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1.
Front Med (Lausanne) ; 11: 1254467, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38695016

RESUMO

Background: Preeclampsia (PE) is a pregnancy complication defined by new onset hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Although non-invasive prenatal testing (NIPT) has been widely used to detect fetal chromosomal abnormalities during pregnancy, its performance in combination with maternal risk factors to screen for PE has not been extensively validated. Our aim was to develop and validate classifiers that predict early- or late-onset PE using the maternal plasma cell-free DNA (cfDNA) profile and clinical risk factors. Methods: We retrospectively collected and analyzed NIPT data of 2,727 pregnant women aged 24-45 years from four hospitals in China, which had previously been used to screen for fetal aneuploidy at 12 + 0 ~ 22 + 6 weeks of gestation. According to the diagnostic criteria for PE and the time of diagnosis (34 weeks of gestation), a total of 143 early-, 580 late-onset PE samples and 2,004 healthy controls were included. The wilcoxon rank sum test was used to identify the cfDNA profile for PE prediction. The Fisher's exact test and Mann-Whitney U-test were used to compare categorical and continuous variables of clinical risk factors between PE samples and healthy controls, respectively. Machine learning methods were performed to develop and validate PE classifiers based on the cfDNA profile and clinical risk factors. Results: By using NIPT data to analyze cfDNA coverages in promoter regions, we found the cfDNA profile, which was differential cfDNA coverages in gene promoter regions between PE and healthy controls, could be used to predict early- and late-onset PE. Maternal age, body mass index, parity, past medical histories and method of conception were significantly differential between PE and healthy pregnant women. With a false positive rate of 10%, the classifiers based on the combination of the cfDNA profile and clinical risk factors predicted early- and late-onset PE in four datasets with an average accuracy of 89 and 80% and an average sensitivity of 63 and 48%, respectively. Conclusion: Incorporating cfDNA profiles in classifiers might reduce performance variations in PE models based only on clinical risk factors, potentially expanding the application of NIPT in PE screening in the future.

2.
Adv Sci (Weinh) ; 11(24): e2309559, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38639394

RESUMO

Idiopathic short stature (ISS) is a common childhood condition with largely unknown underlying causes. Recent research highlights the role of circulating exosomes in the pathogenesis of various disorders, but their connection to ISS remains unexplored. In the experiments, human chondrocytes are cocultured with plasma exosomes from ISS patients, leading to impaired chondrocyte growth and bone formation. Elevated levels of a specific long non-coding RNA (lncRNA), ISSRL, are identified as a distinguishing factor in ISS, boasting high specificity and sensitivity. Silencing ISSRL in ISS plasma exosomes reverses the inhibition of chondrocyte proliferation and bone formation. Conversely, overexpression of ISSRL in chondrocytes impedes their growth and bone formation, revealing its mechanism of action through the miR-877-3p/GZMB axis. Subsequently, exosomes (CT-Exo-siISSRL-oeGH) with precise cartilage-targeting abilities are engineered, loaded with customized siRNA for ISSRL and growth hormone. This innovative approach offers a therapeutic strategy to address ISS by rectifying abnormal non-coding RNA expression in growth plate cartilage and delivering growth hormone with precision to promote bone growth. This research provides valuable insights into ISS diagnosis and treatment, highlighting the potential of engineered exosomes.


Assuntos
Condrócitos , Exossomos , Lâmina de Crescimento , Nanopartículas , RNA Interferente Pequeno , Humanos , Exossomos/metabolismo , Exossomos/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/administração & dosagem , Lâmina de Crescimento/metabolismo , Condrócitos/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Transtornos do Crescimento/genética , Transtornos do Crescimento/metabolismo , Transtornos do Crescimento/tratamento farmacológico , Criança , Feminino , Masculino
3.
Talanta ; 273: 125836, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38458080

