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1.
J Cutan Med Surg ; : 12034754241269120, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39086263
2.
Chem Sci ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39184302

RESUMO

Developing exciplex-based organic long-persistent luminescence (OLPL) materials with high stability is very important but remains a formidable challenge in a single-component system. Here, we report a facile strategy to achieve highly stable OLPL in an amorphous exciplex copolymer system via through-space charge transfer (TSCT). The copolymer composed of electron donor and acceptor units can not only exhibit effective TSCT for intra/intermolecular exciplex emission but also construct a rigid environment to isolate oxygen and suppress non-radiative decay, thereby enabling stable exciplex-based OLPL emission with color-tunable feature for more than 100 h under ambient conditions. These single-component OLPL copolymers demonstrate robust antibacterial activity against Escherichia coli under visible light irradiation. These results provide a solid example to exploit highly stable exciplex-based OLPL in polymers, shedding light on how the TSCT mechanism may potentially contribute to OLPL in a single-component molecular system and broadening the scope of OLPL applications.

3.
Environ Pollut ; 360: 124764, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39154884

RESUMO

Cigarette smoke (CS) is an important indoor air pollutant associated with an increased risk of ocular surface disease. As the eye's outermost layer, the cornea is highly sensitive to air pollutants like CS. However, the specific mechanisms linking CS exposure to corneal dysfunction have not been fully elucidated. In the present study, we found that CS exposure damages corneal epithelial cells, accompanied by increased iron (Fe2+) levels and lipid peroxidation, both hallmarks of ferroptosis. Ferroptosis inhibitors, including Ferrostatin-1 (Fer-1) and Deferoxamine mesylate (DFO), protect against CS-induced cell damage. To understand the underlying mechanisms, we investigated how CS affects iron and lipid metabolism. Our results showed that CS could upregulate intracellular iron levels by increasing TFRC expression and promote lipid peroxidation by increasing ACSL4 expression. Silencing ACSL4 or TFRC expression prevented CS-induced ferroptosis. Furthermore, we found that the upregulation of TFRC and ACSL4 was driven by increased YAP transcription. Pharmacological or genetic inhibition of YAP effectively prevented corneal epithelial cell ferroptosis under CS stimulation. Additionally, our results suggest that CS exposure could increase O-GlcNAc transferase activity, leading to YAP O-GlcNAcylation. This glycosylation of YAP interfered with its K48-linked ubiquitination, resulting in YAP stabilization. Collectively, we found that CS exposure induces corneal epithelial cell ferroptosis via the YAP O-GlcNAcylation, and provide evidence that CS exposure is a strong risk factor for ocular surface disease.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39173895

RESUMO

CONTEXT: Limited data existed on the efficacy and safety of novel antiepileptic drugs (pregabalin and gabapentin) in treating pruritus. OBJECTIVES: To assess their role in managing either acute or chronic pruritus. METHODS: A systematic search was conducted in PubMed, EMBASE, the Cochrane Library, and Web of Science databases for relevant randomized controlled trials. Pooled odd ratio (OR) with 95% CI were performed using RevMan5.4 and R4.3.1. RESULTS: Analysis of 27 articles involving 2,016 patients showed significant reduction in pruritus incidence (OR, 0.30 [CI, 0.22-0.4]; I2=1%) and improvements in VAS (MD, 2.76 [CI, 0.95-4.57]; I2=98%) and 5-D scores (MD, 3.42 [CI, 2.10-4.75]; I2=92%) with pregabalin/gabapentin compared to controls. Adverse effects mainly included dizziness, somnolence, nausea and vomiting, dry mouth, constipation, and anxiety, with no significant difference between the groups (OR, 1.08 [CI, 0.32-3.59]; I2=76%). CONCLUSION: The novel antiepileptic drugs pregabalin and gabapentin demonstrated significant therapeutic value in the treatment of pruritus, with a favorable safety profile. Compared to commonly used pruritus treatments such as antihistamines and antidepressants, these medications offered a promising alternative.

