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1.
Circ J ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631864

RESUMO

BACKGROUND: Foam cell formation is an important step for atherosclerosis (AS) progression. We investigated the mechanism by which the long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) regulates foam cell formation during AS progression.Methods and Results: An in vivo AS model was created by feeding ApoE-/-mice a high-fat diet. Oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages were used as a cellular AS model. Interactions between NEAT1, miR-17-5p, itchy E3 ubiquitin protein ligase (ITCH) and liver kinase B1 (LKB1) were analyzed. NEAT1 and ITCH were highly expressed in clinical samples collected from 10 AS patients and in ox-LDL-treated macrophages, whereas expression of both miR-17-5p and LKB1 was low. ITCH knockdown inhibited ox-LDL-induced lipid accumulation and LDL uptake in macrophages. Mechanistically speakingly, ITCH promoted LDL uptake and lipid accumulation in macrophages by mediating LKB1 ubiquitination degradation. NEAT1 knockdown reduced LDL uptake and lipid accumulation in macrophages and AS progression in vivo. NEAT1 promoted ITCH expression in macrophages by acting as a sponge for miR-17-5p. Inhibition of miR-17-5p facilitated ox-LDL-induced increase in LDL uptake and lipid accumulation in macrophages, which was reversed by NEAT1/ITCH knockdown. CONCLUSIONS: NEAT1 accelerated foam cell formation during AS progression through the miR-17-5p/ITCH/LKB1 axis.

2.
Cell ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38608703

RESUMO

Knudson's "two-hit" paradigm posits that carcinogenesis requires inactivation of both copies of an autosomal tumor suppressor gene. Here, we report that the glycolytic metabolite methylglyoxal (MGO) transiently bypasses Knudson's paradigm by inactivating the breast cancer suppressor protein BRCA2 to elicit a cancer-associated, mutational single-base substitution (SBS) signature in nonmalignant mammary cells or patient-derived organoids. Germline monoallelic BRCA2 mutations predispose to these changes. An analogous SBS signature, again without biallelic BRCA2 inactivation, accompanies MGO accumulation and DNA damage in Kras-driven, Brca2-mutant murine pancreatic cancers and human breast cancers. MGO triggers BRCA2 proteolysis, temporarily disabling BRCA2's tumor suppressive functions in DNA repair and replication, causing functional haploinsufficiency. Intermittent MGO exposure incites episodic SBS mutations without permanent BRCA2 inactivation. Thus, a metabolic mechanism wherein MGO-induced BRCA2 haploinsufficiency transiently bypasses Knudson's two-hit requirement could link glycolysis activation by oncogenes, metabolic disorders, or dietary challenges to mutational signatures implicated in cancer evolution.

3.
Immun Inflamm Dis ; 12(4): e1251, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38607251

RESUMO

BACKGROUND: For a long time, the prevailing viewpoint suggests that shorter telomere contribute to chromosomal instability, which is a shared characteristic of both aging and cancer. The newest research presented that T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to some cancers. However, the relationship between genetically determined telomere length (TL) and immune cells remains unclear. METHODS: The two-sample Mendelian randomization analysis was conducted to elucidate the potential causal relationship. The genetic data of TL and immune cells were obtained from the Genome-Wide Association Study. The inverse variance weighted (IVW) method was used to estimate the effects primarily and another four methods were as a supplement. Sensitivity analysis was used to test the results. RESULTS: The IVW method showed a significant correlation between TL and the percentage of T cells in lymphocytes (odds ratio [OR]: 1.222, 95% confidence interval [CI]: 1.014-1.472, p = .035), indicating that shorter TL significantly increases the risk of low T cell percentage. Further analysis of T cell subsets indicated that shorter TL may primarily lead to a lower percentage of Natural Killer T cells (OR: 1.574, 95% CI: 1.281-1.935, p < .001). Analysis of B cell subsets revealed that shorter TL may be associated with a higher percentage of Naive-mature B cells, and a lower percentage of Memory B cells. And the sensitivity analysis indicated the validity and robustness of our findings. CONCLUSION: In summary, our findings suggest that shorter TL may be associated with a decline in the percentage of T cell, as well as impediments in the differentiation of B cell, consequently leading to the onset of immunosenescence and immunodeficiency. The relevant mechanisms and potential therapeutic avenues still need further investigation.


