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1.
Risk Manag Healthc Policy ; 17: 1211-1225, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742137

RESUMO

Background: Given the importance of diabetic kidney disease (DKD) management, this study aims to explore the knowledge, attitudes, and practices in disease management demonstrated by healthcare workers from the nephrology department. Materials and Methods: This study is a multi-centered cross-sectional study, and adopts snowball sampling, with 530 healthcare workers being recruited to complete a questionnaire covering areas such as demographic characteristics, knowledge, attitude, and practices (KAP) of DKD management. This data was analyzed using descriptive statistics and binary logistics analysis. Results: In this study, 530 healthcare workers were studied, including 94 doctors and 436 nurses. The participants were mainly from general tertiary hospitals in 14 provinces. For Chinese nurse, the results indicate that both poor knowledge level (Odds Ratio (OR) =0.63, 95% Confidence Interval (CI): 0.42-0.94) and having experience in further medical training in nephrology (OR=1.92, 95% CI: 1.20-3.08) are associated with the practice levels. For Chinese doctors, having not experience in further medical training in nephrology (OR=0.36, 95% CI: 0.15-0.83) are associated with their practice levels. Conclusion: In summary, Chinese doctors and nurses in this study showed positive attitudes towards DKD management, but their knowledge and practical skills were lacking. This underscores a notable gap in achieving optimal DKD care. Notably, nurses' knowledge influenced their management practices, and additional nephrology training correlated with better engagement. To improve patient care, enhancing nephrology healthcare professional training and addressing knowledge-practice disparities are recommended.

3.
J Food Sci ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700357

RESUMO

The abilities of Chinese quince free proanthocyanidins (FP) and bound proanthocyanidins (BP) at different levels (0.1%, 0.15%, and 0.3%) to mitigate heterocyclic aromatic amine (HAA) formation in fried chicken patties were investigated for the first time and compared with vitamin C (Vc). FP and BP reduced HAAs in a dose-dependent manner. Significantly, high concentrations of FP (0.3%) resulted in a reduction of PhIP, harman, and norharman levels by 59.84%, 22.91%, and 38.21%, respectively, in chicken patties. The addition of proanthocyanidins significantly (p < 0.05) reduced the weight loss of fried chicken patties. Furthermore, a positive correlation was observed among pH, weight loss, and total HAA formation in all three groups (FP, BP, and Vc). Multivariate analysis showed that FP had a more pronounced effect than BP from the perspective of enhancing the quality of fried chicken patties and reducing the formation of HAAs. These results indicate that proanthocyanidins, both BP and FP, but especially FP, from Chinese quince can inhibit the formation of carcinogenic HAAs when added to protein-rich foods that are subsequently fried.

4.
Biomater Sci ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656316

RESUMO

The development of targeted anti-cancer therapeutics offers the potential for increased efficacy of drugs and diagnostics. Utilizing modalities agnostic to tumor type, such as the hypoxic tumor microenvironment (TME), may assist in the development of universal tumor targeting agents. The hypoxia-inducible factor (HIF), in particular HIF1, plays a key role in tumor adaptation to hypoxia, and inhibiting its interaction with p300 has been shown to provide therapeutic potential. Using a multivalent assembled protein (MAP) approach based on the self-assembly of the cartilage oligomeric matrix protein coiled-coil (COMPcc) domain fused to the critical residues of the C-terminal transactivation domain (C-TAD) of the α subunit of HIF1 (HIF1α), we generate HIF1α-MAP (H-MAP). The resulting H-MAP demonstrates picomolar binding affinity to p300, the ability to downregulate hypoxia-inducible genes, and in vivo tumor targeting capability.

5.
Sci Total Environ ; 927: 172368, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38614346

RESUMO

BACKGROUND: Disinfection byproducts (DBPs) have been shown to impair thyroid function in experimental models. However, epidemiological evidence is scarce. METHODS: This study included 1190 women undergoing assisted reproductive technology (ART) treatment from the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. Serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured as indicators of thyroid function. FT4/FT3 and TSH/FT4 ratios were calculated as markers of thyroid hormone homeostasis. Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the two most abundant HAAs, in urine were detected to assess individual DBP exposures. RESULTS: After adjusting for relevant covariates, positive associations were observed between urinary TCAA concentrations and serum TSH and TSH/FT4 levels (e.g., percent change = 5.82 %, 95 % CI: 0.70 %, 11.21 % for TSH), whereas inverse associations were found for serum FT3 and FT4 (e.g., percent change = -1.29 %, 95 % CI: -2.49 %, -0.07 % for FT3). There also was a negative association between urinary DCAA concentration and serum FT4/FT3 (percent change = -2.49 %, 95 % CI: -4.71 %, -0.23 %). These associations were further confirmed in the restricted cubic spline and generalized additive models with linear or U-shaped dose-response relationships. CONCLUSION: Urinary HAAs were associated with altered thyroid hormone homeostasis among women undergoing ART treatment.


