Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 457
Filtrar
Mais filtros

Bases de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Artigo em Inglês | MEDLINE | ID: mdl-38761998

RESUMO

BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.

2.
Analyst ; 149(5): 1489-1495, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38314794

RESUMO

A novel cyclooxygenase-2 (COX-2) targeted H2S-activated cancer-specific fluorescent probe, namely, COX2-H2S, was designed and synthesized, with naphthalimide as the fluorophore and indomethacin as the targeting group. This H2S-sensing probe was developed to differentiate tumor cells from normal cells and was tested in living cells, Caenorhabditis elegans (C. elegans), and zebrafish. The probe could successfully be used for imaging endogenous and exogenous H2S in living cells, demonstrating high sensitivity and specificity and strong anti-interference. COX2-H2S had the ability to not only discern cancer cells from normal cells but also specifically recognize 9L/lacZ cells from other glioblastoma cells (U87-MG and LN229). It could also be successfully applied for the fluorescent live imaging of H2S in both C. elegans and zebrafish.


Assuntos
Sulfeto de Hidrogênio , Neoplasias , Animais , Humanos , Caenorhabditis elegans , Ciclo-Oxigenase 2 , Corantes Fluorescentes , Sulfeto de Hidrogênio/análise , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos , Peixe-Zebra , Linhagem Celular Tumoral
3.
Bioorg Chem ; 144: 107111, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38218068

RESUMO

To mine fascinating molecules from the rhizomes of Atractylodes chinensis, the known molecular formula of atrachinenin A was used as a bait to search LC-HRMS data in different subfractions. Sixteen new meroterpenoids, atrachinenins D-S (1-16) including three unprecedented carbon skeletons (1-5) and eleven new oxygen-bridged hybrids (6-16) were obtained by the targeted isolation. Their structures and absolute configurations were elucidated by the spectroscopic data and electronic circular dichroism (ECD) calculations. The isolated compounds were evaluated for their inhibitory activity of NO production and compounds 1, 4, 8, and 13 showed moderate anti-inflammatory activity. The proposed biosynthetic pathways of 1-5 were also discussed.


Assuntos
Atractylodes , Atractylodes/química , Hidroquinonas , Anti-Inflamatórios , Dicroísmo Circular , Estrutura Molecular
4.
Acta Pharmacol Sin ; 45(1): 180-192, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37644132

RESUMO

Adhesion molecules play essential roles in the homeostatic regulation and malignant transformation of hematopoietic cells. The dysregulated expression of adhesion molecules in leukemic cells accelerates disease progression and the development of drug resistance. Thus, targeting adhesion molecules represents an attractive anti-leukemic therapeutic strategy. In this study, we investigated the prognostic role and functional significance of cytohesin-1 (CYTH1) in acute myeloid leukemia (AML). Analysis of AML patient data from the GEPIA and BloodSpot databases revealed that CYTH1 was significantly overexpressed in AML and independently correlated with prognosis. Functional assays using AML cell lines and an AML xenograft mouse model confirmed that CYTH1 depletion significantly inhibited the adhesion, migration, homing, and engraftment of leukemic cells, delaying disease progression and prolonging animal survival. The CYTH1 inhibitor SecinH3 exerted in vitro and in vivo anti-leukemic effects by disrupting leukemic adhesion and survival programs. In line with the CYTH1 knockdown results, targeting CYTH1 by SecinH3 suppressed integrin-associated adhesion signaling by reducing ITGB2 expression. SecinH3 treatment efficiently induced the apoptosis and inhibited the growth of a panel of AML cell lines (MOLM-13, MV4-11 and THP-1) with mixed-lineage leukemia gene rearrangement, partly by reducing the expression of the anti-apoptotic protein MCL1. Moreover, we showed that SecinH3 synergized with the BCL2-selective inhibitor ABT-199 (venetoclax) to inhibit the proliferation and promote the apoptosis of ABT-199-resistant leukemic cells. Taken together, our results not only shed light on the role of CYTH1 in cell-adhesion-mediated leukemogenesis but also propose a novel combination treatment strategy for AML.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Camundongos , Animais , Leucemia Mieloide Aguda/tratamento farmacológico , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Moléculas de Adesão Celular , Progressão da Doença , Linhagem Celular Tumoral
5.
Acta Pharmacol Sin ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914677

