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1.
Vasc Health Risk Manag ; 20: 141-155, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567028

RESUMO

Background and Aim: An elevated triglyceride-glucose (TyG) level is associated with increased risk of mortality in patients with CAD. Trimethylamine N-oxide (TMAO) has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is correlated with adverse outcomes. However, the incremental prognostic value of TMAO and TyG in the cohort of optical coherence tomography (OCT)-defined high-risk ST-segment elevation myocardial infarction (STEMI) patients is unknown. Methods: We studied 274 consecutive aged ≥18 years patients with evidence of STEMI and detected on pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019. Outcomes: There were 22 (22.68%), 27 (27.84%), 26 (26.80%), and 22 (22.68%) patients in groups A-D, respectively. The baseline characteristics according to the level of TMAO and TyG showed that patients with higher level in both indicators were more likely to have higher triglycerides (p < 0.001), fasting glucose (p < 0.001) and higher incidence of diabetes (p = 0.008). The group with TMAO > median and TyG ≤ median was associated with higher rates of MACEs significantly (p = 0.009) in fully adjusted analyses. During a median follow-up of 2.027 years, 20 (20.6%) patients experienced MACEs. To evaluate the diagnostic value of the TyG index combined with TMAO, the area under the receiver operating characteristic curve for predicting MACEs after full adjustment was 0.815 (95% confidence interval, 0.723-0.887; sensitivity, 85.00%; specificity, 72.73%; cut-off level, 0.577). Among the group of patients with TMAO > median and TyG ≤ median, there was a significantly higher incidence of MACEs (p=0.033). A similar tendency was found in the cohort with hyperlipidemia (p=0.016) and diabetes mellitus (p=0.036). Conclusion: This study demonstrated the usefulness of combined measures of the TyG index and TMAO in enhancing risk stratification in STEMI patients with OCT-defined high-risk plaque characteristics. Trial Registration: This study was registered at ClinicalTrials.gov as NCT03593928.


Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus , Metilaminas , Placa Aterosclerótica , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Adolescente , Adulto , Tomografia de Coerência Óptica/efeitos adversos , Glucose , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Triglicerídeos , Biomarcadores , Fatores de Risco , Placa Aterosclerótica/complicações , Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus/diagnóstico , Glicemia , Medição de Risco , Sistema de Registros
2.
Org Biomol Chem ; 22(11): 2187-2191, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38391292

RESUMO

The Friedel-Crafts alkylation of arenes is an important part of electrophilic aromatic substitution reactions. However, the reactivity of arenes is weakened by electron-withdrawing substituents, leading to limited substrate scopes and applications. Herein, we developed an efficient HOTf-promoted Friedel-Crafts alkylation reaction of broad arenes with α-aryl-α-diazoesters under metal-free and solvent-free conditions.

3.
Mutat Res ; 828: 111852, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38368811

RESUMO

OBJECTIVES: Our group previously found that LINC00665 was upregulated in hepatocellular carcinoma (HCC) tissues through database analysis; however, the potential molecular mechanism of LINC00665 in HCC progression still needs further study. METHODS: qRTPCR was performed to determine the differential expression of LINC00665 and let-7i in HCC cells. Dual-luciferase reporter assays were performed to analyze the interaction of LINC00665 and let-7i. CCK-8 assays, scratch assays, Transwell invasion assays, qRTPCR and western blotting were performed to determine the regulatory mechanism of LINC00665/let-7i/HMGA1 in HCC cells. RESULTS: LINC00665 was upregulated in HCC cells compared with normal hepatocytes. A potential binding site between LINC00665 and let-7i was confirmed by dual-luciferase reporter assay. In HCC cells, inhibition of LINC00665 significantly reduced cell proliferation, migration and invasion ability via the let-7i/HMGA1 signaling axis. CONCLUSION: LINC00665 promotes the proliferation and invasion of HCC cells via the let-7i/HMGA1 signaling axis.

