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1.
Foot Ankle Surg ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38987122

RESUMO

BACKGROUND: Smoking has long been recognized as a risk factor for impaired wound and bone healing, particularly in the context of ankle and foot surgery. Despite numerous studies exploring the association between smoking and complications following ankle replacement, there remains significant inconsistency in their findings. Therefore, this meta-analysis study aims to elucidate whether smoking increases the rate of complications after total ankle arthroplasty (TAA), providing valuable insights for clinical management. METHODS: A comprehensive systematic search was conducted in the PubMed, Embase, and Wiley databases to identify relevant English studies on the influence of smoking on postoperative complications following ankle replacement without any restrictions on publication dates. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Random-effect models were used to calculate odds ratios (OR) and 95 % confidence intervals (CI). This study adhered to PRISMA guidelines for transparent reporting and was registered with PROSPERO. RESULTS: The analysis incorporated data from 12 retrospective cohort studies, totaling 17331 subjects, 2580 of whom were smokers and 791 complications following TAA. The findings revealed a statistically significant disparity in wound-related complications (OR: 2.26; 95 % CI: 1.13-4.50; P = .02), particularly evident in current smokers with an OR of 3.30 (95 % CI: 2.12-5.14; P < .00001). However, we lacked sufficient evidence to substantiate an association between smoking and complications related to the prosthesis (OR: 1.09; 95 % CI: 0.77-1.53; P = .64) or systemic complications (OR: 1.18; 95 % CI: 0.10-14.13; P = .90) following TAA. CONCLUSIONS: Smoking, especially current smoking, is associated with increased wound complication risk post-operation for total ankle arthroplasty. Despite a lack of definitive evidence on the optimal timeframe for smoking cessation before surgery, discontinuing smoking appears to be a prudent measure to mitigate these complications.

2.
Dalton Trans ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995223

RESUMO

Copper-catalysed intramolecular Ullman arylation has been frequently used to synthesise benzoxazoles and benzothiazoles. Despite widespread use, investigations into the mechanism and speciation of copper-containing complexes relevant to the catalytic pathway have remained relatively limited. Accordingly, this study aims to elucidate the structural details of potential copper(I) intermediates through the analysis of their solid-state structures using X-ray crystallography, while also investigating the reactivities of these complexes. Five novel copper complexes are reported which are formed prior to the aryl halide activation step and feature distinct aggregation modes based on either Cu4N4O4C4 or Cu4N4S4C4 clusters.

3.
Life (Basel) ; 14(6)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38929694

RESUMO

There is limited information regarding the influence of mangrove growth on the morphological evolution of intertidal mudflats. In this study, Tan Phu Dong district, Tien Giang Province, Vietnam, was selected for investigating how mangrove growth influenced the morphological evolution of an intertidal mudflat. The authors analyzed a series of satellite images (from 1995 and 2022), calculated the enhanced vegetation index (EVI), and documented field visits and observations in pursuit of the objective of the study. The findings revealed that fine-grained sediment accumulated as unconsolidated substratum (US) in the first step of the morphological evolution of the intertidal mudflat, with sediment accumulation of 910 ha in 1995. The US provided favorable conditions for mangroves to grow, while mangrove growth helped compact the US into a compact substratum (CS) in addition to promoting continuous sediment accumulation, increased the vegetation cover of the island, and elevated the substrate density of the remaining areas. As a result, the US and CS decreased steadily between 1995 and 2020, from 910 ha in 1995 to 401 ha in 2020 and from 433 ha in 2005 to 111 ha in 2020, respectively. Meanwhile, the low-vegetation area (LVA), medium-vegetation area (MVA), and high vegetation area (HVA) gradually increased between 1995 and 2015, from 0 ha in 1995 to 104 ha in 2015, from 0 ha in 1995 to 96 ha in 2015, and from 0 ha in 1995 to 114 ha in 2015, respectively. However, the LVA decreased slightly between 2015 and 2020 due to significant sand accumulation, which significantly killed the mangrove trees. In contrast, the MVA and HVA steadily increased between 2015 and 2020, from 96 ha in 2015 to 116 ha in 2020 and from 114 ha in 2015 to 221 ha in 2020, respectively. In 2022, there was a steady increase in HVA (298 ha in 2022), although the date of the 2022 satellite retrieval was 28 January 2022. This study recommends that the technical design of the existing coastal protection works should be revised or adapted to take account of sediment accumulation as the first step in the morphological evolution of the examined intertidal mudflat, rather than mangrove growth.

