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1.
Acta Pharmacol Sin ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886550

RESUMO

Urolithin A (UroA), a dietary phytochemical, is produced by gut bacteria from fruits rich in natural polyphenols ellagitannins (ETs). The efficiency of ETs metabolism to UroA in humans depends on gut microbiota. UroA has shown a variety of pharmacological activities. In this study we investigated the effects of UroA on atherosclerotic lesion development and stability. Apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat and high-cholesterol diet for 3 months to establish atherosclerosis model. Meanwhile the mice were administered UroA (50 mg·kg-1·d-1, i.g.). We showed that UroA administration significantly decreased diet-induced atherosclerotic lesions in brachiocephalic arteries, macrophage content in plaques, expression of endothelial adhesion molecules, intraplaque hemorrhage and size of necrotic core, while increased the expression of smooth muscle actin and the thickness of fibrous cap, implying features of plaque stabilization. The underlying mechanisms were elucidated using TNF-α-stimulated human endothelial cells. Pretreatment with UroA (10, 25, 50 µM) dose-dependently inhibited TNF-α-induced endothelial cell activation and monocyte adhesion. However, the anti-inflammatory effects of UroA in TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) were independent of NF-κB p65 pathway. We conducted RNA-sequencing profiling analysis to identify the differential expression of genes (DEGs) associated with vascular function, inflammatory responses, cell adhesion and thrombosis in UroA-pretreated HUVECs. Human disease enrichment analysis revealed that the DEGs were significantly correlated with cardiovascular diseases. We demonstrated that UroA pretreatment mitigated endothelial inflammation by promoting NO production and decreasing YAP/TAZ protein expression and TEAD transcriptional activity in TNF-α-stimulated HUVECs. On the other hand, we found that UroA administration modulated the transcription and cleavage of lipogenic transcription factors SREBP1/2 in the liver to ameliorate cholesterol metabolism in ApoE-/- mice. This study provides an experimental basis for new dietary therapeutic option to prevent atherosclerosis.

2.
Environ Res ; 227: 115792, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-36997045

RESUMO

This work designed and synthesized novelly selective, highly efficient and friendly environmental biochar nanomaterial (ZMBC@ChCl-EG) by screening suitable deep eutectic solvent (DES) as the functional monomer via Density Functional Theory (DFT). The prepared ZMBC@ChCl-EG achieved the highly efficient adsorption of methcathinone (MC) and exhibited excellent selectivity as well as good reusability. Selectivity analysis concluded that the distribution coefficient value (KD) of ZMBC@ChCl-EG towards MC was 3.247 L/g, which was about 3 times higher than that of ZMBC, corresponding to stronger selective adsorption capacity. The studies of isothermal and kinetics indicated that ZMBC@ChCl-EG had an excellent adsorption capacity towards MC and the adsorption was mainly chemically controlled. In addition, DFT was used to calculate the binding energies between MC and each component. The binding energies were -10.57 kcal/mol for ChCl-EG/MC, -3.15∼-9.51 kcal/mol for BCs/MC, -2.33 kcal/mol for ZIF-8/MC, respectively, suggesting that DES played a major role in enhancing methcathinone adsorption. Lastly, the adsorption mechanisms were revealed by variables experiment combined with characterizations and DFT calculation. The main mechanisms were hydrogen bonding and π-π interaction.


Assuntos
Solventes Eutéticos Profundos , Solventes/química , Teoria da Densidade Funcional , Adsorção
3.
Sensors (Basel) ; 23(20)2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37896495

RESUMO

Sidelobe suppression is a major challenge in wideband beamforming for acoustic research, especially in high noise and reverberation environments. In this paper, we propose a multi-objective NSGA-II wideband beamforming method based on a spherical harmonic domain for spherical microphone arrays topology. The method takes white noise gain, directional index and maximum sidelobe level as the optimization objectives of broadband beamforming, adopts the NSGA-II optimization strategy with constraints to estimate the Pareto optimal solution, and provides three-dimensional broadband beamforming capability. Our method provides superior sidelobe suppression across different spherical harmonic orders compared to commonly used multi-constrained single-objective optimal beamforming methods. We also validate the effectiveness of our proposed method in a conference room setting. The proposed method achieves a white noise gain of 8.28 dB and a maximum sidelobe level of -23.42 dB at low frequency, while at high frequency it yields comparable directivity index results to both DolphChebyshev and SOCP methods, but outperforms them in terms of white noise gain and maximum sidelobe level, measuring 16.14 dB and -25.18 dB, respectively.