5.
JMIR Hum Factors ; 11: e56669, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39178408

RESUMO

BACKGROUND: This study examined the social well-being of single older adults through the companionship of a social robot, LOVOT (Love+Robot; Groove X). It is designed as a companion for older adults, providing love and affection through verbal and physical interaction. We investigated older adults' perceptions of the technology and how they benefitted from interacting with LOVOT, to guide the future development of social robots. OBJECTIVE: This study aimed to use a phenomenological research design to understand the participants' experiences of companionship provided by the social robot. Our research focused on (1) examining the social well-being of single older adults through the companionship of social robots and (2) understanding the perceptions of single older adults when interacting with social robots. Given the prevalence of technology use to support aging, understanding single older adults' social well-being and their perceptions of social robots is essential to guide future research on and design of social robots. METHODS: A total of 5 single women, aged 60 to 75 years, participated in the study. The participants interacted independently with the robot for a week in their own homes and then participated in a poststudy interview to share their experiences. RESULTS: In total, 4 main themes emerged from the participants' interactions with LOVOT, such as caring for a social robot, comforting presence of the social robot, meaningful connections with the social robot, and preference for LOVOT over pets. CONCLUSIONS: The results indicate that single older adults can obtain psychosocial support by interacting with LOVOT. LOVOT is easily accepted as a companion and makes single older adults feel like they have a greater sense of purpose and someone to connect with. This study suggests that social robots can provide companionship to older adults who live alone. Social robots can help alleviate loneliness by allowing single older adults to form social connections with robots as companions. These findings are particularly important given the rapid aging of the population and the increasing number of single-person households in Singapore.


Assuntos
Pesquisa Qualitativa , Robótica , Interação Social , Humanos , Idoso , Feminino , Pessoa de Meia-Idade , Relações Interpessoais
6.
J Inflamm Res ; 17: 5271-5283, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39139580

RESUMO

Purpose: Impaired quality of life (QOL) is common in patients with inflammatory bowel disease (IBD). A tool to more quickly identify IBD patients at high risk of impaired QOL improves opportunities for earlier intervention and improves long-term prognosis. The purpose of this study was to use a machine learning (ML) approach to develop risk stratification models for evaluating IBD-related QOL impairments. Patients and Methods: An online questionnaire was used to collect clinical data on 2478 IBD patients from 42 hospitals distributed across 22 provinces in China from September 2021 to May 2022. Eight ML models used to predict the risk of IBD-related QOL impairments were developed and validated. Model performance was evaluated using a set of indexes and the best ML model was explained using a Local Interpretable Model-Agnostic Explanations (LIME) algorithm. Results: The support vector machine (SVM) classifier algorithm-based model outperformed other ML models with an area under the receiver operating characteristic curve (AUC) and an accuracy of 0.80 and 0.71, respectively. The feature importance calculated by the SVM classifier algorithm revealed that glucocorticoid use, anxiety, abdominal pain, sleep disorders, and more severe disease contributed to a higher risk of impaired QOL, while longer disease course and the use of biological agents and immunosuppressants were associated with a lower risk. Conclusion: An ML approach for assessing IBD-related QOL impairments is feasible and effective. This mechanism is a promising tool for gastroenterologists to identify IBD patients at high risk of impaired QOL.

7.
Nat Cardiovasc Res ; 3(8): 933-950, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39196035

RESUMO

Valve remodeling is a process involving extracellular matrix organization and elongation of valve leaflets. Here, through single-cell RNA sequencing of human fetal valves, we identified an elastin-producing valve interstitial cell (VIC) subtype (apolipoprotein E (APOE)+, elastin-VICs) spatially located underneath valve endothelial cells (VECs) sensing unidirectional flow. APOE knockdown in fetal VICs resulted in profound elastogenesis defects. In valves with pulmonary stenosis (PS), we observed elastin fragmentation and decreased expression of APOE along with other genes regulating elastogenesis. Cell-cell interaction analysis revealed that jagged 1 (JAG1) from unidirectional VECs activates elastogenesis in elastin-VICs through NOTCH2. Similar observations were made in VICs cocultured with VECs under unidirectional flow. Notably, a drastic reduction of JAG1-NOTCH2 was also observed in PS valves. Lastly, we found that APOE controls JAG1-induced NOTCH activation and elastogenesis in VICs through the extracellular signal-regulated kinase pathway. Our study suggests important roles of both APOE and NOTCH in regulating elastogenesis during human valve remodeling.