RESUMO

Herein, a highly novel and effective electrochemiluminescence (ECL) sensor based on metal-organic framework (MOF, HKUST-1) derived CuO nanoneedles (HKUST-1 derived CuO NNs), gold nanoparticles (AuNPs) and TiO2 was developed for ultrasensitive detection of catechol and luteolin. The HKUST-1 derived CuO NNs were employed as luminophore for the first time, which were successfully fabricated by using HKUST-1 as precursor. The results revealed that the HKUST-1 derived CuO NNs exhibit excellent ECL activity ascribed to its abundant active site and the high specific surface area, thus obviously promoting the separation and transfer of charge and further improving the current density of ECL sensor. To binary-amplify the signal of the ECL sensor, the AuNPs and TiO2 nano-materials with good biocompatibility, great electron transport efficiency and high catalytic activity were used as co-reaction accelerators in the ECL process. Dependent on the above brilliant strategy, the proposed ECL sensor achieved wide linear ranges from 3 × 10-9 - 1 × 10-4 M for catechol and 1 × 10-8 - 2 × 10-4 M for luteolin, with the detection limits of 1.5 × 10-9 M for catechol and 5.3 × 10-9 M for luteolin, respectively. Furthermore, the ECL sensor exhibited outstanding selectivity, repeatability, stability and obtained great feedback on determination of catechol and luteolin in actual samples. The method not only filled a gap in the ECL application of MOF-derived materials but also provided a novel sight for design other highly efficient luminescent materials.

4.
Int J Psychophysiol ; 195: 112276, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38056632

RESUMO

Hyperarousal, recognized as a fundamental characteristic of insomnia for decades, has yielded limited evidence concerning its direct psychological associations. This study aimed to explore the psychological factors linked to hyperarousal within the framework of interrelated variables. Two independent samples, comprising n = 917 and n = 652 young adults, were included in the study. Employing the first dataset as a discovery sample and the second dataset as a replication sample, network analyses were conducted using 26 variables derived from 17 scales. The objective was to estimate the direct and indirect associations between psychological issues, including hyperarousal and insomnia. Additionally, linear regression analysis was employed to assess the convergence of findings obtained from the network analysis. Network analyses in both samples converged to reveal direct associations between insomnia severity and several psychological factors, including negative sleep beliefs, physical fatigue, insomnia response to stress, hyperarousal, self-reported depression, and mental fatigue. Notably, the nodes with relative importance within the network include trait anxiety, depressive rumination, hyperarousal, perfectionism sub-dimension of concern over mistakes, and private self-consciousness. Hyperarousal is one of the key factors linking insomnia with a variety of psychological issues, including emotion-related factors (rumination, perveived stress), sleep-related factors (dysfunctional sleep beliefs and attitudes, insomnia response to stress, fatigue, chronotype), and self-related factors (self-consciousness, perfectionism). The results suggest that forthcoming strategies for enhancing the treatment efficacy of insomnia could consider supplementary interventions that specifically address hyperarousal, other factors directly linked to insomnia, or the hub nodes within the network.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Adulto Jovem , Humanos , Nível de Alerta/fisiologia , Emoções/fisiologia , Sono/fisiologia , Ansiedade
5.
Cardiovasc Diabetol ; 22(1): 352, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38124109

RESUMO

BACKGROUND AND AIMS: Primary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD). METHODS: We included 39,713 patients with diabetes and 419,312 participants without diabetes from UK Biobank. We derived a polygenic risk score (PRS) for PA based on previous genome-wide association studies (GWAS). Outcomes included LEAD and LEAD related gangrene or amputation. We conducted a two-sample Mendelian randomization analysis for PA and outcomes to explore their potential causal relationship. RESULTS: In whole population, individuals with a higher PA PRS had an increased risk of LEAD. Among patients with diabetes, compared to the subjects in the first tertile of PA PRS, subjects in the third tertile showed a 1.24-fold higher risk of LEAD (OR 1.24, 95% CI 1.03-1.49) and a 2.09-fold higher risk of gangrene (OR 2.09, 95% CI 1.27-3.44), and 1.72-fold higher risk of amputation (OR 1.72, 95% CI 1.10-2.67). Among subjects without diabetes, there was no significant association between PA PRS and LEAD, gangrene or amputation. Two-sample Mendelian randomization analysis indicated that genetically predictors of PA was significantly associated with higher risks of LEAD and gangrene (inverse variance weighted OR 1.20 [95% CI 1.08-1.34]) for LEAD, 1.48 [95% CI 1.28-1.70] for gangrene), with no evidence of significant heterogeneity or directional pleiotropy. CONCLUSIONS: Primary aldosteronism is genetically and causally associated with higher risks of LEAD and gangrene, especially among patients with diabetes. Targeting on the autonomous aldosterone secretion may prevent LEAD progression.


Assuntos
Diabetes Mellitus , Hiperaldosteronismo , Doenças Vasculares , Humanos , Gangrena , Aldosterona , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Estratificação de Risco Genético , Extremidade Inferior , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/epidemiologia , Hiperaldosteronismo/genética , Polimorfismo de Nucleotídeo Único
6.
Sci Rep ; 13(1): 16970, 2023 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-37806983

RESUMO

Accurate assessment of infection presence risk level, timely diagnosis, and effective control are critical for decreasing mortality of Acute­on­chronic liver failure (ACLF). We aimed to develop and validate a novel diagnostic model to accurately assess infection presence risk level in ACLF patients. 185 ACLF patients with/without infection were enrolled, and their demographic, physical findings, immune-inflammatory, hepatic function, metabolism, and coagulation-fibrinolysis indicators were analyzed. Regression analysis was performed to identify the independent diagnostic parameters, which were further used to establish diagnostic models with a nomogram for visual. An area under receiver operating characteristic curve (AUROC), calibration plots, clinical impact curves, decision curve analysis, and net reclassification index were used to evaluate and identify the best model. An external validating cohort was introduced to verify the diagnostic accuracy. We screened out white blood cell (WBC) count, LYM%, blood urea nitrogen (BUN), and D-dimer for assessing infection presence risk levels in ACLF patients. WBD (WBC + BUN + D-dimer) was established and proposed as a novel diagnostic model for infection presence risk levels assessment in ACLF patients with an AUROC of 0.803 (95%CI 0.723-0.883), 0.885 (95%CI 0.786-0.984) in training and external cohorts, respectively. In stratification analysis by ACLF etiology and stages, WBD achieved an AUROC of 0.791 (95%CI 0.691-0.891) and 0.873 (95%CI 0.78-0.966) in HBV-related and early-stage patients, respectively. Whereas a higher AUROC of 0.905 (95%CI 0.807-1.00) in the early-stage of HBV-related ACLF patients indicated its optimum application scope. WBD, a novel laboratory-based nomogram, can serve as a decision-making support tool for clinicians to assess infection presence risk levels in ACLF patients.


Assuntos
Insuficiência Hepática Crônica Agudizada , Nomogramas , Humanos , Insuficiência Hepática Crônica Agudizada/diagnóstico , Prognóstico , Nitrogênio da Ureia Sanguínea , Curva ROC , Estudos Retrospectivos
7.
Front Immunol ; 14: 1260663, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841264

RESUMO

Multiple sclerosis (MS) is a prevalent neuroimmunological illness that leads to neurological disability in young adults. Although the etiology of MS is heterogeneous, it is well established that aberrant activity of adaptive and innate immune cells plays a crucial role in its pathogenesis. Several immune cell abnormalities have been described in MS and its animal models, including T lymphocytes, B lymphocytes, dendritic cells, neutrophils, microglia/macrophages, and astrocytes, among others. Physical exercise offers a valuable alternative or adjunctive disease-modifying therapy for MS. A growing body of evidence indicates that exercise may reduce the autoimmune responses triggered by immune cells in MS. This is partially accomplished by restricting the infiltration of peripheral immune cells into the central nervous system (CNS) parenchyma, curbing hyperactivation of immune cells, and facilitating a transition in the balance of immune cells from a pro-inflammatory to an anti-inflammatory state. This review provides a succinct overview of the correlation between physical exercise, immune cells, and MS pathology, and highlights the potential benefits of exercise as a strategy for the prevention and treatment of MS.


Assuntos
Esclerose Múltipla , Animais , Sistema Nervoso Central , Linfócitos T , Macrófagos/patologia , Exercício Físico
8.
Ageing Res Rev ; 90: 102026, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37532007

RESUMO

Since the discovery of the mechanosensitive Piezo1 channel in 2010, there has been a significant amount of research conducted to explore its regulatory role in the physiology and pathology of various organ systems. Recently, a growing body of compelling evidence has emerged linking the activity of the mechanosensitive Piezo1 channel to health and disease of the central nervous system. However, the exact mechanisms underlying these associations remain inadequately comprehended. This review systematically summarizes the current research on the mechanosensitive Piezo1 channel and its implications for central nervous system mechanobiology, retrospects the results demonstrating the regulatory role of the mechanosensitive Piezo1 channel on various cell types within the central nervous system, including neural stem cells, neurons, oligodendrocytes, microglia, astrocytes, and brain endothelial cells. Furthermore, the review discusses the current understanding of the involvement of the Piezo1 channel in central nervous system disorders, such as Alzheimer's disease, multiple sclerosis, glaucoma, stroke, and glioma.


Assuntos
Canais Iônicos , Células-Tronco Neurais , Humanos , Canais Iônicos/metabolismo , Células Endoteliais/metabolismo , Mecanotransdução Celular/fisiologia , Sistema Nervoso Central/metabolismo
9.
Int J Biol Macromol ; 242(Pt 4): 125063, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37245770

RESUMO

Tumor-associated macrophages (TAMs) with an M2-phenotype mediate gemcitabine resistance to cancer by influencing the metabolic enzymes of gemcitabine and releasing competitive deoxycytidine (dC). Our previous studies showed that Danggui Buxue Decoction (DBD), a traditional Chinese medicinal recipe, enhances the anti-tumor activity of gemcitabine in vivo and alleviates gemcitabine-induced myelosuppression. However, the material basis and exact mechanism underlying its enhanced effects remain unclear. In this study, a bioactive polysaccharide consisting of arabinose, mannose, ribose, and glucose was isolated from DBD. In vivo results demonstrated that DBD crude polysaccharide (DBDP) ameliorated gemcitabine-induced immune system disorders. Moreover, DBDP improved the sensitivity of Lewis lung carcinoma-bearing mice to gemcitabine by reshaping the tumor-promoting M2-like macrophages into tumor-inhibiting M1-phenotypes. Furthermore, in vitro results further revealed that DBDP blocked the protective effects of TAMs and M2-macrophages against gemcitabine by inhibiting the excessive secretion of dC and decreasing the high expression of cytidine deaminase. In conclusion, our results demonstrated that DBDP, as the pharmacodynamic material basis of DBD, enhanced the anti-tumor activity of gemcitabine against lung cancer in vitro and in vivo, which was associated with remodeling of the M2-phenotype.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Camundongos , Animais , Gencitabina , Macrófagos Associados a Tumor , Medicamentos de Ervas Chinesas/farmacologia , Polissacarídeos/farmacologia
10.
Sensors (Basel) ; 23(9)2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37177436

RESUMO

Abnormal posture or movement is generally the indicator of musculoskeletal injuries or diseases. Mechanical forces dominate the injury and recovery processes of musculoskeletal tissue. Using kinematic data collected from wearable sensors (notably IMUs) as input, activity recognition and musculoskeletal force (typically represented by ground reaction force, joint force/torque, and muscle activity/force) estimation approaches based on machine learning models have demonstrated their superior accuracy. The purpose of the present study is to summarize recent achievements in the application of IMUs in biomechanics, with an emphasis on activity recognition and mechanical force estimation. The methodology adopted in such applications, including data pre-processing, noise suppression, classification models, force/torque estimation models, and the corresponding application effects, are reviewed. The extent of the applications of IMUs in daily activity assessment, posture assessment, disease diagnosis, rehabilitation, and exoskeleton control strategy development are illustrated and discussed. More importantly, the technical feasibility and application opportunities of musculoskeletal force prediction using IMU-based wearable devices are indicated and highlighted. With the development and application of novel adaptive networks and deep learning models, the accurate estimation of musculoskeletal forces can become a research field worthy of further attention.


Assuntos
Transtornos dos Movimentos , Dispositivos Eletrônicos Vestíveis , Humanos , Fenômenos Biomecânicos , Movimento/fisiologia , Postura
11.
Neurosci Lett ; 805: 137218, 2023 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-37003299

RESUMO

Previous research has suggested that long-term exercise training can influence trusting behaviors, but the supporting evidence is limited. Therefore, exploring inter-athlete trust behaviors and its neural mechanism could better answer the potential association between athletic training and trust behaviors. Accordingly, the present study used a trust game (TG) task to assess interpersonal trust behavior in the sex-specific athlete group and the ordinary college group; and a functional near-infrared spectroscopy (fNIRS) hyperscanning technology was used to capture the interpersonal neural synchronization (INS) in brain regions of interest to the dyads. The results showed that the athlete group had significantly higher trust behaviors and significantly higher INS in the left frontal pole and left dorsolateral prefrontal than the college group; male athletes had significantly higher trust behaviors and significantly higher INS in the left dorsolateral prefrontal than female athletes. This study suggests that athletes have better trusting behaviors and that this advantage may be related to enhanced INS in the left dorsolateral prefrontal lobe.


Assuntos
Atletas , Mapeamento Encefálico , Exercício Físico , Córtex Pré-Frontal , Confiança , Feminino , Humanos , Masculino , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Comportamento Cooperativo , Relações Interpessoais , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Confiança/psicologia , Atletas/psicologia , Exercício Físico/fisiologia , Exercício Físico/psicologia , Fatores Sexuais , Espectroscopia de Luz Próxima ao Infravermelho , Estudantes/psicologia
12.
J Affect Disord ; 325: 386-391, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36634855

RESUMO

BACKGROUND: Depression prevails throughout the world. Young females are more likely to suffer from depression because of lack of sleep. METHODS: We recruited 405 young female participants to assess their subjective sleep duration and self-rating depression. The resting-state magnetic resonance imaging (rs-fMRI) data were collected to identify the brain regions related to sleep duration and depression, and a mediating model was established among sleep duration, depression and functional connectivity (FC) of rs-fMRI. RESULTS: Correlation analysis indicated that subjective sleep duration was negatively associated with self-rating depression in young females (r = -0.22, p < .001). The network connectivity between dorsal attention network (DAN) and default mode network (DMN) positively correlated with self-rating depression (r = 0.13, p < .05), and negatively correlated with subjective sleep duration (r = -0.14, p < .01). Furthermore, the mediation analysis revealed that the FC of DAN-DMN significantly mediated the effect of sleep duration on depression. LIMITATIONS: The study was a cross-section design and the sleep duration of the participants was subjectively reported. Future studies should consider to track the participants longitudinally and to measure the objective sleep duration by actigraph or polysomnography. CONCLUSIONS: The participants with less sleep duration are more prone to develop depression feelings. The FC of DAN-DMN mediated the effect of sleep duration on depression. Thus, the FC of DAN-DMN could be consider as a neural target to relieve depression by increasing sleep duration in young females.


Assuntos
Mapeamento Encefálico , Depressão , Humanos , Feminino , Mapeamento Encefálico/métodos , Depressão/diagnóstico por imagem , Duração do Sono , Encéfalo/diagnóstico por imagem , Sono , Imageamento por Ressonância Magnética/métodos , Vias Neurais/diagnóstico por imagem
13.
Cells ; 11(18)2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36139420

RESUMO

Preservation of human spermatozoa in vitro at normothermia or hypothermia maintaining their functions and fertility for several days plays a significant role in reproductive biology and medicine. However, it is well known that human spermatozoa left in vitro deteriorate over time irreversibly as the consequence of various stresses such as the change of osmolarity, energy deficiency, and oxidative damage, leading to substantial limitations including the need for semen examinations, fertility preservation, and assisted reproductive technology. These problems may be addressed with the aid of non-freezing storage techniques. The main and most effective preservation strategies are the partial or total replacement of seminal plasma with culture medium, named as extenders, and temperature-induced metabolic restriction. Semen extenders consist of buffers, osmolytes, and antioxidants, etc. to protect spermatozoa against the above-mentioned adverse factors. Extended preservation of human spermatozoa in vitro has a negative effect on sperm parameters, whereas its effect on ART outcomes remains inconsistent. The storage duration, temperature, and pre-treatment of semen should be determined according to the aims of preservation. Advanced techniques such as nanotechnology and omics have been introduced and show great potential in the lifespan extension of human sperm. It is certain that more patients will benefit from it in the near future. This review provided an overview of the current knowledge and prospects of prolonged non-freezing storage of human sperm in vitro.


Assuntos
Preservação do Sêmen , Fertilidade , Humanos , Masculino , Sêmen , Análise do Sêmen , Preservação do Sêmen/métodos , Espermatozoides
14.
J Sci Food Agric ; 102(15): 6984-6991, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35679427

RESUMO

BACKGROUND: Aluminum (Al) toxicity caused by soil acidification is the main constraint for crop growth in tropical and subtropical areas of southern China. The critical values of soil solution Al3+ activity and pH for crops in acidic soils can provide a useful reference for soil acidity amelioration. RESULTS: A pot experiment in a greenhouse was conducted to investigate the critical values of soil solution Al3+ activity and pH for canola and maize in an Ultisol and an Alfisol. The critical values of soil solution Al3+ activity in Ultisol and Alfisol for canola were 1.5 and 10.0 µmol L-1 , and 13.9 and 30.4 µmol L-1 for maize, respectively. The Al tolerance varied with soil type for the same variety of crop. There was more biomass of roots and shoots and higher plant height under the same Al3+ activity, and thus greater critical values of soil solution Al3+ activity for both crops in Alfisol than those in Ultisol, owing to higher Ca2+ /Al3+ , Mg2+ /Al3+ and K+ /Al3+ ratios in soil solution caused by higher cation exchange capacity and exchangeable base cations in Alfisol, when compared with those in Ultisol. The critical values of soil solution pH for canola and maize in Ultisol were 5.09 and 4.72, respectively; while those in Alfisol were 4.87 and 4.54, respectively. CONCLUSION: The critical values of Al3+ activity were higher for maize than for canola and the critical values for both crops were higher in Alfisol than in Ultisol. The critical soil pH for both crops showed opposite trends to soil Al3+ activity. © 2022 Society of Chemical Industry.


Assuntos
Brassica napus , Poluentes do Solo , Solo , Alumínio/análise , Zea mays , Poluentes do Solo/análise , Ácidos , Produtos Agrícolas , Cátions , Concentração de Íons de Hidrogênio
15.
Front Aging Neurosci ; 14: 869507, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35663578

RESUMO

Alzheimer's disease (AD) is an age-related neurodegenerative disorder, characterized by the accumulation of proteinaceous aggregates and neurofibrillary lesions composed of ß-amyloid (Aß) peptide and hyperphosphorylated microtubule-associated protein tau, respectively. It has long been known that dysregulation of cholinergic and monoaminergic (i.e., dopaminergic, serotoninergic, and noradrenergic) systems is involved in the pathogenesis of AD. Abnormalities in neuronal activity, neurotransmitter signaling input, and receptor function exaggerate Aß deposition and tau hyperphosphorylation. Maintenance of normal neurotransmission is essential to halt AD progression. Most neurotransmitters and neurotransmitter-related drugs modulate the pathology of AD and improve cognitive function through G protein-coupled receptors (GPCRs). Exercise therapies provide an important alternative or adjunctive intervention for AD. Cumulative evidence indicates that exercise can prevent multiple pathological features found in AD and improve cognitive function through delaying the degeneration of cholinergic and monoaminergic neurons; increasing levels of acetylcholine, norepinephrine, serotonin, and dopamine; and modulating the activity of certain neurotransmitter-related GPCRs. Emerging insights into the mechanistic links among exercise, the neurotransmitter system, and AD highlight the potential of this intervention as a therapeutic approach for AD.

16.
FASEB J ; 36(3): e22235, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35199864

RESUMO

Matricellular proteins, a group of extracellular matrix (ECM) proteins, are key regulators of skin repair and their dysregulation impairs wound healing in diabetes. Tubulointerstitial nephritis antigen like 1 (TINAGL1) is a new member of matricellular protein family, and the understanding of its functional role is still relatively limited. In the current study, we detected the expression of TINAGL1 in diabetic skin wound tissues through RT-PCR, ELISA and Western blot analysis, investigated the contribution of TINAGL1 to wound healing through cutaneous administration of recombinant TINAGL1 protein, and characterized its regulation by hyperglycemia through RNA-seq and signal pathway inhibition assay. We showed that TINAGL1 expression has dynamic change and reaching a peak on day-9 after wound during the wound healing process in wild-type (WT) mice. Interestingly, decreased TINAGL1 expression is detected in skin tissues of diabetic patients and mice after wound. Then, we found that high glucose (HG), an important factor that impairs wound healing, reduces the expression of TINAGL1 in fibroblasts through JNK pathway. Notably, the histology analysis, Masson trichrome assay and IHC assay showed that exogenous TINAGL1 promotes wound healing in diabetic mice by accelerating the formation of granulation tissues. Our study provides evidence that TINAGL1 has an essential role in diabetic wound healing, and meanwhile, indicates that manipulation of TINAGL1 might be a possible therapeutic approach.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Lipocalinas/metabolismo , Proteínas de Neoplasias/metabolismo , Cicatrização , Adulto , Animais , Células Cultivadas , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Regulação para Baixo , Feminino , Glucose/metabolismo , Humanos , Lipocalinas/genética , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Células NIH 3T3 , Proteínas de Neoplasias/genética
17.
Zygote ; 30(1): 92-97, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34158133

