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1.
iScience ; 27(6): 110111, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38957790

RESUMO

Osteophyte formation, a key indicator of osteoarthritis (OA) severity, remains poorly understood in its relation to gut microbiota and metabolites in knee osteoarthritis (KOA). We conducted 16S rDNA sequencing and untargeted metabolomics on fecal and serum samples from 20 healthy volunteers, 80 KOA patients in Guangdong, and 100 in Inner Mongolia, respectively. Through bioinformatics analysis, we identified 3 genera and 5 serum metabolites associated with KOA osteophyte formation. Blautia abundance negatively correlated with meat, cheese, and bean consumption. The 5 serum metabolites negatively correlated with dairy, beef, cheese, sugar, and salt intake, yet positively with age and oil consumption. Higher Blautia levels in the gut may contribute to KOA osteophyte formation, with serum metabolites LTB4 and PGD2 potentially serving as biomarkers. KOA patients in Inner Mongolia exhibited lower Blautia levels and reduced expression of 5 serum metabolites, possibly due to cheese consumption habits, resulting in less osteophyte formation.

2.
Chem Biodivers ; : e202401093, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867371

RESUMO

Two previously undescribed coumarins (1-2) were isolated from the root of Notopterygium incisum. The structures of new findings were elucidated by analyses of spectral evidences in HRESIMS, NMR, as well as ICD. The absolute configurations were further confirmed by chemical calculations. 1-2 exhibits obviously anti-inflammatory activity by inhibiting the expression of inflammatory mediators (COX-2, iNOS), as well as reducing the release of NO and the accumulation of ROS in cells. Western blotting analysis revealed that 2 could inhibit the PI3K/AKT pathway by reducing the expression of p-PI3K and p-AKT.

3.
Bone Joint Res ; 13(6): 294-305, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884556

RESUMO

Aims: In this study, we aimed to visualize the spatial distribution characteristics of femoral head necrosis using a novel measurement method. Methods: We retrospectively collected CT imaging data of 108 hips with non-traumatic osteonecrosis of the femoral head from 76 consecutive patients (mean age 34.3 years (SD 8.1), 56.58% male (n = 43)) in two clinical centres. The femoral head was divided into 288 standard units (based on the orientation of units within the femoral head, designated as N[Superior], S[Inferior], E[Anterior], and W[Posterior]) using a new measurement system called the longitude and latitude division system (LLDS). A computer-aided design (CAD) measurement tool was also developed to visualize the measurement of the spatial location of necrotic lesions in CT images. Two orthopaedic surgeons independently performed measurements, and the results were used to draw 2D and 3D heat maps of spatial distribution of necrotic lesions in the femoral head, and for statistical analysis. Results: The results showed that the LLDS has high inter-rater reliability. As illustrated by the heat map, the distribution of Japanese Investigation Committee (JIC) classification type C necrotic lesions exhibited clustering characteristics, with the lesions being concentrated in the northern and eastern regions, forming a hot zone (90% probability) centred on the N4-N6E2, N3-N6E units of outer ring blocks. Statistical results showed that the distribution difference between type C2 and type C1 was most significant in the E1 and E2 units and, combined with the heat map, indicated that the spatial distribution differences at N3-N6E1 and N1-N3E2 units are crucial in understanding type C1 and C2 necrotic lesions. Conclusion: The LLDS can be used to accurately measure the spatial location of necrotic lesions and display their distribution characteristics.

4.
Mol Plant ; 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38859588

RESUMO

Root nodule symbiosis (RNS) between legume and rhizobia is a major source of nitrogen in agricultural systems. Effective symbiosis requires precise regulation of plant defense responses. The role of the defense hormone jasmonic acid in the immune response has been extensively studied. The current research shows that JA can play either a positive or negative regulatory role in RNS depending on its concentration, while the molecular mechanisms remain to be elucidated. Here, we found that inoculation with rhizobia Sm1021 induced the JA pathway response in Medicago truncatula, and blocking JA pathway significantly reduced the number of infection threads. Mutations in the MtMYC2 gene, a JA signaling master transcription factor, significantly inhibited rhizobia infection, terminal differentiation, and symbiotic cell formation. Combining RNA-seq and ChIP-seq, we discovered that MtMYC2 regulates the expression of nodule-specific MtDNF2, MtNAD1, and MtSymCRK to suppress host defense. MtMYC2 activates MtDNF1 expression to regulate the maturation of MtNCRs, which in turn promotes bacteroid formation. More importantly, MtMYC2 promotes the expression of MtIPD3 to participate in symbiotic signaling transduction. Notably, the MtMYC2-MtIPD3 transcriptional regulation module is specifically present in legumes. Additionally, The Mtmyc2 mutants exhibits a susceptible phenotype to Rhizoctonia solani. Collectively, our findings reveal the molecular mechanisms of the JA pathway in RNS and further broaden the understanding of JA in the plant-microbe interaction network.

