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1.
J Nat Prod ; 87(4): 705-712, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38547118

RESUMO

Penicilloneines A (1) and B (2) are the first reported quinolone-citrinin hybrids. They were isolated from the starfish-derived fungus Penicillium sp. GGF16-1-2, and their structures were elucidated using spectroscopic, chemical, computational, and single-crystal X-ray diffraction methods. Penicilloneines A (1) and B (2) share a common 4-hydroxy-1-methyl-2(1H)-quinolone unit; however, they differ in terms of citrinin moieties, and these two units are linked via a methylene bridge. Penicilloneines A (1) and B (2) exhibited antifungal activities against Colletotrichum gloeosporioides, with lethal concentration 50 values of 0.02 and 1.51 µg/mL, respectively. A mechanistic study revealed that 1 could inhibit cell growth and promote cell vacuolization and consequent disruption of the fungal cell walls via upregulating nutrient-related hydrolase genes, including putative hydrolase, acetylcholinesterase, glycosyl hydrolase, leucine aminopeptidase, lipase, and beta-galactosidase, and downregulating their synthase genes 3-carboxymuconate cyclase, pyruvate decarboxylase, phosphoketolase, and oxalate decarboxylase.


Assuntos
Antifúngicos , Citrinina , Colletotrichum , Penicillium , Quinolonas , Penicillium/química , Colletotrichum/efeitos dos fármacos , Quinolonas/farmacologia , Quinolonas/química , Quinolonas/isolamento & purificação , Estrutura Molecular , Animais , Citrinina/farmacologia , Citrinina/química , Citrinina/isolamento & purificação , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Testes de Sensibilidade Microbiana
2.
Artigo em Inglês | MEDLINE | ID: mdl-38798241

RESUMO

A prominent cause of cancer-related fatalities with a poor prognosis is lung adenocarcinoma (LUAD). KIF5A, a crucial member of the kinesin superfamily, is linked to drug resistance in malignancies. This work aims to investigate the mechanism of KIF5A in docetaxel (DTX) resistance in LUAD cells. The results of bioinformatics analysis, qRT-PCR and western blot analysis show that KIF5A, which is involved in the glycolysis pathway, is highly expressed in LUAD and is positively correlated with glycolysis-related genes. We further verify that silencing of KIF5A inhibits DTX resistance, glycolysis, and lactate production in LUAD cells via cell counting kit-8 (CCK-8), flow cytometry, Seahorse XFe 96, lactate, and glucose assays. Mechanistically, KIF5A promotes DTX resistance in LUAD, and this effect is attenuated upon the addition of an LDHA inhibitor. Chromatin immunoprecipitation and dual-luciferase reporter assays reveal that FOXP3 transcriptionally activates KIF5A. Knockdown of FOXP3 reduces lactate production and enhances DTX sensitivity in LUAD, which is restored upon simultaneous overexpression of KIF5A. Our findings reveal that FOXP3 increases DTX resistance in LUAD cells by enhancing lactate production through the upregulation of KIF5A level. In conclusion, our study provides a novel treatment target for improving chemosensitivity in LUAD.

3.
J Asian Nat Prod Res ; : 1-10, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38334077

RESUMO

One new rare carbon-bridged citrinin dimer quinocitrindimer C (1) as a pair of epimers, two new polyketide penicilliodes D (3) and E (4) together with nine known citrinin derivatives, were isolated from the fermentation broth of starfish-derived symbiotic fungus Penicillium sp. GGF16-1-2. Their structures and configurations were elucidated by comprehensively spectroscopic data analysis and electronic circular dichroism calculations. Eleven citrinin derivatives were tested by Colletotrichum gloeosporioides, and compound 2 played a significant antifungal activity against Colletotrichum gloeosporioides with LC50 value of 0.27 µg/ml.