RESUMO

This study examined the effect of a cryoprotectant with and without pentoxifylline supplementation on the motility and viability of human testicular sperm, both before and after freezing. Testicular samples were obtained from 68 patients with azoospermia who came to the Andrology Service of West China Second University Hospital, Sichuan University, for testicular biopsies from December 2019 to April 2020. All patients were assigned randomly to two groups: experimental, whose testicular sperm were added to the cryoprotectant with pentoxifylline, and the control, whose testicular sperm were added to the cryoprotectant without pentoxifylline. Both groups used the same freezing and thawing methods. Testicular sperm motility in the experimental group was significantly higher than that of the control group, both before and after cryopreservation. The recovery rate of sperm motility in the experimental group was significantly higher than that of the control group. The percentage of samples with motile testicular sperm in the experimental group was significantly higher than that of the control group after thawing. Sperm viability was unchanged between the experimental and control groups, both before and after freezing. Overall, a pentoxifylline-supplemented cryoprotectant can significantly improve the motility of testicular sperm before and after cryopreservation.


Assuntos
Pentoxifilina , Preservação do Sêmen , Criopreservação , Crioprotetores/farmacologia , Suplementos Nutricionais , Congelamento , Humanos , Masculino , Pentoxifilina/farmacologia , Motilidade dos Espermatozoides , Espermatozoides
18.
J Sleep Res ; 31(1): e13419, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34131989

RESUMO

As the pace of life accelerates, poor sleep quality has become a common health problem. A wealth of sleep studies based on electroencephalogram (EEG) have found that poor sleep quality has decreased alpha rhythm during night-time sleep. However, whether the EEG rhythm during an afternoon nap has a similar impairment has seldom been investigated. By recruiting 35 subjects for a 90-min nap, we explored the relationship between sleep quality and the alpha rhythm, and the contribution of naps to subjective sleep experience. We found that the power of alpha rhythm in the occipital lobe negatively correlated with sleep quality. However, there was no correlation between the sleep quality at night and the sleep duration of the nap, nor the sleep quality and the proportion of each sleep period of a nap. Our present results indicated that the quality of night-time sleep did not affect the macrostructure of the nap. Interestingly, the negative correlation between the alpha rhythm of a nap and sleep quality at night continuously existed in Wake, N1 sleep, and N2 sleep, and had the most substantial value during N2 sleep of a nap. This implies that an impaired occipital lobe alpha rhythm is a robust biomarker for poor sleep. The research is of particular significance for developing electrical neural stimulation therapy to improve sleep quality, especially for the stimuli regions for selection and the time windows for implementation.


Assuntos
Ritmo alfa , Qualidade do Sono , Ritmo Circadiano , Eletroencefalografia , Humanos , Polissonografia , Sono , Vigília
19.
Andrologia ; 54(2): e14318, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34787338

RESUMO

Cryopreservation of small quantities of human spermatozoa whilst maintaining adequate post-thawing motility has been found an essential challenge for male fertility preservation. Therefore, the study used an effective, and convenient rapid-freezing method to freeze small amounts of human spermatozoa by adding self-prepared cryoprotectant (SPC) without animal component. In the feasibility experiment, no significant differences in progressive motility, normal sperm morphology, vitality or DNA fragmentation index between the conventional slow freezing and rapid freezing were realised. The present study prospectively analysed the effects of sperm freezing and resuscitation in 175 patients with severe oligozoospermia (sperm concentration <1 × 106 /ml). We observed the 120 severe oligozoospermia specimens had a mean recovery rate of 60.19% ± 10.43% and a mean cryosurvival rate of 68.0% ± 9.17%. In addition, 55 cryptozoospermia specimens were analysed. The small-volume cryopreservation showed advantages. The total sperm recovery, motility recovery and sperm loss rates were 98.48%, 50.17% and 1.52% respectively. In short, the SPC is safe and effective, and can be used to rapidly freeze severe oligozoospermia specimens. That is useful for successful sperm freezing whilst avoiding the risk of azoospermia in the later stages and promoting comprehensive fertility preservation.


