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1.
Br J Anaesth ; 133(3): 508-518, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38527923

RESUMEN

BACKGROUND: Numerous models have been developed to predict acute kidney injury (AKI) after noncardiac surgery, yet there is a lack of independent validation and comparison among them. METHODS: We conducted a systematic literature search to review published risk prediction models for AKI after noncardiac surgery. An independent external validation was performed using a retrospective surgical cohort at a large Chinese hospital from January 2019 to October 2022. The cohort included patients undergoing a wide range of noncardiac surgeries with perioperative creatinine measurements. Postoperative AKI was defined according to the Kidney Disease Improving Global Outcomes creatinine criteria. Model performance was assessed in terms of discrimination (area under the receiver operating characteristic curve, AUROC), calibration (calibration plot), and clinical utility (net benefit), before and after model recalibration through intercept and slope updates. A sensitivity analysis was conducted by including patients without postoperative creatinine measurements in the validation cohort and categorising them as non-AKI cases. RESULTS: Nine prediction models were evaluated, each with varying clinical and methodological characteristics, including the types of surgical cohorts used for model development, AKI definitions, and predictors. In the validation cohort involving 13,186 patients, 650 (4.9%) developed AKI. Three models demonstrated fair discrimination (AUROC between 0.71 and 0.75); other models had poor or failed discrimination. All models exhibited some miscalibration; five of the nine models were well-calibrated after intercept and slope updates. Decision curve analysis indicated that the three models with fair discrimination consistently provided a positive net benefit after recalibration. The results were confirmed in the sensitivity analysis. CONCLUSIONS: We identified three models with fair discrimination and potential clinical utility after recalibration for assessing the risk of acute kidney injury after noncardiac surgery.


Asunto(s)
Lesión Renal Aguda , Complicaciones Posoperatorias , Humanos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Medición de Riesgo/métodos , Estudios Retrospectivos , Estudios de Cohortes , Creatinina/sangre , Procedimientos Quirúrgicos Operativos/efectos adversos , Persona de Mediana Edad , Masculino , Femenino , Factores de Riesgo , Anciano
2.
Chem Biodivers ; 21(8): e202400963, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38778509

RESUMEN

The Sterculia genus is comprised of approximately 300 species, which have been widely used as traditional medicines to treat inflammation, snake bites, gastrointestinal diseases, skin diseases, microbial infections and many other diseases. To gain a comprehensive understanding of the therapeutic potential of Sterculia plants, an extensive literature search was conducted in CNKI, Bing, Wanfang Database, Springer Database, Elsevier Database, Google Scholar, Baidu Scholar, PubMed, and other similar websites from January 1971 to March 2024. The research indicated that Sterculia species predominantly contain flavonoids, terpenoids, phenylpropanoids, fatty acids, alkaloids and other chemical components. A wide range of pharmacologic activities such as anti-inflammatory, antioxidant, antibacterial and other biological activities have been reported. Nevertheless, there isn't much scholarly research on the therapeutic material basis of the genus Sterculia. This review reports the ethnobotany, phytochemicals, and biological activities of the plants in the Sterculia genus as herbal remedies.


Asunto(s)
Fitoquímicos , Sterculia , Fitoquímicos/química , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Humanos , Sterculia/química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación
3.
Ren Fail ; 45(2): 2287130, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38031451