RESUMO

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have obvious advantages over MSC therapy. But the strong procoagulant properties of MSC-EVs pose a potential risk of thromboembolism, an issue that remains insufficiently explored. In this study, we systematically investigated the procoagulant activity of large EVs derived from human umbilical cord MSCs (UC-EVs) both in vitro and in vivo. UC-EVs were isolated from cell culture supernatants. Mice were injected with UC-EVs (0.125, 0.25, 0.5, 1, 2, 4 µg/g body weight) in 100 µL PBS via the tail vein. Behavior and mortality were monitored for 30 min after injection. We showed that these UC-EVs activated coagulation in a dose- and tissue factor-dependent manner. UC-EVs-induced coagulation in vitro could be inhibited by addition of tissue factor pathway inhibitor. Notably, intravenous administration of high doses of the UC-EVs (1 µg/g body weight or higher) led to rapid mortality due to multiple thrombus formations in lung tissue, platelets, and fibrinogen depletion, and prolonged prothrombin and activated partial thromboplastin times. Importantly, we demonstrated that pulmonary thromboembolism induced by the UC-EVs could be prevented by either reducing the infusion rate or by pre-injection of heparin, a known anticoagulant. In conclusion, this study elucidates the procoagulant characteristics and mechanisms of large UC-EVs, details the associated coagulation risk during intravenous delivery, sets a safe upper limit for intravenous dose, and offers effective strategies to prevent such mortal risks when high doses of large UC-EVs are needed for optimal therapeutic effects, with implications for the development and application of large UC-EV-based as well as other MSC-EV-based therapies.

6.
Cereb Cortex ; 33(14): 8858-8875, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37183178

RESUMO

Major depressive disorder is a frequent and debilitating psychiatric disease. We have shown in some of the acute animal models of major depressive disorder (tail suspension test and forced swim test) that depression-like behavior can be aggravated in mice by the microinjection into the medial prefrontal cortex of the P2X7R agonistic adenosine 5'-triphosphate or its structural analog dibenzoyl-ATP, and these effects can be reversed by the P2X7R antagonistic JNJ-47965567. When measuring tail suspension test, the prolongation of immobility time by the P2YR agonist adenosine 5'-[ß-thio]diphosphate and the reduction of the adenosine 5'-(γ-thio)triphosphate effect by P2Y1R (MRS 2179) or P2Y12R (PSB 0739) antagonists, but not by JNJ-47965567, all suggest the involvement of P2YRs. In order to elucidate the localization of the modulatory P2X7Rs in the brain, we recorded current responses to dibenzoyl-ATP in layer V astrocytes and pyramidal neurons of medial prefrontal cortex brain slices by the whole-cell patch-clamp procedure; the current amplitudes were not altered in preparations taken from tail suspension test or foot shock-treated mice. The release of adenosine 5'-triphosphate was decreased by foot shock, although not by tail suspension test both in the hippocampus and PFC. In conclusion, we suggest, that in the medial prefrontal cortex, acute stressful stimuli cause supersensitivity of P2X7Rs facilitating the learned helplessness reaction.


