, stimulus-responsive release of the guest is essential for precisely activating its function. In this context, we expanded hydrophobic cavity surface of a hypoxia-responsive azocalix[4]arene, affording Naph-SAC4A. This modification significantly enhanced its aqueous binding affinity to 1013 M-1, akin to the naturally occurring strongest recognition pair, biotin/(strept-)avidin. Consequently, Naph-SAC4A emerges as the first artificial receptor to simultaneously integrate ultrahigh recognition affinity and actively controllable release. The markedly enhanced affinity not only improved Naph-SAC4A's sensitivity in detecting rocuronium bromide in serum, but also refined the precision of hypoxia-responsive doxorubicin delivery at the cellular level, demonstrating its immense potential for diverse practical applications.

3.
J Ethnopharmacol ; 329: 118136, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38583731

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C.A. Meyer., a famous and valuable traditional Chinese medicine with thousand years of history for its healthcare and therapeutic effects. It is necessary and meaningful to study the pharmacokinetic behavior of ginsenosides in vivo as they are the most active components. Dried blood spots (DBS) are a mature and advanced blood collection method with meet the needs for the measurement of numerous analytes. AIM OF THE STUDY: This study aimed to explore the feasibility on DBS in the metabolic profile analysis of complex herbal products. MATERIALS AND METHODS: An ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of ginsenosides. The preparation of DBS samples was conducted by spiking the whole blood with analytes to obtain 20 µL of blood spots on Whatman 903 collection card. A punched dish of 10 mm in diameter was extracted with 70 % methanol aqueous solution, digoxin was used as an internal standard. Target compounds were separated on a Waters T3 column (2.1 × 100 mm, 1.8 µm) with acetonitrile and water (0.1 % formic acid) at a flow rate of 0.4 mL/min. RESULTS: The various ginsenosides showed good linearity in the range of 1-2000 ng/mL. The extraction recoveries and matrix effects of the target analytes were above 82.2%. The intra- and inter-batch accuracy and precision were within the limits of ≤15% for all tested concentrations. Moreover, the collected dried blood spot samples could be stably stored at room temperature for 14 days and 4 °C for 1 month without being affected. And it is delightful that the DBS-based analysis is compatible or even superior to the conventional protein precipitation in terms of sensitivity, linearity, and stability. In particular, the target analytes are stable in the DBS sampling under normal storing condition and the sensitivity for some trace metabolites of ginsenosides, such as 20(S)-Rg3, 20(R)-Rg3, F1, Rk1, Rg5, etc. increases 3-4 folds as evaluated by LLOQ. CONCLUSIONS: The established method was successfully applied to pharmacokinetic studies of ginseng extract in mice, this suggests a more feasible strategy for pharmacokinetic study of traditional and natural medicines both in animal tests and clinical trials.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38527651

RESUMO

OBJECTIVE: KRAS G12V is one of the most common KRAS mutation variants in lung adenocarcinoma (LUAD), and yet its prognostic value is still unrevealed. In this study, we investigated the clinicopathologic characteristics and prognostic value of the KRAS G12V mutation in LUAD. METHODS: Data of 3829 patients who underwent LUAD resection between 2008 and 2020 were collected. Mutations were classified as wild-type, G12V, or non-G12V. The clinicopathologic characteristics, postoperative outcomes, and recurrence pattern were analyzed among groups. RESULTS: In total, 3554 patients were wild-type and 275 patients harbored a KRAS mutation: 60 patients with G12V (22.2%) and 215 patients with non-G12V (77.8%). The KRAS G12V mutation was more frequent in male patients, older patients (≥60 years), former/current smokers, those patients with radiologic solid nodules, and those with highly invasive histologic subtypes. Tumors carrying KRAS G12V mutation exhibited elevated programmed death-ligand 1 expression in comparison with wild-type tumors. KRAS G12V was more prevalent in older patients and had less lymphovascular invasion compared with other mutation types. FGF3, RET, and KDR co-mutations occurred more frequently in the KRAS G12V group. Multivariate analysis demonstrated that the KRAS G12V mutation was an independent prognostic factor in stage Ⅰ tumors, whereas the KRAS non-G12V mutation was not. KRAS G12V was associated with early recurrence and locoregional recurrence. CONCLUSIONS: The KRAS G12V mutation was associated with aggressive clinical-pathologic phenotype and early recurrence. To note, this mutation exhibited a significantly worse prognosis in patients with part-solid and stage Ⅰ lung adenocarcinoma. Meanwhile, the prognostic significance of KRAS G12C and G12V variants was comparable.