4.
Molecules ; 29(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38930872

RESUMO

This study is the first to investigate the chemical composition and antioxidant, anti-inflammatory, and cytotoxic activities of Peperomia leptostachya leaf oil. A yellow oil was obtained through hydro-distillation, with a yield of 0.1% (w/w). The GC-MS analysis revealed 66 compounds, constituting 99.6% of the oil. Sesquiterpene hydrocarbons predominated (70.4%), followed by monoterpene hydrocarbons (13.2%), oxygenated sesquiterpenes (12.4%), non-terpenic compounds (2.0%), and oxygenated monoterpenes (1.6%). Major constituents included germacrene D (25.1%), (E)-caryophyllene (17.4%), bicyclogermacrene (6.6%), α-pinene (6.2%), and ß-pinene (4.7%). The assessment of antioxidant capacity via 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay yielded a weak effect, with an IC50 value > 100 µg/mL. The inhibition of lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells was quantified using the MTT assay, showing an IC50 value of 15.15 ± 0.68 µg/mL. Furthermore, cytotoxic effects on SK-LU-1 cell line growth were evaluated using the sulforhodamine B assay, resulting in an IC50 value of 37.45 ± 2.43 µg/mL. The anti-inflammatory activity was notable among the analyzed bioactivities of this oil. By employing a computational model, the predominant secondary metabolites in the essential oil were selected as candidates for interaction analysis with cyclooxygenase-2, an enzyme implicated in the inflammatory response. Our findings suggest that P. leptostachya leaf oil could serve as a potential source of natural compounds with prospective therapeutic effects in treating inflammatory conditions.


Assuntos
Anti-Inflamatórios , Antioxidantes , Óleos Voláteis , Peperomia , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Antioxidantes/farmacologia , Antioxidantes/química , Camundongos , Animais , Células RAW 264.7 , Peperomia/química , Óxido Nítrico/metabolismo , Folhas de Planta/química , Cromatografia Gasosa-Espectrometria de Massas , Simulação por Computador , População do Sudeste Asiático
5.
Nat Chem ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858517

RESUMO

Maxwell's demon describes a thought experiment in which a 'demon' regulates the flow of particles between two adjoining spaces, establishing a potential gradient without appearing to do work. This seeming paradox led to the understanding that sorting entails thermodynamic work, a foundational concept of information theory. In the past centuries, many systems analogous to Maxwell's demon have been introduced in the form of molecular information, molecular pumps and ratchets. Here we report a functional example of a Maxwell's demon that pumps material over centimetres, whereas previous examples operated on a molecular scale. In our system, this demon drives directional transport of o-fluoroazobenzene between the arms of a U-tube apparatus upon light irradiation, transiting through an aqueous membrane containing a coordination cage. The concentration gradient thus obtained is further harnessed to drive naphthalene transport in the opposite direction.

6.
ACS Omega ; 9(22): 23420-23430, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38854528

RESUMO

Pakchoi (Brassica rapa subsp. chinensis) is one of the most widely consumed vegetables in Asian countries, and it is high in secondary metabolites. The availability, quantity, and quality of light play a critical role in the growth and development of plants. In this study, we investigated the effect of LEDs (light-emitting diodes; white, blue, red, and red + blue) on anthocyanin, glucosinolates, and phenolic levels in red pakchoi baby leaves. On the 24th day after sowing (DAS), red baby pakchoi leaves were harvested, and shoot length, root length, and fresh weight were measured. Among the different LED treatments, there was no significant difference in shoot length, whereas the highest root length was achieved in the red + blue LED treatment (23.8 cm). The fresh weight also showed a significant difference among the different LED treatments. In total, 12 phenolic and 7 glucosinolate individual compounds were identified using high-performance liquid chromatography (HPLC) analysis. The highest total glucosinolate (2937 µg/g dry wt) and phenolic (1589 µg/g dry wt) contents were achieved in baby leaves exposed to red + blue light. Similarly, the highest contents of total anthocyanins (1726 µg/g dry wt), flavonoids (4920 µg/g dry wt), and phenolics (5900 µg/g dry wt) were achieved in the red + blue treatment. Plants exposed to red + blue LED light showed the highest accumulation of anthocyanin, glucosinolates, and phenolic compounds. For antioxidant activity, DPPH (2,2-diphenyl-1-picrylhydrazylradical) free radical scavenging, ABTS (2,2-azinobis (3-ethylbenzothiazoline)-6-sulfonic acid) radical scavenging, and reducing power assays were performed, and the antioxidant activity of red pakchoi baby leaves grown under red + blue LED light was found to be the best. The metabolic profiling of the identified metabolites revealed distinct separation based on the secondary metabolites. This research will be helpful for farmers to choose the best LED light combination to increase the secondary metabolic content in pakchoi plants.