RESUMEN

BACKGROUND: Bispectral index (BIS) is a processed electroencephalography monitoring tool and is widely used in anesthetic depth monitoring. Deep anesthesia exposure may be associated with multiple adverse outcomes. However, the relationship between anesthetic depth and postoperative acute kidney injury (AKI) remains unclear. We sought to determine the effect of BIS-based deep anesthesia duration on postoperative AKI following noncardiac surgery. METHODS: This retrospective study used data from the Vital Signs DataBase, including patients undergoing noncardiac surgeries with BIS monitoring. The BIS values were collected every second during anesthesia. Restricted cubic splines and logistic regression were used to assess the association between the cumulative duration of deep anesthesia and postoperative AKI. RESULTS: 4774 patients were eligible, and 129 (2.7%) experienced postoperative AKI. Restricted cubic splines showed that a cumulative duration of BIS < 45 was nonlinearly associated with postoperative AKI (P-overall = 0.033 and P-non-linear = 0.023). Using the group with the duration of BIS < 45 less than 15 min as the reference, ORs of postoperative AKI were 2.59 (95% confidence interval [CI]:0.60 to 11.09, p = 0.200) in the 15-100 min group, and 4.04 (95%CI:0.92 to 17.76, p = 0.064) in the ≥ 100 min group after adjusting for preoperative and intraoperative covariates in multivariable logistic regression. CONCLUSIONS: The cumulative duration of BIS < 45 was independently and nonlinearly associated with the risk of postoperative AKI in patients undergoing noncardiac surgery.


Asunto(s)
Lesión Renal Aguda , Anestesia , Anestésicos , Humanos , Estudios Retrospectivos , Factores de Riesgo , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
4.
Int J Mol Sci ; 23(23)2022 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-36499553

RESUMEN

The liquid-liquid phase separation (LLPS) of proteins has been found ubiquitously in eukaryotic cells, and is critical in the control of many biological processes by forming a temporary condensed phase with different bimolecular components. TDP-43 is recruited to stress granules in cells and is the main component of TDP-43 granules and proteinaceous amyloid inclusions in patients with amyotrophic lateral sclerosis (ALS). TDP-43 low complexity domain (LCD) is able to de-mix in solution, forming the protein condensed droplets, and amyloid aggregates would form from the droplets after incubation. The molecular interactions regulating TDP-43 LCD LLPS were investigated at the protein fusion equilibrium stage, when the droplets stopped growing after incubation. We found the molecules in the droplet were still liquid-like, but with enhanced intermolecular helix-helix interactions. The protein would only start to aggregate after a lag time and aggregate slower than at the condition when the protein does not phase separately into the droplets, or the molecules have a reduced intermolecular helix-helix interaction. In the protein condensed droplets, a structural transition intermediate toward protein aggregation was discovered involving a decrease in the intermolecular helix-helix interaction and a reduction in the helicity. Our results therefore indicate that different intermolecular interactions drive LLPS and fibril formation. The discovery that TDP-43 LCD aggregation was faster through the pathway without the first protein phase separation supports that LLPS and the intermolecular helical interaction could help maintain the stability of TDP-43 LCD.


Asunto(s)
Esclerosis Amiotrófica Lateral , Humanos , Amiloide , Proteínas Amiloidogénicas , Esclerosis Amiotrófica Lateral/metabolismo , Agregado de Proteínas
5.
Proteome Sci ; 19(1): 7, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33836751

RESUMEN

BACKGROUND: The black soldier fly (Hermetia illucens) has significant economic potential. The larvae can be used in financially viable waste management systems, as they are voracious feeders able to efficiently convert low-quality waste into valuable biomass. However, most studies on H. illucens in recent decades have focused on optimizing their breeding and bioconversion conditions, while information on their biology is limited. METHODS: About 200 fifth instar well-fed larvae were sacrificed in this work. The liquid chromatography-tandem mass spectrometry and scanning electron microscopy were employed in this study to perform a proteomic and ultrastructural analysis of the peritrophic matrix (PM) of H. illucens larvae. RESULTS: A total of 565 proteins were identified in the PM samples of H. illucen, of which 177 proteins were predicted to contain signal peptides, bioinformatics analysis and manual curation determined 88 proteins may be associated with the PM, with functions in digestion, immunity, PM modulation, and others. The ultrastructure of the H. illucens larval PM observed by scanning electron microscopy shows a unique diamond-shaped chitin grid texture. CONCLUSIONS: It is the first and most comprehensive proteomics research about the PM of H. illucens larvae to date. All the proteins identified in this work has been discussed in details, except several unnamed or uncharacterized proteins, which should not be ignored and need further study. A comparison of the ultrastructure between H. illucens larval PM and those of other insects as observed by SEM indicates that the PM displays diverse textures on an ultra-micro scale and we suscept a unique diamond-shaped chitin grid texture may help H. illucens larval to hold more food. This work deepens our understanding of the molecular architecture and ultrastructure of the H. illucens larval PM.