5.
Eur J Cancer ; 202: 113985, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38452722

RESUMO

BACKGROUND: In light of the ongoing clinical development of KRAS G12D-specific inhibitors, we sought to investigate the clinicopathologic, co-occurring genomic features and outcomes of patients with KRAS G12D-mutant lung adenocarcinoma. METHODS: 3828 patients with completely resected primary lung adenocarcinomas were examined for KRAS mutations between 2008 and 2020. The association between KRAS G12D and clinicopathologic features, molecular profiles, and outcomes was investigated. RESULTS: 65 patients (1.7%) with KRAS G12D-mutant lung adenocarcinoma were identified. KRAS G12D mutation was more frequent in males, former/current smokers, radiologic solid tumors, and invasive mucinous adenocarcinoma. TP53 and STK11 were the two most frequent concomitant mutations in the KRAS G12D group. KRAS G12D mutation did not appear to be a prognostic factor in resected stage I-III lung adenocarcinomas, while KRAS non-G12D mutation was related to worse survival, especially in stage I tumors. KRAS G12D mutations were associated with positive but low (1-49%) PD-L1 expression compared to negative (<1%), while KRAS non-G12D mutation was associated with high PD-L1 expression (≥50%). TP53 co-mutation indicated higher PD-L1 expression, while STK11 co-mutation had a negligible impact on PD-L1 expression. Furthermore, data mining of MSK datasets from cBioPortal revealed that KRAS G12D and SKT11 co-mutation were associated with a diminished response to immunotherapy. CONCLUSIONS: KRAS G12D-mutant lung adenocarcinoma harbored unique clinicopathologic and genomic characteristics. Despite not being prognostic in resected lung adenocarcinoma, KRAS G12D might be a valuable biomarker in combination with certain co-mutations for identifying relevant subgroups of patients that could eventually influence treatment regimens.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Masculino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Antígeno B7-H1/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Adenocarcinoma/metabolismo , Mutação , Prognóstico , Genômica
6.
Ophthalmic Res ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38555640

RESUMO

INTRODUCTION: This study aimed to investigate the relationship between age of myopia onset and high myopia and to explore if age of onset mediated the associations of high myopia with parental myopia and time spent on electronics. METHODS: This cross-sectional study enrolled 1118 myopic patients aged 18 to 40. Information was obtained via a detailed questionnaire. Multivariable logistic regression and linear regression models were utilized to assess age of onset in relation to high myopia and spherical equivalent refractive error, respectively. Structural equation models examined the mediated effect of onset age on the association between parental myopia, time spent on electronics and high myopia. RESULTS: An early age at myopia onset was negatively correlated with spherical equivalent refractive power. Subjects who developed myopia before the age of 12 were more likely to suffer from high myopia than those who developed myopia after the age of 15. Age of myopia onset was the strongest predictor of high myopia, with an area under the curve (AUC) in Receiver Operator Characteristic (ROC) analysis of 0.80. Additionally, age of myopia onset served as a mediator in the relationships between parental myopia, electronic device usage duration, and the onset of high myopia in adulthood. CONCLUSIONS: Age of myopia onset might be the single best predictor for high myopia, and age at onset appeared to mediate the associations of high myopia with parental myopia and time spent on electronics.

7.
J Am Chem Soc ; 146(14): 9801-9810, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38551407

RESUMO

The sequence-controlled assembly of nucleic acids and amino acids into well-defined superstructures constitutes one of the most revolutionary technologies in modern science. The elaboration of such superstructures from carbohydrates, however, remains elusive and largely unexplored on account of their intrinsic constitutional and configurational complexity, not to mention their inherent conformational flexibility. Here, we report the bottom-up assembly of two classes of hierarchical superstructures that are formed from a highly flexible cyclo-oligosaccharide─namely, cyclofructan-6 (CF-6). The formation of coordinative bonds between the oxygen atoms of CF-6 and alkali metal cations (i) locks a myriad of flexible conformations of CF-6 into a few rigid conformations, (ii) bridges adjacent CF-6 ligands, and (iii) gives rise to the multiple-level assembly of three extended frameworks. The hierarchical superstructures present in these frameworks have been shown to modulate their nanomechanical properties. This research highlights the unique opportunities of constructing convoluted superstructures from carbohydrates and should encourage future endeavors in this underinvestigated field of science.