5.
Heart Rhythm ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38815780

RESUMO

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia with high morbidity and mortality implications. Several studies have described a paradoxical inverse relationship between serum cholesterol and the risk of AF, but it remains unknown whether remnant cholesterol (RC) is associated with AF incidence. OBJECTIVE: This study aims to prospectively investigate the association between RC and AF. METHODS: A total of 392,783 participants free of AF at baseline from the UK Biobank were included for the analysis. Cox proportional hazards model, subgroup analysis, and sensitivity analyses were used to evaluate the independent association between RC levels and the risk of new-onset AF. Furthermore, we performed a discordance analysis by using the median cutoff points of low-density lipoprotein cholesterol (LDL-C) and RC. RESULTS: After a median follow-up of 12.8 years (interquartile range 12.0-13.6 years), a total of 23,558 participants experienced incident AF. Compared with the highest RC level, the lower RC level was associated with an increased risk of AF incidence (quartile 1 vs quartile 4: hazard ratio 1.396; 95% confidence interval [CI] 1.343-1.452). The results remained robust across a series of sensitivity analyses. In the discordance analyses, a significantly higher risk of AF was observed in participants with discordant low RC/high LDL-C levels than in those with concordant high RC/LDL-C levels. In the low LDL-C group, RC reduction even contributed to an additional 15.8% increased rate of incident AF (low RC/low LDL-C: hazard ratio 1.303; 95% CI 1.260-1.348 vs high RC/low LDL-C: hazard ratio 1.125; 95% CI 1.079-1.172). CONCLUSION: Low RC levels were associated with an increased risk of incident AF independent of traditional cardiovascular risk factors.

6.
Small ; : e2401335, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693088

RESUMO

Exploration of multifunctional integrated catalysts is of great significance for photocatalysis toward practical application. Herein, a 1D confined nanoreactor with a heterogeneous core-shell structure is designed for synergies of efficient catalysis and temperature monitoring by custom encapsulation of Z-scheme heterojunction CuS quantum dots/BiVO4 (CuS QDs/BiVO4) and Y2O2S-Er, Yb. The dispersed active sites created by the QDs with high surface energy improve the mass transfer efficiency, and the efficient electron transport channels at the heterogeneous interface extend the carrier lifetime, which endows the nanoreactor with excellent catalytic performance. Meanwhile, real-time temperature monitoring is realized based on the thermally coupled levels 2H11/2/4S3/2→4I15/2 of Er3+ using fluorescence intensity ratio, which enables the monitorable photocatalysis. Furthermore, the nanoreactor with a multidimensional structure increases effective intermolecular collisions to facilitate the catalytic process by restricting the reaction within distinct enclosed spaces and circumvents potential unknown interaction effects. The design of multi-space nanoconfined reactors opens up a new avenue to modulate catalyst function, providing a unique perspective for photocatalytic applications in the mineralization of organic pollutants, hydrogen production, and nitrogen fixation.