7.
Plant Dis ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902876

RESUMO

Hot chili pepper (Capsicum annuum) cultivation has been on the rise in South East Asia to meet export demands. In Thailand, the top chili exporter in South East Asia, chili production has been severely hampered by pepper yellow leaf curl disease (YLCD) caused by the begomovirus pepper yellow leaf curl Thailand virus (PepYLCThV) (Chiemsombat et al., 2018; Suwor et al., 2021). In the neighbouring countries of Laos and Vietnam, a limited survey of chili fields (200 plants in total) in Savannakhet (Savannakhet University campus, n = 150), Laos and Quang Nam province (Ka Dang commune, Dong Giang district, n = 50), central Vietnam in 2023 led to the finding of eight plants (5 in Laos and 3 in Vietnam) exhibiting YLCD-like symptoms, which included bright yellow color in young leaves and leaf curl and mosaic chlorosis in mature leaves (Fig. S1). Total DNA was extracted from leaves of two symptomatic plants (one from Savannakhet and one from Quang Nam) using a cetyltrimethylammonium bromide-based DNA extraction protocol (Doyle & Doyle, 1987; Nguyen et al., 2023). Next, PCR were performed using newly designed PepYLCThV-specific primers based on PepYLCThV sequences in GenBank (Table 1). PCR products of expected sizes were observed in samples with disease symptoms, but not from DNA extracted from C. annuum (cv. VA.99999) grown at the Institute of Biotechnology in Thua Thien Hue, Vietnam (Fig. S2). The amplicons were Sanger sequenced (Apical Scientific, Selangor, Malaysia) and the complete bipartite genome sequence of two isolates ('Sava01' from Laos and 'QNam01' from Vietnam) were obtained. The sequences of the DNA-A component from isolates 'Sava01' (GenBank PP437580) and 'QNam01' (GenBank PP437581) exhibited the highest sequence identity of 99.2% and 94.7% with the PepYLCThV isolate 'ChiangDaoS1' (GenBank OM677627), respectively (Table 2). Conversely, the sequences of the DNA-B component from the isolates 'Sava01' (GenBank PP437579) and 'QNam01' (GenBank PP437582) exhibited the highest similarity of 91.8% and 90.9% with the PepYLCThV isolate 'KKN601' (GenBank MW715820), respectively (Table 2). These results confirmed the presence of PepYLCThV in hot chili pepper plants exhibiting YLCD-like symptoms in central Vietnam and Laos. Infectious clones of PepYLCThV DNA-A and DNA-B (isolate 'QNam01') were created based on the pLX-AS vector as described by Pasin (2022), and transformed into Agrobacterium tumefaciens EHA105. The resulting bacteria were cultured in LB broth containing rifampicin (25 µg/mL) and kanamycin (50 µg/mL) at 28°C and used for agroinoculation of Nicotiana benthamiana (n = 6) and C. annuum (cv. VA.99999, n = 6) (4-6 leaf plants) as described by Pasin (2022). In all N. benthamiana plants, agroinoculation with both DNA-A and DNA-B infectious clones caused stunted growth, severe leaf curl, with yellow and white patches 21 days post inoculation (Fig. S3). In C. annuum plants, symptom expression, which included leaf curl and stunted leaves with yellow mosaic patterns, was observed in two out of six inoculated plants six weeks postinoculation (Fig. S3). PCR assays confirmed the presence of PepYLCThV DNA in N. benthamiana and C. annuum symptomatic leaves (Fig. S4). To our knowledge, this is the first report of pepper yellow leaf curl Thailand virus in hot chili pepper in Laos and central Vietnam. Appropriate containment and management strategies should be developed and implemented to control the spread of this disease in hot chili pepper crops in both countries.