Assuntos
Carboidratos , Metais , Metais/química , Carboidratos/química , Conformação Molecular , Aminoácidos
8.
Adv Sci (Weinh) ; : e2401254, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483920

RESUMO

Pancreatic fibrosis (PF) is primarily characterized by aberrant production and degradation modes of extracellular matrix (ECM) components, resulting from the activation of pancreatic stellate cells (PSCs) and the pathological cross-linking of ECM mediated by lysyl oxidase (LOX) family members. The excessively deposited ECM increases matrix stiffness, and the over-accumulated reactive oxygen species (ROS) induces oxidative stress, which further stimulates the continuous activation of PSCs and advancing PF; challenging the strategy toward normalizing ECM homeostasis for the regression of PF. Herein, ROS-responsive and Vitamin A (VA) decorated micelles (named LR-SSVA) to reverse the imbalanced ECM homeostasis for ameliorating PF are designed and synthesized. Specifically, LR-SSVA selectively targets PSCs via VA, thereby effectively delivering siLOXL1 and resveratrol (RES) into the pancreas. The ROS-responsive released RES inhibits the overproduction of ECM by eliminating ROS and inactivating PSCs, meanwhile, the decreased expression of LOXL1 ameliorates the cross-linked collagen for easier degradation by collagenase which jointly normalizes ECM homeostasis and alleviates PF. This research shows that LR-SSVA is a safe and efficient ROS-response and PSC-targeted drug-delivery system for ECM normalization, which will propose an innovative and ideal platform for the reversal of PF.

9.
Anal Chim Acta ; 1295: 342306, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38355230

RESUMO

Point-of-care quantitative analysis of tracing microRNA disease-biomarkers remains a great challenge in the clinical diagnosis. In this paper, we developed a portable fluorescent lateral flow assay for ultrasensitive quantified detection of acute myocardial infarction related microRNAs in bio-samples. SiO2@DQD (bilayer quantum dots assembly with SiO2 core) based fluorescent lateral flow strip was fabricated as the analysis tool. In order to quantify the tracing microRNA in biosamples, a catalytic hairpin assembly and CRISPR/Cas12a cascade amplification method was performed and combined with the fabricated SiO2@DQD lateral flow strip. Thus, our platform gathered double advantages of portability and ultrasensitive quantification. Based on our strips, target myocardial biomarker microRNA-133a can be detected with a detection limit of 0.32 fM, which was almost 1000-fold sensitive compared with previous reported microRNAs-lateral flow strips. Significantly, this portable fluorescent strip can directly detect microRNAs in serum without any pretreatment and PCR amplification steps. When spiked in serum samples, a recovery of 99.65 %-102.38 % can be obtained. Therefore, our method offers a potential tool for ultrasensitive quantification of diseases related microRNA in the point-of-care diseases diagnosis field.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Infarto do Miocárdio , Humanos , MicroRNAs/análise , Sistemas Automatizados de Assistência Junto ao Leito , Dióxido de Silício , Corantes , Infarto do Miocárdio/diagnóstico , Técnicas Biossensoriais/métodos
10.
Appl Opt ; 63(2): 437-444, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38227240

RESUMO

Polarization imaging, based on the measurement of polarization parameters containing specific physical information, has found extensive applications across various domains. Among these parameters, polarization angle information plays a crucial role in revealing texture details. However, in practical scenarios, noise during image acquisition can lead to significant degradation of polarization angle information. To address this issue, we introduce a novel, to the best of our knowledge, polarization angle information enhancement method based on polarimetric array imaging. Our proposed method utilizes the principles of polarimetric array imaging to effectively restore texture information embedded within polarization angle images. Through the deployment of a self-designed polarimetric array imaging system, we conducted experiments in diverse scenes to validate the efficacy of our approach. The acquired polarization angle data were subjected to our method for enhancement. The experimental outcomes distinctly illustrate the noise suppression capabilities of our method, showcasing its ability to faithfully reconstruct intricate details obscured by substantial noise interference.