4.
Biochem Biophys Res Commun ; 622: 163-169, 2022 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-35868060

RESUMO

Preclinical mouse models of cardiometabolic diseases are crucial to study the pathological mechanisms of cardiometabolic diseases and to explore potential new therapeutic agents. Using double-knockouts in the background of ApoE-/- or Ldlr-/- mice requires an extensive amount of breeding and is costly. A significant breakthrough in atherosclerosis research is the use of AAV8-PCSK9-D377Y (a gain-of-function mutant of PCSK9 which promotes LDLR degradation) injection which can induce hyperlipidemia, increased endothelial stiffness, vascular calcification, aneurysm, and atherosclerotic plaque development in normal C57BL/6J mice. The purpose of this study was to assess the possibility that the injection of AAV8-PCSK9 vectors in db/db mice (a well-established animal model of type 2 diabetes mellitus) produces a novel mouse model of diabetes, atherosclerosis and fatty liver disease to study the pathomechanisms of cardiometabolic disease and its complications. Db/db mice were injected with AAV8-PCSK9-D377Y (AAV8-PCSK9 for simplicity) or AAV8-control and fed with high-cholesterol diets for 8 weeks. Levels of total cholesterol (TC) and triglyceride (TG) were significantly elevated in AAV8-PCSK9-injected mice compared to the controls. AAV8-PCSK9 injection led to increased serum level of PCSK9, serious liver steatosis, hypercholesterolemia and atherosclerotic plaque as determined by aortic arch/roots histopathological staining, with Oil Red O, Masson-trichrome and hematoxylin-eosin staining. RNA sequencing and bioinformatics were used to assess the global gene expression in liver tissues. We conclude that AAV8-PCSK9 injection in db/db mice is a promising and time-efficient approach to induce diabetic atherosclerosis with fatty liver. This mouse model can be a new one to investigate the etiology and therapeutics of atherosclerosis with diabetes and fatty liver beyond the traditional model established in ApoE-/- mice or LDLR-/- mice receiving streptozotocin (STZ) injection.


Assuntos
Aterosclerose , Diabetes Mellitus Tipo 2 , Fígado Gorduroso , Hipercolesterolemia , Hepatopatias , Placa Aterosclerótica , Animais , Apolipoproteínas E/genética , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/terapia , Colesterol , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Dieta , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Placa Aterosclerótica/genética , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo
5.
BMC Cancer ; 22(1): 1138, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335288

RESUMO

BACKGROUND: Radical nephrectomy (RN) is the standard treatment for localized renal cell carcinoma. The decrease in nephrons from RN could lead to postoperative chronic kidney disease (CKD). In this study, we aim to investigate the incidence and risk factors for CKD in patients who have received RN. METHODS: A Total of 1233 patients underwent radical nephrectomy in Zhejiang Provincial People's Hospital from January 2010 to December 2018. Those who had an abnormal renal function before surgery or were lost to follow-up were excluded. Five hundred patients were enrolled in the end. eGFR was calculated using the abbreviated MDRD equation. CKD was defined as eGFR less than 60 ml/min/1.73m2. The incidence of postoperative CKD was estimated using the Kaplan-Meier method. The independent risk factors for CKD occurrence were determined through logistic multivariate regression analysis. RESULTS: Patients were followed up for a median of 40 month (3-96 months), with CKD occurring in 189 cases. The 5-year cumulative incidence of CKD was 43.4%. There was a significant difference between these189 patients and the remaining patients without post nephrectomy CKD in terms of age, sex, weight, and preoperative eGFR(P<0.05). Multivariate regression analysis showed that age (OR = 1.038, 95%CI = 1.002-1.076), preoperative eGFR of the contralateral kidney (OR = 0.934, 95%CI = 0.884-0.988) and Immediate postoperative eGFR (OR = 0.892, 95%CI = 0.854-0.931) were independent risk factors for postoperative CKD. CONCLUSIONS: The incidence of CKD after radical nephrectomy was not uncommon. Age, preoperative eGFR of the contralateral kidney and Immediate postoperative eGFR are independent risk factors for postoperative CKD.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Insuficiência Renal Crônica , Humanos , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/complicações , Incidência , Neoplasias Renais/epidemiologia , Neoplasias Renais/cirurgia , Neoplasias Renais/complicações , Taxa de Filtração Glomerular , Estudos Retrospectivos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Fatores de Risco
6.
Pharmacol Res ; 175: 106043, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34954030