Assuntos
Estudo de Associação Genômica Ampla , Transtornos do Crescimento , Hipercalcemia , Síndromes de Imunodeficiência , Doenças Metabólicas , Nefrocalcinose , Timo/anormalidades , Humanos , Análise da Randomização Mendeliana , Linfócitos
5.
Exp Ther Med ; 27(5): 229, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38596661

RESUMO

The mechanism by which ubiquitin-specific protease 18 (USP18) (enzyme commission: 3.4.19.12) inhibition in cancer promotes cell pyroptosis via the induction of interferon (IFN)-stimulated genes has been recently demonstrated. It is also known that USP18 influences the epithelial-mesenchymal transition of glioma cells. In the present study, the upregulation of USP18 in glioma was revealed through bulk transcriptome analysis, which was associated with poor prognosis in patients with glioma. Furthermore, USP18 levels affected the response to immunotherapy in patients with glioma. Single-cell transcriptome and enrichment analyses demonstrated that USP18 was associated with type 1 IFN responses in glioma T cells. To demonstrate the effect of USP18 expression levels on glioma cells, USP18 expression was knocked down in U251 and U87MG ATCC cell lines. A subsequent Cell Counting Kit-8 assay revealed that glioma cell viability was significantly decreased 4 days after USP18 knockdown. In addition, the knockdown of USP18 expression significantly inhibited the clonogenicity of U251 and U87MG ATCC cells. In conclusion, the present study demonstrated that knockdown of USP18 expression inhibited the proliferation of glioma cells, which may be mediated by the effect of USP18 on the IFN-I response.

6.
PLoS One ; 19(4): e0298699, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38574042

RESUMO

Sign language recognition presents significant challenges due to the intricate nature of hand gestures and the necessity to capture fine-grained details. In response to these challenges, a novel approach is proposed-Lightweight Attentive VGG16 with Random Forest (LAVRF) model. LAVRF introduces a refined adaptation of the VGG16 model integrated with attention modules, complemented by a Random Forest classifier. By streamlining the VGG16 architecture, the Lightweight Attentive VGG16 effectively manages complexity while incorporating attention mechanisms that dynamically concentrate on pertinent regions within input images, resulting in enhanced representation learning. Leveraging the Random Forest classifier provides notable benefits, including proficient handling of high-dimensional feature representations, reduction of variance and overfitting concerns, and resilience against noisy and incomplete data. Additionally, the model performance is further optimized through hyperparameter optimization, utilizing the Optuna in conjunction with hill climbing, which efficiently explores the hyperparameter space to discover optimal configurations. The proposed LAVRF model demonstrates outstanding accuracy on three datasets, achieving remarkable results of 99.98%, 99.90%, and 100% on the American Sign Language, American Sign Language with Digits, and NUS Hand Posture datasets, respectively.


Assuntos
Algoritmo Florestas Aleatórias , Língua de Sinais , Humanos , Reconhecimento Automatizado de Padrão/métodos , Gestos , Extremidade Superior
7.
Pestic Biochem Physiol ; 199: 105774, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38458681

RESUMO

Aphis gossypii, a globally distributed and economically significant pest of several crops, is known to infest a wide range of host plants. Heat shock proteins (Hsps), acting as molecular chaperones, are essential for the insect's environmental stress responses. The present study investigated the molecular characteristics and expression patterns of AgHsp70, a heat shock protein gene, in Aphis gossypii. Our phylogenetic analysis revealed that AgHsp70 shared high similarity with homologs from other insects, suggesting a conserved function across species. The developmental expression profiles of AgHsp70 in A. gossypii showed that the highest transcript levels were observed in the fourth instar nymphs, while the lowest levels were detected in the third instar nymphs. Heat stress and exposure to four different xenobiotics (2-tridecanone, tannic acid, gossypol, and flupyradifurone (4-[(2,2-difluoroethyl)amino]-2(5H)-furanone)) significantly up-regulated AgHsp70 expression. Knockdown of AgHsp70 using RNAi obviously increased the susceptibility of cotton aphids to 2-tridecanone, gossypol and flupyradifurone. Dual-luciferase reporter assays revealed that gossypol and flupyradifurone significantly enhanced the promoter activity of AgHsp70 at a concentration of 10 mg/L. Furthermore, we identified the transcription factor heat shock factor (HSF) as a regulator of AgHsp70, as silencing AgHSF reduced AgHsp70 expression. Our results shed light on the role of AgHsp70 in xenobiotic adaptation and thermo-tolerance.