6.
J Am Chem Soc ; 142(7): 3412-3421, 2020 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-32003979

RESUMEN

TDP-43 is a primary pathological hallmark protein of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, which may exist in the form of amyloid inclusions in the cells of patients. In addition to serving as a biomarker for these diseases, TDP-43 can also directly trigger neurodegeneration. We previously determined the amyloidogenic core region of TDP-43 (residues 311-360) and showed by solution NMR that this region includes two α-helices [(321-330) and (335-343)] in solution. We suggested that the helix-to-sheet structural transformation initiates TDP-43 aggregation. In the present study, X-ray diffraction shows that TDP-43 (311-360) aggregates adopt a cross-ß structure. Thioredoxin (Trx)-fused TDP-43 (311-360) can undergo liquid-liquid phase separation (LLPS) before fibrillation, suggesting that phase separation is an intermediate step before amyloid formation. Solid-state NMR (SSNMR), carried out to elucidate the structural changes of TDP-43 (311-360) at the atomic level, indicates five ß-strands of the amyloids formed, with the major two ß-strands contributed by the first helical region in the solution structure. The NMR evidence is also in support of the fibril having a parallel in-register conformation, implying a mechanism in which the helix-helix interactions in LLPS are converted into ß-strand parallel lateral association upon fibrillation. Our studies have assigned many key interresidue interactions that contribute to the stability of the fibril, including F316 with I318 and Q327 and W334 with A325, A326, A329, and S332. SSNMR with 1H detection reveals a unique close interaction between the indole Nε1-Hε1 of W334 and the side-chain carbonyl of Q343. This interaction could be a very important factor in initiating TDP-43 (311-360) folding/misfolding in LLPS.


Asunto(s)
Proteínas Amiloidogénicas/metabolismo , Proteínas de Unión al ADN/metabolismo , Fragmentos de Péptidos/metabolismo , Secuencia de Aminoácidos , Proteínas Amiloidogénicas/química , Proteínas de Unión al ADN/química , Humanos , Resonancia Magnética Nuclear Biomolecular , Fragmentos de Péptidos/química , Transición de Fase , Conformación Proteica , Multimerización de Proteína
7.
Nat Mater ; 18(5): 476-481, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30833780

RESUMEN

The experimental manifestation of topological effects in bulk materials is attracting enormous research interest. However, direct experimental evidence of the effective k-space monopole of the Weyl nodes has so far been lacking. Here, signatures of the singular topology of the type-II Weyl semimetal TaIrTe4 are revealed in the photoresponses, which are related to divergence of the Berry curvature. TaIrTe4 exhibits a large photoresponsivity of 130.2 mA W-1-with 4 µm excitation in an unbiased field-effect transistor at room temperature-arising from the third-order nonlinear optical response, approaching the performance of commercial low-temperature detectors. In addition, the circularly polarized galvanic response is enhanced at 4 µm, possibly due to the same Berry curvature singularity enhancement. Considering the optical selection rule of chiral Weyl cones, this may open the door for studying and controlling the chiral polarization of Weyl fermions with an electric field in addition to the optical helicities.