Assuntos
Transtorno Depressivo Maior , Receptores Purinérgicos P2X7 , Camundongos , Animais , Depressão , Córtex Pré-Frontal , Trifosfato de Adenosina , Adenosina , Modelos Animais de Doenças
7.
Artigo em Inglês | MEDLINE | ID: mdl-38349421

RESUMO

PURPOSE: To compare corneal haze between active ulcer and healed scarring using a Scheimpflug densitometry. MATERIALS AND METHODS: A prospective longitudinal study enrolled 30 patients (30 eyes) with ulcerative keratitis (UK). Each subject's corneal optical density (COD) was measured with a Scheimpflug corneal densitometry, Pentacam® AXL (Oculus GmbH, Wetzlar, Germany), at the active ulcerative and complete scarring stage. The COD data were analyzed through distinct methods (inbuilt, sorted annular partitions, and ulcer-matching densitometric maps). We compared different CODs to select the better index for clinically monitoring the transition from corneal ulceration to healed scar. RESULTS: The CODs of the periphery (P = 0.0024) and outside of the active ulcer (P = 0.0002) significantly decreased after scarring. Partitioning the cornea into different depths and annular zones, the anterior layer, center layer, and the 2-6 mm annular zone had a more remarkable COD decrease after scar formation. The 3rd-sorted COD in the anterior layer revealed the highest area under the receiver-operating characteristic curves (0.709), in which 90% of subjects had COD reduction during the ulcer-to-scar transition. CONCLUSIONS: Aside from subjective judgment based on clinical signs, the Scheimpflug tomography-based densitometry could provide objective and efficient monitoring of the corneal opacity evolution in UK patients. Because the 3rd-sorted annular COD is a better index than the inbuilt or mapping CODs in differentiating active ulcers from healed scars, this COD could be a clinically promising parameter to monitor the progression of UK patients.

8.
BMC Geriatr ; 24(1): 222, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439017

RESUMO

BACKGROUND: This study aimed to investigate the association of high-sensitivity C-reactive protein (hs-CRP) with incident frailty as well as its effects on pre-frailty progression and regression among middle-aged and older adults. METHODS: Based on the frailty index (FI) calculated with 41 items, 6890 eligible participants without frailty at baseline from China Health and Retirement Longitudinal Study (CHARLS) were categorized into health, pre-frailty, and frailty groups. Logistic regression models were used to estimate the longitudinal association between baseline hs-CRP and incident frailty. Furthermore, a series of genetic approaches were conducted to confirm the causal relationship between CRP and frailty, including Linkage disequilibrium score regression (LDSC), pleiotropic analysis, and Mendelian randomization (MR). Finally, we evaluated the association of hs-CRP with pre-frailty progression and regression. RESULTS: The risk of developing frailty was 1.18 times (95% CI: 1.03-1.34) higher in participants with high levels of hs-CRP at baseline than low levels of hs-CRP participants during the 3-year follow-up. MR analysis suggested that genetically determined hs-CRP was potentially positively associated with the risk of frailty (OR: 1.06, 95% CI: 1.03-1.08). Among 5241 participants with pre-frailty at baseline, we found pre-frailty participants with high levels of hs-CRP exhibit increased odds of progression to frailty (OR: 1.39, 95% CI: 1.09-1.79) and decreased odds of regression to health (OR: 0.84, 95% CI: 0.72-0.98) when compared with participants with low levels of hs-CRP. CONCLUSIONS: Our results suggest that reducing systemic inflammation is significant for developing strategies for frailty prevention and pre-frailty reversion in the middle-aged and elderly population.


Assuntos
Proteína C-Reativa , Fragilidade , Idoso , Humanos , Pessoa de Meia-Idade , Estudos Longitudinais , Proteína C-Reativa/genética , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/genética , Estudos de Coortes , Inflamação
9.
Phytother Res ; 38(1): 214-230, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37859562