4.
Neuropathology ; 44(1): 3-20, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37345225

RESUMO

In the central nervous system (CNS), a large group of glial cells called astrocytes play important roles in both physiological and disease conditions. Astrocytes participate in the formation of neurovascular units and interact closely with other cells of the CNS, such as microglia and neurons. Stroke is a global disease with high mortality and disability rate, most of which are ischemic stroke. Significant strides in understanding astrocytes have been made over the past few decades. Astrocytes respond strongly to ischemic stroke through a process known as activation or reactivity. Given the important role played by reactive astrocytes (RAs) in different spatial and temporal aspects of ischemic stroke, there is a growing interest in the potential therapeutic role of astrocytes. Currently, interventions targeting astrocytes, such as mediating astrocyte polarization, reducing edema, regulating glial scar formation, and reprogramming astrocytes, have been proven in modulating the progression of ischemic stroke. The aforementioned potential interventions on astrocytes and the crosstalk between astrocytes and other cells of the CNS will be summarized in this review.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Astrócitos/patologia , AVC Isquêmico/terapia , AVC Isquêmico/patologia , Sistema Nervoso Central/patologia , Acidente Vascular Cerebral/patologia , Gliose/patologia
5.
J Atheroscler Thromb ; 31(1): 23-35, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37423723

RESUMO

AIMS: Plaque erosion (PE) is one of the main plaque phenotypes of acute coronary syndrome (ACS). However, the underlying plaque component and distribution have not been systematically analysed. This study aims to investigate the distribution of lipid and calcium content in culprit lesions assessed by optical coherence tomography (OCT) in patients with PE and explore its relationship with prognosis in a cohort of ST segment elevation myocardial infarction (STEMI) patients. METHODS: A prospective cohort of 576 patients with STEMI was enrolled in our study. After exclusion, 152 PE patients with clear underlying plaque components were ultimately analysed. The culprit lesion was divided into the border zone, external erosion zone and erosion site in the longitudinal view. Each pullback of the culprit lesions was assessed by 3 independent investigators frame-by-frame, and the quantity and distribution of lipid and calcium components were recorded. RESULTS: Of the 152 PE patients, lipid and calcium contents were more likely to exist in the external erosion zone than in the other regions. In particular, a high level of lipid content proximal to the erosion site was significantly associated with plaque vulnerability and a higher incidence of MACEs. CONCLUSION: This study revealed that high level of lipid content in the proximal external erosion zone was related to high-risk plaque characteristics and poor prognosis, which provided a novel method for risk stratification and precise management in patients with plaque erosion.


Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Placa Aterosclerótica , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia , Estudos Prospectivos , Cálcio , Angiografia Coronária/métodos , Infarto do Miocárdio/etiologia , Placa Aterosclerótica/patologia , Síndrome Coronariana Aguda/etiologia , Lipídeos , Tomografia de Coerência Óptica/métodos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia
6.
Phytother Res ; 38(1): 11-21, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37767776

RESUMO

Recently, several meta-analyses (MAs) have focused on the health effects of resveratrol. However, the methodological and reporting quality of these MAs has not yet been fully evaluated so far. Therefore, the present study evaluated the quality of these MAs through a methodological systematic review. Systematic searches were conducted in PubMed, Embase, Web of Science, and Cochrane Library from inception until May 20, 2022, and PubMed was used to update the search until September 6, 2023. The methodological and reporting quality of the selected MAs was evaluated using AMSTAR-2 and PRISMA 2009. Fifty-one MAs published during 2013-2023 were included. In each review, the number of primary studies ranged from 3 to 37, and the number of participants ranged from 50 to 2114. Among the first-listed primary outcomes, only 23 (45.10%) were "positive." As for the methodological quality, most MAs (44, 86.27%) on resveratrol were rated critically low. Inadequate reporting of the included MAs mainly involved items 2 ("Structured summary"), 5 ("Protocol and registration"), 8 ("Search"), 9 ("Study selection"), 10 ("Data collection process"), 12 ("Risk of bias in individual studies"), and 24 ("Summary of evidence") based on the PRISMA 2009. Additionally, journal's impact factor, number of authors, and funding support were positively associated with the overall methodological quality but were not statistically significant (p > 0.05). Future MAs on resveratrol require better design, implementation, and reporting by following the Cochrane Handbook, AMSTAR-2, and PRISMA.