8.
Heart Rhythm O2 ; 5(4): 217-223, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38690142

RESUMO

Background: Pericardial effusion requiring percutaneous or surgical-based intervention remains an important complication of a leadless pacemaker implantation. Objective: The study sought to determine real-world prevalence, risk factors, and associated outcomes of pericardial effusion requiring intervention in leadless pacemaker implantations. Methods: The National Inpatient Sample and International Classification of Diseases-Tenth Revision codes were used to identify patients who underwent leadless pacemaker implantations during the years 2016 to 2020. The outcomes assessed in our study included prevalence of pericardial effusion requiring intervention, other procedural complications, and in-hospital outcomes. Predictors of pericardial effusion were also analyzed. Results: Pericardial effusion requiring intervention occurred in a total of 325 (1.1%) leadless pacemaker implantations. Patient-level characteristics that predicted development of a serious pericardial effusion included >75 years of age (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08-1.75), female sex (OR 2.03, 95% CI 1.62-2.55), coagulopathy (OR 1.50, 95% CI 1.12-1.99), chronic pulmonary disease (OR 1.36, 95% CI 1.07-1.74), chronic kidney disease (OR 1.53, 95% CI 1.22-1.94), and connective tissue disorders (OR 2.98, 95% CI 2.02-4.39). Pericardial effusion requiring intervention was independently associated with mortality (OR 5.66, 95% CI 4.24-7.56), prolonged length of stay (OR 1.36, 95% CI 1.07-1.73), and increased cost of hospitalization (OR 2.49, 95% CI 1.92-3.21) after leadless pacemaker implantation. Conclusion: In a large, contemporary, real-world cohort of leadless pacemaker implantations in the United States, the prevalence of pericardial effusion requiring intervention was 1.1%. Certain important patient-level characteristics predicted development of a significant pericardial effusion, and such effusions were associated with adverse outcomes after leadless pacemaker implantations.

9.
BMC Cancer ; 24(1): 631, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783218

RESUMO

BACKGROUND: Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are currently recommended by the National Comprehensive Cancer Network (NCCN) guidelines and the European Society for Medical Oncology (ESMO) guidelines as the first-line (1 L) treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced/metastatic breast cancer (HR+/HER2- LABC/mBC). Although there are many treatment options, there is no clear standard of care for patients following 1 L CDK4/6i. Understanding the real-world effectiveness of subsequent therapies may help to identify an unmet need in this patient population. This systematic literature review qualitatively synthesized effectiveness and safety outcomes for treatments received in the real-world setting after 1 L CDK4/6i therapy in patients with HR+/ HER2- LABC/mBC. METHODS: MEDLINE®, Embase, and Cochrane were searched using the Ovid® platform for real-world evidence studies published between 2015 and 2022. Grey literature was searched to identify relevant conference abstracts published from 2019 to 2022. The review was conducted in accordance with PRISMA guidelines (PROSPERO registration: CRD42023383914). Data were qualitatively synthesized and weighted average median real-world progression-free survival (rwPFS) was calculated for NCCN/ESMO-recommended post-1 L CDK4/6i treatment regimens. RESULTS: Twenty records (9 full-text articles and 11 conference abstracts) encompassing 18 unique studies met the eligibility criteria and reported outcomes for second-line (2 L) treatments after 1 L CDK4/6i; no studies reported disaggregated outcomes in the third-line setting or beyond. Sixteen studies included NCCN/ESMO guideline-recommended treatments with the majority evaluating endocrine-based therapy; five studies on single-agent ET, six studies on mammalian target of rapamycin inhibitors (mTORi) ± ET, and three studies with a mix of ET and/or mTORi. Chemotherapy outcomes were reported in 11 studies. The most assessed outcome was median rwPFS; the weighted average median rwPFS was calculated as 3.9 months (3.3-6.0 months) for single-agent ET, 3.6 months (2.5-4.9 months) for mTORi ± ET, 3.7 months for a mix of ET and/or mTORi (3.0-4.0 months), and 6.1 months (3.7-9.7 months) for chemotherapy. Very few studies reported other effectiveness outcomes and only two studies reported safety outcomes. Most studies had heterogeneity in patient- and disease-related characteristics. CONCLUSIONS: The real-world effectiveness of current 2 L treatments post-1 L CDK4/6i are suboptimal, highlighting an unmet need for this patient population.