RESUMO

Osteoporosis is a chronic progressive bone disease characterized by the decreased osteogenic ability of osteoblasts coupled with increased osteoclast activity. Natural products showing promising therapeutic potential for postmenopausal osteoporosis remain underexplored. In this study, we aimed to analyze the therapeutic effects of isoliquiritin (ISL) on osteoporosis in mice and its possible mechanism of action. An ovariectomy-induced osteoporosis mouse model and bone marrow mesenchymal stem cells (BMSCs) were used to analyze the effects of ISL on bone regeneration in vivo and in vitro, respectively. Mitogen-activated protein kinase (MAPK) and autophagy inhibitors were used, to investigate whether the MAPK signaling pathway and autophagy affect the osteogenic differentiation of BMSCs. ISL significantly improved bone formation and reduced bone resorption in mouse femurs without inducing any detectable toxicity in critical organs such as the liver, kidney, brain, heart, and spleen. In vitro experiments showed that ISL enhanced the proliferation and osteogenic differentiation of BMSCs and that its osteogenic effect was attenuated by p38/extracellular regulated protein kinase (ERK) and autophagy inhibitors. Further studies showed that the inhibition of phosphorylated p38/ERK blocked ISL autophagy in BMSCs. ISL promoted the osteogenic differentiation of BMSCs through the p38/ERK-autophagy pathway and was therapeutically effective in treating osteoporosis in ovariectomized mice without any observed toxicity to vital organs. These results strongly suggest the promising potential of ISL as a safe and efficacious candidate drug for the treatment of osteoporosis.


Assuntos
Chalcona/análogos & derivados , Glucosídeos , Células-Tronco Mesenquimais , Osteoporose , Feminino , Camundongos , Animais , Osteogênese , Células Cultivadas , Diferenciação Celular , Osteoporose/tratamento farmacológico , Autofagia , Células da Medula Óssea/metabolismo
10.
Nursing ; 54(3): 30-38, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38386448

RESUMO

ABSTRACT: Debridement is a core component of chronic wound management. Although various debridement methods exist, each carries a unique patient risk level. This article discusses the different normal tissue components that are critical to safe debridement practice, various methods of wound debridement for nurses, and the importance of an interprofessional team and consulting a wound specialist.


Assuntos
Desbridamento , Humanos
11.
Int J Syst Evol Microbiol ; 73(10)2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37861399

RESUMO

Two Gram-stain-negative, aerobic, non-motile and short-rod-shaped bacteria, designated as strains GL-53T and GL-15-2-5, were isolated from the seamount area of the West Pacific Ocean and identified using a polyphasic taxonomic approach. The growth of strains GL-53ᵀ and GL-15-2-5 occurred at pH 5.5-10.0, 4-40 °C (optimum at 28 °C) and 0-10.0 % NaCl concentrations (optimum at 0-5.0 %). On the basis of 16S rRNA gene sequence analysis, strains GL-53ᵀ and GL-15-2-5 exhibited the highest similarity to Rheinheimera lutimaris YQF-2T (98.4 %), followed by Rheinheimera pacifica KMM 1406T (98.1 %), Rheinheimera nanhaiensis E407-8T (97.4 %), Rheinheimera aestuarii H29T (97.4 %), Rheinheimera hassiensis E48T (97.2 %) and Rheinheimera aquimaris SW-353T (97.2 %). Phylogenetic analysis revealed that the isolates were affiliated with the genus Rheinheimera and represented an independent lineage. The major fatty acids were summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), C16 : 0 and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The sole isoprenoid quinone was ubiquinone 8. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminophospholipid (and one unidentified glycolipid. The DNA G+C content was 48.5 mol%. The average nucleotide identity, average amino acid identity and in silico DNA-DNA hybridization values among the genomes of strain GL-53ᵀ and the related strains in the genus Rheinheimera were 75.5-90.1 %, 67.5-93.9 % and 21.4-41.4 %, respectively. Based on their phenotypic, chemotaxonomic and genotypic properties, the two strains were identified as representing a novel species of the genus Rheinheimera, for which the name Rheinheimera oceanensis sp. nov. is proposed. The type strain is GL-53T (=KCTC 82651T=MCCC M20598T).