RESUMO

Inflammation associated endothelial dysfunction represents a pivotal contributor to atherosclerosis. Increasingly, evidence has demonstrated that interleukin 1 receptor (IL1-R) / toll-like receptor (TLR) signaling participates in the development of atherosclerosis. Recent large-scale clinical trials have supported the therapeutic potential of anti-inflammatory therapies targeting IL-1ß and IL-6 in reducing atherosclerosis. The present study examined the pharmacological effects of IL-1R-associated kinase 1 and 4 inhibitors (IRAK1/4i) in regulating inflammation of the endothelium and atherosclerosis. We demonstrate that dual pharmacological inhibition of IRAK1 and IRAK4 by an IRAK1/4i is more effective against LPS induced endothelial inflammation, compared with IRAK1 inhibitor or IRAK4 inhibitor monotherapy. IRAK1/4i showed little endothelial cell toxicity at concentrations from 1 µM up to 10 µM. Inhibition of IRAK1/4 reduced endothelial activation induced by LPS in vitro as evidenced by attenuated monocyte adhesion to the endothelium. Mechanistically, blockade of IRAK1/4 ameliorated the transcriptional activity of NF-κB. To assess the pharmacological effects of IRAK1/4i on atherosclerosis in vivo, ApoE-/- mice were orally administered IRAK1/4i (20 mg/kg/d) for 8 weeks. We show that IRAK1/4i reduced atherosclerotic lesion size in the aortic sinus and increased hepatic LDLR protein levels as well as lowered LDL-C level, without affecting other lipid parameters or glucose tolerance. Taken together, our findings demonstrate that dual pharmacological inhibition of IRAK1 and IRAK4 attenuates endothelial inflammation, lowers LDL-C levels and reduces atherosclerosis. Our study reinforces the evolving standing of anti-inflammatory approaches in cardiovascular therapeutics.


Assuntos
Anti-Inflamatórios/uso terapêutico , Aterosclerose/tratamento farmacológico , Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Aorta/efeitos dos fármacos , Aorta/patologia , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Células Cultivadas , LDL-Colesterol/sangue , LDL-Colesterol/metabolismo , Colágeno/metabolismo , Endotélio Vascular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Lipopolissacarídeos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos Knockout para ApoE , NF-kappa B/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Receptores de LDL/genética , Receptores de LDL/metabolismo , Células THP-1
7.
Urol Int ; 106(2): 109-115, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34515249

RESUMO

Raman spectroscopy is an optical technique that can potentially serve as a molecular diagnosis method. This approach is excellent in many aspects for diagnosing bladder tumors, and over the last 20 years, there has been a rapid increase in the number of related studies. However, no review article has covered the wide use of Raman spectroscopy in bladder tumors. A total of 26 original studies have suggested that Raman spectroscopy shows good performance in diagnosing bladder tumors from 4 aspects, including tissue sections, endoscopic methods, cell screening, and biomarkers. However, Raman spectroscopy needs to be modified by combining it with other techniques, and studies based on a large population are still urgently needed to expand its clinical value.