Assuntos
Neoplasias da Mama , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Inibidores de Proteínas Quinases , Receptor ErbB-2 , Humanos , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Feminino , Inibidores de Proteínas Quinases/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Intervalo Livre de Progressão
10.
RSC Adv ; 14(23): 16389-16399, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38774621

RESUMO

In this work, we introduce a novel defective analogue of the representative 6-connected zirconium-based metal-organic framework (MOF-808), by employing 5-sulfoisophthalic acid monosodium salt (H2BTC-SO3Na) as a defect inducer via a mixed-linker approach. The structural integrity and different physicochemical properties were investigated by various characterization techniques, including powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and nitrogen physisorption at 77 K. Additionally, proton nuclear magnetic resonance (1H-NMR), energy-dispersive X-ray (EDX), and inductively coupled plasma optical emission spectroscopy (ICP-OES) were employed to confirm the presence of 6.9 mol% of the 5-sulfoisophthalate ligand within the highly crystalline MOF-808 structure. The defective material exhibited significant enhancements in the removal efficiency of various organic dyes, including approximately 64% and 77% for quinoline yellow and sunset yellow, and 56% and 13% for rhodamine B and malachite green, compared to its pristine counterpart. Importantly, the defective MOF-808 showed a remarkable selectivity toward anionic species in binary-component dyes comprising both anionic and cationic dyes.

11.
J Ginseng Res ; 48(3): 310-322, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38707648

RESUMO

Background: Osteosarcopenia is a common condition characterized by the loss of both bone and muscle mass, which can lead to an increased risk of fractures and disability in older adults. The study aimed to elucidate the response of various mouse strains to treatment with Rg3, one of the leading ginsenosides, on musculoskeletal traits and immune function, and their correlation. Methods: Six Collaborative Cross (CC) founder strains induced muscle atrophy and bone loss with dexamethasone (15 mg/kg) treatment for 1 month, and half of the mice for each strain were orally administered Rg3 (20 mg/kg). Different responses were observed depending on genetic background and Rg3 treatment. Results: Rg3 significantly increased grip strength, running performance, and expression of muscle and bone health-related genes in a two-way analysis of variance considering the genetic backgrounds and Rg3 treatment. Significant improvements in grip strength, running performance, bone area, and muscle mass, and the increased gene expression were observed in specific strains of PWK/PhJ. For traits related to muscle, bone, and immune functions, significant correlations between traits were confirmed following Rg3 administration compared with control mice. The phenotyping analysis was compiled into a public web resource called Rg3-OsteoSarco. Conclusion: This highlights the complex interplay between genetic determinants, pathogenesis of muscle atrophy and bone loss, and phytochemical bioactivity and the need to move away from single inbred mouse models to improve their translatability to genetically diverse humans. Rg3-OsteoSarco highlights the use of CC founder strains as a valuable tool in the field of personalized nutrition.

12.
Vascular ; : 17085381241256442, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775171

RESUMO

BACKGROUND: Prior abdominal surgery (PAS) has the potential to affect outcomes of abdominal aortic aneurysm (AAA) repair. Recently, endovascular aneurysm repair (EVAR) has been expanded among patients with complex AAA, which involves visceral branches in the upper abdominal aortic. However, outcomes of EVAR for complex AAA in patients with PAS have not been examined. This study aimed to investigate the impact of PAS on 30-day outcomes in EVAR for complex AAA. METHODS: Patients who underwent EVAR for complex AAA were identified in ACS-NSQIP targeted database from 2012 to 2022. Complex AAA was defined as juxtarenal, suprarenal, or pararenal proximal extent, Type IV thoracoabdominal aneurysm, or aneurysms treated with Zenith Fenestrated endograft. Patients with age less than 18 years, ruptured AAA with or without hypotension, acute intraoperative conversion to open, and emergency presentation were excluded. Multivariable logistic regression was used to compare 30-day postoperative outcomes of patients with and without PAS. Demographics, baseline characteristics, aneurysm diameter, indication for surgery, proximal and distant aneurysm extent, anesthesia, and concomitant procedures were adjusted. RESULTS: There were 515 (28.34%) and 1302 (71.66%) patients with and without PAS, respectively, who underwent EVAR for complex AAA. Patients with and without PAS had comparable 30-day mortality (3.11% vs 3.00%, aOR = 0.766, 95 CI = 0.407-1.442, p = .41). Organ system complications including cardiac complications, stroke, pulmonary complications, and renal complications were comparable between patients with and without PAS. All other 30-day outcomes were similar between groups. However, patients with PAS had higher 30-day readmission rate (11.65% vs 7.14%, aOR = 1.634, 95 CI = 1.145-2.331, p = .01). CONCLUSION: While PAS has high prevalence among patients undergoing EVAR for complex AAA, it does not impact 30-day mortality and morbidities. Thus, EVAR for complex AAA can be considered safe for patients with PAS in terms of short-term outcomes, despite the long-term prognosis in these patients being needed in further studies.