Assuntos
Resveratrol , Humanos , Coleta de Dados
7.
ACS Nano ; 18(1): 410-427, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38147452

RESUMO

Focused ultrasound-stimulated microbubbles can induce blood flow shutdown and ischemic necrosis at higher pressures in an approach termed antivascular ultrasound. Combined with conventional therapies of chemotherapy, immunotherapy, and radiation therapy, this approach has demonstrated tumor growth inhibition and profound synergistic antitumor effects. However, the lower cavitation threshold of microbubbles can potentially yield off-target damage that the polydispersity of clinical agent may further exacerbate. Here we investigate the use of a monodisperse nanodroplet formulation for achieving antivascular effects in tumors. We first develop stable low boiling point monodisperse lipid nanodroplets and examine them as an alternative agent to mediate antivascular ultrasound. With synchronous intravital imaging and ultrasound monitoring of focused ultrasound-stimulated nanodroplets in tumor microvasculature, we show that nanodroplets can trigger blood flow shutdown and do so with a sharper pressure threshold and with fewer additional events than conventionally used microbubbles. We further leverage the smaller size and prolonged pharmacokinetic profile of nanodroplets to allow for potential passive accumulation in tumor tissue prior to antivascular ultrasound, which may be a means by which to promote selective tumor targeting. We find that vascular shutdown is accompanied by inertial cavitation and complex-order sub- and ultraharmonic acoustic signatures, presenting an opportunity for effective feedback control of antivascular ultrasound.


Assuntos
Neoplasias , Humanos , Ultrassonografia , Acústica , Microvasos/diagnóstico por imagem , Microscopia Intravital , Microbolhas
8.
Thromb Haemost ; 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38109905

RESUMO

OBJECTIVE: Aldehyde dehydrogenase 4A1 (ALDH4A1) was recently reported to be a novel autoantigen of atherosclerosis. However, its role in different phenotypes of acute coronary syndrome remains unclear. Herein, we planned to explore the circulating and regional expression of ALDH4A1 in patients with plaque rupture (PR) and plaque erosion (PE) determined by optical coherence tomography (OCT). METHODS AND RESULTS: After applying the inclusion and exclusion criteria, a prospective series of 312 patients with ST segment elevated myocardial infarction (STEMI), including 161 patients with PR and 151 patients with PE determined by OCT, were enrolled for plasma ALDH4A1 testing. In addition, ALDH4A1 was quantified using immunofluorescence in aspirated coronary thrombus samples obtained from 31 patients with PR and 25 patients with PE. In addition, we established an atherosclerosis mouse model and analyzed the distribution of ALDH4A1 expression in different mouse organs. Furthermore, we compared the level of ALDH4A1 in the spleen and carotid artery between Apoe-/- and C57 mice. The results showed that the plasma level of ALDH4A1 was significantly higher in STEMI patients with PE than in those with PR (4.6 ng/mL [2.2-8.7] vs. 3.5 ng/mL [1.6-5.6] p = 0.005). The expression of ALDH4A1 in aspirated coronary thrombi was also significantly higher in patients with PE than in those with PR (mean gray value: 32.0 [23.6-40.6] vs. 16.8 [14.0-24.5], p < 0.001). In animal models, the expression of ALDH4A1 is much higher in the spleen than in other organs, and the level of ALDH4A1 is significantly elevated in the spleen and carotid artery of Apoe-/- mice compared with C57 mice. CONCLUSION: The high levels of ALDH4A1 in the plasma and aspirated coronary thrombi independently correlated with PE in patients with STEMI. These results suggested that ALDH4A1 is involved in the mechanism of PE and serves as a promising biomarker and treatment target for patients with PE.