8.
BMC Genomics ; 20(1): 161, 2019 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-30813894

RESUMEN

BACKGROUND: Mermithid nematodes, such as Ovomermis sinensis, display a broad host range including some lepidopteran pests. Infective juveniles penetrate their host through the cuticle, complete their growth within the hemocoel and eventually kill the host upon their emergence. Hence, mermithid nematodes are considered potential biological control agents of insect pests. Our previous data indicate that the infection rate of O. sinensis on cotton bollworm (Helicoverpa armigera) is low, which may be largely due to the strong immune system of the host. However, current knowledge on the interactions of mermithid nematodes with their hosts and the mechanisms employed by hosts to defend themselves against mermithid nematodes is limited. RESULTS: Here, we investigated the response of H. armigera to O. sinensis infection. Parasitism by O. sinensis caused a sharp decline in the survival rate of H. armigera. The hemocytic phagocytosis ability, antibacterial activity, and phenoloxidase (PO) activity in plasma of H. armigera increased at 1 d post parasitism (dpp) but decreased at 3 dpp. Further, we investigated gene expression in the fat body of parasitized and non-parasitized H. armigera larvae at 1, 3, and 5 dpp using a digital gene expression system. In total, 41, 60 and 68 immune-related differentially expressed genes were identified at 1, 3, and 5 dpp, respectively. These genes encoded pattern recognition receptors (PRRs), antimicrobial peptides (AMPs), serine proteases (SPs), SP inhibitors, mucins and other immune-related proteins. The expression of most PRRs, AMPs, SPs, and mucins was upregulated in the fat body of larvae at 1 dpp, downregulated at 3 dpp, and then again upregulated at 5 dpp by O. sinensis. The increased expression of SP inhibitors may contribute to the inhibited PO activity at 5 dpp. CONCLUSIONS: This study demonstrates that parasitism by O. sinensis modulates the immune reaction of the host H. armigera by altering the expression of immune-related genes. Our data provide a basis for future investigation of the molecular mechanisms employed by the mermithid nematode O. sinensis to modulate the immunity of the host H. armigera. These data will also likely facilitate the improvement of success in parasitism of H. armigera by O. sinensis.


Asunto(s)
Mermithoidea/fisiología , Mariposas Nocturnas/inmunología , Mariposas Nocturnas/parasitología , Animales , Perfilación de la Expresión Génica , Larva/inmunología , Larva/parasitología , Mariposas Nocturnas/genética , Mariposas Nocturnas/metabolismo , Receptores de Reconocimiento de Patrones/genética , Receptores de Reconocimiento de Patrones/metabolismo , Análisis de Secuencia de ARN , Serina Proteasas/genética , Serina Proteasas/metabolismo , Análisis de Supervivencia
10.
Mol Cell Biochem ; 449(1-2): 47-54, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29532226

RESUMEN

Hepatocellular carcinoma (HCC) is among the most common lethal cancers of the digestive system with poor prognosis rates and ineffective therapeutic options. Matrine, a traditional Chinese medicine found in the roots of sophora species, has been used in the clinical treatment of liver fibrosis, chronic hepatitis B and other diseases. We have synthesized a matrine derivatives named WM622 (C26H35ON3S2) with a significant inhibitory effect on transplanted tumors in vivo. The half inhibitory concentration (IC50) of WM622 is 34 µM, which is much lower than matrine. WM622 inhibited the proliferation and promoted apoptosis of hepatocellular carcinoma cells significantly, and the cell cycle was blocked in G0/G1 phase. The protein phosphorylation levels of EGFR, AKT, PI3K and GSK3ß (p-EGFR, p-AKT, p-PI3K, and p-GSK3ß) were also decreased by WM622 treatment dose dependently. In tumor-bearing mice, WM622 could reduce the tumor volumes. In conclusion, the study demonstrated that WM622 could inhibit the proliferation of the hepatocellular carcinoma both in vivo and in vitro by inducing apoptosis, blocking cell cycle in G0/G1 phase and inhibiting the PI3K/AKT signal pathways.