Assuntos
Glândula Tireoide , Humanos , Feminino , Adulto , Tiroxina/sangue , Tri-Iodotironina/sangue , Tireotropina/sangue , Hormônios Tireóideos/sangue , Testes de Função Tireóidea , Desinfetantes , Acetatos , China
6.
iScience ; 27(4): 109549, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38623328

RESUMO

Independently run single microgrids (MGs) encounter difficulties with inadequate self-consumption of local renewable energy and frequent power exchange with the grid. Combining numerous MGs to form a multi-microgrid (MMG) is a viable approach to enhance smart distribution networks' operational and financial performance. However, the correlation and coordination of intermittent power generation within each MG network pose many techno-economic challenges for energy sharing and trading. This review offers a comprehensive analysis of these challenges within the framework of MMG operations. It examines state-of-the-art methodologies for optimizing multi-energy dispatch and scrutinizes contemporary strategies within energy markets that contribute to the resilience of power systems. The discourse extends to the burgeoning role of blockchain technology in revolutionizing decentralized market frameworks and the intricacies of MMG coordination for reliable and cost-effective energy distribution. Overall, this study provides ample inspiration for theoretical and practical research to the new entrants and experts alike to develop new concepts for energy markets, scheduling and novel operating models for future resilient multi-energy networked systems/MMGs.

7.
Chem Commun (Camb) ; 60(34): 4561-4564, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38572604

RESUMO

Two templated borates, [Co(1-EI)2]·[B5O7(OH)3] (1) and [Ga(1-MI)2·B6O9(OH)4]·[H3BO3]·H[1-MI] (2), have been synthesized using a mild method. Notably, they exhibit an excellent ORR performance with an E1/2 value of 0.84 V and are the first to be used as the positive electrode catalyst for a zinc-air battery, which opens a pathway for the application of borate-based oxide catalysts.

8.
Int J Womens Health ; 16: 527-541, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558831

RESUMO

Background: The basic medical education stage is not enough to support physicians to fully diagnose and evaluate polycystic ovary syndrome (PCOS). The study aims to discover the difference in treatment choice between participants with different annual consultation number of PCOS, to promote lifelong learning, and drive balanced development within healthcare. Methods: This is a multicenter cross-sectional survey. Participants' basic information, knowledge of PCOS and treatment options were collected online. According to the annual consultation number of patients with PCOS, physicians were divided into three groups: 0-50 people/yr, 50-200 people/yr, and >200 people/yr, and the results were derived from χ2 test, Fisher exact test, and multivariate logistic regression analysis. Results: The study analyzed 1689 questionnaires, and 1206 physicians (71.4%) received less than 50 women per year, 388 physicians (30.0%) with an annual number of 50-200 women, and 95 physicians (5.6%) with patient turnover for more than 200 people. Reproductive endocrinologists generally have higher access to the clinic. As the number of visits increases, more and more physicians would perceive patients as more likely to have abnormal blood glucose and heavy weight. Physicians with large numbers of consultations are more likely to use Asian or Chinese standards to assess obesity. The multivariate analysis involved variables such as age, hospital level, specialty, and patient turnover annually, and more young doctors actively assessed lipid profile (odds ratio (OR) 1.56, 95% confidence interval (CI) (1.16, 2.16)), and primary hospitals (OR 0.65 CI (0.44, 0.89)) chose OGTT for blood glucose assessment less than tertiary hospitals. Physicians in secondary hospitals are more aggressive in evaluating androgens. Conclusion: Our survey found differences in endocrine assessment, metabolic screening, and treatment in PCOS women in terms of the number of obstetrician-gynecologists who received different patient consultation numbers. The importance of continuing education for physicians is emphasized, to promote lifelong learning.