9.
Zhongguo Zhong Yao Za Zhi ; 48(21): 5957-5964, 2023 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-38114191

RESUMO

This study evaluated the clinical effectiveness of Ruyi Zhenbao Pills in the treatment of osteoarthritis, aiming to clarify its clinical advantages and promote rational drug use and related policy transformation. Following the relevant standards in Guidelines for the Comprehensive Evaluation of Drugs in Clinical Practice and Technical Specifications for the Clinical Comprehensive Evaluation of Chinese Patent Medicine, comprehensive research and related data on Ruyi Zhenbao Pills in the treatment of osteoarthritis were collected in the dimensions of safety, effectiveness, economy, innovation, suitability, accessibility, and traditional Chinese medicine(TCM) cha-racteristics(referred to as the "6+1" dimensions). Through evidence-based medicine, questionnaire surveys, health technology assessment, pharmacoeconomic evaluation, and other methods, a multi-criteria decision analysis(MCDA) model and CSC v2.0 software were used to comprehensively evaluate the clinical value of Ruyi Zhenbao Pills. Spontaneous reporting system data on adverse reactions and literature data indicate that the adverse reactions of Ruyi Zhenbao Pills are mostly general adverse reactions, with no reports of se-rious adverse reactions. The known risks are small, and its safety is rated as class A. It has been shown to effectively relieve joint pain and restore joint function in the treatment of osteoarthritis. However, more high-quality, large-sample randomized controlled trials are needed to further validate its effectiveness, which is rated as class B. There is evidence supporting its economic viability, and its economic is rated as class B. It demonstrates good clinical innovation, innovative enterprise service system, and industrial innovation, and innovation is rated as class A. Medical professionals and patients have a favorable perception of the suitability of Ruyi Zhenbao Pills, and further improvement can be made in terms of convenience of administration and promotion to facilitate rational drug use by healthcare professionals and patients. Suitability is rated as class B. The drug has a favorable price level, availability, and affordability, and accessibility is rated as class A. Ruyi Zhenbao Pills are a classic Tibetan medicinal prescription with excellent TCM theoretical characteristics. However, further research is needed on its use in human studies. TCM characteristics are rated as class B. Based on the evaluation results of the "6+1" dimensions, the comprehensive clinical evaluation is rated as grade B. Ruyi Zhenbao Pills have good clinical value in the treatment of osteoarthritis, and it is recommended to undergo the necessary procedures for conditional transformation into a policy for the management of essential clinical drugs.


Assuntos
Medicamentos de Ervas Chinesas , Medicamentos Essenciais , Osteoartrite , Humanos , Medicina Tradicional Chinesa , Padrões de Referência , Medicamentos sem Prescrição , Osteoartrite/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos
10.
Zhongguo Zhong Yao Za Zhi ; 48(18): 5078-5090, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37802850

RESUMO

Bayesian network Meta-analysis was employed to compare the efficacy of different oral Chinese patent medicines in treating type 2 diabetes mellitus with angina pectoris of coronary heart disease. Randomized controlled trial(RCT) of oral Chinese patent medicines in treating type 2 diabetes mellitus complicated with angina pectoris of coronary heart disease were retrieved from 8 Chinese and English databases including CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, Cochrane Library, and Web of Science with the time interval from inception to November 2022. The BUGSnet package in R 4.2.1 was used to conduct Meta-analysis. A total of 45 RCTs were included, involving 4 727 patients and 7 oral Chinese patent medicines. Network Meta-analysis showed that the conventio-nal western medicine combined with Chinese patent medicines improved the outcome indicators. Shexiang Baoxin Pills + conventional western medicine had the best effect on reducing the incidence of adverse cardiovascular events, and Yixinshu Capsules + conventional western medicine on reducing the frequency and duration of angina pectoris. The conventional western medicine combined with oral Chinese patent medicines can reduce blood glucose indicators. Yindan Xinnaotong Soft Capsules + conventional western medicine had the best effect on reducing fasting blood glucose(FBG), 2 hours postprandial blood glucose(PBG), and glycosylated hemoglobin(HbA1c). The conventional western medicine combined with oral Chinese patent medicines can reduce blood lipid indicators. Yixinshu Capsules + conventional western medicine had the best effect on reducing total cholesterol(TC) and low density lipoprotein-cholesterol(LDL-C), and Yindan Xinnaotong Soft Capsules + conventional western medicine on reducing triglyceride(TG). Current evidence suggests that the patients with type 2 diabetes mellitus complicated with angina pectoris of coronary heart disease could reasonably choose oral Chinese patent medicines on the basis of routine antiplatelet, anticoagulant, hypoglycemic, and antihypertensive therapies, which could reduce the incidence of adverse cardiovascular events, alleviate the symptoms of angina pectoris, and reduce the glucose and lipid metabolism indicators. Shexiang Baoxin Pills + conventional treatment and Yixinshu Capsules + conventional western medicine have better effect on angina pectoris, Yindan Xinnaotong Soft Capsules + conventional western medicine on lowering blood glucose, and Yindan Xinnaotong Soft Capsules + conventional western medicine and Yixinshu Capsules + conventional western medicine on reducing blood lipid. Due to the lack of direct comparative results between Chinese patent medicines and other factors, high-quality studies remain to be carried out for further verification.