7.
Heliyon ; 10(10): e31088, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38803913

RESUMO

Background: The impact of capsular closure vs non-closure in hip arthroscopy for femoracetabular impingement (FAI) was assessed by a meta-analysis. Methods: With the most recent search update occurring in August 2022, relevant studies were found by searching the Pubmed and EMBASE databases. A collection of studies was made that conducted hip arthroscopy for FAI. Review Manager 5.3 was used to carry out the meta-analysis. The dichotomous and continuous factors were compared using the odds ratios (OR) and mean differences (MD). A fixed-effect or random-effect model was chosen, depending on the degree of heterogeneity (I2). Forest plots were used to assess the results. A significance level of P < 0.05 was applied to the statistical analysis. Results: Ultimately, 15 studies were incorporated into the meta-analysis. The surgery time was longer for the capsular closure group (CC group) compared to the non-closure (NC group) group. (P < 0.001, SMD = 8.59, 95%CI [7.40, 9.77], I2 = 32 %). Following hip arthroscopy, the CC group's mHHS was superior to that of the NC group (P = 0.001, MD = 2.05, 95%CI [0.83, 3.27], I2 = 42 %), HOS-ADL (P < 0.001, MD = 4.29, 95%CI [3.08, 5.50], I2 = 0 %). The capsular closure group had a reduced rate of postoperative complications (P = 0.001, OR = 0.21, 95%CI [0.08, 0.54], I2 = 0 %) and conversion to THA (P = 0.01, OR = 0.42, 95%CI [0.21, 0.83], I2 = 0 %) following hip arthroscopy than the non-closure group. The revision rate, VAS, and postoperative HOS-SSS did not significantly differ between these two groups (P>0.05). Conclusion: The current meta-analysis found that the closed group had a lower complication rate and considerably greater mHHS and HOS-ADL following surgery compared to the non-closed capsule group. Whether this is related to the continuous progress of biomechanical and clinical research techniques deserves our attention. Level of evidence: Level IV, systematic review of Level I through Level III studies.

8.
Mol Neurobiol ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38795301

RESUMO

Spinal cord injury (SCI) is a severe neurological condition that can lead to paralysis or even death. This study explored the potential benefits of bone marrow mesenchymal stem cell (BMSC) transplantation for repairing SCI. BMSCs also differentiate into astrocytes within damaged spinal cord tissues hindering the cell transplantation efficacy, therefore it is crucial to enhance their neuronal differentiation rate to facilitate spinal cord repair. Wnt5a, an upstream protein in the non-classical Wnt signaling pathway, has been implicated in stem cell migration, differentiation, and neurite formation but its role in the neuronal differentiation of BMSCs remains unclear. Thus, this study investigated the role and underlying mechanisms of Wnt5a in promoting neuronal differentiation of BMSCs both in vivo and in vitro. Wnt5a enhanced neuronal differentiation of BMSCs in vitro while reducing astrocyte differentiation. Additionally, high-throughput RNA sequencing revealed a correlation between Wnt5a and phosphoinositide 3-kinase (PI3K)/protein kinase B(AKT) signaling, which was confirmed by the use of the PI3K inhibitor LY294002 to reverse the effects of Wnt5a on BMSC neuronal differentiation. Furthermore, transplantation of Wnt5a-modified BMSCs into SCI rats effectively improved the histomorphology (Hematoxylin and eosin [H&E], Nissl and Luxol Fast Blue [LFB] staining), motor function scores (Footprint test and Basso-Beattie-Bresnahan [BBB]scores)and promoted neuron production, axonal formation, and remodeling of myelin sheaths (microtubule associated protein-2 [MAP-2], growth-associated protein 43 [GAP43], myelin basic protein [MBP]), while reducing astrocyte production (glial fibrillary acidic protein [GFAP]). Therefore, targeting the Wnt5a/PI3K/AKT pathway could enhance BMSC transplantation for SCI treatment.