9.
Front Cardiovasc Med ; 11: 1340289, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38576423

RESUMO

Purpose: Vector flow mapping and treadmill exercise stress echocardiography were used to evaluate and explore changes in the left ventricular (LV) flow field of patients with nonobstructive coronary artery disease. Methods: Overall, 34 patients with nonobstructive (<50%) left anterior descending coronary artery stenosis (case group) and 36 patients with no coronary artery stenosis (control group) were included. Apical four-, three-, and two-chamber echocardiographic images were collected at rest and during early recovery from treadmill exercise. LV flow field, vortex area, and circulation (cir) changes were recorded in different phases: isovolumetric systole (S1), rapid ejection (S2), slow ejection (S3), isovolumetric diastole (D1), rapid filling (D2), slow filling (D3), and atrial systole (D4). Intra- and inter-group differences were compared before and after exercise loading. Results: The control and case groups demonstrated regular trends of eddy current formation and dissipation at rest and under stress. Compared with the control group, the case group had irregular streamline distributions. Abnormal vortices formed in the S1 and D3 apical segments and D1 left ventricular middle segment in the resting group. Compared with the control group, the resting group had decreased left ventricular S1 vortex areas and increased S3 vortex areas. The post-stress D1 and D3 vortex areas and D1 and D2 cir increased. Compared with at rest, after stress, the control group had decreased S1, S3, D2, and D3 vortex areas; increased S2, D1, D3, and D4 cir; and decreased D2 cir. After stress, the case group had decreased S3 and D2 vortex areas, increased D1 vortex areas, and increased S2, D1, D3, and D4 cir (P all < 0.001). Logistic regression and ROC curve analyses show that increased D1 vortex area after stress is an independent risk factor for stenosis in nonobstructive stenosis of coronary arteries (OR: 1.007, 95% CI: 1.005-1.010, P < 0.05). A D1 vortex area cutoff value of 82.26 had an AUC, sensitivity, and specificity of 0.67, 0.655, and 0.726, respectively. Conclusion: The resting left ventricular flow field changed in patients with nonobstructive left anterior descending coronary artery stenosis. Both groups had more disordered left ventricular blood flow after stress. The increased D1 vortex area after stress is an independent risk factor for mild coronary stenosis and may contribute to the assessment of nonobstructive coronary stenosis. VFM combined with treadmill stress is useful in evaluating left ventricular flow field changes in patients with nonobstructive coronary artery disease, which is valuable in the early evaluation of coronary heart disease.

10.
Anal Methods ; 16(18): 2905-2912, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38660709

RESUMO

The presence of lead ions (Pb2+) in the environment not only leads to environmental contamination but also poses a significant risk to public health through their migration into food and drinking water. Therefore, the development of rapid and effective techniques for detection of trace amounts of Pb2+ is crucial for safeguarding both the environment and biosafety. In this study, an aptamer-based electrochemical sensor was developed for specific detection of Pb2+ by modifying a polylysine (PLL) coated silver-thiolated graphene (Ag-SH-G) nanocomposite (PLL/Ag-SH-G) on the surface of a glassy carbon electrode, which was further modified with gold nanoparticles (AuNPs) for attachment of aptamers (Apt) that specifically recognized Pb2+. The Ag-SH-G particles were synthesized using a one-step in situ method, resulting in significantly enhanced electrochemical properties upon incorporating Ag nanoparticles into the PLL/Ag-SH-G composite. Coating of the covalently or no-covalently bonded Ag-SH-G particles with PLL provides an excellent supporting matrix, facilitating the assembly of AuNPs and a thiol-modified aptamer for Pb2+. Under optimized conditions, Apt/AuNPs/PLL/Ag-SH-G/GCE exhibited excellent sensing performance for Pb2+ with a wide linear response range (10-1000 nM), a low detection limit (0.047 nM) and extraordinary selectivity. The sensor was employed and satisfactory results were obtained in river water, soil and vegetable samples for the detection of Pb2+.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Eletroquímicas , Ouro , Grafite , Chumbo , Nanopartículas Metálicas , Prata , Grafite/química , Chumbo/análise , Chumbo/química , Aptâmeros de Nucleotídeos/química , Técnicas Eletroquímicas/métodos , Prata/química , Nanopartículas Metálicas/química , Ouro/química , Técnicas Biossensoriais/métodos , Compostos de Sulfidrila/química , Compostos de Sulfidrila/análise , Limite de Detecção , Poluentes Químicos da Água/análise , Nanocompostos/química
11.
Exp Neurol ; 377: 114803, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38679281