Asunto(s)
Alcaloides , Carcinoma Hepatocelular/metabolismo , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Neoplasias Hepáticas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Quinolizinas , Fase de Descanso del Ciclo Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Alcaloides/química , Alcaloides/farmacología , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Puntos de Control de la Fase G1 del Ciclo Celular/genética , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Quinolizinas/química , Quinolizinas/farmacología , Fase de Descanso del Ciclo Celular/genética , Transducción de Señal/genética , Matrinas
11.
Lab Invest ; 97(5): 543-554, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28218740

RESUMEN

Maresin1 (MaR1) is a new docosahexaenoic acid-derived pro-resolving agent that promotes the resolution of inflammation. In this study, we sought to investigate the effect and underlining mechanisms of MaR1 in modulating alveolar fluid clearance (AFC) on LPS-induced acute lung injury. MaR1 was injected intravenously or administered by instillation (200 ng/kg) 8 h after LPS (14 mg/kg) administration and AFC was measured in live rats. In primary rat alveolar type II epithelial cells, MaR1 (100 nM) was added to the culture medium with lipopolysaccharide for 6 h. MaR1 markedly stimulated AFC in LPS-induced lung injury, with the outcome of decreased pulmonary edema and lung injury. In addition, rat lung tissue protein was isolated after intervention, and we found MaR1 improved epithelial sodium channel (ENaC), Na,K-adenosine triphosphatase (ATPase) protein expression and Na,K-ATPase activity. MaR1 down-regulated Nedd4-2 protein expression though PI3k/Akt but not though PI3k/SGK1 pathway in vivo. In primary rat alveolar type II epithelial cells stimulated with LPS, MaR1-upregulated ENaC and Na,K-ATPase protein abundance in the plasma membrane. Finally, the lipoxin A4 Receptor inhibitor (BOC-2) and PI3K inhibitor (LY294002) not only blocked MaR1's effects on cAMP/cGMP, the expression of phosphorylated Akt and Nedd4-2, but also inhibited the effect of MaR1 on AFC in vivo. In conclusion, MaR1 stimulates AFC through a mechanism partly dependent on alveolar epithelial ENaC and Na,K-ATPase activation via the ALX/PI3K/Nedd4-2 signaling pathway. Our findings reveal a novel mechanism for pulmonary edema fluid reabsorption and MaR1 may provide a new therapy for the resolution of ALI/ARDS.


Asunto(s)
Lesión Pulmonar Aguda/metabolismo , Ácidos Docosahexaenoicos/farmacología , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Canales Epiteliales de Sodio/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Receptores de Lipoxina/metabolismo , Transducción de Señal/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Lipopolisacáridos , Pulmón/química , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Ubiquitina-Proteína Ligasas Nedd4 , Alveolos Pulmonares/metabolismo , Ratas , Ratas Sprague-Dawley , ATPasa Intercambiadora de Sodio-Potasio/metabolismo
12.
Int J Mol Sci ; 17(7)2016 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-27428960

RESUMEN

Tea (Camellia sinensis L.) is recalcitrant to Agrobacterium-mediated genetic transformation largely due to the bactericidal effects of tea polyphenols and phenolics oxidation induced by necrosis of explant tissue over the process of transformation. In this study, different antioxidants/adsorbents were added as supplements to the co-cultivation and post co-cultivation media to overcome these problems for the transformation improvement. Tea-cotyledon-derived calli were used as explants and Agrobacterium rhizognes strain ATCC 15834 was used as a mediator. Results showed that Agrobacterium growth, virulence (vir) gene expression and browning of explant tissue were greatly influenced by different supplements. Murashige and Skoog (MS) basal salts medium supplemented with 30 g·L(-1) sucrose, 0.1 g·L(-1) l-glutamine and 5 g·L(-1) polyvinylpolypyrrolidone (PVPP) as co-cultivation and post co-cultivation media could maintain these parameters better that ultimately led to significant improvement of hairy root generation efficiency compared to that in the control (MS + 30 g·L(-1) sucrose). Additionally, the reporter genes ß-glucuronidase (gusA) and cyan fluorescent protein (cfp) were also stably expressed in the transgenic hairy roots. Our study would be helpful in establishing a feasible approach for tea biological studies and genetic improvement of tea varieties.