9.
Orthop Surg ; 16(6): 1364-1373, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38693612

RESUMO

OBJECTIVE: Early articular cartilage lesion (CL) is a vital sign in the onset of posttraumatic knee osteoarthritis (PTOA) in patients with anterior cruciate ligament deficiency (ACLD). Researchers have suggested that altered kinematics could accelerate CLs and, therefore, lead to the onset of PTOA. However, little is known about whether specific knee kinematics exist that lead to early CL in chronic ACLD knees. Level walking is the most frequent and relevant in vivo activity, which greatly impacts knee health. We hypothesized that the knee kinematics during level walking in chronic ACLD knees with early tibiofemoral CL would significantly differ from those of chronic ACLD knees without early tibiofemoral CL. METHODS: Thirty patients with a chronic ACLD history, including 18 subjects with CLs and 12 subjects without CLs, and 35 healthy control subjects were recruited for the study from July 2020 to August 2022. The knee kinematic data during level walking were collected using a three-dimensional motion analysis system. The kinematic differences between groups were compared using statistical parametric mapping with one dimension for One-Way ANOVA. The cartilage statuses of the ACLD knees were assessed via MRI examination. The CLs distribution of subjects was evaluated using a modified Noyes scale and analyzed by chi-square tests. RESULTS: ACLD knees with CLs had significantly greater posterior tibial translation (7.7-8.0mm, 12%-18% gait cycle GC, p = 0.014) compared to ACLD knees without CLs during level walking. ACLD knees with CLs had greater posterior tibial translation (4.6-5.5mm, 0%-23% GC, p < 0.001; 5.8-8.0mm, 86%-100% GC, p < 0.001) than healthy controls during level walking. In the group of ACLD knees with CLs, CL is mainly located in the back of the tibia plateau and front of load bearing area of the medial femoral condyle (p < 0.05). CONCLUSION: Chronic anterior cruciate ligament deficient knees with cartilage lesions have increased posterior tibial translation compared to anterior cruciate ligament deficient knees without cartilage lesions and healthy subjects. The posterior tibial translation may play an important role in knee cartilage degeneration in ACLD knees. The increased posterior tibial translation and cartilage lesion characteristics may improve our understanding of the role of knee kinematics in cartilage degeneration and could be a helpful potential reference for anterior cruciate ligament deficient therapy, such as physical training to improve abnormal kinematic behavior.


Assuntos
Lesões do Ligamento Cruzado Anterior , Cartilagem Articular , Caminhada , Humanos , Masculino , Feminino , Fenômenos Biomecânicos , Cartilagem Articular/fisiopatologia , Caminhada/fisiologia , Adulto , Lesões do Ligamento Cruzado Anterior/fisiopatologia , Adulto Jovem , Estudos de Casos e Controles , Doença Crônica , Tíbia/fisiopatologia , Imageamento por Ressonância Magnética , Osteoartrite do Joelho/fisiopatologia
10.
Fitoterapia ; 175: 105945, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38575091

RESUMO

Four previously undescribed isoprenoid flavonoids (2-5) were isolated from Sophora davidii, along with five known analogues. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR, and absolute configurations determined by theoretical calculations, including ECD and NMR calculation. The cytotoxic effects of the isolated compounds on human HT29 colon cancer cells were evaluated using the MTT assay, compound 1 exhibited cytotoxicity against human HT29 colon cancer cells with an IC50 value of 8.39 ± 0.09 µM. Studies conducted with compound 1 in HT29 cells demonstrated that it may induce apoptosis and autophagy in HT29 by promoting the phosphorylation of P38 MAPK and inhibiting the phosphorylation of Erk MAPK.


Assuntos
Antineoplásicos Fitogênicos , Apoptose , Autofagia , Flavonoides , Sophora , Humanos , Sophora/química , Autofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Células HT29 , Estrutura Molecular , Flavonoides/farmacologia , Flavonoides/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , China , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Terpenos/farmacologia , Terpenos/isolamento & purificação , Fosforilação
11.
Fitoterapia ; 175: 105970, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38653340

RESUMO

Eleven new highly oxygenated eremophilane-type sesquiterpenoids were isolated from the whole plant of Synotis solidaginea, including two pairs of C-8 S/R epimers. The structures of the new compounds were elucidated on the basis of detailed spectroscopic analysis and the absolute configurations of 1 and 9 were confirmed by single-crystal X-ray crystallography using Cu Kα radiation. All the isolates were tested for the inhibition of LPS-stimulated NO production in macrophage-like mouse monocytic leukemia RAW264.7 cells. Compound 1 exhibited weak inhibitory effects with an IC50 of 71.2 µM.