4.
Proc Natl Acad Sci U S A ; 117(46): 28667-28677, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33139557

RESUMO

The treatment of diabetic ulcer (DU) remains a major clinical challenge due to the complex wound-healing milieu that features chronic wounds, impaired angiogenesis, persistent pain, bacterial infection, and exacerbated inflammation. A strategy that effectively targets all these issues has proven elusive. Herein, we use a smart black phosphorus (BP)-based gel with the characteristics of rapid formation and near-infrared light (NIR) responsiveness to address these problems. The in situ sprayed BP-based gel could act as 1) a temporary, biomimetic "skin" to temporarily shield the tissue from the external environment and accelerate chronic wound healing by promoting the proliferation of endothelial cells, vascularization, and angiogenesis and 2) a drug "reservoir" to store therapeutic BP and pain-relieving lidocaine hydrochloride (Lid). Within several minutes of NIR laser irradiation, the BP-based gel generates local heat to accelerate microcirculatory blood flow, mediate the release of loaded Lid for "on-demand" pain relief, eliminate bacteria, and reduce inflammation. Therefore, our study not only introduces a concept of in situ sprayed, NIR-responsive pain relief gel targeting the challenging wound-healing milieu in diabetes but also provides a proof-of-concept application of BP-based materials in DU treatment.


Assuntos
Pé Diabético/terapia , Fósforo/administração & dosagem , Terapia Fototérmica , Materiais Inteligentes/administração & dosagem , Cicatrização/efeitos dos fármacos , Anestésicos Locais/administração & dosagem , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental , Avaliação Pré-Clínica de Medicamentos , Células Endoteliais/efeitos dos fármacos , Fibrinogênio/administração & dosagem , Géis , Células Endoteliais da Veia Umbilical Humana , Humanos , Lidocaína/administração & dosagem , Masculino , Camundongos Endogâmicos BALB C , Neovascularização Fisiológica/efeitos dos fármacos , Trombina/administração & dosagem
5.
Mar Drugs ; 20(7)2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35877736

RESUMO

Four novel, rare carbon-bridged citrinin dimers, namely dicitrinones G-J (1-4), and five known analogs (5-9) were isolated from the starfish-derived fungus Penicillium sp. GGF 16-1-2. Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculations. Compounds 1-9 exhibited strong antifungal activities against Colletotrichum gloeosporioides with LD50 values from 0.61 µg/mL to 16.14 µg/mL. Meanwhile, all compounds were evaluated for their cytotoxic activities against human pancreatic cancer BXPC-3 and PANC-1 cell lines; as a result, compound 1 showed more significant cytotoxicities than the positive control against both cell lines. In addition, based on the analyses of the protein-protein interaction (PPI) network and Western blot, 1 could induce apoptosis by activating caspase 3 proteins (CASP3).


Assuntos
Citrinina , Penicillium , Animais , Carbono/metabolismo , Citrinina/química , Fungos , Humanos , Estrutura Molecular , Penicillium/química , Estrelas-do-Mar
6.
Nano Lett ; 20(3): 1637-1646, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32013452

RESUMO

Nanotechnology-based RNA interference (RNAi) has shown great promise in overcoming the limitations of traditional clinical treatments for glioblastoma (GBM). However, because of the complexity of brain physiology, simple blood-brain barrier (BBB) penetration or tumor-targeting strategies cannot entirely meet the demanding requirements of different therapeutic delivery stages. Herein, we developed a charge conversional biomimetic nanoplatform with a three-layer core-shell structure to programmatically overcome persistent obstacles in siRNA delivery to GBM. The resulting nanocomplex presents good biocompatibility, prolonged blood circulation, high BBB transcytosis, effective tumor accumulation, and specific uptake by tumor cells in the brain. Moreover, red blood cell membrane (RBCm) disruption and effective siRNA release can be further triggered elegantly by charge conversion from negative to positive in the endo/lysosome (pH 5.0-6.5) of tumor cells, leading to highly potent target-gene silencing with a strong anti-GBM effect. Our study provides an intelligent biomimetic nanoplatform tailored for systemically siRNA delivery to GBM, leveraging Angiopep-2 peptide-modified, immune-free RBCm and charge conversional components. Improved therapeutic efficacy, higher survival rates, and minimized systemic side effects were achieved in orthotopic U87MG-luc human glioblastoma tumor-bearing nude mice.