RESUMO

Disruption of corticospinal tracts (CST) is a leading factor for motor impairments following intracerebral hemorrhage (ICH) in the striatum. Previous studies have shown that therapeutic hypothermia (HT) improves outcomes of ICH patients. However, whether HT has a direct protection effect on the CST integrity and the underlying mechanisms remain largely unknown. In this study, we employed a chemogenetics approach to selectively activate bilateral warm-sensitive neurons in the preoptic areas to induce a hypothermia-like state. We then assessed effects of HT treatment on the integrity of CST and motor functional recovery after ICH. Our results showed that HT treatment significantly alleviated axonal degeneration around the hematoma and the CST axons at remote midbrain region, ultimately promoted skilled motor function recovery. Anterograde and retrograde tracing revealed that HT treatment protected the integrity of the CST over an extended period. Mechanistically, HT treatment prevented mitochondrial swelling in degenerated axons around the hematoma, alleviated mitochondrial impairment by reducing mitochondrial ROS accumulation and improving mitochondrial membrane potential in primarily cultured cortical neurons with oxyhemoglobin treatment. Serving as a proof of principle, our study provided novel insights into the application of HT to improve functional recovery after ICH.

12.
World J Clin Cases ; 12(7): 1235-1242, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38524515

RESUMO

BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is a common complication that significantly impacts the patient's recovery process, even leading to adverse outcomes. Currently, there is a lack of effective preventive measures. AIM: To identify significant risk factors for ICU-AW through iterative machine learning techniques and offer recommendations for its prevention and treatment. METHODS: Patients were categorized into ICU-AW and non-ICU-AW groups on the 14th day post-ICU admission. Relevant data from the initial 14 d of ICU stay, such as age, comorbidities, sedative dosage, vasopressor dosage, duration of mechanical ventilation, length of ICU stay, and rehabilitation therapy, were gathered. The relationships between these variables and ICU-AW were examined. Utilizing iterative machine learning techniques, a multilayer perceptron neural network model was developed, and its predictive performance for ICU-AW was assessed using the receiver operating characteristic curve. RESULTS: Within the ICU-AW group, age, duration of mechanical ventilation, lorazepam dosage, adrenaline dosage, and length of ICU stay were significantly higher than in the non-ICU-AW group. Additionally, sepsis, multiple organ dysfunction syndrome, hypoalbuminemia, acute heart failure, respiratory failure, acute kidney injury, anemia, stress-related gastrointestinal bleeding, shock, hypertension, coronary artery disease, malignant tumors, and rehabilitation therapy ratios were significantly higher in the ICU-AW group, demonstrating statistical significance. The most influential factors contributing to ICU-AW were identified as the length of ICU stay (100.0%) and the duration of mechanical ventilation (54.9%). The neural network model predicted ICU-AW with an area under the curve of 0.941, sensitivity of 92.2%, and specificity of 82.7%. CONCLUSION: The main factors influencing ICU-AW are the length of ICU stay and the duration of mechanical ventilation. A primary preventive strategy, when feasible, involves minimizing both ICU stay and mechanical ventilation duration.

13.
Biosensors (Basel) ; 14(3)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38534228

RESUMO

Development of an efficient technique for accurate and sensitive dibutyl phthalate (DBP) determination is crucial for food safety and environment protection. An ultrasensitive molecularly imprinted polymers (MIP) voltammetric sensor was herein engineered for the specific determination of DBP using poly-l-lysine/poly(3,4-ethylenedioxythiophene)/porous graphene nanocomposite (PLL/PEDOT-PG) and poly(o-phenylenediamine)-imprinted film as a label-free and sensing platform. Fabrication of PEDOT-PG nanocomposites was achieved through a simple liquid-liquid interfacial polymerization. Subsequently, poly-l-lysine (PLL) functionalization was employed to enhance the dispersibility and stability of the prepared PEDOT-PG, as well as promote its adhesion on the sensor surface. In the presence of DBP, the imprinted poly(o-phenylenediamine) film was formed on the surface of PLL/PEDOT-PG. Investigation of the physical properties and electrochemical behavior of the MIP/PLL/PEDOT-PG indicates that the incorporation of PG into PEDOT, with PLL uniformly wrapping its surface, significantly enhanced conductivity, carrier mobility, stability, and provided a larger surface area for specific recognition sites. Under optimal experimental conditions, the electrochemical response exhibited a linear relationship with a logarithm of DBP concentration within the range of 1 fM to 5 µM, with the detection limit as low as 0.88 fM. The method demonstrated exceptional stability and repeatability and has been successfully applied to quantify DBP in plastic packaging materials.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Grafite , Impressão Molecular , Nanocompostos , Fenilenodiaminas , Polímeros , Dibutilftalato , Polímeros Molecularmente Impressos , Técnicas Eletroquímicas/métodos , Grafite/química , Polilisina , Porosidade , Nanocompostos/química , Impressão Molecular/métodos , Limite de Detecção , Eletrodos
14.
Metabolites ; 14(3)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38535303

