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1.
Circ Res ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39229723

RESUMO

BACKGROUND: Cardiac hypertrophy and its associated remodeling are among the leading causes of heart failure. Lysine crotonylation is a recently discovered posttranslational modification whose role in cardiac hypertrophy remains largely unknown. NAE1 (NEDD8-activating enzyme E1 regulatory subunit) is mainly involved in the neddylation modification of protein targets. However, the function of crotonylated NAE1 has not been defined. This study aims to elucidate the effects and mechanisms of NAE1 crotonylation on cardiac hypertrophy. METHODS: Crotonylation levels were detected in both human and mouse subjects with cardiac hypertrophy through immunoprecipitation and Western blot assays. TMT-labeled quantitative lysine crotonylome analysis was performed to identify the crotonylated proteins in a mouse cardiac hypertrophic model induced by transverse aortic constriction. We generated NAE1 knock-in mice carrying a crotonylation-defective lysine to arginine K238R (lysine to arginine mutation at site 238) mutation (NAE1 K238R) and NAE1 knock-in mice expressing a crotonylation-mimicking lysine to glutamine K238Q (lysine to glutamine mutation at site 238) mutation (NAE1 K238Q) to assess the functional role of crotonylation of NAE1 at K238 in pathological cardiac hypertrophy. Furthermore, we combined coimmunoprecipitation, mass spectrometry, and dot blot analysis that was followed by multiple molecular biological methodologies to identify the target GSN (gelsolin) and corresponding molecular events contributing to the function of NAE1 K238 crotonylation. RESULTS: The crotonylation level of NAE1 was increased in mice and patients with cardiac hypertrophy. Quantitative crotonylomics analysis revealed that K238 was the main crotonylation site of NAE1. Loss of K238 crotonylation in NAE1 K238R knock-in mice attenuated cardiac hypertrophy and restored the heart function, while hypercrotonylation mimic in NAE1 K238Q knock-in mice significantly enhanced transverse aortic constriction-induced pathological hypertrophic response, leading to impaired cardiac structure and function. The recombinant adenoviral vector carrying NAE1 K238R mutant attenuated, while the K238Q mutant aggravated Ang II (angiotensin II)-induced hypertrophy. Mechanistically, we identified GSN as a direct target of NAE1. K238 crotonylation of NAE1 promoted GSN neddylation and, thus, enhanced its protein stability and expression. NAE1 crotonylation-dependent increase of GSN promoted actin-severing activity, which resulted in adverse cytoskeletal remodeling and progression of pathological hypertrophy. CONCLUSIONS: Our findings provide new insights into the previously unrecognized role of crotonylation on nonhistone proteins during cardiac hypertrophy. We found that K238 crotonylation of NAE1 plays an essential role in mediating cardiac hypertrophy through GSN neddylation, which provides potential novel therapeutic targets for pathological hypertrophy and cardiac remodeling.