Assuntos
Análise Espectral Raman , Neoplasias da Bexiga Urinária/diagnóstico , Humanos
8.
J Med Internet Res ; 22(6): e17417, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32459637

RESUMO

BACKGROUND: The benefits of telemedicine include cost savings and decentralized care. Video consultation is one form that enables early detection of deteriorating patients and promotion of self-efficacy in patients who are well but anxious. Abdominal pain is a common symptom presented by patients in emergency departments. These patients could benefit from video consultation, as it enables remote follow-up of patients who do not require admission and facilitates early discharge of patients from overcrowded hospitals. OBJECTIVE: The study aimed to evaluate the safety and efficacy of the use of digital telereview in patients presenting with undifferentiated acute abdominal pain. METHODS: The SAVED study was a prospective randomized controlled trial in which follow-up using existing telephone-based telereview (control) was compared with digital telereview (intervention). Patients with undifferentiated acute abdominal pain discharged from the emergency department observation ward were studied based on intention-to-treat. The control arm received routine, provider-scheduled telereview with missed reviews actively coordinated and rescheduled by emergency department staff. The intervention arm received access to a platform for digital telereview (asynchronous and synchronous format) that enabled patient-led appointment rescheduling. Patients were followed-up for 2 weeks for outcomes of service utilization, efficacy (compliance with their disposition plan), and safety (re-presentation for the same condition). RESULTS: A total of 70 patients participated, with patients randomly assigned to each arm (1:1 ratio). Patients were a mean age of 40.0 (SD 13.8; range 22-71) years, predominantly female (47/70, 67%), and predominantly of Chinese ethnicity (39/70, 56%). The telereview service was used by 32 patients in the control arm (32/35, 91%) and 18 patients in the intervention arm (18/35, 51%). Most patients in control (33/35, 94%; 95% CI 79.5%-99.0%) and intervention (34/35, 97%; 95% CI 83.4%-99.9%) arms were compliant with their final disposition. There was a low rate of re-presentation at 72 hours and 2 weeks for both control (72 hours: 2/35, 6%; 95% CI 1.0%-20.5%; 2 weeks: 2/35, 6%, 95% CI 1.0%-20.5%) and intervention (72 hours: 2/35, 6%; 95% CI 1.0%-20.5%; 2 weeks: 3/35, 9%, 95% CI 2.2%-24.2%) arms. There were no significant differences in safety (P>.99) and efficacy (P>.99) between the two groups. CONCLUSIONS: The application of digital telereview for the follow-up of patients with abdominal pain may be safe and effective. Future studies are needed to evaluate its cost-effectiveness and usefulness for broader clinical application. TRIAL REGISTRATION: ISRCTN Registry ISRCTN28468556; http://www.isrctn.com/ISRCTN28468556.


Assuntos
Dor Abdominal/terapia , Telemedicina/métodos , Gravação em Vídeo/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Encaminhamento e Consulta , Segurança , Resultado do Tratamento , Adulto Jovem
9.
Emerg Med J ; 37(4): 212-216, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31919233

RESUMO

OBJECTIVE: The use of tissue adhesives has become a popular option for closure of wounds in the ED. There have been a growing number of reports of inadvertent tissue adhesive injuries including closure of the eyelids. We aim to identify and compare various removal methods of tissue adhesives described in the literature in an exploratory trial. METHODS: A review was first conducted to establish all published methods for the removal of medical-grade tissue adhesives as well as commercial cyanoacrylates. This search was conducted on PubMed, Google Scholar and Google. All articles that reported attempts at removal of cyanoacrylate glues were included. These methods were then tested on a porcine model in an exploratory trial. Incisions were made on pigskin and closed with Histoacryl, a tissue adhesive. Three removal methods were tested-gentle rubbing with test compound after 45 or 90 s, as well as soaking in test compound. Removal methods that were successful underwent repeat testing. RESULTS: A total of 37 sources were reviewed with 13 different removal methods suggested. Based on the information, we tested 24 different compounds. Soaking of Histoacryl-closed wounds in Polydexa ear/eye drops displayed consistent success in achieving complete separation of incision edges after 2 hours. Several other soapy substances and antibiotic ointments showed potential but were not as consistent. CONCLUSION: In conclusion, in our trial of removal methods of Histoacryl, soaking in Polydexa antibiotic drops consistently facilitated removal after 2 hours. This approach can be attempted after inadvertent Histoacryl injury.