14.
Leukemia ; 38(7): 1581-1591, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38811818

RESUMO

Internal tandem duplication mutations of FLT3 (FLT3/ITD) confer poor prognosis in AML. FLT3 tyrosine kinase inhibitors (TKIs) alone have limited and transient clinical efficacy thus calling for new targets for more effective combination therapy. In a loss-of-function RNAi screen, we identified NOTCH4 as one such potential target whose inhibition proved cytotoxic to AML cells, and also sensitized them to FLT3 inhibition. Further investigation found increased NOTCH4 expression in FLT3/ITD AML cell lines and primary patient samples. Inhibition of NOTCH4 by shRNA knockdown, CRISPR-Cas9-based knockout or γ-secretase inhibitors synergized with FLT3 TKIs to kill FLT3/ITD AML cells in vitro. NOTCH4 inhibition sensitized TKI-resistant FLT3/ITD cells to FLT3 TKI inhibition. The combination reduced phospho-ERK and phospho-AKT, indicating inhibition of MAPK and PI3K/AKT signaling pathways. It also led to changes in expression of genes involved in regulating cell cycling, DNA repair and transcription. A patient-derived xenograft model showed that the combination reduced both the level of leukemic involvement of primary human FLT3/ITD AML cells and their ability to engraft secondary recipients. In summary, these results demonstrate that NOTCH4 inhibition synergizes with FLT3 TKIs to eliminate FLT3/ITD AML cells, providing a new therapeutic target for AML with FLT3/ITD mutations.


Assuntos
Leucemia Mieloide Aguda , Inibidores de Proteínas Quinases , Receptor Notch4 , Ensaios Antitumorais Modelo de Xenoenxerto , Tirosina Quinase 3 Semelhante a fms , Humanos , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/metabolismo , Animais , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Camundongos , Receptor Notch4/genética , Mutação , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Transdução de Sinais/efeitos dos fármacos
15.
J Cardiovasc Electrophysiol ; 35(7): 1351-1359, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38695242

RESUMO

INTRODUCTION: Leadless pacemakers (LPM) have established themselves as the important therapeutic modality in management of selected patients with symptomatic bradycardia. To determine real-world utilization and in-hospital outcomes of LPM implantation since its approval by the Food and Drug Administration in 2016. METHODS: For this retrospective cohort study, data were extracted from the National Inpatient Sample database from the years 2016-2020. The outcomes analyzed in our study included implantation trends of LPM over study years, mortality, major complications (defined as pericardial effusion requiring intervention, any vascular complication, or acute kidney injury), length of stay, and cost of hospitalization. Implantation trends of LPM were assessed using linear regression. Using years 2016-2017 as a reference, adjusted outcomes of mortality, major complications, prolonged length of stay (defined as >6 days), and increased hospitalization cost (defined as median cost >34 098$) were analyzed for subsequent years using a multivariable logistic regression model. RESULTS: There was a gradual increased trend of LPM implantation over our study years (3230 devices in years 2016-2017 to 11 815 devices in year 2020, p for trend <.01). The adjusted mortality improved significantly after LPM implantation in subsequent years compared to the reference years 2016-2017 (aOR for the year 2018: 0.61, 95% CI: 0.51-0.73; aOR for the year 2019: 0.49, 95% CI: 0.41-0.59; and aOR for the year 2020: 0.52, 95% CI: 0.44-0.62). No differences in adjusted rates of major complications were demonstrated over the subsequent years. The adjusted cost of hospitalization was higher for the years 2019 (aOR: 1.33, 95% CI: 1.22-1.46) and 2020 (aOR: 1.69, 95% CI: 1.55-1.84). CONCLUSION: The contemporary US practice has shown significantly increased implantation rates of LPM since its approval with reduced rates of inpatient mortality.