RESUMO

In vitro fertilization (IVF) is a highly effective treatment for infertility; however, it poses challenges for women with decreased ovarian reserve (DOR). Despite the importance of understanding the impact of DOR on IVF outcomes, limited research has explored this relationship, particularly using omics approaches. Hence, we conducted a study to investigate the association between DOR and IVF outcomes, employing a metabolomic approach. We analyzed serum samples from 207 women undergoing IVF treatment, including 89 with DOR and 118 with normal ovarian reserve (NOR). Our findings revealed that DOR was significantly associated with unfavorable IVF outcomes, characterized by a reduced oocyte count, lower embryo quality, and decreased rates of pregnancy and live births. Furthermore, we identified 82 metabolites that displayed significant alterations in DOR patients, impacting diverse metabolic pathways. Notably, a distinct panel of metabolites, including palmitic acid, stearic acid, LysoPC(9:0(CHO)/0:0), PC(18:0/9:0(CHO)), and PC(16:0/9:0(CHO)), exhibited discriminatory power between the DOR and NOR groups, showcasing a strong correlation with IVF outcomes. These findings emphasize the crucial role of metabolomic disruptions in influencing IVF outcomes among women with DOR.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38461202

RESUMO

Pulmonary arterial hypertension (PAH) is a common complication of systemic lupus erythematosus (SLE), and PAH can cause right ventricle (RV) remodel and dyssynchrony. The aim of this study was to explore the value of RV dyssynchrony in predicting adverse clinical events in patients with systemic lupus erythematosus-aaociated pulmonary arterial hypertension (SLE-PAH) using two-dimensional speckle tracking echocardiography (2D-STE). A total of 53 patients with SLE-PAH were enrolled in this study. The dyssynchrony of the RV (RV-SD6) was evaluated by 2D-STE. The clinical data of all participants were collected, and routine cardiac function parameters were measured by two-dimensional echocardiography, and analyzed for their correlation with RV-SD6. The predictive value of RV-SD6 in clinical adverse event was evaluated. RV-SD6 was negatively correlated with RV-FLS, RV-FAC, and TAPSE (r = - 0.788, r = - 0.363 and r = - 0.325, respectively, all P < 0.01), while the correlation with RV-FLS was the strongest. linear regression analysis showed that RV-FLS was an independent risk factor for RV-SD6 (ß = - 1.40, 95% CI - 1.65 ~ - 1.14, P < 0.001). Cox regression analysis showed that RV-SD6 was a predictor with clinical adverse events (HR = 1.03, 95% CI 1 ~ 1.06, P < 0.05). RV-SD6 was highly discriminative in predicting clinical adverse events (AUC = 0.764), at a cutoff of 51.10 ms with a sensitivity of 83.3% and specificity of 68.3%. RV-FLS was negatively correlated with RV-SD6 and was an independent risk factor for it. RV-SD6 can serve as an indicator for predicting the occurrence of adverse clinical events in SLE-PAH patients, with high sensitivity and specificity.