Assuntos
Dexametasona/uso terapêutico , Pálpebras/anormalidades , Neomicina/uso terapêutico , Polimixina B/uso terapêutico , Aderências Teciduais/complicações , Aderências Teciduais/tratamento farmacológico , Adesivos Teciduais/efeitos adversos , Animais , Dexametasona/normas , Combinação de Medicamentos , Embucrilato , Pálpebras/efeitos dos fármacos , Pálpebras/fisiopatologia , Humanos , Neomicina/normas , Polimixina B/normas , Suínos , Adesivos Teciduais/uso terapêutico
10.
Med J Aust ; 211(11): 509, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31736080
11.
Environ Pollut ; 342: 123044, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38042474

RESUMO

Mephedrone (4-methylmethcathinone, MEPH) exhibited severe ecologic hazards and health detriments. A novel deep eutectic solvent functionalized magnetic ZIF-8/hierarchical porous carbon (DMZH) with excellent selectivity, interference resistance and recyclability, was developed for the rapid adsorption of MEPH. Initially, potential adsorption sites of MEPH were predicted. Then, π-π and hydrogen bonding interactions were proposed and verified from characterizations, comparative experiments and theoretical calculations. The synergistic effects of the hydrogen bonding and π-π interactions increased the adsorption energies from -15.26 kcal⋅mol-1 to -21.83 kcal⋅mol-1, enhanced the degree of π-dissociation, enlarged the π-π isosurface area, extended the van der Waals surface mutual penetration distance, achieving stronger affinity and remarkable adsorption. Furthermore, offset (parallel-displaced) π-π stacking form existed between DMZH and MEPH. DMZH acted as the hydrogen bond donor and MEPH served as the hydrogen bond acceptor to form O-H⋯O and N-H⋯O hydrogen bonding interaction. Profiting from the synergistic effects, DMZH showed satisfactory adsorption for MEPH within 20 min with a maximum adsorption capacity of 3270.11 µg∙g-1, displayed excellent performance in wide pH range of 5∼11 and in the coexistence of multi-chemicals.


Assuntos
Metanfetamina , Ligação de Hidrogênio , Adsorção , Metanfetamina/química , Carbono
12.
Neurol Clin Pract ; 14(5): e200325, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38939047

RESUMO

Background and Objectives: Endovascular therapy (EVT) for stroke has emerged as an important therapy for selected stroke patients, and shorter times to clot removal improve functional outcomes. EVT requires the close coordination of multiple departments and poses unique challenges to care coordination in large hospitals. We present the results of our quality improvement project that aimed to improve our door-to-groin puncture (DTP) times for patients who undergo EVT after direct presentation to our emergency department. Methods: We conducted time-motion studies to understand the full process of an EVT activation and conducted Gemba walks in multiple hospitals. We also reviewed the literature and interviewed stakeholders to create interventions that were implemented over 4 Plan-Do-Study-Act (PDSA) cycles. We retrospectively collected data starting from baseline and during every PDSA cycle. During each cycle, we studied the impact of the interventions, adjusted the interventions, and generated further interventions. A variety of interventions were introduced targeting all aspects of the EVT process. This included parallel processing to reduce waiting time, standardization of protocols and training of staff, behavioral prompts in the form of a stroke clock, and push systems to empower staff to facilitate the forward movement of the patient. A novel role-based communication app to facilitate group communications was also used. Results: Eighty-eight patients spanning across 22 months were analyzed. After the final PDSA cycle, the median DTP time was reduced by 36.5% compared with baseline (130 minutes (interquartile range [IQR] 111-140) to 82.5 minutes (IQR 74.8-100)). There were improvements in all phases of the EVT process with the largest time savings occurring in EVT decision to patient arrival at the angiosuite. Interventions that were most impactful are described. Discussion: EVT is a complex process involving multiple processes and local factors. Analysis of the process from all angles and intervening on multiple small aspects can add up to significant improvements in DTP times.