Assuntos
Apolipoproteínas E , Elastina , Células Endoteliais , Proteína Jagged-1 , Transdução de Sinais , Humanos , Proteína Jagged-1/metabolismo , Proteína Jagged-1/genética , Elastina/metabolismo , Elastina/genética , Células Endoteliais/metabolismo , Apolipoproteínas E/metabolismo , Apolipoproteínas E/genética , Receptor Notch2/metabolismo , Receptor Notch2/genética , Células Cultivadas , Valva Pulmonar/metabolismo , Técnicas de Cocultura , Comunicação Celular/fisiologia , Valvas Cardíacas/embriologia , Valvas Cardíacas/metabolismo
8.
Analyst ; 149(18): 4623-4632, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39101528

RESUMO

The "antenna effect" is one of the most important energy transfer modes in lanthanide light-emitting polymers. In this study, novel luminescent nanostructured coordination polymers (Eu-PCP) were synthesized in one step using Eu3+ as the central metal ion and 5,10,15,20-tetrakis (4-carboxyphenyl) porphyrin (TCPP) as the organic ligand. The unique "antenna effect" observed between Eu3+ and TCPP leads to a substantial improvement in the electrochemiluminescence (ECL) emission efficiency. Eu-PCP exhibits good cathodic ECL characteristics. Additionally, Au@SnS2 nanosheets exhibit favorable electrical conductivity, biocompatibility, and a significant specific surface area. This makes them a suitable choice as substrate materials for the modification of electrode surfaces and capturing antigens. Being well known, the development of sensitive and rapid methods to detect chloramphenicol is essential for food safety. Based on this, we report a novel competitive electrochemiluminescence immunoassay to achieve ultra-sensitive and highly specific detection of chloramphenicol. The linear range was 0.0002-500 ng mL-1 and the detection limit was 0.09 pg mL-1. Apart from that, the experimental results proved that it provided a new analytical tool for the detection of antibiotic residues in food safety.


Assuntos
Cloranfenicol , Técnicas Eletroquímicas , Európio , Ouro , Limite de Detecção , Medições Luminescentes , Polímeros , Porfirinas , Európio/química , Cloranfenicol/análise , Cloranfenicol/química , Imunoensaio/métodos , Porfirinas/química , Medições Luminescentes/métodos , Técnicas Eletroquímicas/métodos , Ouro/química , Polímeros/química , Contaminação de Alimentos/análise , Antibacterianos/análise , Antibacterianos/química , Compostos de Estanho/química , Animais , Complexos de Coordenação/química
9.
Nat Commun ; 15(1): 6727, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39112477

RESUMO

Optically addressable spin defects hosted in two-dimensional van der Waals materials represent a new frontier for quantum technologies, promising to lead to a new class of ultrathin quantum sensors and simulators. Recently, hexagonal boron nitride (hBN) has been shown to host several types of optically addressable spin defects, thus offering a unique opportunity to simultaneously address and utilise various spin species in a single material. Here we demonstrate an interplay between two separate spin species within a single hBN crystal, namely S = 1 boron vacancy defects and carbon-related electron spins. We reveal the S = 1/2 character of the carbon-related defect and further demonstrate room temperature coherent control and optical readout of both S = 1 and S = 1/2 spin species. By tuning the two spin ensembles into resonance with each other, we observe cross-relaxation indicating strong inter-species dipolar coupling. We then demonstrate magnetic imaging using the S = 1/2 defects and leverage their lack of intrinsic quantization axis to probe the magnetic anisotropy of a test sample. Our results establish hBN as a versatile platform for quantum technologies in a van der Waals host at room temperature.

10.
Front Microbiol ; 15: 1434521, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39161603

RESUMO

Background: Growing evidence indicates a potential association between the gut microbiome and psoriasis. Nevertheless, the precise nature of these associations and whether they constitute causal relationships remain unclear. Methods: A rigorous bidirectional two-sample Mendelian randomization study was undertaken to establish a putative causal link between gut microbiota and psoriasis. We drew upon publicly available datasets containing summary statistics from GWAS to accomplish this. Utilizing various analytical techniques, including inverse variance weighting, MR-Egger, weighted median, weighted model, and MR-PRESSO, we sought to validate the putative causal association between gut microbiota and psoriasis. A reverse Mendelian randomization analysis was conducted to further investigate the relationship. Results: After conducting a forward Mendelian randomization analysis, a causal relationship was established between 19 gut microbiota and psoriasis. Furthermore, the reverse MR study revealed causality between psoriasis and 13 gut microbiota. Notably, no substantial heterogeneity of instrumental variables or horizontal pleiotropy was observed. Conclusion: This research suggests a potential genetic association and causal nexus between gut microorganisms and psoriasis, indicating potential implications for the clinical management and therapy of psoriasis. Additional observational studies with a larger population sample size and animal model experiments are imperative to fully elucidate this association's underlying mechanisms.