Assuntos
Doença das Coronárias , Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Humanos , Medicamentos sem Prescrição , Metanálise em Rede , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Teorema de Bayes , Glicemia , Angina Pectoris/complicações , Angina Pectoris/tratamento farmacológico , Doença das Coronárias/complicações , Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Cápsulas , Lipídeos , Colesterol
11.
J Mol Model ; 29(10): 314, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37707644

RESUMO

CONTEXT: The adsorptions of toxic gases SO2 and H2S on 2D α/ß/γ-FeB6 monolayer were investigated using density functional theory calculations. To analyze the interaction between gas molecule H2S/SO2 and α/ß/γ-FeB6 monolayer, we calculated adsorption energy, adsorption distance, Mullikan charge, charge density difference, band structure, the density of states, work function, and theoretical recovery time. The adsorption energies show that H2S/SO2 is chemisorbed on α/ß-FeB6 while H2S/SO2 is physiosorbed on γ-FeB6 monolayer. As a result, γ-FeB6 has a short recovery time for H2S (5.71×10-8 s)/SO2 (1.94×10-5 s) due to modest adsorption. Therefore, γ-FeB6 may be a promising candidate for reusable H2S/SO2 sensors at room temperature. Although H2S is chemisorbed on α/ß-FeB6, as the working temperature rises to 500 K, the recovery time of α/ß-FeB6 for H2S can decrease to 1.13×10-1 s and 2.08×10-1 s, respectively, which are well within the detectable range. So, α/ß-FeB6 monolayer also may be a good candidate for H2S gas sensor. METHODS: Calculations were performed at GGA-PBE/DNP level using the Dmol3 module implemented in the Material Studio 2018 software package.

12.
Front Hum Neurosci ; 17: 1195220, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37529406

RESUMO

Background: Whereas the Montreal Cognitive Assessment (MoCA) and Addenbrooke's cognitive examination-revised (ACE-R) are commonly used tests for the detection of post-stroke cognitive impairment (PSCI), these instruments take 10-30 min to administer and do not assess processing speed, which is a critical impairment in PSCI. MemTrax (MTx) is a continuous recognition test, which evaluates complex information processing, accuracy, speed, and attention, in 2 min. Aim: To evaluate whether MTx is an effective and practical tool for PSCI assessment. Methods: This study enrolled acute ischemic stroke (AIS) patients who have assessed the cognitive status including MTx, clinical dementia rating (CDR), MoCA, Neuropsychiatric Inventory (NPI), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), the National Institute of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), and Barthel Index of activity of daily living (BI) combined with the physical examinations of the neurologic system at the 90-day (D90) after the AIS. The primary endpoint of this study was establishing MTx cut-offs for distinguishing PSCI from AIS. Results: Of the 104 participants, 60 were classified to the PSCI group. The optimized cut-off value of MTx-%C (percent correct) was 78%, with a sensitivity and specificity for detecting PSCI from Non-PSCI of 90.0 and 84.1%, respectively, and an AUC of 0.919. Regarding the MTx-Cp (Composite score = MTx-%C/MTx-RT), using 46.3 as a cut-off value, the sensitivity and specificity for detecting PSCI from Non-PSCI were 80.0 and 93.2%, with an AUC of 0.925. Multivariate linear regression showed that PSCI reduced the MTx-%C (Coef. -14.18, 95% CI -18.41∼-9.95, p < 0.001) and prolonged the MTx-RT (response time) (Coef. 0.29, 95% CI 0.16∼0.43, p < 0.001) and reduced the MTx-CP (Coef. -19.11, 95% CI -24.29∼-13.93, p < 0.001). Conclusion: MemTrax (MTx) is valid and effective for screening for PSCI among target patients and is a potentially valuable and practical tool in the clinical follow-up, monitoring, and case management of PSCI.

13.
J Org Chem ; 88(16): 11735-11747, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37525574

RESUMO

Borate esters have been applied widely as coupling partners in organic synthesis. However, the direct utilization of borate acceptors in O-glycosylation with glycal donors remains underexplored. Herein, we describe a novel O-glycosylation resulting in the formation of 2,3-unsaturated O-glycosides and 2-deoxy O-glycosides mediated by palladium and copper catalysis, respectively. This O-glycosylation method tolerated a broad scope of trialkyl/triaryl borates and various glycals with exclusive stereoselectivities in high yields. All the desired aliphatic/aromatic O-glycosides and 2-deoxy O-glycosides were generated successfully, without the hemiacetal byproducts and O→C rearrangement because of the nature of borate esters. The utility of this strategy was demonstrated by functionalizing the 2,3-unsaturated glycoside products to form saturated ß-O-glycosides, 2,3-deoxy O-glycosides, and 2,3-epoxy O-glycosides.