13.
Singapore Med J ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38449072

RESUMO

ABSTRACT: Due to the narrow window of opportunity for stroke therapeutics to be employed, effectiveness of stroke care systems is predicated on the efficiency of prehospital stroke systems. A robust prehospital stroke system of care that provides a rapid and well-coordinated response maximises favourable poststroke outcomes, but achieving this presents a unique set of challenges dependent on demographic and geographical circumstances. Set in the context of a highly urbanised first-world nation with a rising burden of stroke, Singapore's prehospital stroke system has evolved to reflect the environment in which it operates. This review aims to characterise the current state of prehospital stroke care in Singapore, covering prehospital aspects of the stroke survival chain from symptom onset till arrival at the emergency department. We identify areas for improvement and innovation, as well as provide insights into the possible future of prehospital stroke care in Singapore.

14.
J Med Chem ; 67(6): 4904-4915, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38499004

RESUMO

A selective tumor-penetrating strategy generally exploits tumor-targeted ligands to modify drugs so that the conjugate preferentially enters tumors and subsequently undergoes transcellular transport to penetrate tumors. However, this process shields ligands from their corresponding targets on the cell surface, possibly inducing an off-target effect during drug penetration at the tumor-normal interface. Herein, we first describe a selective tumor-penetrating drug (R11-phalloidin conjugates) for intravesical therapy of bladder cancer. The intravesical conjugates rapidly translocated across the mucus layer, specifically bound to tumors, and infiltrated throughout the tumor via direct intercellular transfer. Notably, direct transfer from normal cells to tumor cells was unidirectional because the pathways required for direct transfer, termed F-actin-rich tunneling nanotubes, were more unidirectionally extended from normal cells to tumor cells. Moreover, the intravesical conjugates displayed strong anticancer activity and well-tolerated biosafety in murine orthotopic bladder tumor models. Our study demonstrated the potential of a selective tumor-penetrating conjugate for effective intravesical anticancer therapy.


Assuntos
Neoplasias da Bexiga Urinária , Camundongos , Animais , Administração Intravesical , Neoplasias da Bexiga Urinária/patologia
15.
J Adv Res ; 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38432393

RESUMO

INTRODUCTION: Vascular calcification, a devastating vascular complication accompanying atherosclerotic cardiovascular disease and chronic kidney disease, increases the incidence of adverse cardiovascular events and compromises the efficacy of vascular interventions. However, effective therapeutic drugs and treatments to delay or prevent vascular calcification are lacking. OBJECTIVES: This study was designed to test the therapeutic effects and mechanism of Moscatilin (also known as dendrophenol) from Dendrobium huoshanense (an eminent traditional Chinese medicine) in suppressing vascular calcification in vitro, ex vivo and in vivo. METHODS: Male C57BL/6J mice (25-week-old) were subjected to nicotine and vitamin D3 (VD3) treatment to induce vascular calcification. In vitro, we established the cellular model of osteogenesis of human aortic smooth muscle cells (HASMCs) under phosphate conditions. RESULTS: By utilizing an in-house drug screening strategy, we identified Moscatilin as a new naturally-occurring chemical entity to reduce HASMC calcium accumulation. The protective effects of Moscatilin against vascular calcification were verified in cultured HASMCs. Unbiased transcriptional profiling analysis and cellular thermal shift assay suggested that Moscatilin suppresses vascular calcification via binding to interleukin 13 receptor subunit A2 (IL13RA2) and augmenting its expression. Furthermore, IL13RA2 was reduced during HASMC osteogenesis, thus promoting the secretion of inflammatory factors via STAT3. We further validated the participation of Moscatilin-inhibited vascular calcification by the classical WNT/ß-catenin pathway, among which WNT3 played a key role in this process. Moscatilin mitigated the crosstalk between WNT3/ß-catenin and IL13RA2/STAT3 to reduce osteogenic differentiation of HASMCs. CONCLUSION: This study supports the potential of Moscatilin as a new naturally-occurring candidate drug for treating vascular calcification via regulating the IL13RA2/STAT3 and WNT3/ß-catenin signalling pathways.