Assuntos
Materiais Biomiméticos , Neoplasias Encefálicas , Glioblastoma , Interferência de RNA , RNA Interferente Pequeno , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacocinética , Materiais Biomiméticos/farmacologia , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Camundongos , Camundongos Nus , RNA Interferente Pequeno/química , RNA Interferente Pequeno/farmacocinética , RNA Interferente Pequeno/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Chem Biodivers ; 17(5): e2000106, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32212241

RESUMO

Three new indole diketopiperazine alkaloids, 11-methylneoechinulin E and variecolorin M, and (+)-variecolorin G, along with 12 known analogs, were isolated from a soft coral-associated epiphytic fungus Aspergillus sp. EGF 15-0-3. The structures of the new compounds were unambiguously established by extensive spectroscopic analyses including HR-ESI-MS, 1D and 2D NMR spectroscopy and optical rotation measurements. The absolute configurations of (+)- and (-)-variecolorin G were determined by experimental and quantum-chemical ECD investigations and single-crystal X-ray diffraction analysis. Variecolorin G is a pair of enantiomeric mixtures with a ratio of 1 : 2. Moreover, (+)-neoechinulin A is firstly reported as a natural product. The cytotoxic activities of all the isolated compounds against NCI-H1975 gefitinib resistance (NCI-H1975/GR) cell lines were preliminarily evaluated by MTT method.


Assuntos
Alcaloides/farmacologia , Antineoplásicos/farmacologia , Aspergillus/química , Dicetopiperazinas/farmacologia , Indóis/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Dicetopiperazinas/química , Dicetopiperazinas/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indóis/química , Indóis/isolamento & purificação , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade
8.
Crit Care ; 23(1): 378, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775838

RESUMO

BACKGROUND: This study examined the feasibility of transabdominal intestinal ultrasonography in evaluating acute gastrointestinal injury (AGI). METHODS: A total of 116 patients were included. Intestinal ultrasonography was conducted daily within 1 week after admission to the intensive care unit. Ultrasonography indicators including intestinal diameter, changes in the intestinal folds, thickness of the intestinal wall, stratification of the intestinal wall, and intestinal peristalsis (movement of the intestinal contents) were observed to determine the acute gastrointestinal injury ultrasonography (AGIUS) score. The gastrointestinal and urinary tract sonography ultrasound (GUTS) protocol score was also calculated. During the first week of the study, the gastrointestinal failure (GIF) score was determined daily. The correlations between transabdominal intestinal scores (AGIUS and GUTS) and the GIF score were analyzed to clarify the feasibility of evaluating AGI through observation of the intestine. The utility of intestinal ultrasonography indicators in predicting feeding intolerance was investigated to improve the ability of clinicians to manage AGI. RESULTS: A total of 751 ultrasonic examinations were performed with 511 images (68%) considered to be of "good quality." AGIUS and GUTS scores differed significantly between AGI patients (GIF score 0-2) and non-AGI patients (GIF score 3-4) (p < 0.001). Both scores correlated positively with GIF score (r = 0.54, p < 0.001; r = 0.66, p < 0.001). These ultrasonography indicators could predict feeding intolerance, with an area under the receiver operating characteristic curve of 0.60 (0.48-0.71; intestinal diameter), 0.76 (0.67-0.85; intestinal folds), 0.71 (0.62-0.80; wall thickness), 0.77 (0.69-0.86; wall stratification), and 0.78 (0.68-0.88; intestinal peristalsis). Compared to patients with a normal rate of peristalsis (5-10/min), patients with abnormal peristalsis rates (< 5/min or > 10/min) have increased risk for feeding intolerance (16/83 vs. 25/33, p < 0.001). CONCLUSIONS: The transabdominal intestinal ultrasonography represents an effective means for assessing gastrointestinal injury in critically ill patients. Intestinal ultrasonography indicators, especially the degree of intestinal peristalsis, may be used to predict feeding intolerance. TRIAL REGISTRATION: ClinicalTrial.gov, NCT03589248. Registered 04 July 2018-retrospectively registered.