Assuntos
Boratos , Glicosídeos , Estereoisomerismo , Glicosilação , Ésteres , Catálise
14.
Eur J Med Res ; 28(1): 239, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37461056

RESUMO

BACKGROUND: Human papillomavirus (HPV) has been proposed as a potential pathogenetic organism involved in prostate cancer (PCa), but the association between HPV infection and relevant genomic changes in PCa is poorly understood. METHODS: To evaluate the relationship between HPV genotypes and genomic alterations in PCa, HPV capture sequencing of DNA isolated from 59 Han Chinese PCa patients was performed using an Illumina HiSeq2500. Additionally, whole-exome sequencing of DNA from these 59 PCa tissue samples and matched normal tissues was carried out using the BGI DNBSEQ platform. HPV infection status and genotyping were determined, and the genetic disparities between HPV-positive and HPV-negative PCa were evaluated. RESULTS: The presence of the high-risk HPV genome was identified in 16.9% of our cohort, and HPV16 was the most frequent genotype detected. The overall mutational burden in HPV-positive and HPV-negative PCa was similar, with an average of 2.68/Mb versus 2.58/Mb, respectively, in the targeted whole-exome region. HPV-negative tumors showed a mutational spectrum concordant with published PCa analyses with enrichment for mutations in SPOP, FOXA1, and MED12. HPV-positive tumors showed more mutations in KMT2C, KMT2D and ERCC2. Copy number alterations per sample were comparable between the two groups. However, the significantly amplified or deleted regions of the two groups only partially overlapped. We identified amplifications in oncogenes, including FCGR2B and CCND1, and deletions of tumor suppressors, such as CCNC and RB1, only in HPV-negative tumors. HPV-positive tumors showed unique deletions of tumor suppressors such as NTRK1 and JAK1. CONCLUSIONS: The genomic mutational landscape of PCa differs based on HPV infection status. This work adds evidence for the direct involvement of HPV in PCa etiology. Different genomic features render HPV-positive PCa a unique subpopulation that might benefit from virus-targeted therapy.


Assuntos
Infecções por Papillomavirus , Neoplasias da Próstata , Masculino , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , População do Leste Asiático , Neoplasias da Próstata/genética , Neoplasias da Próstata/complicações , Neoplasias da Próstata/patologia , Genômica , Genótipo , Proteína Grupo D do Xeroderma Pigmentoso/genética , Proteínas Nucleares/genética , Proteínas Repressoras/genética
15.
Cardiovasc Diabetol ; 22(1): 151, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37365608

RESUMO

OBJECTS: This study aimed to investigate the impact of lipoprotein(a) [Lp(a)] levels on the prognosis of Chinese patients with ST-segment elevation myocardial infarction (STEMI), and to explore if the impact may differ in the diabetes mellitus (DM) and nonDM groups. METHODS: Between March 2017 and January 2020, 1543 patients with STEMI who underwent emergency percutaneous coronary intervention (PCI) were prospectively recruited. The primary outcome was a composite of all-cause death, MI recurrence (reMI), and stroke, known as major adverse cardiovascular events (MACE). Analyses involving the Kaplan-Meier curve, Cox regression, and restricted cubic spline (RCS) were conducted. RESULTS: During the 1446-day follow-up period, 275 patients (17.8%) experienced MACEs, including 141 with DM (20.8%) and 134 (15.5%) without DM. As for the DM group, patients with Lp(a) ≥ 50 mg/dL showed an apparently higher MACE risk compared to those with Lp(a) < 10 mg/dL (adjusted hazard ratio [HR]: 1.85, 95% confidence interval [CI]:1.10-3.11, P = 0.021). The RCS curve indicates that the HR for MACE appeared to increase linearly with Lp(a) levels exceeding 16.9 mg/dL. However, no similar associations were obtained in the nonDM group, with an adjusted HR value of 0.57 (Lp(a) ≥ 50 mg/dL vs. < 10 mg/dL: 95% CI 0.32-1.05, P = 0.071). Besides, compared to patients without DM and Lp(a) ≥ 30 mg/dL, the MACE risk of patients in the other three groups (nonDM with Lp(a) < 30 mg/dL, DM with Lp(a) < 30 mg/dL, and DM with Lp(a) ≥ 30 mg/dL) increased to 1.67-fold (95% CI 1.11-2.50, P = 0.013), 1.53-fold (95% CI 1.02-2.31, P = 0.041), and 2.08-fold (95% CI 1.33-3.26, P = 0.001), respectively. CONCLUSIONS: In this contemporary STEMI population, high Lp(a) levels were linked to an increased MACE risk, and very high Lp(a) levels (≥ 50 mg/dL) significantly indicated poor outcomes in patients with DM, while not for those without DM. TRIAL REGISTRATION: clinicaltrials.gov NCT: 03593928.