16.
Membranes (Basel) ; 13(11)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37999367

RESUMO

The traditional fuel cell power system requires external ventilation and humidification systems for both the anode and cathode, which not only increases the application cost but also restrict its widespread use. In order to further enhance the applicability and reduce the operating costs of fuel cell power systems, this paper investigates the open-cathode proton exchange membrane fuel cell power system. This approach not only lowers the cost but also reduces the weight of the power system, enabling its potential application in a wider range of vehicles. In this study, two versions of the open-cathode fuel cell stacks were developed and performance and stability tests were conducted under various operating conditions. Additionally, tests were carried out with different materials of carbon paper to find a balance between performance and stability. Through the research presented in this paper, the application scope of fuel cells has been expanded, providing valuable insights for their further development.

17.
Chemosphere ; 323: 138276, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36863627

RESUMO

The efficient and selective removal of amphetamine (AMP) from water bodies is significant for environmental remediation. In this study, a novel strategy for screening deep eutectic solvent (DES) functional monomers was proposed based on density functional theory (DFT) calculations. Using magnetic GO/ZIF-67 (ZMG) as substrates, three DES-functionalized adsorbents (ZMG-BA, ZMG-FA, and ZMG-PA) were successfully synthesized. The isothermal results showed that the DES-functionalized materials introduced more adsorption sites and mainly contributed to the formation of hydrogen bonds. The order of the maximum adsorption capacity (Qm) was as follows: ZMG-BA (732.110 µg⋅g-1) > ZMG-FA (636.518 µg⋅g-1) > ZMG-PA (564.618 µg⋅g-1) > ZMG (489.913 µg⋅g-1). The adsorption rate of AMP on ZMG-BA was the highest (98.1%) at pH 11, which could be explained by the less protonation of -NH2 from AMP being more favorable for forming hydrogen bonds with the -COOH of ZMG-BA. The strongest affinity of the -COOH of ZMG-BA for AMP was reflected in the most hydrogen bonds and the shortest bond length. The hydrogen bonding adsorption mechanism was fully explained by experimental characterization (FT-IR, XPS) and DFT calculations. Frontier Molecular Orbital (FMO) calculations showed that ZMG-BA had the lowest HOMO-LUMO energy gap (Egap), the highest chemical activity and the best adsorption capability. The experimental results agreed with the results of theoretical calculations, proving the validity of the functional monomer screening method. This research offered fresh suggestions for the functionalized modification of carbon nanomaterials to achieve effective and selective adsorption for psychoactive substances.


Assuntos
Estruturas Metalorgânicas , Nanocompostos , Ligação de Hidrogênio , Solventes Eutéticos Profundos , Adsorção , Espectroscopia de Infravermelho com Transformada de Fourier , Nanocompostos/química , Anfetaminas , Solventes/química
18.
Front Oncol ; 13: 1221217, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37560465

RESUMO

Objective: To investigate the outcome of patients underwent anatomic periurethral reconstruction during robotic assisted laparoscopic radical prostatectomy (RARP). Materials and methods: During August 2016 to May 2018, periurethral structure anatomic reconstruction was performed during RARP in 58 consecutive patients. The control group consists of another 50 patients had no reconstruction procedure during RARP. Perioperative data of these patients were collected retrospectively, including operation time, anastomosis time, intraoperative blood loss, duration of indwelling catheter, length of hospital stay, complications, postoperative pathology, and continence outcome at 1,3,6 and 12 months. Results: All cases were successfully performed without conversion to open or laparoscopic surgery. There were no major intraoperative or postoperative complications.The percentage of patients maintain continence in the reconstruction group versus non-reconstruction group: At 1 month 84.5% (49/58)versus 70.0% (35/50), at 3 months 89.7% (52/58)versus 78.0% (39/50), at 6 months 91.3% (53/58)versus 86.0% (43/50) and 1 year after surgery 100.0% (58/58)versus 96.0% (48/50). Reconstruction group showed better continence outcome in 1 and 3 months (P<0.05). There is no statistical differences in 6 month and 1 year. Conclusion: Anatomic reconstruction of periurethral structure during RARP is safe and feasible with reduced duration of indwelling catheter and better continence outcome.