Assuntos
4-Butirolactona/análogos & derivados , Afídeos , Gossipol , Cetonas , Polifenóis , Piridinas , Animais , Afídeos/genética , Afídeos/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Gossipol/metabolismo , Filogenia , Xenobióticos/farmacologia , Xenobióticos/metabolismo
8.
Sci Total Environ ; 926: 171984, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38547983

RESUMO

Mesoporous silica nanoparticles (MSNs) are efficient carriers of drugs, and are promising in developing novel pesticide formulations. The cotton aphids Aphis gossypii Glover is a world devastating insect pest. It has evolved high level resistance to various insecticides thus resulted in the application of higher doses of insecticides, which raised environmental risk. In this study, the MSNs based pesticide/antibiotic delivery system was constructed for co-delivery of ampicillin (Amp) and imidacloprid (IMI). The IMI@Amp@MSNs complexes have improved toxicity against cotton aphids, and reduced acute toxicity to zebrafish. From the 16S rDNA sequencing results, Amp@MSNs, prepared by loading ampicillin to the mesoporous of MSNs, greatly disturbed the gut community of cotton aphids. Then, the relative expression of at least 25 cytochrome P450 genes of A. gossypii was significantly suppressed, including CYP6CY19 and CYP6CY22, which were found to be associated with imidacloprid resistance by RNAi. The bioassay results indicated that the synergy ratio of ampicillin to imidacloprid was 1.6, while Amp@MSNs improved the toxicity of imidacloprid by 2.4-fold. In addition, IMI@Amp@MSNs significantly improved the penetration of imidacloprid, and contributed to the amount of imidacloprid delivered to A. gossypii increased 1.4-fold. Thus, through inhibiting the relative expression of cytochrome P450 genes and improving penetration of imidacloprid, the toxicity of IMI@Amp@MSNs was 6.0-fold higher than that of imidacloprid. The greenhouse experiments further demonstrated the enhanced insecticidal activity of IMI@Amp@MSNs to A. gossypii. Meanwhile, the LC50 of IMI@Amp@MSNs to zebrafish was 3.9-fold higher than that of IMI, and the EC50 for malformation was 2.8-fold higher than IMI, respectively, which indicated that the IMI@Amp@MSNs complexes significantly reduced the environmental risk of imidacloprid. These findings encouraged the development of pesticide/antibiotic co-delivery nanoparticles, which would benefit pesticide reduction and environmental safety.


Assuntos
Afídeos , Inseticidas , Nanosferas , Animais , Inseticidas/metabolismo , Peixe-Zebra , Resistência a Inseticidas/genética , Neonicotinoides/metabolismo , Nitrocompostos/toxicidade , Nitrocompostos/metabolismo , Afídeos/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Ampicilina
9.
J Tradit Chin Med ; 44(2): 303-314, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38504536