2.
Health Qual Life Outcomes ; 22(1): 76, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39256723

RESUMO

PURPOSES: Chronic obstructive pulmonary disease (COPD) is a major cause of the rapid decline of health-related quality of life (HRQoL), associated with accelerated frailty in older populations. This study aimed to analyse the long-term dynamic changes of HRQoL and the predictive factors for the rapid decline of HRQoL in older patients with COPD. METHODS: Overall 244 patients with COPD, aged ≧ 65 years from one medical centre were enrolled between March 2012 and July 2020. Further, we prospectively assessed HRQoL scores with utility values, using EuroQol Five-Dimension (EQ-5D) questionnaires. Additionally, long-term dynamic changes in HRQoL were analysed using the Kernel smoothing method and examined the factors contributing to the deterioration of HRQoL using a linear mixed effects model. RESULTS: Older patients with COPD with forced expiration volume (FEV1) < 50% of prediction entered the phase of rapid and continuous decline of HRQoL ~ 2 years after enrolment, but patients with FEV1 ≥ 50% of prediction without rapidly declined HRQoL during 7 years follow up. Therefore, FEV1 < 50% of prediction is a novel predictor for the rapid decline of HRQoL. The course of rapidly declining HRQoL occurred, initially in the usual activities and pain/discomfort domains, followed by the morbidity, self-care, and depression/anxiety domains ~ 2 and 4 years after enrolment, respectively. The mixed effects model indicated that both FEV1 < 50% of prediction and a history of severe acute exacerbation (SAE) requiring hospitalisation were contributing factors for deterioration in HRQoL . CONCLUSIONS: Both FEV1 < 50% of prediction and exacerbations requiring hospitalisation were contributing factors for the deterioration of HRQoL in long-term follow up. Additionally, FEV1 < 50% of prediction was a novel predictor for patients entering the phase of rapid decline of HRQoL.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Doença Pulmonar Obstrutiva Crônica/psicologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Masculino , Idoso , Feminino , Seguimentos , Inquéritos e Questionários , Estudos Prospectivos , Idoso de 80 Anos ou mais , Volume Expiratório Forçado
3.
Heliyon ; 10(15): e34321, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39144947

RESUMO

Ultraviolet B (UVB) light exposure accelerates skin photoaging. Human adipose-derived stem cell exosomes (hADSC-Exos) and some antioxidants may have anti-photoaging effects. However, it is unknown whether the combination of hADSC-Exos and antioxidants plays a synergistic role in anti-photoaging. In cellular and 3D skin models, we showed that vitamin E (VE) and hADSC-Exos were optimal anti-photoaging combinations. In vivo, VE and hADSC-Exos increased skin tightening and elasticity in UVB-induced photoaging mice Combined treatment with VE and hADSC-Exos inhibited SIRT1/NF-κB pathway. These findings contribute to the understanding of hADSC-Exos in conjunction with other antioxidants, thereby providing valuable insights for the future pharmaceutical and cosmetic industries.

4.
J Thorac Imaging ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39129435

RESUMO

PURPOSE: To investigate the clinical and radiographic features of PNLH and the relationship with pathologic features. MATERIALS AND METHODS: A total of 11 patients in whom PNLH was confirmed in our department were retrospectively studied. The clinical and radiographic features were extracted and analyzed, and we also discussed the relationship between radiologic and pathologic features. RESULTS: Of the 11 patients with PNLH, 5 were discovered incidentally, while 4 presented with chest symptoms. Laboratory tests showed no specificity and the lesions were located under the pleura with an adjacent pleural indentation. Most lesions were solid, with some showing signs of spiculation or spiculate protuberance. In some cases, hypodense areas and vocules were visible. The enhanced scan showed marked enhancement, but most had no lymph node enlargement, and there was no pleural effusion. CONCLUSIONS: The clinical manifestations of PNLH are nonspecific and the imaging features overlap with those of malignant lung tumors, and the diagnosis depends on pathologic examination.

5.
Chin J Traumatol ; 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39179446

RESUMO

Spinal intradural (subdural and subarachnoid) hematoma following percutaneous kyphoplasty is an extremely rare complication. In this report, we described a case of 2 episodes of subarachnoid hemorrhage with delayed paralysis after kyphoplasty. A 73-year-old man underwent percutaneous kyphoplasty in our hospital an osteoporotic vertebral fracture at the T12 level. On the 55 h after kyphoplasty for T12 osteoporotic vertebral fracture, he developed paralysis of the lower limbs. An emergency posterior decompression from T8 to L2 was performed. And the subarachnoid hematomas were removed. Postoperatively, the neurological symptoms improved rapidly. However, 2 weeks after the operation, the patient experienced a setback with severe neurological decline (paraplegia with sensory and autonomic dysfunction). An emergency posterior decompression from T5 to L2 was performed. The subarachnoid hematomas were removed. This case reflects the cause and progression of spinal subdural hematoma. Previous literature has debated the best treatment approach for spinal subarachnoid hemorrhage, but the prognosis of patients is heavily dependent on precise symptom evaluation and localization.