Assuntos
Ácidos Graxos , Fosfolipídeos , Ácidos Graxos/química , Fosfolipídeos/química , Oceano Pacífico , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , DNA Bacteriano/genética , Composição de Bases , Técnicas de Tipagem Bacteriana
12.
Bioorg Med Chem ; 92: 117400, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37556912

RESUMO

The oxetane functional group offers a variety of potential advantages when incorporated within appropriate therapeutic agents as a ketone surrogate. OXi8006, a 2-aryl-3-aroyl-indole analogue, functions as a small-molecule inhibitor of tubulin polymerization that has a dual mechanism of action as both an antiproliferative agent and a tumor-selective vascular disrupting agent. Replacement of the bridging ketone moiety in OXi8006 with an oxetane functional group has expanded structure activity relationship (SAR) knowledge and provided insights regarding oxetane incorporation within this class of molecules. A new synthetic method using an oxetane-containing tertiary alcohol subjected to Lewis acid catalyzed conditions led to successful Friedel-Crafts alkylation and yielded fourteen new oxetane-containing indole-based molecules. This synthetic approach represents the first method to successfully install an oxetane ring at the 3-position of a 2-aryl-indole system. Several analogues showed potent cytotoxicity (micromolar GI50 values) against human breast cancer cell lines (MCF-7 and MDA-MB-231) and a pancreatic cancer cell line (PANC-1), although they proved to be ineffective as inhibitors of tubulin polymerization. Molecular docking studies comparing colchicine with the OXi8006-oxetane analogue 5m provided a rationale for the differential interaction of these molecules with the colchicine site on the tubulin heterodimer.


Assuntos
Antineoplásicos , Humanos , Antineoplásicos/química , Linhagem Celular Tumoral , Tubulina (Proteína)/metabolismo , Simulação de Acoplamento Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Relação Estrutura-Atividade , Indóis/química , Colchicina/farmacologia , Moduladores de Tubulina/farmacologia , Proliferação de Células , Estrutura Molecular
13.
J Nat Prod ; 86(5): 1230-1239, 2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-37146221

RESUMO

Amethystoidesic acid (1), a triterpenoid with an unprecedented 5/6/6/6 tetracyclic skeleton, and six undescribed diterpenoids, amethystoidins A-F (2-7), were isolated from the rhizomes of Isodon amethystoides along with 31 known di- and triterpenoids (8-38). Their structures were fully elucidated via extensive spectroscopic analysis including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. Compound 1 is the first example of a triterpenoid possessing a rare ring system (5/6/6/6) derived from a contracted A-ring and the 18,19-seco-E-ring of ursolic acid. Compounds 6, 16, 21, 22, 24, and 27 significantly inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, which could be partly mediated by the downregulation of LPS-induced inducible nitric oxide synthase (iNOS) protein expression.


Assuntos
Isodon , Triterpenos , Isodon/química , Rizoma/metabolismo , Triterpenos/farmacologia , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Óxido Nítrico , Estrutura Molecular
14.
Genomics ; 114(2): 110311, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35176445

RESUMO

The mitogen-activated protein kinase (MAPK) cascade plays a crucial role in regulating many important biological processes in plants. Here, we identified and characterized eight MAPKK and 49 MAPKKK genes in sorghum and analyzed their differential expression under drought treatment; we also characterized 16 sorghum MAPK genes. RNA-seq analysis revealed that 10 MAPK cascade genes were involved in drought stress response at the transcriptome level in sorghum. Overexpression of SbMPK14 in Arabidopsis and maize resulted in hypersensitivity to drought by promoting water loss, indicating that SbMPK14 functions as a negative regulator of the drought response. Subsequent transcriptome analysis and qRT-PCR verification of maize SbMPK14 overexpression lines revealed that SbMPK14 likely increases plant drought sensitivity by suppressing the activity of specific ERF and WRKY transcription factors. This comprehensive study provides valuable insight into the mechanistic basis of MAPK cascade gene function and their responses to drought in sorghum.