Assuntos
Óxido Nítrico , Compostos Fitoquímicos , Sesquiterpenos , Camundongos , Animais , Células RAW 264.7 , Estrutura Molecular , Óxido Nítrico/metabolismo , Sesquiterpenos/farmacologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , China , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/isolamento & purificação
12.
Diabetes Obes Metab ; 26(7): 2673-2683, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38558498

RESUMO

AIM: To investigate the association between cardiovascular health metrics defined by Life's Essential 8 (LE8) scores and vascular complications among individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: This prospective study included 11 033 participants with T2D, all devoid of macrovascular diseases (including cardiovascular and peripheral artery disease) and microvascular complications (e.g. diabetic retinopathy, neuropathy and nephropathy) at baseline from the UK Biobank. The LE8 score comprised eight metrics: smoking, body mass index, physical activity, non-high-density lipoprotein cholesterol, blood pressure, glycated haemoglobin, diet and sleep duration. Cox proportional hazards models were established to assess the associations of LE8 scores with incident macrovascular and microvascular complications. RESULTS: During a median follow-up of 12.1 years, we identified 1975 cases of incident macrovascular diseases and 1797 cases of incident microvascular complications. After adjusting for potential confounders, each 10-point increase in the LE8 score was associated with an 18% lower risk of macrovascular diseases and a 15% lower risk of microvascular complications. Comparing individuals in the highest and lowest quartiles of LE8 scores revealed hazard ratios of 0.55 (95% confidence interval 0.47-0.62) for incident macrovascular diseases, and 0.61 (95% confidence interval 0.53-0.70) for incident microvascular complications. This association remained robust across a series of sensitivity analyses and nearly all subgroups. CONCLUSION: Higher LE8 scores were associated with a lower risk of incident macrovascular and microvascular complications among individuals with T2D. These findings underscore the significance of adopting fundamental strategies to maintain optimal cardiovascular health and curtail the risk of developing diabetic vascular complications.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Angiopatias Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/etiologia , Reino Unido/epidemiologia , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Adulto , Fatores de Risco , Índice de Massa Corporal , Fumar/efeitos adversos , Fumar/epidemiologia , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Exercício Físico , Seguimentos , Pressão Sanguínea , Incidência
14.
Fitoterapia ; 174: 105880, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38431026

RESUMO

An undescribed trichodenone derivative (1), two new diketopiperazines (3 and 4) along with a bisabolane analog (2) were isolated from Trichoderma hamatum b-3. The structures of the new findings were established through comprehensive analyses of spectral evidences in HRESIMS, 1D and 2D NMR, Marfey's analysis as well as comparisons of ECD. The absolute configuration of 2 was unambiguously confirmed by NMR, ECD calculation and Mo2(AcO)4 induced circular dichroism. Compounds 1-4 were tested for their fungicidal effects against eight crop pathogenic fungi, among which 1 showed 51% inhibition against Sclerotinia sclerotiorum at a concentration of 50 µg/mL.


Assuntos
Hypocreales , Trichoderma , Estrutura Molecular , Dicetopiperazinas/química , Trichoderma/química
15.
Acta Cardiol ; 79(3): 374-382, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38469674

RESUMO

BACKGROUND: The potential influence of tinnitus on cardiovascular disease (CVD) and all-cause mortality has yet to be explored. We aim to examine the correlations between tinnitus and the risk of cardiovascular events and all-cause mortality. METHODS: We conducted a prospective cohort study utilising data from the UK Biobank. The presence of tinnitus was evaluated through a questionnaire. The primary outcome was defined as a composition of cardiovascular events, including myocardial infarction (MI), stroke, and mortality from CVD, as well as all-cause mortality. Cox proportional hazard models were employed to examine the associations between tinnitus and both the primary outcome and its individual components. Sensitivity analyses were conducted to evaluate the robustness of the primary analysis. RESULTS: A total of 140,146 participants were included in the study. The presence of tinnitus was found to be associated with a higher incident rate of the primary outcome (HR = 1.057, 95%CI: 1.017-1.099, p = 0.005), MI (HR = 1.139, 95%CI: 1.061-1.222, p < 0.001) and all-cause mortality (HR = 1.053, 95%CI: 1.003-1.105, p = 0.038) after adjusting for confounders. However, there was no significant association between tinnitus and stroke or mortality from CVD. Subgroup analysis revealed that the association between tinnitus and the primary outcome was significant in females, participants with abnormal BMI, and those without hearing difficulty, depression or anxiety. Sensitivity analyses yielded consistent results. CONCLUSION: The findings from this study contribute to the existing body of evidence suggesting an association between tinnitus and an increased risk of cardiovascular events and all-cause mortality.