6.
Curr Biol ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39216485

RESUMO

Biological shape diversity is often manifested in modulation of organ symmetry and modification of the patterned elaboration of repeated shape elements.1,2,3,4,5 Whether and how these two aspects of shape determination are coordinately regulated is unclear.5,6,7 Plant leaves provide an attractive system to investigate this problem, because they often show asymmetries along the proximodistal (PD) axis of their blades, along which they can also produce repeated marginal outgrowths such as serrations or leaflets.1 One aspect of leaf shape diversity is heteroblasty, where the leaf form in a single genotype is modified with progressive plant age.8,9,10,11 In Arabidopsis thaliana, a plant with simple leaves, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 9 (SPL9) controls heteroblasty by activating CyclinD3 expression, thereby sustaining proliferative growth and retarding differentiation in adult leaves.12,13 However, the precise significance of SPL9 action for leaf symmetry and marginal patterning is unknown. By combining genetics, quantitative shape analyses, and time-lapse imaging, we show that PD symmetry of the leaf blade in A. thaliana decreases in response to an age-dependent SPL9 expression gradient, and that SPL9 action coordinately regulates the distribution and shape of marginal serrations and overall leaf form. Using comparative analyses, we demonstrate that heteroblastic growth reprogramming in Cardamine hirsuta, a complex-leafed relative of A. thaliana, also involves prolonging the duration of cell proliferation and delaying differentiation. We further provide evidence that SPL9 enables species-specific action of homeobox genes that promote leaf complexity. In conclusion, we identified an age-dependent layer of organ PD growth regulation that modulates leaf symmetry and has enabled leaf shape diversification.

7.
Huan Jing Ke Xue ; 45(7): 3839-3848, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-39022932

RESUMO

In order to control the increasing ozone (O3) pollution in Hebi, Henan Province, clarifying the pollution characteristics of ozone and its precursors is vital. Therefore, we conducted a comprehensive analysis of O3 pollution utilizing the OFP-PMF-EKMA method combined with online hourly resolution monitoring data of conventional pollutants and volatile organic compounds (VOCs) in the summer of 2022 (June-September). Ozone formation potential (OFP) was used to identify the key VOCs species, and the PMF model was used to identify the VOCs emission sources, whereas EKMA curves and scenario analysis were used to identify the main ozone control area in Hebi and to determine the reduction ratio of VOCs and NOx in a scientifically refined way. In 2022, Hebi had persistent O3 pollution, with the highest concentration in June. Conditions of high temperature, low humidity, and low atmospheric pressure contributed to the O3 accumulation. Aromatic and oxygenated volatile organic compounds (OVOCs) contributed significantly to the OFP and VOCs fraction, which were the dominant active substance and concentration dominant species. The results of the VOCs source analysis indicated that vehicle exhaust sources (25.3%) were the main source of atmospheric VOCs, followed by process sources (17.7%) and biomass combustion sources (17.6%). Thus, emission sources associated with the combustion of fossil fuels and industrial production emissions were the most urgent sources of atmospheric VOCs to be controlled in Hebi. The O3 generation in Hebi occurred in the VOCs-sensitive zones, and the emission reduction results showed that a synergistic emission reduction of VOCs and nitrogen oxide (NOx) could effectively control O3 pollution with a 75% reduction in VOCs and a 10% reduction in NOx.