12.
BMC Genomics ; 25(1): 52, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212682

RESUMO

BACKGROUND: Most skin-related traits have been studied in Caucasian genetic backgrounds. A comprehensive study on skin-associated genetic effects on underrepresented populations such as Vietnam is needed to fill the gaps in the field. OBJECTIVES: We aimed to develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole-genome sequencing (WGS) data from the 1000 Genomes Project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). Also, we compared the genetic predispositions of 25 skin-related traits of Vietnamese population to others to acquire population-specific insights regarding skin health. METHODS: Vietnamese cohorts of whole-genome sequencing (WGS) of 1008 healthy individuals for the reference and 96 genotyping samples (which do not have any skin cutaneous issues) by Infinium Asian Screening Array-24 v1.0 BeadChip were employed to predict skin-associated genetic variants of 25 skin-related and micronutrient requirement traits in population analysis and correlation analysis. Simultaneously, we compared the landscape of cutaneous issues of Vietnamese people with other populations by assessing their genetic profiles. RESULTS: The skin-related genetic profile of Vietnamese cohorts was similar at most to East Asian cohorts (JPT: Fst = 0.036, CHB: Fst = 0.031, CHS: Fst = 0.027, CDX: Fst = 0.025) in the population study. In addition, we identified pairs of skin traits at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p = 1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3)). CONCLUSION: This is the first investigation in Vietnam to explore genetic variants of facial skin. These findings could improve inadequate skin-related genetic diversity in the currently published database.


Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Pele , População do Sudeste Asiático , Humanos , Estudo de Associação Genômica Ampla , Fenótipo , Vietnã
13.
Sci Rep ; 14(1): 1757, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38242950

RESUMO

Tree canopies are known to elevate atmospheric inputs of both mercury (Hg) and methylmercury (MeHg). While foliar uptake of gaseous Hg is well documented, little is known regarding the temporal dynamics and origins of MeHg in tree foliage, which represents typically less than 1% of total Hg in foliage. In this work, we examined the foliar total Hg and MeHg content by following the growth of five individual trees of American Beech (Fagus grandifolia) for one growing season (April-November, 2017) in North Carolina, USA. We show that similar to other studies foliar Hg content increased almost linearly over time, with daily accumulation rates ranging from 0.123 to 0.161 ng/g/day. However, not all trees showed linear increases of foliar MeHg content along the growing season; we found that 2 out of 5 trees showed elevated foliar MeHg content at the initial phase of the growing season but their MeHg content declined through early summer. However, foliar MeHg content among all 5 trees showed eventual increases through the end of the growing season, proving that foliage is a net accumulator of MeHg while foliar gain of biomass did not "dilute" MeHg content.


Assuntos
Mercúrio , Compostos de Metilmercúrio , Poluentes Químicos da Água , Árvores , Monitoramento Ambiental , Mercúrio/análise , Biomassa , Poluentes Químicos da Água/análise
14.
Cell Rep Med ; 5(1): 101358, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38183982

RESUMO

Lung adenocarcinoma follows a stepwise progression from pre-invasive to invasive. However, there remains a knowledge gap regarding molecular events from pre-invasive to invasive. Here, we conduct a comprehensive proteogenomic analysis comprising whole-exon sequencing, RNA sequencing, and proteomic and phosphoproteomic profiling on 98 pre-invasive and 99 invasive lung adenocarcinomas. The deletion of chr4q12 contributes to the progression from pre-invasive to invasive adenocarcinoma by downregulating SPATA18, thus suppressing mitophagy and promoting cell invasion. Proteomics reveals diverse enriched pathways in normal lung tissues and pre-invasive and invasive adenocarcinoma. Proteomic analyses identify three proteomic subtypes, which represent different stages of tumor progression. We also illustrate the molecular characterization of four immune clusters, including endothelial cells, B cells, DCs, and immune depression subtype. In conclusion, this comprehensive proteogenomic study characterizes the molecular architecture and hallmarks from pre-invasive to invasive lung adenocarcinoma, guiding the way to a deeper understanding of the tumorigenesis and progression of this disease.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Proteogenômica , Humanos , Neoplasias Pulmonares/patologia , Proteômica , Células Endoteliais/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/genética
15.
bioRxiv ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-37546948

RESUMO

Most human pancreatic ductal adenocarcinoma (PDAC) are not infiltrated with cytotoxic T cells and are highly resistant to immunotherapy. Over 90% of PDAC have oncogenic KRAS mutations, and phosphoinositide 3-kinases (PI3Ks) are direct effectors of KRAS. Our previous study demonstrated that ablation of Pik3ca in KPC (KrasG12D; Trp53R172H; Pdx1-Cre) pancreatic cancer cells induced host T cells to infiltrate and completely eliminate the tumors in a syngeneic orthotopic implantation mouse model. Now, we show that implantation of Pik3ca-/- KPC (named αKO) cancer cells induces clonal expansion of cytotoxic T cells infiltrating the pancreatic tumors. To identify potential molecules that can regulate the activity of these anti-tumor T cells, we conducted an in vivo genome-wide gene-deletion screen using αKO cells implanted in the mouse pancreas. The result shows that deletion of propionyl-CoA carboxylase subunit B gene (Pccb) in αKO cells (named p-αKO) leads to immune evasion, tumor progression and death of host mice. Surprisingly, p-αKO tumors are still infiltrated with clonally expanded CD8+ T cells but they are inactive against tumor cells. However, blockade of PD-L1/PD1 interaction reactivated these clonally expanded T cells infiltrating p-αKO tumors, leading to slower tumor progression and improve survival of host mice. These results indicate that Pccb can modulate the activity of cytotoxic T cells infiltrating some pancreatic cancers and this understanding may lead to improvement in immunotherapy for this difficult-to-treat cancer.

16.
Angew Chem Int Ed Engl ; 63(5): e202317402, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38078790

RESUMO

The pursuit of synthetic receptors with high binding affinities has long been a central focus in supramolecular chemistry, driven by their significant practical relevance in various fields. Despite the numerous synthetic receptors that have been developed, most exhibit binding affinities in the micromolar range or lower. Only a few exceptional receptors achieve binding affinities exceeding 109  M-1 , and their substrate scopes remain rather limited. In this context, we introduce SC[5]A, a conjugated corral-shaped macrocycle functionalized with ten sulfate groups. Owing to its deep one-dimensional confined hydrophobic cavity and multiple sulfate groups, SC[5]A displays an extraordinarily high binding strength of up to 1011  M-1 towards several size-matched, rod-shaped organic dications in water. Besides, its conformation exhibits good adaptability, allowing it to encapsulate a wide range of other guests with diverse molecular sizes, shapes, and functionalities, exhibiting relatively strong affinities (Ka =106 -108  M-1 ). Additionally, we've explored the preliminary application of SC[5]A in alleviating blood coagulation induced by hexadimethrine bromide in vitro and in vivo. Therefore, the combination of ultrahigh binding affinities (towards complementary guests) and adaptive recognition capability (towards a wide range of functional guests) of SC[5]A positions it as exceptionally valuable for numerous practical applications.

17.
Eur J Prev Cardiol ; 31(1): 13-20, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37697428

RESUMO

AIMS: Denture use may potentially increase the risk of cardiometabolic diseases (CMDs), but the casual relevance and strength of the associations are currently unknown. METHODS AND RESULTS: A total of 495 938 participants from the UK Biobank were included in the observational analyses. Linkage disequilibrium score (LDSC) regression and Mendelian randomization analyses were employed to estimate genetic correlation and the associations between the genetic liability for denture use with coronary artery disease, myocardial infarction, heart failure (HF), any stroke (AS), ischaemic stroke, haemorrhagic stroke, type 2 diabetes (T2D), and related clinical risk factors. In observational analysis, denture use was associated with 14-25% higher risks of various CMDs. The LDSC analysis found that denture use showed a positive genetic correlation with CMDs (rg 0.21-0.38). Genetic liability for denture use was associated with an elevated risk of HF [odds ratio: 1.49 (1.20-1.83)] and T2D [1.11 (1.01-1.24)]. By integrating genetic summary data of denture use with the sum of decayed, missing, and filled tooth surfaces (DMFS), a clinical measure of dental caries obtained from an independent source, genetically determined denture use/DMFS was also associated with an elevated risk of AS [1.21 (1.04-1.40)]. Furthermore, genetically predicted denture use/DMFS was significantly associated with established cardiometabolic risk factors, including HDL cholesterol, triglycerides, waist circumference, waist-to-hip ratio, and height. CONCLUSION: Our study supported potential causal associations between the genetic liability for denture use and risks for HF, AS, T2D, and related clinical risk factors. These findings may inform prevention and intervention strategies targeting dental diseases and CMDs.


This study examined the association of denture use with cardiometabolic diseases (CMDs) and related clinical risk factors through Mendelian randomization analyses using data from UK Biobank and published consortia. Genetic liability for denture use was associated with an 11­49% higher risk of heart failure, stroke, and type 2 diabetes.The potential causal relationship between denture use and CMDs was further strengthened by the associations of denture use with HDL cholesterol, triglycerides, waist circumference, waist-to-hip ratio, and height, which are among the major risk factors of CMDs.