Assuntos
Estimulação Cardíaca Artificial , Bases de Dados Factuais , Custos Hospitalares , Tempo de Internação , Marca-Passo Artificial , Humanos , Marca-Passo Artificial/tendências , Marca-Passo Artificial/economia , Estados Unidos , Estudos Retrospectivos , Masculino , Feminino , Idoso , Resultado do Tratamento , Custos Hospitalares/tendências , Fatores de Tempo , Pessoa de Meia-Idade , Estimulação Cardíaca Artificial/tendências , Estimulação Cardíaca Artificial/economia , Estimulação Cardíaca Artificial/mortalidade , Estimulação Cardíaca Artificial/efeitos adversos , Tempo de Internação/tendências , Fatores de Risco , Idoso de 80 Anos ou mais , Bradicardia/terapia , Bradicardia/mortalidade , Bradicardia/diagnóstico , Frequência Cardíaca , Mortalidade Hospitalar/tendências , Desenho de Equipamento/tendências
16.
Clin Oral Investig ; 28(6): 307, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733524

RESUMO

PURPOSE: The factors related to pericoronitis severity are unclear, and this study aimed to address this knowledge gap. MATERIALS AND METHODS: In total, 113 patients with pericoronitis were included, and their demographic, clinical, and radiographic characteristics were recorded. The Patient-Clinician Pericoronitis Classification was used to score and categorize the severity of pericoronitis. Statistical analysis was conducted to examine the participants' characteristics, validity of the Patient-Clinician Pericoronitis Classification, and risk factors associated with the severity of pericoronitis. RESULTS: The demographic, clinical, and radiographic characteristics of males and females were similar, except for Winter's classification, pain, and intraoral swelling. The constructive validity of the Patient-Clinician Pericoronitis Classification was confirmed with three latent factors, including infection level, patient discomfort, and social interference. Ordinal logistic multivariate regression analysis revealed that upper respiratory tract infection was the sole risk factor associated with pericoronitis severity in males (odds ratio = 4.838). In females, pericoronitis on the right side (odds ratio = 2.486), distal radiolucency (odds ratio = 5.203), and menstruation (odds ratio = 3.416) were significant risk factors. CONCLUSION: This study demonstrated the constructive validity of the Patient-Clinician Pericoronitis Classification. Among females, pericoronitis in mandibular third molars on the right side with radiolucency in menstruating individuals was more severe. In males, upper respiratory tract infection was the sole risk factor associated with pericoronitis severity. CLINICAL RELEVANCE: Individuals with risk factors should be aware of severe pericoronitis in the coming future.


Assuntos
Dente Serotino , Pericoronite , Índice de Gravidade de Doença , Humanos , Masculino , Feminino , Fatores de Risco , Dente Serotino/diagnóstico por imagem , Pericoronite/complicações , Adulto , Adolescente , Mandíbula/diagnóstico por imagem
17.
Cell Rep ; 43(6): 114288, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38814782

RESUMO

Lipids have emerged as potent regulators of immune cell function. In the skin, adipocyte lipolysis increases the local pool of free fatty acids and is essential for coordinating early macrophage inflammation following injury. Here, we investigate G-protein-coupled receptor 84 (GPR84), a medium-chain fatty acid (MCFA) receptor, for its potential to propagate pro-inflammatory signaling after skin injury. GPR84 signaling was identified as a key component of regulating myeloid cell numbers and subsequent tissue repair through in vivo administration of a pharmacological antagonist and the MCFA decanoic acid. We found that impaired injury-induced dermal adipocyte lipolysis is a hallmark of diabetes, and lipidomic analysis demonstrated that MCFAs are significantly reduced in diabetic murine wounds. Furthermore, local administration of decanoic acid rescued myeloid cell numbers and tissue repair during diabetic wound healing. Thus, GPR84 is a readily targetable lipid signaling pathway for manipulating injury-induced tissue inflammation with beneficial effects on acute diabetic healing.


Assuntos
Diabetes Mellitus Experimental , Inflamação , Receptores Acoplados a Proteínas G , Pele , Cicatrização , Animais , Masculino , Camundongos , Adipócitos/metabolismo , Ácidos Decanoicos/farmacologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Inflamação/patologia , Inflamação/metabolismo , Lipólise/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Células Mieloides/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Pele/patologia , Pele/metabolismo , Pele/lesões , Cicatrização/efeitos dos fármacos , Feminino
18.
J Vasc Interv Radiol ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38704139