16.
J Ethnopharmacol ; 328: 118116, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548118

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Aristolochic acids (AAs) are naturally occurring nitro phenanthrene carboxylic acids primarily found in plants of the Aristolochiaceae family. Aristolochic acid D (AAD) is a major constituent in the roots and rhizomes of the Chinese herb Xixin (the roots and rhizomes of Asarum heterotropoides F. Schmidt), which is a key material for preparing a suite of marketed Chinese medicines. Structurally, AAD is nearly identical to the nephrotoxic aristolochic acid I (AAI), with an additional phenolic group at the C-6 site. Although the nephrotoxicity and metabolic pathways of AAI have been well-investigated, the metabolic pathway(s) of AAD in humans and the influence of AAD metabolism on its nephrotoxicity has not been investigated yet. AIM OF THE STUDY: To identify the major metabolites of AAD in human tissues and to characterize AAD O-glucuronidation kinetics in different enzyme sources, as well as to explore the influence of AAD O-glucuronidation on its nephrotoxicity. MATERIALS AND METHODS: The O-glucuronide of AAD was biosynthesized and its chemical structure was fully characterized by both 1H-NMR and 13C-NMR. Reaction phenotyping assays, chemical inhibition assays, and enzyme kinetics analyses were conducted to assess the crucial enzymes involved in AAD O-glucuronidation in humans. Docking simulations were performed to mimic the catalytic conformations of AAD in human UDP-glucuronosyltransferases (UGTs), while the predicted binding energies and distances between the deprotonated C-6 phenolic group of AAD and the glucuronyl moiety of UDPGA in each tested human UGT isoenzyme were measured. The mitochondrial membrane potentials (MMP) and reactive oxygen species (ROS) levels in HK-2 cells treated with either AAI, or AAD, or AAD O-glucuronide were tested, to elucidate the impact of O-glucuronidation on the nephrotoxicity of AAD. RESULTS: AAD could be rapidly metabolized in human liver and intestinal microsomes (HLM and HIM, respectively) to form a mono-glucuronide, which was purified and fully characterized as AAD-6-O-ß-D-glucuronide (AADG) by NMR. UGT1A1 was the predominant enzyme responsible for AAD-6-O-glucuronidation, while UGT1A9 contributed to a lesser extent. AAD-6-O-glucuronidation in HLM, HIM, UGT1A1 and UGT1A9 followed Michaelis-Menten kinetics, with the Km values of 4.27 µM, 9.05 µM, 3.87 µM, and 7.00 µM, respectively. Docking simulations suggested that AAD was accessible to the catalytic cavity of UGT1A1 or UGT1A9 and formed catalytic conformations. Further investigations showed that both AAI and AAD could trigger the elevated intracellular ROS levels and induce mitochondrial dysfunction and in HK-2 cells, but AADG was hardly to trigger ROS accumulation and mitochondrial dysfunction. CONCLUSION: Collectively, UGT1A-catalyzed AAD 6-O-glucuronidation represents a crucial detoxification pathway of this naturally occurring AAI analogs in humans, which is very different from that of AAI.


Assuntos
Ácidos Aristolóquicos , Doenças Mitocondriais , Humanos , Ácidos Aristolóquicos/toxicidade , Glucuronídeos/metabolismo , Microssomos Hepáticos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Glucuronosiltransferase/metabolismo , Cinética , Catálise , Difosfato de Uridina/metabolismo
17.
Int J Gen Med ; 17: 871-884, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38468820

RESUMO

Purpose: The research on symptom management in patients with diabetic kidney disease (DKD) has shifted from separate symptoms to symptom clusters and networks recently. This study aimed to evaluate the unpleasant symptoms of DKD patients, and to investigate how these symptom clusters could affect patients. Methods: 408 DKD patients were recruited in this cross-sectional study. The symptoms of DKD patients were measured using the modified Dialysis Symptom Index. Network analysis was employed to evaluate the symptom network and the characteristics of individual nodes, while factor analysis was utilized to identify symptom clusters. Results: Blurred vision was the most prevalent symptom among DKD patients. The symptoms identified as the most distressing, severe, and frequent were light headache or dizziness, arteriovenous fistula/catheterization pain, and diarrhea, respectively. Five symptom clusters were obtained from factor analysis, and the most central symptom cluster in the entire symptom network was sexual dysfunction. Conclusion: This study identified five symptom clusters in Chinese DKD patients, with sexual dysfunction emerging as the most central cluster. These findings carry significant clinical implications, underscoring the necessity of assessing symptom clusters and their associations to enhance symptom management in DKD patients. Further research is essential to elucidate the underlying mechanisms of symptoms and to clarify the associations among symptoms in DKD patients across different disease trajectories or treatment modalities.