19.
J Chromatogr A ; 1695: 463927, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-36948110

RESUMO

Exploring the structure-dependent adsorption mechanism of contaminants in wastewater is beneficial to high-efficiency adsorbents design and environmental remediation. In this study, emerging porous material of zeolitic imidazolate framework-67 (ZIF-67) has been modified by the magnetic graphene oxide-polydopamine nanohybrid (mGOP) to obtain three-dimensional ZIF-67/mGOP through an in-situ growth strategy, which was applied to adsorb 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in wastewater. A combination of characterizations, experiments (pH, humic acid and ion strength effect) and quantum chemical calculations revealed the microscopic adsorption mechanism involves each single component, of which the hydrogen bond (O/N…HO) and π-π electron donor acceptor (π-π EDA) interactions of mGOP endowed favourable adsorption of ZIF-67/mGOP, and mechanisms of the pore filling and Co-O chelation of ZIF-67 played synergistic effect. Such nanocomposite as a ZIFs-based adsorbent exhibited ultra-high porosity (total pore volume = 0.4033 cm3/g) and specific surface area (995.22 m2/g), revealed the heterogeneity and multilayer adsorption properties, and obtained a theoretical maximum adsorption capacity of 159.845 µg/g which higher than that of mZIF-67 alone. Overall, this work provided an effective strategy for rationally modulate ZIFs-based composites and exploration of adsorption mechanism.


Assuntos
N-Metil-3,4-Metilenodioxianfetamina , Zeolitas , Adsorção , Águas Residuárias , Zeolitas/química , Fenômenos Magnéticos
20.
Ann Acad Med Singap ; 52(7): 356-363, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-38904501

RESUMO

Introduction: Exertional rhabdomyolysis (ER) is caused by myocyte breakdown after strenuous physical activity. In recent years, the incidence of spin-induced ER (SER) has been increasing. We describe the clinical characteristics, management and outcomes of patients admitted for SER. Method: A review was conducted for all patients admitted to Singapore General Hospital for SER from 1 March 2021 to 31 March 2022. All patients with the admission diagnosis of "rhabdomyolysis", "raised creatine kinase (CK) level", or "elevated CK level" with a preceding history of spin-related physical exertion were included. Patients without a history of exertion, with a history of non-spin related exertion, or with a peak serum CK <1000 U/L were excluded. Results: There were 93 patients in our final analysis; mean age was 28.6±5.6 years and 66 (71.0%) were female patients. Mean body mass index was 25.0±5.7 kg/m2; 81 (87.1%) patients were first-time spin participants. All patients had muscle pain, 68 (73.1%) had dark urine, 16 (17.2%) muscle swelling and 14 (15.1%) muscle weakness. There were 80 (86.0%) patients with admission CK of >20,000 U/L. Mean admission creatinine was 59.6±15.6 µmol/L. Mean intravenous (IV) hydration received was 2201±496 mL/ day, oral hydration 1217±634 mL/day and total hydration 3417±854 mL/day. There was 1 (1.1%) patient with acute kidney injury, which resolved the next day with IV hydration. Conclusion: Inpatient management of SER includes laboratory investigations, analgesia and hydration. Risk of complications is low in SER patients. SER patients without risk factors for complications can be considered for hospital-at-home management with bed rest, aggressive hydration and early outpatient review.


Assuntos
Creatina Quinase , Hospitalização , Esforço Físico , Rabdomiólise , Humanos , Rabdomiólise/etiologia , Rabdomiólise/terapia , Rabdomiólise/epidemiologia , Rabdomiólise/diagnóstico , Feminino , Masculino , Adulto , Singapura/epidemiologia , Hospitalização/estatística & dados numéricos , Creatina Quinase/sangue , Esforço Físico/fisiologia , Adulto Jovem , Estudos Retrospectivos , Hidratação/métodos , Exercício Físico
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