Asunto(s)
Agrobacterium/crecimiento & desarrollo , Antioxidantes/farmacología , Camellia sinensis/genética , Medios de Cultivo Condicionados/farmacología , Raíces de Plantas/crecimiento & desarrollo , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Agrobacterium/efectos de los fármacos , Agrobacterium/genética , Regulación de la Expresión Génica de las Plantas , Raíces de Plantas/efectos de los fármacos , Plantas Modificadas Genéticamente/efectos de los fármacos , Plantas Modificadas Genéticamente/genética , Reacción en Cadena de la Polimerasa , Transformación Genética
13.
Cardiology ; 132(3): 182-8, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26278103

RESUMEN

OBJECTIVE: Nuclear factor kappa-B (NF-954;B)-induced inflammation leads to myocarditis and heart dysfunction. How microRNAs (miRNAs) contribute to this process is poorly defined. The aim of this study was to investigate whether miRNAs regulate NF-954;B-induced inflammation in experimental autoimmune myocarditis (EAM) in vivo. METHODS AND RESULTS: NF-954;B and its related proinflammatory genes, including interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a), were activated in EAM. Profiling of NF-954;B-related miRNAs revealed that miR-590-3p was strikingly reduced in EAM. We found IL-6-induced proinflammatory signaling via miR-590-3p reduction, p50 induction, NF-954;B activation and IL-6/TNF-a expression. Moreover, a luciferase reporter assay demonstrated that miR-590-3p directly interacted with the 3' UTR (untranslated region) of the p50 subunit, and that miR-590-3p overexpression inhibited p50 expression. Finally, miR-590-3p transfection through adeno-associated virus significantly inhibited p50 expression, suppressed NF-954;B activity and blocked IL-6/TNF-a expression in vivo, reducing the lesion area and improving cardiac function in EAM. CONCLUSION: miR-590-3p is a novel NF-954;B-related miRNA that directly targets the p50 subunit. This may provide a novel strategy for the treatment of myocarditis.


Asunto(s)
Interleucina-6/genética , MicroARNs/genética , Miocarditis/genética , Subunidad p50 de NF-kappa B/genética , Factor de Necrosis Tumoral alfa/genética , Animales , Masculino , Ratas
14.
Cardiology ; 128(3): 259-65, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24852180

RESUMEN

OBJECTIVE: The systematic pro-inflammatory responses after percutaneous coronary intervention with drug-eluting stents (DES) remain poorly defined. Therefore, we compared the systematic pro-inflammatory state of circulating mononuclear cells (MNCs) between DES and bare metal stent (BMS) implantation. METHODS: Patients with indications for treatment with stents were randomized in a 1:1 ratio to placement of DES or BMS. The primary endpoint was a change of pro-inflammatory state at 12 weeks post-procedure. RESULTS: Thirty-six consecutive patients received DES or BMS. At 12 weeks after stent implantation, the lipid profile and high-sensitivity C-reactive protein (hs-CRP) improved significantly in both groups. The mRNA levels and plasma concentrations of interleukin-6, tumor necrosis factor-α and matrix metalloproteinase-9 were significantly elevated in the DES group, which was not observed in the BMS group. An increase in NF-κB binding activity and a decrease in PPAR-γ expression in MNCs were observed in the DES group, along with increases in IκB phosphorylation and p50 expression. However, similar changes were not observed in the BMS group. CONCLUSIONS: Systematic inflammatory responses were accentuated after the patients were treated percutaneously with DES, despite their improved lipid profile and hs-CRP. These data may provide fundamental information for optimizing therapeutic strategy in the era of DES.


Asunto(s)
Stents/efectos adversos , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Análisis de Varianza , Proteína C-Reactiva/metabolismo , Estenosis Coronaria/terapia , Stents Liberadores de Fármacos/efectos adversos , Ensayo de Inmunoadsorción Enzimática , Everolimus , Humanos , Inmunosupresores/administración & dosificación , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Leucocitos Mononucleares/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , ARN Mensajero/metabolismo , Sirolimus/administración & dosificación , Sirolimus/análogos & derivados , Factor de Necrosis Tumoral alfa/metabolismo
15.
J Huazhong Univ Sci Technolog Med Sci ; 34(5): 646-651, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25318872