RESUMO

OBJECTIVE: To investigate the impact of Yemazhui (Herba Eupatorii Lindleyani, HEL) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore its underlying mechanism in vivo. METHODS: The chemical constituents of HEL were analyzed by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry method. Then, HEL was found to suppress LPS-induced ALI in vivo. Six-week-old male Sprague-Dawley rats were randomly divided into 6 groups: control, LPS, Dexamethasone (Dex), HEL low dose 6 g/kg (HEL-L), HEL medium dose 18 g/kg (HEL-M) and HEL high dose 54 g/kg (HEL-H) groups. The model rats were intratracheally injected with 3 mg/kg LPS to establish an ALI model. Leukocyte counts, lung wet/dry weight ratio, as well as myeloperoxidase (MPO) activity were determined followed by the detection with hematoxylin and eosin staining, enzyme linked immunosorbent assay, quantitative real time polymerase chain reaction, western blotting, immunohistochemistry, and immunofluorescence. Besides, to explore the effect of HEL on ALI-mediated intestinal flora, we performed 16s rRNA sequencing analysis of intestinal contents. RESULTS: HEL attenuated LPS-induced inflammation in lung tissue and intestinal flora disturbance. Mechanism study indicated that HEL suppressed the lung coefficient and wet/dry weight ratio of LPS-induced ALI in rats, inhibited leukocytes exudation and MPO activity, and improved the pathological injury of lung tissue. In addition, HEL reduced the expression of tumor necrosis factor-alpha, interleukin-1beta (IL-1ß) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid and serum, and inhibited nuclear displacement of nuclear factor kappa-B p65 (NF-κBp65). And 18 g/kg HEL also reduced the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88, NF-κBp65, phosphorylated inhibitor kappa B alpha (phospho-IκBα), nod-like receptor family pyrin domain-containing 3 protein (NLRP3), IL-1ß, and interleukin-18 (IL-18) in lung tissue, and regulated intestinal flora disturbance. CONCLUSIONS: In summary, our findings revealed that HEL has a protective effect on LPS-induced ALI in rats, and its mechanism may be related to inhibiting TLR4/ NF-κB/NLRP3 signaling pathway and improving intestinal flora disturbance.


Assuntos
Lesão Pulmonar Aguda , Microbioma Gastrointestinal , Ratos , Masculino , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Lipopolissacarídeos/efeitos adversos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Domínio Pirina , RNA Ribossômico 16S , Ratos Sprague-Dawley , Transdução de Sinais , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/genética , Pulmão , Interleucina-6
10.
Int J Mol Sci ; 25(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38542057

RESUMO

This study investigates the impact of SCs consumption by assessing the effects of three novel synthetic cannabinoids (SCs); MDMB-CHMINACA, 5F-ADB-PINACA, and APICA post-drug treatment. SCs are known for their rapid onset (<1 min) and prolonged duration (≥5 h). Therefore, this research aimed to assess behavioral responses and their correlation with endocannabinoids (ECs) accumulation in the hippocampus, and EC's metabolic enzymes alteration at different timeframes (1-3-5-h) following drug administration. Different extents of locomotive disruption and sustained anxiety-like symptoms were observed throughout all-encompassing timeframes of drug administration. Notably, MDMB-CHMINACA induced significant memory impairment at 1 and 3 h. Elevated levels of anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) were detected 1 h post-MDMB-CHMINACA and 5F-ADB-PINACA administration. Reduced mRNA expression levels of fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL) (AEA and 2-AG degrading enzymes, respectively), and brain-derived neurotrophic factor (BDNF) occurred at 1 h, with FAAH levels remaining reduced at 3 h. These findings suggest a connection between increased EC content and decreased BDNF expression following SC exposure. Cognitive disruption, particularly motor coordination decline and progressive loss manifested in a time-dependent manner across all the analyzed SCs. Our study highlights the importance of adopting a temporal framework when assessing the effects of SCs.


Assuntos
Canabinoides , Drogas Ilícitas , Endocanabinoides , Fator Neurotrófico Derivado do Encéfalo/genética , Canabinoides/farmacologia , Canabinoides/metabolismo , Drogas Ilícitas/metabolismo
11.
Diabetologia ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489029