Assuntos
Diabetes Mellitus , Lipoproteína(a) , Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Lipoproteína(a)/sangue , Infarto do Miocárdio/epidemiologia , Intervenção Coronária Percutânea , Prognóstico , Estudos Prospectivos , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Resultado do Tratamento
16.
Polymers (Basel) ; 15(11)2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37299361

RESUMO

Phenolic pollutants released from industrial activities seriously damage natural freshwater resources, and their elimination or reduction to safe levels is an urgent challenge. In this study, three catechol-based porous organic polymers, CCPOP, NTPOP, and MCPOP, were prepared using sustainable lignin biomass-derived monomers for the adsorption of phenolic contaminants in water. CCPOP, NTPOP, and MCPOP showed good adsorption performance for 2,4,6-trichlorophenol (TCP) with theoretical maximum adsorption capacities of 808.06 mg/g, 1195.30 mg/g, and 1076.85 mg/g, respectively. In addition, MCPOP maintained a stable adsorption performance after eight consecutive cycles. These results indicate that MCPOP is a potential material for the effective treatment of phenol pollutants in wastewater.

17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(3): 491-496, 2023 May.
Artigo em Chinês | MEDLINE | ID: mdl-37248573

RESUMO

Tumor microenvironment incorporates various tumor-related cellular and non-cellular components, playing a crucial role in the process of the pathogenesis, growth, and metastasis of tumors. Long noncoding RNA (lncRNA), a kind of noncoding RNA with a length of more than 200 nt, participates in a variety of physiological and pathological processes. Recent studies have shown that lncRNA plays a vital role in the interaction between tumors and the tumor microenvironment, thereby affecting tumor progression. Herein, we reviewed the research progress on the lncRNA in tumor microenvironment, discussed the potential application of lncRNA in early diagnosis and treatment of tumors, and suggested that some issues should be further explored in future research, including developing effective strategies for knocking out specific lncRNA and selecting appropriate in vivo delivery vehicles targeting specific cells.


Assuntos
Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Microambiente Tumoral/genética , Neoplasias/genética , Regulação Neoplásica da Expressão Gênica
18.
Am Heart J ; 262: 90-99, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37116605

RESUMO

OBJECTS: This study aimed to investigate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at different sampling times and prognosis in patients with acute myocardial infarction (AMI) undergoing emergency percutaneous coronary intervention (PCI). METHODS AND RESULTS: Between March 2017 and January 2020, 1,105 patients with AMI who underwent emergency PCI were included. NT-proBNP levels were measured on days 0, 1, 2, 3, and 7. A composite of all-cause death, MI recurrence (reMI), and rehospitalization due to heart failure, known as major adverse cardiovascular events (MACE), was recorded. During the 36.8-month follow-up, 175 patients (15.8%) experienced MACEs. When patients were grouped based on quartiles of NT-proBNP levels on days 0 and 7, the results demonstrated that patients in quartile 4 showed a substantially increased MACE risk compared to those in quartile 1 (hazard ratio [HR] 2.27, 95% confidence interval [CI]:1.27-4.08, P = .006; HR 2.20, 95%CI:1.23-3.94, P = .008). There were U-shaped relationships between the HR for MACE and NT-proBNP levels on days 2, 3, and 7, as well as peak NT-proBNP (P for nonlinearity = .007, .006, .004, and .009, respectively). A similar relationship was observed in the HR for reMI and NT-proBNP levels on days 2 and 3. For MACE at 3 years, serial NT-proBNP levels improved the predictive accuracy of the Global Registry of Acute Coronary Events (GRACE) risk score (concordance index [C-index]: 0.711; continuous net reclassification improvement [NRI]: 0.192, 95% CI: 0.022-0.445; integrated discrimination improvement [IDI]: 0.034, 95% CI: 0.016-0.064). For all-cause death at 3 years, the combination of NT-proBNP and GRACE score showed excellent performance, with C-index, continuous NRI, and IDI values of 0.801, 0.373 (95%CI: 0.072-0.853), and 0.051 (95%CI: 0.025-0.091), respectively. CONCLUSIONS: Early and sequential measurement of NT-proBNP levels could assist in predicting MACE risk. Moreover, the relationship between MACE risk and NT-proBNP levels was U-shaped. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT: 03593928.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Prognóstico , Peptídeo Natriurético Encefálico , Estudos Prospectivos , Intervenção Coronária Percutânea/efeitos adversos , Medição de Risco/métodos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Fragmentos de Peptídeos , Biomarcadores
19.
Front Cell Infect Microbiol ; 13: 1105126, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36936759