11.
J Clin Neurol ; 20(4): 412-421, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38951974

RESUMO

BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is clinically heterogeneous and can be classified into subgroups according to the clinical presentation, antibody status, age at onset, and thymic abnormalities. This study aimed to determine the clinical characteristics and outcomes of generalized MG (GMG) patients based on these subgroups. METHODS: Medical records of MG patients from 1976 to 2023 were reviewed retrospectively. Patients with pure ocular MG were excluded. Data on demographic, clinical characteristics, laboratory features, and outcomes were analyzed. RESULTS: This study included 120 GMG patients. There was a slight preponderance of female patients over male patients (male:female ratio=1:1.3), with the age at onset exhibiting a bimodal distribution. Female patients peaked at a lower age (21-30 years) whereas male patients peaked at a higher age (61-70 years). Most (92%, 105 of 114) patients had positive anti-acetylcholine receptor antibodies. Five patients were also tested for anti-muscle-specific tyrosine kinase antibodies, with two showing positivity. Thymectomy was performed in 62 (52%) patients, of which 30 had thymoma, 16 had thymic hyperplasia, 7 had an involuted thymus, and 6 had a normal thymus. There were significantly more female patients (68% vs. 45%, p=0.011) with early-onset disease (<50 years old) and thymic hyperplasia (33% vs. 0%, p<0.025). Most (71%) of the patients had a good outcome based on the Myasthenia Gravis Foundation of America postintervention status. GMG patients with early-onset disease had a significantly better outcome than patients with a late onset in univariate (58% vs. 37%, p=0.041) and multivariate (odds ratio=4.68, 95% confidence interval=1.17-18.64, p=0.029) analyses. CONCLUSIONS: Female patients with early-onset MG and thymic hyperplasia had significantly better outcomes, but only early-onset disease was independently associated with a good outcome. These findings are comparable with those of other studies.

12.
J Clin Neurol ; 20(4): 422-430, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38951975

RESUMO

BACKGROUND AND PURPOSE: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited disorder of fatty acid oxidation that causes lipid storage myopathy (LSM). This is the first report on MADD that describes the phenotypic and genetic features of a Malaysian cohort. METHODS: Among the >2,500 patients in a local muscle biopsy database, patients with LSM were identified and their genomic DNA were extracted from muscle samples and peripheral blood. All 13 exons of the electron-transfer flavoprotein dehydrogenase gene (ETFDH) were subsequently sequenced. Fifty controls were included to determine the prevalence of identified mutations in the normal population. RESULTS: Fourteen (82%) of the 17 LSM patients had MADD with ETFDH mutations. Twelve (86%) were Chinese and two were Malay sisters. Other unrelated patients reported that they had no relevant family history. Nine (64%) were females. The median age at onset was 18.5 years (interquartile range=16-37 years). All 14 demonstrated proximal limb weakness, elevated serum creatine kinase levels, and myopathic changes in electromyography. Three patients experienced a metabolic crisis at their presentation. Sanger sequencing of ETFDH revealed nine different variants/mutations, one of which was novel: c.998A>G (p.Y333C) in exon 9. Notably, 12 (86%) patients, including the 2 Malay sisters, carried a common c.250G>A (p.A84T) variant, consistent with the hotspot mutation reported in southern China. All of the patients responded well to riboflavin therapy. CONCLUSIONS: Most of our Malaysian cohort with LSM had late-onset, riboflavin-responsive MADD with ETFDH mutations, and they demonstrated phenotypic and genetic features similar to those of cases reported in southern China. Furthermore, we report a novel ETFDH mutation and possibly the first ever MADD patients of Malay descent.