RESUMO

AIMS/HYPOTHESIS: A hallmark chronic complication of type 2 diabetes mellitus is vascular hyperpermeability, which encompasses dysfunction of the cerebrovascular endothelium and the subsequent development of associated cognitive impairment. The present study tested the hypothesis that during type 2 diabetes circulating small extracellular vesicles (sEVs) exhibit phenotypic changes that facilitate pathogenic disruption of the vascular barrier. METHODS: sEVs isolated from the plasma of a mouse model of type 2 diabetes and from diabetic human individuals were characterised for their ability to disrupt the endothelial cell (EC) barrier. The contents of sEVs and their effect on recipient ECs were assessed by proteomics and identified pathways were functionally interrogated with small molecule inhibitors. RESULTS: Using intravital imaging, we found that diabetic mice (Leprdb/db) displayed hyperpermeability of the cerebrovasculature. Enhanced vascular leakiness was recapitulated following i.v. injection of sEVs from diabetic mice into non-diabetic recipient mice. Characterisation of circulating sEV populations from the plasma of diabetic mice and humans demonstrated increased quantity and size of sEVs compared with those isolated from non-diabetic counterparts. Functional experiments revealed that sEVs from diabetic mice or humans induced the rapid and sustained disruption of the EC barrier through enhanced paracellular and transcellular leak but did not induce inflammation. Subsequent sEV proteome and recipient EC phospho-proteome analysis suggested that extracellular vesicles (sEVs) from diabetic mice and humans modulate the MAPK/MAPK kinase (MEK) and Rho-associated protein kinase (ROCK) pathways, cell-cell junctions and actin dynamics. This was confirmed experimentally. Treatment of sEVs with proteinase K or pre-treatment of recipient cells with MEK or ROCK inhibitors reduced the hyperpermeability-inducing effects of circulating sEVs in the diabetic state. CONCLUSIONS/INTERPRETATION: Diabetes is associated with marked increases in the concentration and size of circulating sEVs. The modulation of sEV-associated proteins under diabetic conditions can induce vascular leak through activation of the MEK/ROCK pathway. These data identify a new paradigm by which diabetes can induce hyperpermeability and dysfunction of the cerebrovasculature and may implicate sEVs in the pathogenesis of cognitive decline during type 2 diabetes.

12.
Langmuir ; 40(12): 6463-6470, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38483327

RESUMO

Endowing paper with highly flexible, conductive, and superhydrophobic properties will effectively expand its applications in fields such as green packaging, smart sensing, and paper-based electronics. Herein, a multifunctional superhydrophobic paper is reported in which a highly flexible transparent conductive substrate is prepared by introducing a hydrophobic deep eutectic polymer into the ethylcellulose network via a matrix swelling-polymerization strategy, and then the substrate is modified using fluorinated silica to impart superhydrophobicity. By introducing soft deep eutectic polymers, (1) the superhydrophobic paper can efficiently dissipate energy during deformation, (2) intrinsically ion-conducting deep eutectic polymers can endow the material with good electrical sensing properties, and (3) meanwhile, enhanced interfacial interactions can anchor inorganic particles, thereby improving the coating stability. The prepared superhydrophobic paper has an ultrahigh water contact angle (contact angle ≈ 162.2°) and exhibits a stable electrical response signal to external deformation/pressure, and the electrical properties are almost unaffected by external water molecules. In addition, the superhydrophobic paper was able to withstand 5000 bending-recovery cycles at a large angle of 150°, exhibiting stable electrical performance. The design concepts demonstrated here will provide insights into the development of superhydrophobic paper-based flexible electronic devices.

13.
Can J Cardiol ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38460612

RESUMO

In Canada and worldwide, the elderly population (i.e., individuals >65 years of age) is increasing disproportionately relative to the total population. This is expected to have a substantial impact on the healthcare system, as increased aged is associated with a greater incidence of chronic non-communicable diseases. Within the elderly population cardiovascular disease is a leading cause of death, therefore developing therapies which can prevent or slow disease progression in this demography is highly desirable. Historically aging research has focused on the development of anti-aging therapies which are implemented early in life and slow the age-dependent decline in cell and organ function. However, accumulating evidence supports that late-in-life therapies can also benefit the aged cardiovascular system by limiting the age-dependent functional decline. Moreover, recent studies have also demonstrated that rejuvenation (i.e. reverting cellular function to that of a younger phenotype) of the already aged cardiovascular system is possible, opening new avenues to develop therapies for older individuals. In this review, we first provide an overview of the functional changes that occur in the cardiomyocyte with aging and how this contributes to the age-dependent decline in heart function. We then discuss the various anti-aging/rejuvenation strategies that have been pursued to improve the function of the aged cardiomyocyte, with a focus on therapies implemented late in life. These strategies include 1) established systemic approaches (caloric restriction, exercise), 2) pharmacological approaches (mTOR, AMPK, SIRT1, and autophagy targeting molecules), and 3) emerging rejuvenation approaches (partial reprogramming, parabiosis/modulation of circulating factors, targeting endogenous stem cell populations, and senotherapeutics). Collectively, these studies demonstrate the exciting potential and limitations of current rejuvenation strategies and highlight future areas of investigation which will contribute to the development of rejuvenation therapies for the aged heart.

14.
Int J Biol Macromol ; 264(Pt 2): 130625, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458295

RESUMO

Electrical stimulation modulates cell behavior and influences bacterial activity, so highly conductive, antimicrobial hydrogels are suitable for promoting wound healing. In this study, highly conductive and antimicrobial Ti3C2Tx (MXene) hydrogels composed of chitosan and poly(vinyl alcohol) and AgCu- H2PYDC MOF were developed. In PVACS/MOF/MXene (PCMM) hydrogels, the MXene layer acts as an electrical conductor. The electrical conductivity is 0.61 ± 0.01 S·cm-1. PCMM hydrogels modulate cell behavior and provide ES antimicrobial capacity under ES at 1 V. The metal ions of MOF form coordination with chitosan molecules and increase the cross-linking density between chitosan molecules, thus improving the mechanical properties of the hydrogel (tensile strength 0.088 ± 0.04 MPa, elongation at break 233 ± 11 %). The PCMM gels had good biocompatibility. The PCMM hydrogels achieved 100 % antibacterial activity against E. coli and S. aureus for 12 h. 1 V electrical stimulation of PCMM hydrogel accelerated the wound healing process in mice by promoting cell migration and neovascularization, achieving 97 ± 0.4 % wound healing on day 14. The hydrogel dressing PCMM-0.1 with MOF addition of 0.1 % had the best wound healing promoting effect and which is a promising dressing for promoting wound healing and is a therapeutic strategy worth developing.


Assuntos
Quitosana , Nitritos , Elementos de Transição , Camundongos , Animais , Quitosana/farmacologia , Hidrogéis/farmacologia , Escherichia coli , Staphylococcus aureus , Cicatrização , Antibacterianos/farmacologia
15.
Front Endocrinol (Lausanne) ; 15: 1305713, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323109

RESUMO

Purpose: This study aimed to investigate the associations between hemoglobin (HGB) levels and bone mineral density (BMD) and fracture risk in type 2 diabetes mellitus(T2DM) population of different ages. Method: This cross-sectional study included 641 patients with T2DM (57.9% males). BMD of the femoral neck (FN), total hip (TH), and lumbar spine (LS) were measured using dual-energy X-ray absorptiometry. The 10-year probability of fracture was assessed using a fracture risk assessment tool (FRAX). HGB and other biochemical indices were measured in a certified laboratory at our hospital. Statistical analysis was performed using SPSS 26.0 and R language (R version 4.1.0). Generalized additive models (GAMs) were used to identify the associations between HGB and BMD and fracture risk. Results: Patients with osteoporosis have lower HGB levels than the non-osteoporotic population and lower FN BMD in patients with anemia than in the non-anemic population. In patients with T2DM, there was sex- and age-related variability in the correlation between HGB levels and BMDs and fracture risk. In older men, HGB level was an independent determinant of BMD and was positively correlated with FN and TH BMD. In non-older women, HGB level was an independent determinant of BMD and fracture risk, positively associated with BMDs and negatively associated with 10-year probability of fracture risk. GAMs revealed a positive linear association between HGB level and BMDs in non-older female patients but not in older male patients. Conclusion: Our study provides a new perspective on the association of HGB level and BMDs with fracture risk. Relatively high HGB levels are a protective factor for bone quality in patients with T2DM. However, the bone-protective effect of HGB is influenced by age and sex and persists only in older men and non-older women with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Fraturas por Osteoporose , Humanos , Feminino , Masculino , Idoso , Diabetes Mellitus Tipo 2/complicações , Fraturas por Osteoporose/epidemiologia , Estudos Transversais , Densidade Óssea , Hemoglobinas , Colo do Fêmur , Probabilidade
16.
Epilepsy Behav ; 152: 109667, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301456

RESUMO

PURPOSE: It has become evident that patients with epilepsy require strong self-efficacy support in various domains, including work, social interaction, and academic performance, to ensure their complete social functioning. Nevertheless, previous studies have predominantly assessed the self-efficacy of individuals with epilepsy from a singular perspective of disease management. This study aimed to develop the Multidimensional Self-Efficacy Scale for Epilepsy (MSESE) to assess multiple dimensions and establish its psychometric properties. METHODS: We compiled a total of 25 questions for the initial version of the questionnaire based on a review of the literature and insights from experts, patients, and family members. The study included 180 adult patients with epilepsy who met the research criteria, with 126 of them serving as pre-test samples. All participants completed the MSESE, Brief Symptom Rating Scale-50 (BSRS-50), Rosenberg Self-Esteem Scale-Chinese version (RSES-C), and General Self-Efficacy Scale (GSES). RESULTS: The final scale consisted of 12 items across four dimensions, with item factor loadings ranging from .51 to .90. Most of the fit indices indicated a good fit. Construct validity was established through significant correlations with the BSRS-50, RSES-C, and GSES (r = -0.51 to 0.69, p < 0.01). Internal consistency coefficients for the MSESE were strong at .90, with individual dimensions ranging from 0.71 to 0.89. The MSESE also demonstrated a satisfactory test-retest reliability of 0.72. CONCLUSIONS: The MSESE is a convenient, multidimensional, and easy-to-use scale with good psychometric properties, making it suitable for both clinical assessments and research purposes.


Assuntos
Epilepsia , Autoeficácia , Adulto , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
17.
Nat Commun ; 15(1): 1472, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368437

RESUMO

Understanding how plants alter their development and architecture in response to ambient temperature is crucial for breeding resilient crops. Here, we identify the quantitative trait locus qMULTIPLE INFLORESCENCE BRANCH 2 (qMIB2), which modulates inflorescence branching in response to high ambient temperature in tomato (Solanum lycopersicum). The non-functional mib2 allele may have been selected in large-fruited varieties to ensure larger and more uniform fruits under varying temperatures. MIB2 gene encodes a homolog of the Arabidopsis thaliana transcription factor SPATULA; its expression is induced in meristems at high temperature. MIB2 directly binds to the promoter of its downstream gene CONSTANS-Like1 (SlCOL1) by recognizing the conserved G-box motif to activate SlCOL1 expression in reproductive meristems. Overexpressing SlCOL1 rescue the reduced inflorescence branching of mib2, suggesting how the MIB2-SlCOL1 module helps tomato inflorescences adapt to high temperature. Our findings reveal the molecular mechanism underlying inflorescence thermomorphogenesis and provide a target for breeding climate-resilient crops.


Assuntos
Arabidopsis , Solanum lycopersicum , Inflorescência , Solanum lycopersicum/genética , 60485 , Melhoramento Vegetal , Meristema/metabolismo , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
18.
Front Mol Neurosci ; 17: 1342371, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38410694

RESUMO

Purpose: The TRAK1 gene is mapped to chromosome 3p22.1 and encodes trafficking protein kinesin binding 1. The aim of this study was to investigate the genotype-phenotype of TRAK1-associated epilepsy. Methods: Trio-based whole-exome sequencing was performed on a cohort of 98 patients with epilepsy of unknown etiologies. Protein modeling and the VarCards database were used to predict the damaging effects of the variants. Detailed neurological phenotypes of all patients with epilepsy having TRAK1 variants were analyzed to assess the genotype-phenotype correlations. Results: A novel TRAK1 compound heterozygous variant comprising variant c.835C > T, p.Arg279Cys and variant c.2560A > C, p.Lys854Gln was identified in one pediatric patient. Protein modeling and VarCards database analyses revealed that the variants were damaging. The patient received a diagnosis of early infantile epileptic spasms with a developmental disorder; he became seizure-free through valproate and adrenocorticotropic hormone treatment. Further results for six variants in 12 patients with epilepsy indicated that biallelic TRAK1 variants (including homozygous or compound heterozygous variants) were associated with epilepsy with developmental disorders. Among these patients, eight (67%) had epileptic spasms and seven (58%) were intractable to anti-seizure medicines. Moreover, eight patients experienced refractory status epilepticus, of which seven (88%) died in early life. To our knowledge, this is the first reported case of epilepsy caused by TRAK1 compound heterozygous variants. Conclusion: Biallelic TRAK1 variants can cause epilepsy and developmental disorders. In these patients, seizures progress to status epilepticus, suggesting a high risk for poor outcomes and the requirement of early treatment.