Assuntos
Doenças Cardiovasculares , Causas de Morte , Zumbido , Humanos , Zumbido/epidemiologia , Zumbido/mortalidade , Feminino , Masculino , Reino Unido/epidemiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Causas de Morte/tendências , Fatores de Risco , Idoso , Medição de Risco/métodos , Incidência , Bancos de Espécimes Biológicos , Adulto , Biobanco do Reino Unido
16.
Sci Rep ; 14(1): 2724, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302672

RESUMO

N6-methyladenosine (m6A) modification, as a common epigenetic modification, has been widely studied in autoimmune diseases. However, the role of m6A in the regulation of the immune microenvironment of ankylosing spondylitis (AS) remains unclear. Therefore, we aimed to investigate the effect of m6A modification on the immune microenvironment of AS. We first evaluated RNA modification patterns mediated by 26 m6A regulators in 52 AS samples and 20 healthy samples. Thereafter, an m6A related classifier composed of seven genes was constructed and could effectively distinguish healthy and AS samples. Then, the correlation between m6A regulators and immune characteristics were investigated, including infiltrating immunocytes, immune reactions activity, and human leukocyte antigen (HLA) genes expression. The results indicated that m6A regulators was closely correlated with immune characteristics. For example, EIF3A was significantly related to infiltrating immunocytes; IGF2BP2 and EIF3A were significant regulators in immune reaction of TGF-ß family member, and the expression of HLA-DPA1 and HLA-E were affected by EIF3A and ALKBH5. Next, two distinct m6A expression patterns were identified through unsupervised clustering analysis, and diverse immune characteristics were found between them. A total of 5889 m6A phenotype-related genes were obtained between the two expression patterns, and their biological functions were revealed. Finally, we validated the expression status of m6A modification regulators using two additional datasets. Our findings illustrate that m6A modifications play a critical role in the diversity and complexity of the AS immune microenvironment.


Assuntos
Doenças Autoimunes , Espondilite Anquilosante , Humanos , Espondilite Anquilosante/genética , Adenina , Biologia Computacional , Proteínas de Ligação a RNA
17.
Heart Rhythm ; 21(6): 743-751, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38336194

RESUMO

BACKGROUND: Emerging evidence has linked daytime napping with the risk of cardiovascular events. Cardiac arrhythmias are considered an early clinical stage for cardiovascular diseases. However, whether napping frequency is associated with incident arrhythmias remains unknown. OBJECTIVE: This study aimed to prospectively investigate the association between napping frequency and cardiac arrhythmias. METHODS: Daytime napping frequency was self-reported in response to touchscreen questionnaires. The primary outcomes were incident arrhythmias including atrial fibrillation/flutter (AF/Af), ventricular arrhythmia, and bradyarrhythmia. Cox regression analysis was conducted on the basis of 491,117 participants free of cardiac arrhythmias from the UK Biobank. The 2-sample mendelian randomization (MR) and 1-sample MR were used to ensure a causal effect of genetically predicted daytime napping on the risk of arrhythmias. RESULTS: During a median follow-up of 11.91 years, 28,801 incident AF/Af cases, 4132 incident ventricular arrhythmias, and 11,616 incident bradyarrhythmias were documented. Compared with never/rarely napping, usually napping was significantly associated with higher risks of AF/Af (hazard ratio, 1.141; 95% CI, 1.083-1.203) and bradyarrhythmia (hazard ratio, 1.138; 95% CI, 1.049-1.235) but not ventricular arrhythmia after adjustment for various covariates. The 2-sample MR and 1-sample MR analysis showed that increased daytime napping frequency was likely to be a potential causal risk factor for AF/Af in FinnGen (odds ratio, 1.626; 95% CI, 1.061-2.943) and bradyarrhythmia in the UK Biobank (odds ratio, 1.005; 95% CI, 1.002-1.008). CONCLUSION: The results of this study add to the burgeoning evidence of an association between daytime napping frequency and an increased risk of cardiac arrhythmias including AF/Af, ventricular arrhythmia, and bradyarrhythmia.