Assuntos
Arabidopsis , Sorghum , Arabidopsis/genética , Secas , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sorghum/metabolismo , Estresse Fisiológico/genética , Zea mays/genética , Zea mays/metabolismo
15.
J Asian Nat Prod Res ; 25(1): 95-101, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35291901

RESUMO

A phytochemical investigation of Menispermum dauricum led to the isolation of five oxoisoaporphine-type alkaloids (1-5) and five aporphine-type alkaloids (6-10), including a novel oxoisoaporphine-type alkaloid: menispeimin A (1). Their structures were elucidated by spectroscopic studies including MS, 1 D and 2 D NMR, and confirmed by comparing with literature data. Among them, alkaloids 4-10 were obtained for the first time from Menispermum genus. Natural products 2, 4 and 6 exhibited significant cytotoxic activity against A549, Bel-7402 and MCF-7 cell lines.


Assuntos
Alcaloides , Antineoplásicos , Menispermum , Alcaloides/química , Espectroscopia de Ressonância Magnética , Menispermum/química , Menispermum/toxicidade , Rizoma/química
16.
Int J Mol Sci ; 24(4)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36834752

RESUMO

The regulation of mammalian reproductive activity is tightly dependent on the HPG axis crosstalk, in which several reproductive hormones play important roles. Among them, the physiological functions of gonadotropins are gradually being uncovered. However, the mechanisms by which GnRH regulates FSH synthesis and secretion still need to be more extensively and deeply explored. With the gradual completion of the human genome project, proteomes have become extremely important in the fields of human disease and biological process research. To explore the changes of protein and protein phosphorylation modifications in the adenohypophysis after GnRH stimulation, proteomics and phosphoproteomics analyses of rat adenohypophysis after GnRH treatment were performed by using TMT markers, HPLC classification, LC/MS, and bioinformatics analysis in this study. A total of 6762 proteins and 15,379 phosphorylation sites contained quantitative information. Twenty-eight upregulated proteins and fifty-three downregulated proteins were obtained in the rat adenohypophysis after GnRH treatment. The 323 upregulated phosphorylation sites and 677 downregulated phosphorylation sites found in the phosphoproteomics implied that a large number of phosphorylation modifications were regulated by GnRH and were involved in FSH synthesis and secretion. These data constitute a protein-protein phosphorylation map in the regulatory mechanism of "GnRH-FSH," which provides a basis for future studies on the complex molecular mechanisms of FSH synthesis and secretion. The results will be helpful for understanding the role of GnRH in the development and reproduction regulated by the pituitary proteome in mammals.


Assuntos
Hormônio Liberador de Gonadotropina , Adeno-Hipófise , Animais , Ratos , Hormônio Foliculoestimulante/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Luteinizante/metabolismo , Adeno-Hipófise/metabolismo , Proteômica
17.
J Reconstr Microsurg ; 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38092022

RESUMO

BACKGROUND: Lower extremity trauma often necessitates reconstruction with flap transfer. One of the reconstructive goals is a thin soft tissue coverage with appropriate contour. Therefore, a secondary debulking of the flap is usually performed. METHODS: Debulking through conventional lipectomy is compared with liposuction followed by excision of the defatted flap excess. Demographic data, surgical details, and postoperative outcomes are compared and analyzed. The perfusion dynamics of the flaps undergoing liposuction debulking are studied by means of perioperative indocyanine green fluorescence angiography, as well as postoperative laser Doppler imaging. RESULTS: Patients undergoing lipectomy (n = 69; 57.5%) or liposuction (n = 51; 42.5%) debulking had a similar rate of postoperative complications. Partial necrosis was observed in 7.2% (lipectomy) versus 7.8% (liposuction) of flaps. Fluorescence angiography showed a substantial decrease in flap perfusion following the infiltration with an epinephrine-containing tumescent solution (74.3% ± 8.2% prior to infiltration versus 16.8% ± 7.1% after infiltration; p < 0.001), resulting in a dark flap appearance. Laser Doppler imaging confirmed the hypoperfusion on postoperative day 1. CONCLUSION: Secondary debulking of a lower extremity flap can be safely and efficiently performed through liposuction combined with peripheral excision of the defatted flap in a single stage. Perfusion studies may show a misleading hypoperfusion of the defatted flap, which does not accurately predict subsequent necrosis or complications.