8.
Front Psychiatry ; 15: 1408095, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39056021

RESUMO

Background: Being ready for discharge is vital to successful hospital-to-home transitions. For many patients, however, the transition from psychiatric hospital care to outpatient care can be challenging. An in-depth understanding of the mental health conditions of patients at discharge is crucial and instructive for recovery research. Objective: The purpose of this study was to determine the prevalence and risk factors of depression, anxiety, and poor well-being symptoms among patients who are about to be discharged from psychiatric units in Alberta, Canada. Our aim was to help determine the prevalence of anxiety, depression, and overall well-being among the general psychiatric inpatient population in Alberta before discharge and the potential factors which may influence this. Methods: This epidemiological study used a cross-sectional quantitative survey from March 8, 2022, to November 5, 2023, to assess depression, anxiety, and well-being. Participants were invited to complete an online questionnaire that contained demographics, clinical information, and responses to the PHQ-9, GAD-7, and WHO-5 questionnaires. SPSS version 25 was used to analyze the data. Descriptive, univariate, and multivariate regression analyses were employed. Result: The study found that the prevalence of likely depression, anxiety, and poor well-being among patients about to be discharged was 37.1%, 56.4%, and 48.3%, respectively. Based on a logistic regression model, there was a statistically significant association between anxiety, depression, and poor well-being diagnoses and multiple socio-demographic and clinical factors such as ethnicity, primary mental health diagnoses, education level, housing status, depression, anxiety, and well-being at baseline. Conclusion: Mental health assessment at discharge is a critical step in the recovery and transition of care. There is still a need for further research to identify the underlying causes and robust predictors of mental health symptoms in patients about to be discharged and to provide appropriate interventions and supportive resources both before and following discharge. Future research utilizing these findings may help identify key opportunities to improve outcomes for patients after discharge.

9.
World J Psychiatry ; 14(7): 999-1008, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39050195

RESUMO

BACKGROUND: Cognitive-behavioral therapy (CBT) and habit reversal training (HRT) have shown application potential in addressing tic symptoms and comorbid psychiatric conditions. Despite their theoretical potential, empirical evidence on their combined efficacy remains limited. AIM: To evaluate the efficacy of CBT combined with HRT on anxiety disorders in children with Tourette's syndrome (TS). METHODS: Clinical data of children with TS admitted to our hospital from January 2022 to June 2023 were collected, and the patients were grouped into the conventional therapy (control) group and the CBT combined with HRT group. Baseline characteristics, anxiety scores, tic severity scores, treatment adherence, and parental satisfaction were assessed. Statistical analysis was performed using t-tests, chi-square tests, and correlation analysis. RESULTS: A total of 136 patients, including 65 patients in the control group and 71 patients in the CBT combined with HRT group, were included. The CBT combined with HRT group showed remarkable improvements compared with the control group. Post-intervention assessment revealed a decrease in anxiety scores from 63.52 ± 1.81 to 40.53 ± 1.64 (t = 2.022, P = 0.045), and the Yale Global Tic Severity Scale total score decreased from 22.14 ± 5.67 to 16.28 ± 4.91 (t = 2.288, P = 0.024). Treatment adherence was significantly higher in the CBT combined with HRT group (85.47 ± 7.62%) compared with the control group (82.32 ± 6.54%; t = 2.596, P = 0.010). Parental satisfaction scores were also higher in the CBT combined with HRT group (8.69 ± 1.77) compared with the control group (7.87 ± 1.92; t = 2.592, P = 0.011). CONCLUSION: This study demonstrates that CBT combined with HRT significantly reduces anxiety symptoms and tic severity in children with TS, with higher treatment adherence and parental satisfaction. These findings support the potential application of this comprehensive therapeutic approach for TS treatment.

10.
Int J Oncol ; 65(3)2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39027991

RESUMO

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the Transwell invasion assay data shown in Fig. 7B on p. 451 were strikingly similar to data that had appeared in Fig. 3D in a previously published paper written by different authors at a different research institute, which had been received at the journal Cancer Letters at around the same time, and which has subsequently been retracted [Gu J, Wang Y, Wang X, Zhou D, Shao C, Zhou M and He Z: Downregulation of lncRNA GAS5 confers tamoxifen resistance by activating miR­222 in breast cancer. Cancer Lett 434: 1­10, 2018]. In addition, there were potentially anomalous features associated with the western blot and cell cycle data in this paper.  In view of the fact that certain of the data in the above article were also submitted to a different journal within the space of a few days, the Editor of International Journal of Oncology has decided that this paper should be retracted from the publication. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 54: 443­454, 2019; DOI: 10.3892/ijo.2018.4647].