19.
Food Chem ; 445: 138648, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38354639

RESUMO

This research investigates the formation of amyloid fibrils using enzymatically hydrolyzed peptides from gluten, including its components glutenin and gliadin. After completing the fibrillation incubation, the gluten group demonstrated the most significant average particle size (908.67 nm) and conversion ratio (57.64 %), with a 19.21 % increase in thioflavin T fluorescence intensity due to self-assembly. The results indicated increased levels of ß-sheet structures after fibrillation. The gliadin group exhibited the highest zeta potential (∼13 mV) and surface hydrophobicity (H0 = 809.70). Around 71.15 % of predicted amyloidogenic regions within gliadin peptides showed heightened hydrophobicity. These findings emphasize the collaborative influence of both glutenin and gliadin in the formation of gluten fibrils, influenced by hydrogen bonding, hydrophobic, and electrostatic interactions. They also highlight the crucial role played by gliadin with amyloidogenic fragments such as ILQQIL and SLVLQTL, aiming to provide a theoretical basis for understanding the utilization of gluten proteins.


Assuntos
Amiloide , Gliadina , Amiloide/metabolismo , Gliadina/química , Peptídeos/química , Glutens/química , Conformação Proteica em Folha beta , Fragmentos de Peptídeos/química
20.
Adv Healthc Mater ; 13(10): e2304207, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38175149

RESUMO

Myocardial infarction (MI) results in cardiomyocyte necrosis and conductive system damage, leading to sudden cardiac death and heart failure. Studies have shown that conductive biomaterials can restore cardiac conduction, but cannot facilitate tissue regeneration. This study aims to add regenerative capabilities to the conductive biomaterial by incorporating human endometrial mesenchymal stem cell (hEMSC)-derived exosomes (hEMSC-Exo) into poly-pyrrole-chitosan (PPY-CHI), to yield an injectable hydrogel that can effectively treat MI. In vitro, PPY-CHI/hEMSC-Exo, compared to untreated controls, PPY-CHI, or hEMSC-Exo alone, alleviates H2O2-induced apoptosis and promotes tubule formation, while in vivo, PPY-CHI/hEMSC-Exo improves post-MI cardiac functioning, along with counteracting against ventricular remodeling and fibrosis. All these activities are facilitated via increased epidermal growth factor (EGF)/phosphoinositide 3-kinase (PI3K)/AKT signaling. Furthermore, the conductive properties of PPY-CHI/hEMSC-Exo are able to resynchronize cardiac electrical transmission to alleviate arrythmia. Overall, PPY-CHI/hEMSC-Exo synergistically combines the cardiac regenerative capabilities of hEMSC-Exo with the conductive properties of PPY-CHI to improve cardiac functioning, via promoting angiogenesis and inhibiting apoptosis, as well as resynchronizing electrical conduction, to ultimately enable more effective MI treatment. Therefore, incorporating exosomes into a conductive hydrogel provides dual benefits in terms of maintaining conductivity, along with facilitating long-term exosome release and sustained application of their beneficial effects.


Assuntos
Quitosana , Exossomos , Células-Tronco Mesenquimais , Infarto do Miocárdio , Humanos , Polímeros/metabolismo , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Pirróis , Exossomos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Preparações de Ação Retardada/farmacologia , Peróxido de Hidrogênio/metabolismo , Infarto do Miocárdio/terapia , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/metabolismo , Miócitos Cardíacos/metabolismo
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