18.
Heliyon ; 10(5): e26853, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38439876

RESUMO

Background: Cisplatin (DDP) is the principal agent used for chemotherapy in patients with non-small cell lung cancer (NSCLC). Nevertheless, DDP resistance is an essential cause for a worse prognosis of patient. Therefore, this study proposes to discover features of miR-424-5p in DDP resistance of NSCLC. Method: After exogenous modulation of miR-424-5p expression, A549 cell activity was measured using CCK-8 and flow cytometry. A549/DDP and A549/DDP-associated subcutaneous tumor model were constructed to investigate the effect of miR-424-5p on DDP resistance in NSCLC in vivo. TargetScan and JASPAR databases predicted the potential molecular mechanism of miR-424-5p. A549-and A549/DDP-derived exosomes were isolated and characterized using a transmission electron microscope and nanoparticle tracking analysis. Result: Overexpression of miR-424-5p facilitated proliferation and DDP resistance in A549 cells, and knockdown of miR-424-5p did the opposite. Knockdown of miR-424-5p enhanced DDP restriction on tumor weight and volume. Moreover, SOCS5 and SOCS56 (SOCS5/6) were downstream targets of miR-424-5p. miR-424-5p down-regulated SOCS5/6 expression to activate JAK2/STAT3 and PI3K/AKT pathways. Notably, tumor protein p53 (TP53) is a transcription factor for the miR-424-5p host gene, as confirmed by the dual-luciferase reporter gene. Cellular and animal experiments indicated that TP53 limited the regulatory function of miR-424-5p on NSCLC growth, DDP resistance, and related molecules. Interestingly, miR-424-5p was markedly enriched in A549/DDP cell-derived exosomes than in A549 cell-derived exosomes, and TP53 down-regulated miR-424-5p expression in A549/DDP cell-derived exosomes. Conclusion: DDP-resistant cell-derived exosome miR-424-5p contributes to NSCLC growth and DDP resistance by targeting SOCS5 and SOCS6 to activate JAK2/STAT3 and PI3K/AKT pathways, which are blocked by TP53.

19.
Front Plant Sci ; 15: 1319680, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444531

RESUMO

Pigments derived from red pepper fruits are widely used in food and cosmetics as natural colorants. Nitrogen (N) is a key nutrient affecting plant growth and metabolism; however, its regulation of color-related metabolites in pepper fruit has not been fully elucidated. This study analyzed the effects of N supply (0, 250, and 400 kg N ha-1) on the growth, fruit skin color, and targeted and non-target secondary metabolites of field-grown pepper fruits at the mature red stage. Overall, 16 carotenoids were detected, of which capsanthin, zeaxanthin, and capsorubin were the dominant ones. N application at 250 kg ha-1 dramatically increased contents of red pigment capsanthin, yellow-orange zeaxanthin and ß-carotene, with optimum fruit yield. A total of 290 secondary metabolites were detected and identified. The relative content of most flavonoids and phenolic acids was decreased with increasing N supply. Correlation analysis showed that color parameters were highly correlated with N application rates, carotenoids, flavonoids, phenolic acids, lignans, and coumarins. Collectively, N promoted carotenoid biosynthesis but downregulated phenylpropanoid and flavonoid biosynthesis, which together determined the spectrum of red color expression in pepper fruit. Our results provide a better understanding of the impact of N nutrition on pepper fruit color formation and related physiology, and identification of target metabolites for enhancement of nutritional quality and consumer appeal.

20.
J Vis Exp ; (204)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38465928

RESUMO

Cationic nanostructures have emerged as an adjuvant and antigen delivery system that enhances dendritic cell maturation, ROS generation, and antigen uptake and then promotes antigen-specific immune responses. In recent years, retinoic acid (RA) has received increasing attention due to its effect in activating the mucosal immune response; however, in order to use RA as a mucosal adjuvant, it is necessary to solve the problem of its dissolution, loading, and delivery. Here, we describe a cationic nanoemulsion-encapsulated retinoic acid (CNE-RA) delivery system composed of the cationic lipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOTAP), retinoic acid, squalene as the oil phase, polysorbate 80 as surfactant, and sorbitan trioleate 85 as co-surfactant. Its physical and chemical properties were characterized using dynamic light scattering and a spectrophotometer. Immunization of mice with the mixture of antigen (ovalbumin, OVA) and CNE-RA significantly elevated the levels of anti-OVA secretory immunoglobulin A (sIgA) in vaginal lavage fluid and the small intestinal lavage fluid of mice compared with OVA alone. This protocol describes a detailed method for the preparation, characterization, and evaluation of the adjuvant effect of CNE-RA.


Assuntos
Adjuvantes Imunológicos , Imunização , Feminino , Animais , Camundongos , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/química , Mucosa , Vacinação , Antígenos , Imunidade nas Mucosas , Tensoativos/farmacologia , Ovalbumina , Camundongos Endogâmicos BALB C
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