11.
Nat Commun ; 15(1): 5985, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39013850

RESUMO

The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 participants were recruited for the screening of differentially expressed plasma microRNAs (miRNAs). We found that miR-1204 is significantly increased in both the plasma and aorta of elder patients with AAD and is positively correlated with age. Cell senescence induces the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induces vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. Furthermore, miR-1204 aggravates angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuates ß-aminopropionitrile monofumarate-induced AAD development in mice. Mechanistically, miR-1204 directly targets myosin light chain kinase (MYLK), leading to the acquisition of a senescence-associated secretory phenotype (SASP) by VSMCs and loss of their contractile phenotype. MYLK overexpression reverses miR-1204-induced VSMC senescence, SASP and contractile phenotypic changes, and the decrease of transforming growth factor-ß signaling pathway. Our findings suggest that aging aggravates AAD via the miR-1204-MYLK signaling axis.


Assuntos
Envelhecimento , Aneurisma Aórtico , Dissecção Aórtica , Senescência Celular , MicroRNAs , Músculo Liso Vascular , Quinase de Cadeia Leve de Miosina , Transdução de Sinais , Animais , Feminino , Humanos , Masculino , Camundongos , Envelhecimento/genética , Envelhecimento/metabolismo , Angiotensina II/metabolismo , Aneurisma Aórtico/metabolismo , Aneurisma Aórtico/genética , Aneurisma Aórtico/patologia , Dissecção Aórtica/metabolismo , Dissecção Aórtica/genética , Dissecção Aórtica/patologia , Proteínas de Ligação ao Cálcio , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Quinase de Cadeia Leve de Miosina/metabolismo , Quinase de Cadeia Leve de Miosina/genética , Fator de Crescimento Transformador beta/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética
12.
Int J Environ Health Res ; : 1-15, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38825775

RESUMO

The widely believed Helicobacter pylori infection has never explained the birth-cohort phenomenon of peptic ulcers. Although numerous studies have observed that environmental factors are associated with peptic ulcers, their role in the disease has yet to be identified. A new etiological theory proposed that environmental factors cause peptic ulcers via inducing psychological stress. Starting from this etiology, an integration of the mortality rates caused by social and natural environmental factors reproduced a representative fluctuation curve in the birth-cohort phenomenon, where a causal role of environmental factors in peptic ulcers was hidden. The reproduced fluctuation curve revealed that multiple environmental factors caused the birth-cohort phenomenon by Superposition Mechanism, and the causal role of each individual environmental factor surfaced if the fluctuation curves in the birth-cohort phenomenon were properly differentiated. A full understanding of the birth-cohort phenomenon highlights the importance of environmental management in improving clinical outcomes, and suggests that the Superposition Mechanism is an indispensable methodological concept for life science and medicine.

13.
J Agric Food Chem ; 72(26): 14684-14700, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38905352

RESUMO

The overuse of antibiotics in animal farming and aquaculture has led to multidrug-resistant methicillin-sensitive Staphylococcus aureus (MR-MSSA) becoming a common pathogen in foodborne diseases. Sophora flavescens Ait. serves as a traditional plant antibacterial agent and functional food ingredient. A total of 30 compounds (1-30) were isolated from the root bark of S. flavescens, consisting of 20 new compounds (1-20). In the biological activity assay, compound 1 demonstrated a remarkable inhibitory effect on MR-MSSA, with an MIC of 2 µg/mL. Furthermore, 1 was found to rapidly eliminate bacteria, inhibit biofilm growth, and exhibit exceptionally low cytotoxicity. Mechanistic studies have revealed that 1 possesses an enhanced membrane-targeting ability, binding to the bacterial cell membrane components phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and cardiolipin (CL). This disruption of bacterial cell membrane integrity increases intracellular reactive oxygen species, protein and DNA leakage, reduced bacterial metabolism, and ultimately bacterial death. In summary, these findings suggest that compound 1 holds promise as a lead compound against MR-MSSA.