13.
Heliyon ; 10(12): e32595, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38988518

RESUMO

Objective: To investigate the prevalence of subthreshold depression among Chinese college students and to explore the related factors. Methods: The research subjects were Chinese college students participating in the "2022 Psychology and Behavior Investigation of Chinese Residents (PBICR-2022)". Data on respondents' general characteristics, quality of life, perceived pressure, family communication, perceived social support, self-efficacy, and depression status were gathered. To investigate the association between each variable and the risk of subthreshold depression, statistical analyses, including chi-square tests and rank sum tests were conducted. Furthermore, a binary stepwise logistic regression was employed to establish the regression model of the factors related to subthreshold depression among Chinese college students. Results: A prevalence of subthreshold depression of about 39.7 % was found among the 8934 respondents. Logistic regression analysis revealed that respondents who are female, have chronic diseases, are in debt, experience significant impacts from epidemic control policies, have lower self-assessed quality of life, experience challenges in family communication, perceive lower social support, have lower self-efficacy, and feel higher perceived pressure are more likely to develop subthreshold depression compared to the control group. (P < 0.05). Conclusion: The prevalence rate of subthreshold depression among Chinese college students was found to be approximately 40 %. Female college students suffering from chronic diseases, with households in debt, greatly impacted by epidemic control policies, and experiencing high perceived stress, may be at risk for subthreshold depression among Chinese college students. On the other hand, strong family communication, perceived social support, and self-efficacy were identified as potential protective factors. In order to facilitate timely screening, diagnosis, and treatment of subthreshold depression in Chinese college students, it is crucial for the government, local communities, colleges, and families to prioritize the mental health of college students and implement targeted measures accordingly.

14.
Phytochemistry ; 225: 114196, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38936529

RESUMO

One previously undescribed xanthanolide sesquiterpene dimer pungiolide P (1), possessing an unprecedented scaffold with a 5/7/5/7/5 ring system skeleton and its intermediate pungiolide Q (2), ten xanthanolide sesquiterpenes (3-12), two eudesmene sesquiterpene derivatives (13-14), one phenylpropionic acid derivative (15), together with eleven known compounds (16-26) were obtained from the fruits of Xanthium italicum Moretti. A possible biosynthetic pathway for pungiolide P (1) was also proposed, which was supported by its bio-synthetic intermediate (2). Compounds 1, 4-5, 18-21, and 25 exhibited cytotoxic activity against a variety of human cancer cell lines. Furthermore, compounds 1, 4-5, could cause blockage of the cell cycle in the G2/M phase and induce apoptosis in H460 cells. Notably, pungiolide P (1) exhibited significantly superior cytotoxicity compared to previously reported compounds, providing valuable insights for natural anti-tumor sources.


Assuntos
Antineoplásicos Fitogênicos , Apoptose , Ensaios de Seleção de Medicamentos Antitumorais , Frutas , Sesquiterpenos , Xanthium , Xanthium/química , Humanos , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos/isolamento & purificação , Frutas/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Estrutura Molecular , Relação Estrutura-Atividade , Proliferação de Células/efeitos dos fármacos
15.
QJM ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38885411
16.
J Phys Chem B ; 128(25): 6028-6048, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38876465

RESUMO

GENeralized-Ensemble SImulation System (GENESIS) is a molecular dynamics (MD) software developed to simulate the conformational dynamics of a single biomolecule, as well as molecular interactions in large biomolecular assemblies and between multiple biomolecules in cellular environments. To achieve the latter purpose, the earlier versions of GENESIS emphasized high performance in atomistic MD simulations on massively parallel supercomputers, with or without graphics processing units (GPUs). Here, we implemented multiscale MD simulations that include atomistic, coarse-grained, and hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. They demonstrate high performance and are integrated with enhanced conformational sampling algorithms and free-energy calculations without using external programs except for the QM programs. In this article, we review new functions, molecular models, and other essential features in GENESIS version 2.1 and discuss ongoing developments for future releases.

17.
J Asian Nat Prod Res ; 26(9): 1024-1032, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38853517

RESUMO

Investigation of the fruits of Rhododendron molle G. Don led to the isolation of three new grayanane-type diterpenoids, rhodomolleins LIV-LVI (1-3). The structures and absolute configurations of new compounds were fully elucidated by spectroscopic analysis and single-crystal X-ray diffraction, including HRESIMS, 1 D and 2 D NMR data. Compounds 1-3 were evaluated for analgesic activities utilizing an acetic acid-induced writhing test in mice. Compound 1 showed a significant antinociceptive effect with writhe inhibition rates of 72.9% and 100% at doses of 6 mg/kg and 20 mg/kg in mice, respectively. The binding mode of 1 to N-ethylmaleimide-sensitive factor (NSF, PDB: 6IP2) was explored by molecular docking, indicating the presence of hydrogen bond interactions which account for its analgesic activity.