RESUMEN

Inflammation plays an essential role in the pathophysiology of atherosclerosis. Our study was aimed to investigate whether salvianolate, a novel water-soluble phenolic compound of Danshen, alleviates atherosclerosis via regulating the inflammation in rats. High fat diet feeding plus vitamin D3 injection was used to induce atherosclerosis in rats. Salvianolate (60, 120 or 240 mg/kg) or placebo was given to atherosclerotic rats. The plasma lipids, interleukin 6 (IL-6) and C reactive protein (CRP) were measured by ELISA. CD4+CD25+Foxp3+ cells were determined by flow cytometry. Histological changes were examined by hematoxylin and eosin staining. The results showed that the levels of plasma IL-6 and CRP were elevated in the rats fed on high fat diet, and the histological analysis demonstrated the successful establishment of atherosclerosis models. Treatment with salvianolate alleviated the atherosclerotic process and decreased the levels of plasma IL-6 and CRP. Also the number of CD4+CD25+Foxp3+ cells was increased in salvianolate-treated rats. It was concluded that salvianolate could treat atherosclerosis via modulating the inflammation at cytokine and cell levels.


Asunto(s)
Aterosclerosis/prevención & control , Inflamación/prevención & control , Extractos Vegetales/farmacología , Salvia miltiorrhiza/química , Animales , Aterosclerosis/sangre , Aterosclerosis/etiología , Proteína C-Reactiva/metabolismo , Colecalciferol/administración & dosificación , Dieta Alta en Grasa/efectos adversos , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Factores de Transcripción Forkhead/metabolismo , Inflamación/sangre , Interleucina-6/sangre , Lípidos/sangre , Recuento de Linfocitos , Masculino , Fitoterapia , Ratas Wistar , Receptores de Complemento 3b/metabolismo , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/metabolismo , Vitaminas/administración & dosificación
16.
Org Lett ; 26(7): 1393-1398, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38346022

RESUMEN

We disclose herein a photocatalytic radical cascade cyclization of diazoalkanes for the divergent synthesis of important carbocycles and heterocycles. Under the optimal reaction conditions, various indanone, pyrone, and pyridinone derivatives can be obtained in moderate to good yields. Mechanistic experiments support the formation of carbon-centered radicals from diazoalkanes through the proton-coupled electron transfer process. Scale-up reaction using continuous flow technology and useful downstream application of the formed heterocycles further render the strategy attractive and valuable.

17.
Heliyon ; 10(7): e28434, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38560099

RESUMEN

Background: A conclusive evidence regarding the optimal concentration and volume of local anesthetic for quadratus lumborum block is lacking. Methods: In this single-center, prospective, randomized, controlled study, 60 patients scheduled for laparoscopic colorectal surgery were randomly assigned to 3 different combinations of volume and concentration of ropivacaine (3 mg/kg) - Group 0.25%, Group 0.375% and Group 0.5%. All subjects received ultrasound-guided posterior quadratus lumborum block prior to the induction. The primary outcome was the complete sensory block rate of surgical site measured at 30 min after quadratus lumborum block, after extubation, at 12, 24, and 48 h after operation. Secondary outcomes were the changes in hemodynamic parameters before and after incision (ΔSBP, ΔDBP and ΔHR), postoperative pain score, the sufentanil consumption after surgery, length of stay and adverse reactions. Results: The sensory block rate of surgical site at 5 time points differed significantly among the three groups (P < 0.001). Both Group 0.375% (P < 0.001) and Group 0.5% (P < 0.001) had a higher sensory block rate than Group 0.25%, but no significant difference was observed between the former two. Group 0.375% and Group 0.5% had lower postoperative pain scores, lower sufentanil consumption after surgery and shorter length of stay. No statistical difference was observed in ΔSBP, ΔDBP, ΔHR and the incidence of adverse reactions. Conclusions: 0.375% and 0.5% ropivacaine in posterior quadratus lumborum block provide better sensory block of surgical site when compared to 0.25% in laparoscopic colorectal surgery. Trial registration number: Chinese Clinical Trials Registry (ChiCTR2100043949).