RESUMO

Diarrhea is a severe bovine disease, globally prevalent in farm animals with a decrease in milk production and a low fertility rate. Cryptosporidium spp. are important zoonotic agents of bovine diarrhea. However, little is known about microbiota and short-chain fatty acids (SCFAs) changes in yaks infected with Cryptosporidium spp. Therefore, we performed 16S rRNA sequencing and detected the concentrations of SCFAs in Cryptosporidium-infected yaks. Results showed that over 80,000 raw and 70,000 filtered sequences were prevalent in yak samples. Shannon (p<0.01) and Simpson (p<0.01) were both significantly higher in Cryptosporidium-infected yaks. A total of 1072 amplicon sequence variants were shared in healthy and infected yaks. There were 11 phyla and 58 genera that differ significantly between the two yak groups. A total of 235 enzymes with a significant difference in abundance (p<0.001) were found between healthy and infected yaks. KEGG L3 analysis discovered that the abundance of 43 pathways was significantly higher, while 49 pathways were significantly lower in Cryptosporidium-infected yaks. The concentration of acetic acid (p<0.05), propionic acid (p<0.05), isobutyric acid (p<0.05), butyric acid (p<0.05), and isovaleric acid was noticeably lower in infected yaks, respectively. The findings of the study revealed that Cryptosporidium infection causes gut dysbiosis and results in a significant drop in the SCFAs concentrations in yaks with severe diarrhea, which may give new insights regarding the prevention and treatment of diarrhea in livestock.


Assuntos
Criptosporidiose , Cryptosporidium , Microbiota , Bovinos , Animais , Cryptosporidium/genética , RNA Ribossômico 16S/genética , Ácidos Graxos Voláteis , Diarreia/veterinária , Ácido Butírico , Intestinos
20.
Mikrochim Acta ; 190(4): 123, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36892601

RESUMO

A flexible electrochemiluminescence (ECL) hydrogel sensor exhibiting good self-healing was constructed. A transparent self-healing oxidized sodium alginate/hydrazide polyethylene glycol (OSA/PEG-DH) hydrogel was prepared by crosslinking dynamic covalent acylhydrazone bond. The introduction of 4-amino-DL-phenylalanine, a catalyst with good biocompatibility, allows rapid gelation and self-healing of hydrogel under mild conditions. Using the hydrogel as the sensing substrate, the ionic liquid (IL) 2-hydroxy-N,N,N-trimethylethanaminium chloride and the luminescent reagent N-(aminobutyl)-N-(ethylisoluminol) (ABEI) were simultaneously immobilized in the OSA/PEG-DH hydrogel to obtain the ABEI/IL/OSA/PEG-DH hydrogel. The ABEI/IL/OSA/PEG-DH hydrogel can be directly used as a semi-solid electrolyte for constructing a flexible ECL hydrogel sensor for the detection of H2O2, which acted as a coreactant of ABEI. The prepared flexible ECL sensor showed good self-healing performance, can restore ECL signal intensity within 20 min after physical damage, and showed high accuracy in the analysis of complex serum samples. This research shed new light on the development of flexible ECL sensor for bioanalytical applications.

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