RESUMO

PURPOSE: To compare the outcomes of fluoroscopic versus portable placement of peripherally inserted central catheters (PICCs) and central venous catheters (CVCs) in pediatric patients. MATERIALS AND METHODS: This is a single-center, retrospective review of 346 upper-extremity PICC placements (286 fluoroscopic and 60 portable; mean age, 9.83 years [SD ± 5.58]; 49.1% female) and 138 tunneled femoral CVC placements (56 fluoroscopic and 82 portable; mean age, 0.23 years [SD ± 0.36]; 57.0% female). Portable placements used mobile plain-film radiography. All lines were placed by board-certified interventional radiologists. RESULTS: Fluoroscopic PICC placements had a lower procedure time (43.9 vs 57.9 minutes; P < .001), radiation dosage (342 vs 590 mGy·cm2; P < .001), incidence of technical failure (0% vs 3.3%; P = .029), and incidence of catheter malfunction (1.7% vs 12.1%; P < .001) compared with portable PICC placements. Fluoroscopic CVC placements had a lower procedure time (42.6 vs 54.8 minutes; P < .001) and radiation dosage (63.8 vs 405 mGy·cm2; P < .001) compared with portable CVC placements. No technical failures were found in either CVC groups and the difference was nonsignificant for catheter malfunction (0% vs 7.3%; P = .081). Fluoroscopic placements of PICCs and CVCs had a lower incidence rate of central line-associated bloodstream infection compared with portable placements (0.71 vs 2.22 cases per 1,000 line-days; P = .046). Overall, fluoroscopic placements of PICCs and CVCs had fewer adverse events compared with portable placements (3.2% vs 14.8%; P < .001). Portable procedure setting was the only significant factor associated with adverse events (odds ratio, 33.77; 95% CI, 4.56-757.01). CONCLUSIONS: Fluoroscopic placements of PICCs and CVCs are associated with lower procedure time, radiation dose, and risk of adverse events compared with portable placements in pediatric patients.

19.
J Pharm Biomed Anal ; 244: 116126, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38581931

RESUMO

Polydopamine (PDA) is an insoluble biopolymer with a dark brown-black color that forms through the autoxidation of dopamine. Because of its outstanding biocompatibility and durability, PDA holds enormous promise for various applications, both in the biomedical and non-medical domains. To ensure human safety, protect health, and minimize environmental impacts, the assessment of PDA toxicity is important. In this study, metabolomics and lipidomics assessed the impact of acute PDA exposure on Caenorhabditis elegans (C. elegans). The findings revealed a pronounced perturbation in the metabolome and lipidome of C. elegans at the L4 stage following 24 hours of exposure to 100 µg/mL PDA. The changes in lipid composition varied based on lipid classes. Increased lipid classes included lysophosphatidylethanolamine, triacylglycerides, and fatty acids, while decreased species involved in several sub-classes of glycerophospholipids and sphingolipids. Besides, we detected 37 significantly affected metabolites in the positive and 8 in the negative ion modes due to exposure to PDA in C. elegans. The metabolites most impacted by PDA exposure were associated with purine metabolism, biosynthesis of valine, leucine, and isoleucine; aminoacyl-tRNA biosynthesis; and cysteine and methionine metabolism, along with pantothenate and CoA biosynthesis; the citrate cycle (TCA cycle); and beta-alanine metabolism. In conclusion, PDA exposure may intricately influence the metabolome and lipidome of C. elegans. The combined application of metabolomics and lipidomics offers additional insights into the metabolic perturbations involved in PDA-induced biological effects and presents potential biomarkers for the assessment of PDA safety.


Assuntos
Caenorhabditis elegans , Indóis , Lipidômica , Metaboloma , Metabolômica , Polímeros , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efeitos dos fármacos , Animais , Polímeros/metabolismo , Indóis/metabolismo , Metabolômica/métodos , Lipidômica/métodos , Metaboloma/efeitos dos fármacos , Lipídeos , Metabolismo dos Lipídeos/efeitos dos fármacos
20.
Chem Sci ; 15(15): 5764-5774, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38638222

RESUMO

A principal component surfactant_map was developed for 91 commonly accessible surfactants for use in surfactant-enabled organic reactions in water, an important approach for sustainable chemical processes. This map was built using 22 experimental and theoretical descriptors relevant to the physicochemical nature of these surfactant-enabled reactions, and advanced principal component analysis algorithms. It is comprised of all classes of surfactants, i.e. cationic, anionic, zwitterionic and neutral surfactants, including designer surfactants. The value of this surfactant_map was demonstrated in activating simple inorganic fluoride salts as effective nucleophiles in water, with the right surfactant. This led to the rapid development (screening 13-15 surfactants) of two fluorination reactions for ß-bromosulfides and sulfonyl chlorides in water. The latter was demonstrated in generating a sulfonyl fluoride with sufficient purity for direct use in labelling of chymotrypsin, under physiological conditions.

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