Assuntos
Analgésicos , Diterpenos , Frutas , Rhododendron , Animais , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Rhododendron/química , Analgésicos/farmacologia , Analgésicos/química , Camundongos , Estrutura Molecular , Frutas/química , Simulação de Acoplamento Molecular , Masculino , Cristalografia por Raios X
18.
Sci Adv ; 10(22): eadl1123, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38809977

RESUMO

Immunosenescence contributes to systematic aging and plays a role in the pathogenesis of Alzheimer's disease (AD). Therefore, the objective of this study was to investigate the potential of immune rejuvenation as a therapeutic strategy for AD. To achieve this, the immune systems of aged APP/PS1 mice were rejuvenated through young bone marrow transplantation (BMT). Single-cell RNA sequencing revealed that young BMT restored the expression of aging- and AD-related genes in multiple cell types within blood immune cells. The level of circulating senescence-associated secretory phenotype proteins was decreased following young BMT. Notably, young BMT resulted in a significant reduction in cerebral Aß plaque burden, neuronal degeneration, neuroinflammation, and improvement of behavioral deficits in aged APP/PS1 mice. The ameliorated cerebral amyloidosis was associated with an enhanced Aß clearance of peripheral monocytes. In conclusion, our study provides evidence that immune system rejuvenation represents a promising therapeutic approach for AD.


Assuntos
Doença de Alzheimer , Modelos Animais de Doenças , Rejuvenescimento , Animais , Doença de Alzheimer/terapia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/imunologia , Camundongos , Camundongos Transgênicos , Transplante de Medula Óssea , Comportamento Animal , Peptídeos beta-Amiloides/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Placa Amiloide/patologia , Placa Amiloide/metabolismo , Envelhecimento/imunologia , Humanos
19.
Acta Cardiol ; : 1-16, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722068

RESUMO

BACKGROUND AND AIMS: Overweight and obesity have been found to exhibit a statistically significant increase in corrected QT interval (QTc), a major contributing factor to sudden death. However, the influence of widely used weight loss strategies including diet, exercise, anti-obesity drugs, and bariatric surgery on QTc remains inconsistent. Therefore, the present systematic review and meta-analysis aim to quantitatively analyse and evaluate the effect of weight loss on QTc in obese patients after diet control with exercise intervention and anti-obesity drugs, as well as bariatric surgery. METHODS: Twenty randomised controlled trials (RCT) and observational studies were included in the meta-analysis on the effects of weight loss on QTc. The fixed-effects model was employed in the RCTs, and the random-effects model was employed due to the presence of statistical heterogeneity among observational studies. Subgroup analysis was conducted to understand the differences in distinct weight loss methods and follow-up time. RESULTS: Overall, the QTc of people with obesity after weight loss was shorter than that before (mean difference (MD) = 21.97 ms, 95% confidence interval (CI) = 12.42, 31.52, p < .0001). Subgroup analysis restricted to seven included studies whose intervention was diet control with exercise showed a decrease of QTc with statistical significance (MD = 9.35 ms, 95%CI = 2.56, 37.54, p = .007). In the remaining 11 studies, bariatric surgery was the weight loss method. The results also showed a shortening of QTc after surgery, and the difference was statistically significant (MD = 29.04 ms, 95%CI = -16.46, 41.62, p < .00001). A statistically significant difference in QTc shortening at 6 months compared to pre-operation values was further observed (MD = -31.01 ms, 95%CI = -2.89, -59.12, p = .03). The shortening of QTc at 12 months of follow-up was also significantly different from that before surgery (MD = 36.47 ms, 95%CI = 14.17, 58.78, p < .00001). Moreover, the differences became more pronounced as the follow-up time extended. CONCLUSIONS: We demonstrate that weight loss links to a shortened QTc, without considering the means of weight loss. Bariatric surgery has been found to result in a greater reduction in QTc.

20.
World J Stem Cells ; 16(5): 538-550, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38817334

RESUMO

BACKGROUND: Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5'-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of ANKRD26. However, the positive regulators of ANKRD26 are still unknown. AIM: To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on ANKRD26 transcription. METHODS: Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the ANKRD26 expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for ANKRD26. Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on ANKRD26. Moreover, using the GENT2 platform, we analyzed the relationship between ANKRD26 expression and overall survival in cancer patients. RESULTS: In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of ANKRD26 varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for ANKRD26. Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate ANKRD26. Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5'-UTR of ANKRD26 and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of ANKRD26. In addition, we discovered that high ANKRD26 expression is always related to a more favorable prognosis in breast and lung cancer patients. CONCLUSION: We first discovered that the transcription factor GATA2 plays a positive role in ANKRD26 transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers.

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