Assuntos
Arritmias Cardíacas , Análise da Randomização Mendeliana , Sono , Humanos , Análise da Randomização Mendeliana/métodos , Feminino , Masculino , Estudos Prospectivos , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatologia , Incidência , Pessoa de Meia-Idade , Sono/fisiologia , Reino Unido/epidemiologia , Fatores de Risco , Seguimentos , Idoso
19.
Life Sci ; 339: 122414, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38216121

RESUMO

Contamination by pathogens, such as bacteria, can irritate a wound and prevent its healing, which may affect the physical fitness of the infected person. As such, the development of more novel nano-biomaterials able to cope with the inflammatory reaction to bacterial infection during the wound healing process to accelerate wound healing is required. Herein, a halofuginone­silver nano thermosensitive hydrogel (HTPM&AgNPs-gel) was prepared via a physical swelling method. HTPM&AgNPs-gel was characterized based on thermogravimetric analysis, differential scanning calorimetry, morphology, injectability, and rheological mechanics that reflected its exemplary nature. Moreover, HTPM&AgNPs-gel was further tested for its ability to facilitate healing of skin fibroblasts and exert antibacterial activity. Finally, HTPM&AgNPs-gel was tested for its capacity to accelerate general wound healing and treat bacterially induced wound damage. HTPM&AgNPs-gel appeared spherical under a transmission electron microscope and showed a grid structure under a scanning electron microscope. Additionally, HTPM&AgNPs-gel demonstrated excellent properties, including injectability, temperature-dependent swelling behavior, low loss at high temperatures, and appropriate rheological properties. Further, HTPM&AgNPs-gel was found to effectively promote healing of skin fibroblasts and inhibit the proliferation of Escherichia coli and Staphylococcus aureus. An evaluation of the wound healing efficacy demonstrated that HTPM&AgNPs-gel had a more pronounced ability to facilitate wound repair and antibacterial effects than HTPM-gel or AgNPs-gel alone, and exhibited ideal biocompatibility. Notably, HTPM&AgNPs-gel also inhibited inflammatory responses in the healing process. HTPM&AgNPs-gel exhibited antibacterial, anti-inflammatory, and scar repair features, which remarkably promoted wound healing. These findings indicated that HTPM&AgNPs-gel holds great clinical potential as a promising and valuable wound healing treatment.


Assuntos
Nanopartículas Metálicas , Piperidinas , Quinazolinonas , Prata , Humanos , Prata/farmacologia , Prata/química , Staphylococcus aureus , Cicatrização , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Hidrogéis/química , Anti-Inflamatórios/farmacologia
20.
Hypertens Res ; 47(5): 1157-1166, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38212367

RESUMO

Remnant cholesterol (RC) has been associated with atherosclerotic cardiovascular disease, but its relationship with hypertension remains unclear. This prospective cohort study aimed to investigate the association between RC and subsequent hypertension risk. Data from the UK Biobank, comprising 295,062 participants initially free of hypertension, were analyzed. Cox proportional hazards regression assessed the association between RC quartiles and hypertension risk. Discordance analysis evaluated the risk of hypertension in discordant/concordant groups of RC and low-density lipoprotein cholesterol (LDL-C) using the difference in percentile units (>10 units). Restricted cubic spline curves were used to model the relationship between RC and hypertension risk. The mean ± SD age of participants was 55.1 ± 8.1 years, with 40.6% being men and 94.7% White. During a median follow-up of 12.8 years, 39,038 participants developed hypertension. Comparing extreme quartiles of RC, the hazard ratio (HR) for incident hypertension was 1.20 (95% CI: 1.17-1.24). After adjusting for traditional risk factors, each 1 mmol/L increase in RC levels was associated with a 27% higher risk of incident hypertension (HR: 1.27; 95% CI: 1.23-1.31). The discordant group with high RC/low LDL-C exhibited a higher risk of incident hypertension compared to the concordant group (HR: 1.06; 95% CI: 1.03-1.09). Spline curves further demonstrated a positive association between RC and the risk of incident hypertension. We concluded that elevated RC emerged as an independent risk factor of incident hypertension, extending beyond traditional risk factors. Monitoring RC levels and implementing interventions to lower RC may have potential benefits in preventing hypertension.


Assuntos
Colesterol , Hipertensão , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Colesterol/sangue , Adulto , Fatores de Risco , Incidência , LDL-Colesterol/sangue , Idoso , Reino Unido/epidemiologia , Estudos de Coortes
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