Assuntos
Preservação do Sêmen , Animais , Criopreservação , Crioprotetores , Congelamento , Humanos , Masculino , Motilidade dos Espermatozoides , Espermatozoides
20.
Basic Clin Androl ; 31(1): 24, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34525944

RESUMO

BACKGROUND: Sperm cryopreservation, an effective method for preserving male fertility, is very advantageous for men suffering from cancer. Unfortunately, as both physicians and cancer patients are unaware of the possibilities for sperm cryopreservation, the data on evaluation of semen parameters and disposition of cryopreserved samples among Chinese cancer patients are scarce. RESULTS: Male tumours were classified into six major types, germ cell tumours (26 %), haematological neoplasms (28 %), head and neck cancers (19 %), thoracic tumours (4 %), abdominal tumours (10 %), and others (13 %). Haematological neoplasm was the most prevalent cancer among our cohort of patients who opted for sperm banking, followed by germ cell tumours. Patients with germ cell tumours had the lowest pre-thaw and post-thaw seminal sperm concentrations. We separately compared patients with testicular tumours, lymphoma, and leukaemia, and found that leukaemia patients had the lowest pre-thaw sperm concentrations. Most cancer patients (58 %) chose to keep their specimens stored, while 31 % chose to discard the specimens. Over the years, only 13 patients (4 %) returned to use their spermatozoa by assisted reproductive technology. Of the stored samples, patients with germ cell tumours constituted the highest proportion (29.3 %). Moreover, the percentage of haematological neoplasm patients who had no spermatozoa frozen was the highest (46.2 %). CONCLUSIONS: The present data confirm the deleterious impact of various cancers on semen quality. Leukaemia was associated with the worst semen quality and the highest number of semen samples that could not be frozen. We suggest that sperm quality may have decreased even before anti-neoplastic treatment and that sperm banking before treatment should be strongly recommended for cancer patients. A sperm banking programme before gonadotoxic therapy requires close cooperation between assisted reproduction centres and cancer clinics.


RéSUMé: CONTEXTE: Lacryoconservation des spermatozoïdes, méthode efficace pour préserver lafertilité masculine, est très avantageuse pour les hommes atteints de cancer.Malheureusement, comme les médecins et les patients atteints de cancersignorent les possibilités de cryoconservation du sperme, les données surl'évaluation des paramètres spermatiques et le devenir des échantillonscryopréservés parmi les hommes chinois atteints de cancers sont rares. RéSULTATS: Lestumeurs masculines ont été classées en six types principaux, tumeurs germinales(26%), néoplasmes hématologiques (28%), cancers de la tête et du cou (19%),tumeurs thoraciques (4%), les tumeurs abdominales (10%), et les autres (13%).Les néoplasmes hématologiques étaient le cancer le plus répandu parmi notrecohorte de patients qui ont opté pour la mise en banque de leur sperme, suivisdes tumeurs à cellules germinales. Les patients atteints de tumeurs germinalesprésentaient les concentrations de spermatozoïdes pré-congélation etpost-décongélation les plus faibles. Nous avons comparé séparément les patientsatteints de tumeurs testiculaires, de lymphome, et de leucémie, et avonsconstaté que ceux atteins de leucémie présentaient les plus bassesconcentrations de spermatozoïdes pré-congélation. Une majorité de patientsatteints de cancer (58 %) ont choisi de conserver en banque leurs échantillonscongelés, tandis que 31 % ont choisi de jeter leurs échantillons congelés. Aufil des ans, seuls 13 patients (4%) sont revenus pour utiliser leurs spermatozoïdespar Assistance Médicale à la Procréation. Parmi les échantillons mis en banque,ceux des patients atteints de tumeurs germinales constituaient la proportion laplus élevée (29,3 %). Par ailleurs, les patients atteins de cancershématologiques constituaient le pourcentage le plus élevé (46.2%) de patientsqui n'avaient eu aucun spermatozoïde congelé. CONCLUSIONS: Lesdonnées rapportées confirment l'impact délétère des divers cancers sur laqualité du sperme. Les leucémies étaientassociées à la pire qualité du sperme et au plus grand nombre d'échantillons desperme qui ne pouvaient pas être congelés. Nous pensons que la qualité desperme pourrait avoir diminué avant même le traitement antinéoplasique, et quela mise en banque de sperme avant le traitement devrait être fortementrecommandée pour les patients atteints de cancers. Un programme de mise enbanque du sperme avant traitement gonadotoxique nécessite une étroitecoopération entre les centres d'Assistance Médicale à la Procréation et les cliniquesde cancérologie.

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