18.
Nat Prod Res ; : 1-9, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39021087

RESUMEN

A new series of usnic acid (UA) monoesterified derivatives 2-15 were designed and synthesised using UA (1) as starting material. The structural characterisation of all compounds was elucidated using 1H-NMR and 13C-NMR spectral data. In vitro studies demonstrated thatmost UA derivatives exhibited higher inhibitory activity against Candida albicans and Staphylococcus aureus. Among them, compound 7 displayed the highest inhibitory activity against C. albicans with a minimum inhibitory concentration (MIC) of 32 µg/mL. Compounds 5, 8, 9, 11and 13 demonstrated superior inhibition of S. aureus (MIC, 16 µg/mL) and biofilm formation in a concentration-dependent manner. With the exception of 11, compounds 5, 8, 9 and 13 were all more effective than UA in inhibiting S. aureus biofilms. This research highlights the potential of UA monoesterified derivatives for the development of dual antimicrobial and antibiofilm agents.

19.
Apoptosis ; 18(7): 800-10, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23620435

RESUMEN

A prolonged or excessive adrenergic activation leads to myocyte loss and heart dysfunction; however, how it contributes to heart failure remains poorly defined. Here we show that isoproterenol (ISO) induced aberrant endoplasmic reticulum (ER) stress and apoptotic cell death, which was inhibited by activating the AMP-activated protein kinase (AMPK) in vitro and in vivo. Persistent ISO stimulation suppressed the AMPK phosphorylation and function, resulting in enhanced ER stress and the subsequent cell apoptosis in cardiomyocytes in vitro and in vivo. AMPK activation decreased the aberrant ER stress, apoptosis, and brain natriuretic peptide (BNP) release in ISO-treated cardiomyocytes, which was blocked by AMPK inhibitor Compound C. Importantly, increased ER stress and apoptosis were observed in ISO-treated cardiomyocytes isolated from AMPKα2(-/-) mice. Inhibition of ER stress attenuated the apoptosis but failed to reverse AMPK inhibition in ISO-treated cardiomyocytes. Moreover, metformin administration activated AMPK and reduced both ER stress and apoptosis in ISO-induced rat heart failure in vivo. We conclude that ISO, via AMPK inactivation, causes aberrant ER stress, cardiomyocyte injury, BNP release, apoptosis, and hence heart failure in vivo, all of which are inhibited by AMPK activation.


Asunto(s)
Proteínas Quinasas Activadas por AMP/genética , Insuficiencia Cardíaca/inducido químicamente , Isoproterenol/efectos adversos , Metformina/farmacología , Miocitos Cardíacos/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Proteínas Quinasas Activadas por AMP/deficiencia , Animales , Apoptosis/efectos de los fármacos , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/genética , Retículo Endoplásmico/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Regulación de la Expresión Génica , Insuficiencia Cardíaca/enzimología , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/prevención & control , Masculino , Ratones , Ratones Noqueados , Miocardio/enzimología , Miocardio/patología , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/patología , Péptido Natriurético Encefálico/metabolismo , Fosforilación , Pirazoles/farmacología , Pirimidinas/farmacología , Ratas , Ratas Sprague-Dawley , Transducción de Señal
20.
Opt Express ; 21(20): 23486-97, 2013 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-24104262

RESUMEN

We investigate the light emission characteristics for single two level quantum dot (QD) in a realistic photonic crystal (PC) L3 cavity based upon the local coupling strength between the QD and cavity together with the Green's function in which the propagation function related to the position of the detector is taken into account. We find for a PC cavity that the line shape of the propagation function in frequency domain is identical to that of the cavity and independent on the detector's position. We confirm that this identity is not influenced by the horizontal decay of the cavity. Furthermore, it is revealed that the vacuum fluorescence spectrum of the coupled system never give the triplet in strong coupling regime. Our work demonstrates that the experimental spectral-triplet in coupled system of single QD and PC cavity cannot be individually understood by vacuum Rabi splitting without including other physics mechanism.

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