18.
Adv Skin Wound Care ; 36(4): 180-187, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36940374

RESUMO

GENERAL PURPOSE: To enhance the learner's chronic wound debridement competence as an interprofessional team member. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Differentiate healable, maintenance, and nonhealable wounds to create a holistic debridement treatment plan using the Wound Bed Preparation paradigm.2. Evaluate active debridement options including the potential need for an interprofessional referral or specialized investigations.3. Assess chronic wound debridement options.4. Analyze case studies for appropriate clinical application of debridement modalities.


Debridement is a critical component in the management of both acute and chronic wounds. Six reviewed methods of debridement exist, and specific techniques are more appropriate to match patient needs with available clinical resources. Accurate differentiation between healable, maintenance, and nonhealable wounds is paramount when determining whether a wound would benefit from debridement. Clinical assessment includes review of the patient's underlying medical conditions/ previous surgeries along with the history and progression of the wound. Awareness of the physiologic wound bed preparation components that contribute to the current wound status will direct treatment of the abnormal components. Optimal wound status includes complete healing or reduced abnormal wound-related symptoms or signs. Debridement competency requires an awareness of the six types of debridement, their clinical utility, and appropriate patient selection. Providers need to assess patients' wounds, triage them, and refer them as necessary to an interprofessional setting. For stalled but healable wounds, specialized testing may be necessary when managing patients who would benefit from more invasive or advanced forms of wound care. This article informs providers on the training and experience required for specific debridement techniques depending on the wound etiology.


Assuntos
Cicatrização , Ferimentos e Lesões , Humanos , Desbridamento , Planejamento de Assistência ao Paciente , Ferimentos e Lesões/terapia
19.
Angew Chem Int Ed Engl ; 62(29): e202300892, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37067951

RESUMO

Organic electrode materials could revolutionize batteries because of their high energy densities, the use of Earth-abundant elements, and structural diversity which allows fine-tuning of electrochemical properties. However, small organic molecules and intermediates formed during their redox cycling in lithium-ion batteries (LIBs) have high solubility in organic electrolytes, leading to rapid decay of cycling performance. We report the use of three cyclotetrabenzil octaketone macrocycles as cathode materials for LIBs. The rigid and insoluble naphthalene-based cyclotetrabenzil reversibly accepts eight electrons in a two-step process with a specific capacity of 279 mAh g-1 and a stable cycling performance with ≈65 % capacity retention after 135 cycles. DFT calculations indicate that its reduction increases both ring strain and ring rigidity, as demonstrated by computed high distortion energies, repulsive regions in NCI plots, and close [C⋅⋅⋅C] contacts between the naphthalenes. This work highlights the importance of shape-persistency and ring strain in the design of redox-active macrocycles that maintain very low solubility in various redox states.

20.
Opt Lett ; 47(14): 3507-3510, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35838714

RESUMO

A 3D-printed all-dielectric metasurface is presented in this Letter which can generate an accelerating beam with a circularly symmetric non-spreading transverse profile that can propagate along arbitrary convex trajectories. The curved trajectory is mapped to the corresponding direct-space spatial phases by the basic cube units with different geometrical heights. The required phase distribution is derived in detail based on the enveloping theory of differential geometry and the Bessel beam generation method. A metasurface with a preset trajectory is simulated and measured to demonstrate the validity of the phase distribution calculated by the proposed theory. The full-wave simulation and measurement results verify that the Bessel-like beam whose intensity follows a curved (off-axis) trajectory can be produced by the proposed metasurface. The generated hybrid beam merges the advantages of non-accelerating and accelerating diffractive-free beams. Therefore, the proposed metasurface has great potential in ultrahigh-speed communication, secure communication, near-field imaging, wireless energy transmission applications, and so on. The all-dielectric characteristic provides the proposed metasurface with the competitive advantages of low cost and easy large-scale processing.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA