Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 729
Filtrar
1.
Biotechnol J ; : e2200470, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36683552

RESUMO

Bone morphogenetic protein-2 (BMP-2) and transforming growth factor-ß1 (TGF-ß1) reportedly induce the osteogenic and tenogenic differentiation of anterior cruciate ligament (ACL)-derived stem cells (LDSCs), respectively. However, few studies have investigated the effect of BMP-2/TGF-ß1 on the differentiation of LDSC. We developed a BMP-2/TGF-ß1 gene insertion into an LDSC cell sheet that promotes tendon-bone healing in a mouse ACL reconstruction (ACLR) model.. CD34+ LDSCs were isolated from human ACL stump tissues, virally transduced to express BMP-2 or TGF-ß1, and then embedded within cell sheets. All mice underwent ACLR using an autograft wrapped with a cell sheet and were randomly divided into 3 groups: BMP-2-, TGF-ß1-, and BMP-2/TGF-ß1-transduced. At 4 and 8 weeks, tendon-bone healing was evaluated by micro-CT, biomechanical test, and histological analysis. BMP-2 and TGF-ß1 promoted the osteogenic and tenogenic differentiation of LDSC in vitro. BMP-2/TGF-ß1-transduced LDSC sheet application contributed to early improvement in mean failure load and graft stiffness, accelerated maturation of the tendon-bone junction, and inhibited bone tunnel widening. Furthermore, reduced M1 macrophage infiltration and a higher M2 macrophage percentage were observed in the BMP-2/TGF-ß1-transduced LDSC group. This work demonstrated that BMP-2 and TGF-ß1 promoted CD34+ LDSCs osteogenic and tenogenic differentiation in vitro and in vivo, which accelerated the tendon-bone healing after ACLR using autografts wrapped with cell sheets in a mouse model. This article is protected by copyright. All rights reserved.

2.
Clin Chim Acta ; 540: 117224, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36627008

RESUMO

The rapid development of next-generation sequencing (NGS) technology has promoted its wide clinical application in precision medicine for oncology. However, laborious and time-consuming manual operations, highly skilled personnel requirements, and cross-contamination are major challenges for the clinical implementation of NGS technology-based tests. The Automated NGS Diagnostic Solutions (ANDiS) 500 system is a fully enclosed cassette-dependent automated NGS library preparation system. This platform could produce qualified targeted amplicon library in three steps with only 15 min of hands-on time. Rigorous cross-contamination test using simulated contaminant plasmids confirmed that the design of disposable cassette guarantees zero sample cross-contamination. The BRCA1 and BRCA2 mutation detection panel and gastrointestinal cancer-related gene analysis panel for the ANDiS 500 platform showed 100% accuracy and precision in detecting germ-line mutations and somatic mutations respectively. Furthermore, those panels showed 100% concordance with verified methods in a prospective cohort study enrolling 363 patients and a cohort of 45 pan-cancer samples. In conclusion, the ANDiS 500 automated platform could overcome major challenges for implementing NGS assays clinically and is eligible for routine clinical tests.

3.
Mini Rev Med Chem ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650648

RESUMO

Cancer is still one of the most serious diseases that threaten human life. In the past decades, nanomaterials have been found to possess excellent advantages, including controlled drug release, easy modification surface, good biocompatibility, typical optical property, useful chemical ability, and so on, due to which they have become the rising star in the application for multimodal combined cancer treatment (MCT). The emerging avenues of photodynamic therapy, photothermal therapy, magnetocaloric therapy, chemodynamic therapy, immunotherapy, and gene therapy are integrated systematically and intelligently with the traditional methods, realizing the therapeutic effect in cancer treatment. However, there are still several challenges in the development of nanomaterials for MCT, such as the construction of complex systems, deep penetration into solid tumors, effective immune activation at tumor sites, and so on. This review describes the application of multifunctional nanomaterials in the field of MCT for tumor, proposing some suggestions and ideas for future development.

5.
J Agric Food Chem ; 71(1): 143-173, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36545763

RESUMO

Plantago asiatica L. has been used as a vegetable and nutritious food in Asia for thousands of years. According to recent phytochemical and pharmacological research, the active compositions of the plant contribute to various health benefits, such as antioxidant, anti-inflammatory, antibacterial, antiviral, and anticancer. This article reviews the 87 components of the plant and their structures, as well as their biological activities and molecular research progress, in detail. This review provides valuable reference material for further study, production, and application of P. asiatica, as well as its components in functional foods and therapeutic agents.


Assuntos
Plantago , Plantago/química , Antivirais/farmacologia , Anti-Inflamatórios/farmacologia , Compostos Fitoquímicos/farmacologia , Ásia , Extratos Vegetais/farmacologia
6.
Biomed Pharmacother ; 158: 114122, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36566522

RESUMO

Postmenopausal osteoporosis (PMOP) is a common bone disease characterized by decreased bone density and increased bone fragility due to decreased estrogen levels. Qiangguyin (QGY) is transformed from the famous traditional Chinese medicine BuShen Invigorating Blood Decoction. In this study, we used QGY to treat PMOP. We observed that QGY significantly reduced fat accumulation in the chondro-osseous junction. However, its specific mechanism of action remains unclear. To determine the specific molecular mechanism of QGY, we explored the pharmacological mechanism by which QGY reduces fat accumulation in the chondro-osseous junction through network pharmacological analysis. The active components and targets related to PMOP and QGY were screened from different databases, forming a composition-target-disease network. Next, a comprehensive analysis platform including protein-protein interaction (PPI) network, Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were established. The results revealed that QGY inhibits adipogenic differentiation by activating the mitogen-activated protein kinase (MAPK) signaling pathway, thus reducing the accumulation of fat in the chondro-osseous junction. For further verification. In vitro and in vivo experiments were carried out. Our data showed that QGY significantly reversed the high expression of fatty acid binding protein 4 (FABP4) and peroxisome proliferator-activated receptor γ (PPARγ). Further, QGY prevents fat accumulation by inhibiting the expression of p38. In summary, the results of this study suggested that QGY-induced phenotypic changes are related to the activation of the p38 MAPK signaling pathway.


Assuntos
Medicamentos de Ervas Chinesas , Proteína Quinase 14 Ativada por Mitógeno , Camundongos , Animais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Transdução de Sinais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Medicina Tradicional Chinesa
7.
Talanta ; 253: 123970, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36206626

RESUMO

Anti-Müllerian hormone (AMH) is an ideal biomarker for the assessment of ovarian reserve. However, its application in determining ovarian reserve reduction is restricted due to the low sensitivity of existing AMH assays. Herein, a homebrew ultrasensitive digital AMH assay (UD-AMH) was established based on a single-molecule array (SiMoA, HD-X platform), and the analytical performance of UD-AMH was evaluated systematically. The limit of detection (LoD) and limit of quantitation (LoQ) of UD-AMH were 0.13 and 0.14 pg/mL, respectively, which is approximately 100-fold higher than that of the current reported general clinical AMH assay. A comparison study showed a high correlation, with r = 0.988 for the Beckman Access AMH assay and r = 0.945 for the Kangrun AMH assay. In addition, we found that the AMH concentrations of premature ovarian insufficiency (POI) patients were very low (2.59 (0.86, 31.79) pg/mL) and similar to those of perimenopausal women (2.37 (0.65, 35.88) pg/mL) but significantly higher than those of menopausal women (0.43 (0.28, 1.17) pg/mL). Furthermore, we observed that the AMH concentration of most hormone therapy (HT) treated POI patients decreased sharply, suggesting that the ovarian reserve of POI patients declines over time even under HT-treatment.


Assuntos
Reserva Ovariana , Humanos , Feminino , Hormônio Antimülleriano
8.
J Asthma ; : 1-14, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36469748

RESUMO

BACKGROUND: To investigate the relationship between polymorphisms of P2X3, P2X7 genes and environment interaction with susceptibility of childhood asthma. METHODS: We conducted a matched case-control study with 170 cases and 175 healthy controls. The rs10896611, rs2276038, rs3781899 in P2X3 and rs1718119, rs3751143 in P2X7 polymorphisms were genotyped using the technique of an improved multiplex ligation detection reaction. Gene-gene, gene-environment and haplotype-environment interactions were tested using the generalized multi-factor dimensionality reduction method. RESULTS: There were no differences between cases and controls in allele or genotype frequencies of P2X3 and P2X7. The C/C, G/C genotypes of rs10896611, and C/C, C/T genotypes of rs2276038 and G/G, G/A genotypes of rs3781899 were associated with asthmatic cough (p>0.05),. The haplotype GCT of P2X3 reduced the risk of asthma (OR = 0.48, p = 0.048), and the haplotypes AGT (OR = 0.45, p = 0.001) and GCC (OR = 2.16, p = 0.002) were associated with asthmatic cough. The haplotype AA of P2X7 increased risk of asthma severity (p<0.05). The three-locus model indicated a potential haplotype-environment interaction in GCT, ETS, and pet (p = 0.001). CONCLUSIONS: The rs10896611, rs2276038 and rs3781899 of P2X3 minor alleles increased the risk of asthmatic cough. Haplotype GCT of P2X3 was a protective factor for asthma, the haplotype AGT was a protective factor and GCC was a risk factor for asthma with cough. In addition, the interactions of haplotype GCT of P2X3, ETS and pet may increase an individual's susceptibility to asthma.

9.
Colloids Surf B Biointerfaces ; 222: 113099, 2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36584448

RESUMO

Poly(lactide-co-glycolide) (PLGA) is promising carrier material for drugs delivery in cancer therapy. However, the slow degradation and lack of targeting have greatly limited the clinical effectiveness of PLGA-based nanomedicines. Herein, we fabricated a hybrid nanosystem (3 P @ He/Pt-NPs) comprising of acid-sensitive polymer (mPOE-PLGA), active-targeting polymer (PBA-PLGA) and therapeutic agents (hemin+cisplatin) to combat these problems. In neutral environment, PEGylation can effectively improve the blood stability and circulation time of hybrid nanosystem. After reaching tumor regions, this nanosystem efficiently increased cellular uptake by dePEGylation and PBA-mediated active-targeting. Furthermore, encapsulated hemin could catalyze the oxygen bubbles generation, which remarkably increasing the drugs release rate. Subsequently, hybrid particles produced a higher cell-killing effect to lung cancer cells (A549) by the combination therapy (chemotherapy and chemodynamic therapy (CDT)). Importantly, cisplatin further amplified CDT effect by inducing H2O2 regeneration owing to the cascade enzymatic reactions, while hemin decreased intracellular glutathione (GSH) level, resulting in a low detoxification effect to cisplatin. Thus, hybrid particles could efficiently inhibit drug-resistant tumor growth and the inhibition rate reached 83.2%. Overall, this hybrid polymer nanosystem improve the drawbacks of PLGA-based nanocarriers, and can realize a cascading enhanced tumor treatment.

10.
Nanomaterials (Basel) ; 12(24)2022 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-36558276

RESUMO

In recent years, graphene has shown great application prospects in tunable microwave devices due to its tunable conductivity. However, the electromagnetic (EM) properties of graphene, especially the dynamic tunning characteristics, are largely dependent on experimental results, and thus are unable to be effectively predicted according to growth parameters, which causes great difficulties in the design of graphene-based tunable microwave devices. In this work, we systematically explored the impact of chemical vapor deposition (CVD) parameters on the dynamic tunning range of graphene. Firstly, through improving the existing waveguide method, the dynamic tunning range of graphene can be measured more accurately. Secondly, a direct mathematical model between growth parameters and the tunning range of graphene is established. Through this, one can easily obtain needed growth parameters for the desired tunning range of graphene. As a verification, a frequency tunable absorber prototype is designed and tested. The good agreement between simulation and experimental results shows the reliability of our mathematic model in the rapid design of graphene-based tunable microwave devices.

11.
Front Endocrinol (Lausanne) ; 13: 1006480, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36583000

RESUMO

Introduction: Transformation from lung adenocarcinoma (LUAD) to small cell lung cancer (SCLC) is one of the mechanisms responsible for acquired EGFR-TKIs resistance. Although it rarely happens this event determines a rapid disease deterioration and needs specific treatment. Patient and method: We report a case of 75-year-old LUAD female with a p.L858R mutation in Epidermal Growth Factor Receptor (EGFR) who presented with SCLC transformation after responding to first line osimertinib treatment for only 6 months. To understand the underlying molecular mechanism, we retrospectively sequenced the first (LUAD) and the second (SCLC) biopsy using a 56 multi-gene panel. Immunohistochemistry (IHC) staining and Fluorescence In Situ Hybridization (FISH) was applied to confirm the genetic aberrations identified. Results: EGFR p.E709A and p.L858R, Tumor Protein p53 (TP53) p.A159D and Retinoblastoma 1 (RB1) c.365-1G>A were detected in both the diagnostic LUAD and transformed SCLC samples. A high copy number gain for Proto-Oncogene C-Myc (MYC) and a Phosphoinositide 3-Kinase Alpha (PIK3CA) p.E545K mutation were found in the transformed sample specifically. Strong TP53 staining and negative RB1 staining were observed in both LUAD and SCLC samples, but FISH only identified MYC amplification in SCLC tissue. Conclusion: We consider the combined presence of MYC amplification with mutations in TP53 and RB1 as drivers of SCLC transformation. Our results highlight the need to systematically evaluate TP53 and RB1 status in LUAD patients to offer a different therapeutic strategy.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Feminino , Humanos , Carcinoma de Pequenas Células do Pulmão/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteína Supressora de Tumor p53/genética , Estudos Retrospectivos , Hibridização in Situ Fluorescente , Fosfatidilinositol 3-Quinases/genética , Adenocarcinoma de Pulmão/genética , Receptores ErbB/genética , Ubiquitina-Proteína Ligases/genética , Proteínas de Ligação a Retinoblastoma/genética
12.
J Opt Soc Am A Opt Image Sci Vis ; 39(11): 2090-2103, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36520706

RESUMO

The optical radiation force acting on a homogeneous and lossless dielectric spherical particle by a polarized Airy beam is analyzed in terms of the generalized Lorenz-Mie theory. The transverse and longitudinal radiation force components are theoretically evaluated and numerically simulated, emphasizing the transverse scale ω0, attenuation parameter γ, and polarization of the incident Airy beam versus the size parameter ka of the sphere. These results reveal that a polarized Airy beam can trap the dielectric sphere in its main caustic or sidelobes of the beam by the optical transverse force and be guided along the parabolic trajectory of the longitudinal optical force. Moreover, γ and ω0 of the Airy beams and ka of the dielectric sphere can affect the amplitude and distribution of the optical force components. This research may be helpful for the development of Airy optical tweezers in applications involving particle manipulation, optical levitation, particle sorting, and other emergent areas.

13.
Front Genet ; 13: 947317, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36419831

RESUMO

Background: Sepsis is a severe systemic reaction disease induced by bacteria and virus invading the bloodstream and subsequently causing multiple systemic organ dysfunctions. For example, the kidney may stop producing urine, or the lungs may stop taking in oxygen. Recent studies have shown that long non-coding RNAs (lncRNAs) are related to the dysfunction of organs in sepsis. This study aims to screen and validate the sepsis-associated lncRNAs and their functional single nucleotide polymorphisms (SNPs). Result: Unconditional multiple logistic regression based on the recessive model (adjusted odds ratio = 2.026, 95% CI = 1.156-3.551, p = 0.0136) showed that patients with the CC genotype of rs579501 had increased risk of sepsis. Stratification analysis by age and gender indicated that patients with the rs579501 CC genotype had higher risk of sepsis among children aged <12 months (adjusted odds ratio = 2.638, 95% CI = 1.167-5.960, p = 0.0197) and in male patients (adjusted odds ratio = 2.232, 95% CI = 1.127-4.421, p = 0.0213). We also found a significant relationship between rs579501 and severe sepsis risk (CC versus AA/AC: adjusted odds ratio = 2.466, 95% CI = 1.346-4.517, p = 0.0035). Stratification analysis for prognosis and number of organ dysfunctions demonstrated that the rs579501 CC genotype increased non-survivors' risk (adjusted odds ratio = 2.827, 95% CI = 1.159-6.898, p = 0.0224) and one to two organs with dysfunction risk (adjusted odds ratio = 2.253, 95% CI = 1.011-5.926, p = 0.0472). Conclusion: Our findings showed that the lnc-ZNF33B-2:1 rs579501 CC genotype increases the susceptibility to sepsis. From the medical perspective, the lnc-ZNF33B-2:1 rs579501 CC genotype could be serving as a biochemical marker for sepsis.

14.
Exp Hematol Oncol ; 11(1): 98, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371254

RESUMO

Uterine and ovarian cancers are the most common gynecologic cancers. N6-methyladenosine (m6A), an important internal RNA modification in higher eukaryotes, has recently become a hot topic in epigenetic studies. Numerous studies have revealed that the m6A-related regulatory factors regulate the occurrence and metastasis of tumors and drug resistance through various mechanisms. The m6A-related regulatory factors can also be used as therapeutic targets and biomarkers for the early diagnosis of cancers, including gynecologic cancers. This review discusses the role of m6A in gynecologic cancers and summarizes the recent advancements in m6A modification in gynecologic cancers to improve the understanding of the occurrence, diagnosis, treatment, and prognosis of gynecologic cancers.

15.
Infect Drug Resist ; 15: 6441-6450, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36349215

RESUMO

Purpose: To determine the utility of a novel serum biomarker for the outcome prediction of critically ill patients with pneumonia. Patients and Methods: A retrospective analysis of critically ill patients was performed at an emergency department. The expression and prediction value of parameters were assessed. Binary logistic regression analysis was utilized to determine the indicators associated with in-hospital mortality of pneumonia patients. The Last Absolute Shrinkage and Selection Operator was used to further determine the independent predictors, which were validated by multiple logistic regression. The receiver operator characteristic curve was performed to assess their prediction values. A prognostic nomogram model was finally established for the outcome prediction for critically ill patients with pneumonia. Results: Retinol-binding protein (RBP) was significantly reduced in non-survived and pneumonia patients. CURB-65 score, levels of RBP, and blood urea nitrogen (BUN) were associated with in-hospital mortality of critically ill patients with pneumonia. Their combination was determined to be an ideal prognostic predictor (area under the curve of 0.762) and further developed into a nomogram prediction model (c-index 0.764). Conclusion: RBP is a novel in-hospital mortality predictor, which well supplements the CURB-65 score for critical pneumonia patients.

16.
Nanomaterials (Basel) ; 12(21)2022 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-36364500

RESUMO

In the framework of Generalized Lorenz-Mie theory (GLMT), based on the expansion results of electromagnetic field radiation components of Bessel pincer light sheets beam acting on dielectric particles of arbitrary size, the expression of radiation force components in a Cartesian coordinate system is obtained by using the Maxwell stress tensor method. On the one hand, the effects of the refractive index and the equivalent radius of spherical particles on the distribution of radiation force are discussed; On the other hand, the influence of beam scaling parameter and beam order of Bessel pincer light sheets beam on the distribution of radiation force are investigated. The results indicate that the changes of particle's refractive index and effective radius only affect the distribution of radiation force. However, the beam scaling parameter and beam order of Bessel pincer light sheets beam have a very sharp impact on the convergence position, distribution range and bending degree far away from the wave source of the radiation force. Single-beam optical tweezers using the self-focusing and self-bending Bessel pincer light-sheets beam are crucial for applications such as single molecule biophysics, optical manipulation and particle separation/clearing.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36346486

RESUMO

PURPOSE: The status of human epidermal growth factor receptor 2 (HER2) is important for treatment decision-making of breast cancer and was commonly determined by core needle biopsy (CNB). The concordance of CNB with surgical excision biopsy (SEB) has been verified, but remain unclear according to the newly developed classification of HER2 status. Our study aimed to re-evaluate the diagnostic value of CNB for determining HER2 status in breast cancer, especially in the HER2-low population. METHODS: Eligible breast cancer patients in West China Hospital between January 1, 2007 and December 31, 2021 were enrolled consecutively and data were extracted from the Hospital Information System. The agreement of HER2 status between CNB and SEB was calculated by concordance rate and κ statistics, as well as the sensitivity, specificity, positive, and negative predictive values (PPV & NPV). Logistic models were used to explore potential factors associated with the discordance between both tests. RESULTS: Of 1829 eligible patients, 1097 (60.0%) and 1358 (74.2%) were consistent between CNB and SEB by pathological and clinical classifications, respectively, with κ value being 0.46 (0.43-0.49) and 0.57 (0.53-0.60). The sensitivity (50.9%-52.7%) and PPV (50.5%-55.2%) of CNB were especially low among IHC 1+ and 2+/ISH - subgroups by pathological classifications; however, it showed the highest sensitivity (77.5%) and the lowest specificity (73.9%) in HER2-low population by clinical classifications. Advanced N stages might be a stable indicator for the discordance between both tests. CONCLUSION: The diagnostic value of CNB was limited for determining HER2 status in breast cancer, especially in HER2-low population.

18.
Chemosphere ; 311(Pt 2): 137065, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36334755

RESUMO

Phenols and parabens widely exist in personal care and consumer products and have been proved to be endocrine disrupting chemicals that could disturb bone metabolism. The current studies focusing on the associations between phenols and parabens with bone mineral density (BMD) drew contradictory conclusions. Considering the bias might be due to not considering the effects of mixed exposure, we conducted the first cross-sectional study to investigate the associations of both single and mixed metabolites of phenols and parabens with BMD in three populations by setting up four models: generalized linear regression model (GLM), weighted quantile sum (WQS) regression model, quantile g-computation (qgcomp) model and Bayesian kernel machine regression (BKMR) model, based on the US National Health and Nutrition Examination Survey (NHANES) database. We found that the association between the mixtures and total femur BMD in men was significantly negative. Bisphenol A (BPA) was shown to play the most important role in this negative association in the BKMR model, and this negative association was also confirmed in the GLM model with ß coefficient (95% CI) being -0.02 (-0.04, -0.01). The relationships between the mixtures and femoral neck and trochanter BMD in postmenopausal women were significantly positive. Benzophenone-3 (BP-3) played the most significant role in the positive association with trochanter BMD, as confirmed by the WQS, qgcomp and BKMR models, and this positive association was also verified by the GLM model with ß coefficient (95% CI) being 0.01 (0.00, 0.02). In conclusion, the association between the mixed phenols and parabens and BMD was negative in men while was positive in postmenopausal women, which was gender-specific. This study might provide new ideas for the prevention and treatment of osteoporosis and the control of personal care and consumer products containing phenols and parabens in the future.

19.
Artigo em Inglês | MEDLINE | ID: mdl-36450965

RESUMO

Aldehydes as an environmental pollutant may lead to oxidative stress, which is an important mechanism in the development of osteoporosis. This suggests a possible link between aldehyde exposure and osteoporosis. Considering the mixed nature of aldehyde exposure and the interactions between different aldehydes, we explored for the first time the associations between mixed six aldehydes (benzaldehyde, butyraldehyde, heptanal, hexanal, isovaleraldehyde, and propionaldehyde) and BMD in three populations (men, premenopausal women, and postmenopausal women) by applying four statistical models: quantile g-computation (qgcomp) model, Bayesian kernel machine regression (BKMR) model, generalized linear regression model (GLM), and generalized additive model (GAM), based on the National Health and Nutrition Examination Survey (NHANES) 2013-2014. We found that mixed aldehydes could significantly reduce BMD in men, with hexanaldehyde and propanaldehyde having the greatest negative qgcomp model and BKMR model weights, also confirmed by GLM. The associations between isopentanaldehyde and propanaldehyde and femoral BMD in men were non-linear and had threshold effects as derived from the BKMR model and GAM. The associations turned positive when the concentrations of isopentanaldehyde and propanaldehyde exceeded their respective inflection points. To conclude, our study might provide new ideas for the prevention and treatment of osteoporosis, and hexanaldehyde and propanaldehyde should be more regulated to prevent osteoporosis.

20.
Front Pharmacol ; 13: 1052177, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36438800

RESUMO

Introduction: Tremendous evidence indicates that N6-methyladenosine (m6A) epigenetic modification and m6A-related enzymes constitute a complex network, which jointly regulates prevailing pathological processes and various signaling pathways in humankind. Currently, the role of the m6A-mediated molecular regulatory network in hepatocellular carcinoma (HCC) remains elusive. Methods: We recruited expression and pathological files of 368 HCC patients from The Cancer Genome Atlas cohort. Four public datasets serve as external authentication sets for nearest template prediction (NTP) validation. The correlation between 35 regulators and their prognostic value was compared. Gene set variation analysis (GSVA) was used to explore the latent mechanism. Four independent algorithms (ssGSEA, xCell, MCP-counter, and TIMER) were used to calculate the ratio of tumor cells and non-tumor cells to evaluate the tumor immune microenvironment. The m6Ascore model was established by principal component analysis (PCA). Prediction of immunotherapy and potential drugs was performed using TIDE and SubMap. Results: A total of 35 m6A regulators were widely associated, most of which were risk factors for HCC patients. The m6A phenotypic-cluster revealed differences in regulator transcriptional level, gene mutation frequency, functional pathways, and immune cell infiltration abundance under distinct m6A patterns. As expected, the m6A gene cluster confirmed the aforementioned results. The m6Ascore model further found that patients in the high-m6Ascore group were associated with lower tumor purity, higher enrichment of immune and stromal cells, upregulation of metabolic pathways, lower expression of m6A regulators, and favorable outcomes. Low-m6Ascore patients were associated with adverse outcomes. Notably, low-m6Ascore patients might be more sensitive to anti-PD-L1 therapy. Conclusion: This study found that a classification model based on the m6A manner could predict HCC prognosis and response to immunotherapy for HCC patients, which might improve prognosis and contribute to clinical individualized decision-making.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...