Assuntos
Isquemia Encefálica , Cárie Dentária , Diabetes Mellitus Tipo 2 , Acidente Vascular Cerebral , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Análise da Randomização Mendeliana , Cárie Dentária/complicações , Índice de Massa Corporal , Fatores de Risco , Dentaduras/efeitos adversos , Polimorfismo de Nucleotídeo Único
18.
Chem Biol Drug Des ; 103(1): e14366, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37776270

RESUMO

Epigenetic regulation of genes through posttranslational regulation of proteins is a well-explored approach for disease treatment, particularly in cancer chemotherapy. Histone deacetylases have shown significant potential as effective drug targets in therapeutic studies aiming to restore epigenetic normality in oncology. Besides their role in modifying histones, histone deacetylases can also catalyze the deacetylation of various nonhistone proteins and participate in the regulation of multiple biological processes. This paper provides a review of the classification, structure, and functional characteristics of the four classes of human histone deacetylases. The increasing abundance of structural information on HDACs has led to the gradual elucidation of structural differences among subgroups and subtypes. This has provided a reasonable explanation for the selectivity of certain HDAC inhibitors. Currently, the US FDA has approved a total of six HDAC inhibitors for marketing, primarily for the treatment of various hematological tumors and a few solid tumors. These inhibitors all have a common pharmacodynamic moiety consisting of three parts: CAP, ZBG, and Linker. In this paper, the structure-effect relationship of HDAC inhibitors is explored by classifying the six HDAC inhibitors into three main groups: isohydroxamic acids, benzamides, and cyclic peptides, based on the type of inhibitor ZBG. However, there are still many questions that need to be answered in this field. In this paper, the structure-functional characteristics of HDACs and the structural information of the pharmacophore model and enzyme active region of HDAC is are considered, which can help to understand the inhibition mechanism of the compounds as well as the rational design of HDACs. This paper integrates the structural-functional characteristics of HDACs as well as the pharmacophore model of HDAC is and the structural information of the enzymatic active region, which not only contributes to the understanding of the inhibition mechanism of the compounds, but also provides a basis for the rational design of HDAC inhibitors.


Assuntos
Inibidores de Histona Desacetilases , Neoplasias , Humanos , Inibidores de Histona Desacetilases/química , Histona Desacetilases/metabolismo , Epigênese Genética , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Histonas/metabolismo
19.
Small ; 20(8): e2305725, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37828637

RESUMO

From the view of geometry, chirality is that an object cannot overlap with its mirror image, which has been a fundamental scientific problem in biology and chemistry since the 19th century. Chiral inorganic nanomaterials serve as ideal templates for investigating chiral transfer and amplification mechanisms between molecule and bulk materials, garnering widespread attentions. The chiroptical property of chiral plasmonic nanomaterials is enhanced through localized surface plasmon resonance effects, which exhibits distinctive circular dichroism (CD) response across a wide wavelength range. Recently, 3D chiral plasmonic nanomaterials are becoming a focal research point due to their unique characteristics and planar-independence. This review provides an overview of recent progresses in 3D chiral plasmonic nanomaterials studies. It begins by discussing the mechanisms of plasmonic enhancement of molecular CD response, following by a detailed presentation of novel classifications of 3D chiral plasmonic nanomaterials. Finally, the applications of 3D chiral nanomaterials such as biology, sensing, chiral catalysis, photology, and other fields have been discussed and prospected. It is hoped that this review will contribute to the flourishing development of 3D chiral nanomaterials.

20.
J Control Release ; 365: 981-1003, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38123072

RESUMO

Stem cells have garnered significant attention in regenerative medicine owing to their abilities of multi-directional differentiation and self-renewal. Despite these encouraging results, the market for stem cell products yields limited, which is largely due to the challenges faced to the safety and viability of stem cells in vivo. Besides, the fate of cells re-infusion into the body unknown is also a major obstacle to stem cell therapy. Actually, both the functional protection and the fate tracking of stem cells are essential in tissue homeostasis, repair, and regeneration. Recent studies have utilized cell engineering techniques to modify stem cells for enhancing their treatment efficiency or imparting them with novel biological capabilities, in which advances demonstrate the immense potential of engineered cell therapy. In this review, we proposed that the "engineered stem cells" are expected to represent the next generation of stem cell therapies and reviewed recent progress in this area. We also discussed potential applications of engineered stem cells and highlighted the most common challenges that must be addressed. Overall, this review has important guiding significance for the future design of new paradigms of stem cell products to improve their therapeutic efficacy.


Assuntos
Engenharia Celular , Medicina Regenerativa , Medicina Regenerativa/métodos , Transplante de Células-Tronco , Diferenciação Celular
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