Assuntos
Antibacterianos , Permeabilidade da Membrana Celular , Flavonoides , Testes de Sensibilidade Microbiana , Casca de Planta , Extratos Vegetais , Raízes de Plantas , Sophora , Sophora/química , Antibacterianos/farmacologia , Antibacterianos/química , Raízes de Plantas/química , Casca de Planta/química , Permeabilidade da Membrana Celular/efeitos dos fármacos , Flavonoides/farmacologia , Flavonoides/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Biofilmes/efeitos dos fármacos , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Sophora flavescens
14.
Front Psychiatry ; 15: 1386321, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38807690

RESUMO

Intense interest surrounds current research on psychedelics, particularly regarding their potential in treating mental health disorders. Various studies suggest a link between the subjective effects produced by psychedelics and their therapeutic efficacy. Neuroimaging evidence indicates an association of changes in brain functional connectivity with the subjective effects of psychedelics. We conducted a review focusing on psychedelics and brain functional connectivity. The review focused on four psychedelic drugs: ayahuasca, psilocybin and LSD, and the entactogen MDMA. We conducted searches in databases of MEDLINE, Embase, APA PsycInfo and Scopus from inception to Jun 2023 by keywords related to functional connectivity and psychedelics. Using the PRISMA framework, we selected 24 articles from an initial pool of 492 for analysis. This scoping review and analysis investigated the effects of psychedelics on subjective experiences and brain functional connectivity in healthy individuals. The studies quantified subjective effects through psychometric scales, revealing significant experiences of altered consciousness, mood elevation, and mystical experiences induced by psychedelics. Neuroimaging results indicated alterations in the functional connectivity of psychedelics, with consistent findings across substances of decreased connectivity within the default mode network and increased sensory and thalamocortical connectivity. Correlations between these neurophysiological changes and subjective experiences were noted, suggesting a brain network basis of the psychedelics' neuropsychological impact. While the result of the review provides a potential neural mechanism of the subjective effects of psychedelics, direct clinical evidence is needed to advance their clinical outcomes. Our research serves as a foundation for further exploration of the therapeutic potential of psychedelics.

15.
Haematologica ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38813732

RESUMO

Impaired differentiation of megakaryocytes constitutes the principal etiology of thrombocytopenia. The signal transducer and activator of transcription 3 (STAT3) is a crucial transcription factor in regulating megakaryocyte differentiation, yet the precise mechanism of its activation remains unclear. PALLD, an actin-associated protein, has been increasingly recognized for its essential functions in multiple biological processes. This study revealed that megakaryocyte/plateletspecific knockout of PALLD in mice exhibited thrombocytopenia due to diminished platelet biogenesis. In megakaryocytes, PALLD deficiency led to impaired proplatelet formation and polyploidization, ultimately weakening their differentiation for platelet production. Mechanistic studies demonstrated that PALLD bound to STAT3 and interacted with its DNA-binding domain (DBD) and Src homology 2 (SH2) domain via Immunoglobulin domain 3 (Ig3). Moreover, the absence of PALLD attenuated STAT3 Y705 phosphorylation and impeded STAT3 nuclear translocation. Based on the PALLD-STAT3 binding sequence, we designed a peptide C-P3, which can facilitate megakaryocyte differentiation and accelerate platelet production in vivo. In conclusion, this study highlights the pivotal role of PALLD in megakaryocyte differentiation and proposes a novel approach for treating thrombocytopenia by targeting the PALLD-STAT3 interaction.

16.
Elife ; 132024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700136

RESUMO

Cholecystokinin (CCK) is an essential modulator for neuroplasticity in sensory and emotional domains. Here, we investigated the role of CCK in motor learning using a single pellet reaching task in mice. Mice with a knockout of Cck gene (Cck-/-) or blockade of CCK-B receptor (CCKBR) showed defective motor learning ability; the success rate of retrieving reward remained at the baseline level compared to the wildtype mice with significantly increased success rate. We observed no long-term potentiation upon high-frequency stimulation in the motor cortex of Cck-/- mice, indicating a possible association between motor learning deficiency and neuroplasticity in the motor cortex. In vivo calcium imaging demonstrated that the deficiency of CCK signaling disrupted the refinement of population neuronal activity in the motor cortex during motor skill training. Anatomical tracing revealed direct projections from CCK-expressing neurons in the rhinal cortex to the motor cortex. Inactivation of the CCK neurons in the rhinal cortex that project to the motor cortex bilaterally using chemogenetic methods significantly suppressed motor learning, and intraperitoneal application of CCK4, a tetrapeptide CCK agonist, rescued the motor learning deficits of Cck-/- mice. In summary, our results suggest that CCK, which could be provided from the rhinal cortex, may surpport motor skill learning by modulating neuroplasticity in the motor cortex.


Assuntos
Colecistocinina , Aprendizagem , Camundongos Knockout , Córtex Motor , Destreza Motora , Plasticidade Neuronal , Animais , Masculino , Camundongos , Colecistocinina/metabolismo , Aprendizagem/fisiologia , Córtex Motor/fisiologia , Córtex Motor/metabolismo , Córtex Motor/efeitos dos fármacos , Destreza Motora/fisiologia , Plasticidade Neuronal/fisiologia , Plasticidade Neuronal/efeitos dos fármacos
17.
J Affect Disord ; 357: 148-155, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38670463

RESUMO

BACKGROUND: Anxiety disorders are among the most common mental health disorders in the middle aged and older population. Because older individuals are more likely to have multiple comorbidities or increased frailty, the impact of anxiety disorders on their overall well-being is exacerbated. Early identification of anxiety disorders using machine learning (ML) can potentially mitigate the adverse consequences associated with these disorders. METHODS: We applied ML to the data from the Canadian Longitudinal Study on Aging (CLSA) to predict the onset of anxiety disorders approximately three years in the future. We used Shapley value-based methods to determine the top factor for prediction. We also investigated whether anxiety onset can be predicted by baseline depression-related predictors alone. RESULTS: Our model was able to predict anxiety onset accurately (Area under the Receiver Operating Characteristic Curve or AUC = 0.814 ± 0.016 (mean ± standard deviation), balanced accuracy = 0.741 ± 0.016, sensitivity = 0.743 ± 0.033, and specificity = 0.738 ± 0.010). The top predictive factors included prior depression or mood disorder diagnosis, high frailty, anxious personality, and low emotional stability. Depression and mood disorders are well known comorbidity of anxiety; however a prior depression or mood disorder diagnosis could not predict anxiety onset without other factors. LIMITATION: While our findings underscore the importance of a prior depression diagnosis in predicting anxiety, they also highlight that it alone is inadequate, signifying the necessity to incorporate additional predictors for improved prediction accuracy. CONCLUSION: Our study showcases promising prospects for using machine learning to develop personalized prediction models for anxiety onset in middle-aged and older adults using easy-to-access survey data.


Assuntos
Transtornos de Ansiedade , Aprendizado de Máquina , Humanos , Feminino , Masculino , Canadá/epidemiologia , Estudos Longitudinais , Idoso , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Pessoa de Meia-Idade , Envelhecimento/psicologia , Idoso de 80 Anos ou mais , Depressão/epidemiologia , Depressão/diagnóstico , Depressão/psicologia , Comorbidade , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Estudos Prospectivos , Ansiedade/epidemiologia , Ansiedade/diagnóstico , Ansiedade/psicologia
18.
Front Med (Lausanne) ; 11: 1337669, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38651056

RESUMO

The tracheal Y-shaped stent is mainly used for the treatment of critical patients with airway stenosis or esophagotracheal fistula near carina. A novel method for precise implantation of Y-shaped tracheal stents was developed using double-lumen endotracheal intubation and flexible bronchoscopy. This approach aims to address the limitations associated with X-ray or rigid bronchoscopy guidance, such as operational difficulties and the risk of inaccurate stent placement leading to implantation failure or suffocation. With this new technique, 13 tracheal Y-shaped stents were successfully implanted. This method shows promise in reducing the complexity of stent implantation and facilitating timely treatment for patients in need. Additionally, it has the potential to update current operating standards and guidelines for this procedure.

19.
BMC Public Health ; 24(1): 730, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448851

RESUMO

BACKGROUND: Exercise and dietary nutrition are considered crucial in human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS) treatment protocols and people living with HIV/AIDS (PLWHA) rehabilitation care. However, there is no well-studied research evaluating the effects of combined interventions on the fitness and immune systems of PLWHA. Therefore, this study aimed to analyze the effects of exercise and dietary intervention on physical fitness, quality of life and immune response in PLWHA. METHODS: This was an experimental study, with a sample of 25 male PLWHA divided into two groups: the intervention group (IG: 12 participants) and the control group (CG: 13 participants). All participants have not had any exercise habits and nutritional supplements in the past six months. The participants in the IG completed 45 min of exercise (60-80% HRmax) 4 times per week for 4 weeks. The exercise was in the form of brisk walking or running. They were also given a nutritional dietary supplement 3 times a day for 4 weeks. The 13 individuals in the CG continued their normal daily life (physical activity and diet). The following parameters were evaluated before and after the intervention: body composition, physical fitness, immune response, quality of life (QoL), stress, dietary behavior, dietary habits, exercise motivation, and physical self-efficacy. RESULTS: The significant changes were observed in burnout of stress variables and physical efficiency index (PEI) of physical fitness in the IG (p =.023). Moreover, in the saliva samples, sal-T levels significantly increased only after the intervention in the IG (p =.012). Additionally, regarding the analysis of the interaction (group × time), there was a significant improvement in the reaction speed (p =.001) and grip strength (left: p =.002, right: p =.030) and a significant difference in physical satisfaction in QoL (p =.001), stress burnout (p =.043), self-confidence in physical efficacy (p =.045), external display (p =.008), and fulfillment (p =.047) in exercise motivation. Moreover, the significant effect of the intervention on emotional eating in dietary behavior was shown in the comparison of the IG before and after intervention (p =.001) and in the comparison of the IG group with the CG after the experiment (p =.013). However, there was no significant effect of time or interaction between the condition and time on body composition. CONCLUSIONS: In conclusion, exercise training and diet therapy caused changes in physical fitness and Sal-T levels, which had positive effects on the health promotion of PLWHA.


Assuntos
Síndrome da Imunodeficiência Adquirida , Masculino , Humanos , Síndrome da Imunodeficiência Adquirida/terapia , HIV , Qualidade de Vida , Exercício Físico , Aptidão Física , Imunidade
20.
J Multidiscip Healthc ; 17: 1343-1362, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545434

RESUMO

Objective: The objective of this study was to search for, evaluate, and summarize data related to a faster postoperative recovery in patients with colorectal cancer (CRC) based on literature from China as well as internationally. This will serve as an evidence-based foundation for the clinical implementation of enhanced postoperative recovery of gastrointestinal function in patients with CRC. Methods: Based on the hierarchical "6S" evidence model, we conducted a systematic search of computerized decision-support systems, guideline websites, as well as domestic and international databases for evidence, guidelines, expert consensus statements, clinical decision-making, best practices, evidence summaries, and systematic reviews of interventions focusing on accelerating gastrointestinal function rehabilitation after CRC surgery. The time limit for the search was from the date of creation of the database to January 2023. Two researchers evaluated the quality of the literature that was included, and we extracted data and summarized the evidence from those publications that fulfilled the quality criteria. Results: The review included a total of 21 publications, comprising 6 guidelines, 6 systematic reviews, 3 expert consensus statements, 4 randomized controlled trials, and 2 evidence summaries. We summarized 51 best evidence findings across five areas: organizational management, preoperative risk assessment, education, intraoperative monitoring, and postoperative management. Conclusion: There is a wide variety and wealth of information available on interventions to promote enhanced postoperative recovery of gastrointestinal function in patients with CRC. The use of evidence is discussed, keeping in mind the practical situation in China.

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