Assuntos
Traumatismos Abdominais/classificação , Trato Gastrointestinal/diagnóstico por imagem , Valor Preditivo dos Testes , Ultrassonografia/normas , APACHE , Traumatismos Abdominais/diagnóstico , Adulto , Idoso , China , Estado Terminal/terapia , Feminino , Trato Gastrointestinal/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Sistemas Automatizados de Assistência Junto ao Leito , Estudos Prospectivos , Curva ROC , Ultrassonografia/métodos , Ultrassonografia/estatística & dados numéricos
9.
Chem Biodivers ; 16(6): e1900052, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30946516

RESUMO

One new racemic mixture, penicilliode A (1) and four pairs of enantiomeric polyketides, penicilliode B and C (2 and 3) and coniochaetone B and C (4 and 5), were obtained from the starfish-derived symbiotic fungus Penicillium sp. GGF16-1-2. Interestingly, the strain GGF16-1-2 can produce enantiomers. The absolute configuration of 1 was determined by X-ray diffraction (XRD) analysis, and the absolute configurations of 2-4 were determined by the optical rotation (OR) values and electronic circular dichroism (ECD) calculations. Compounds 1-5 were firstly isolated from the marine-derived fungus Penicillium as racemates, and 2-5 were separated by HPLC with a chiral stationary phase. All the compounds were evaluated for their antibacterial, cytotoxic and inhibitory activities against PDE4D2.


Assuntos
Penicillium/metabolismo , Policetídeos/química , Estrelas-do-Mar/microbiologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Conformação Molecular , Penicillium/química , Policetídeos/isolamento & purificação , Policetídeos/farmacologia , Estereoisomerismo , Simbiose
10.
Angew Chem Int Ed Engl ; 58(38): 13405-13410, 2019 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-31365775

RESUMO

As a new family member of the emerging two-dimensional (2D) monoelemental materials (Xenes), germanene has shown promising advantages over the prototypical 2D Xenes, such as black phosphorus (BP) and graphene. However, efficient manufacture of novel germanene nanostructures is still a challenge. Herein, a simple top-down approach for the liquid-exfoliation of ultra-small germanene quantum dots (GeQDs) is presented. The prepared GeQDs possess an average lateral size of about 4.5 nm and thickness of about 2.2 nm. The functionalized GeQDs were demonstrated to be robust photothermal agents (PTAs) with outstanding photothermal conversion efficacy (higher than those of graphene and BPQDs), superior stability, and excellent biocompatibility. As a proof-of-principle, 2D GeQDs-based PTAs were used in fluorescence/photoacoustic/photothermal-imaging-guided hyperpyrexia ablation of tumors. This work could expand the application of 2D germanene to the field of photonic cancer nanomedicine.


Assuntos
Fototerapia/métodos , Pontos Quânticos/química , Nanomedicina Teranóstica/métodos , Humanos
11.
Cell Physiol Biochem ; 44(5): 1775-1784, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29241196

RESUMO

BACKGROUND/AIMS: Calycosin, a phytoestrogenic compound, has recently emerged as a promising antitumor drug. It has been shown that calycosin suppresses growth and induces apoptosis of breast cancer cells. However, the effect of calycosin on migration and invasion of breast cancer cells and the underlying molecular mechanisms have not been elucidated. METHODS: Human breast cancer cells MCF-7 and T47D were treated with, or without, different doses (0, 6.25, 12.5, 25, 50, 100 or 150 µM) of calycosin, and the viability of different groups was determined by MTT assay. Next, the inhibitory effect of higher doses (50, 100 or 150 µM) of calycosin on migration and invasion of the two cell lines was determined by wound healing and transwell assay. The relative expression levels of forkhead box P3 (Foxp3), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in MCF-7 and T47D cells were determined by quantitative RT-PCR and Western blot. RESULTS: Treatment with lower doses (6.25 or 12.5 µM) promoted proliferation of breast cancer cells, but with higher doses significantly reduced the viability of MCF-7 and T47D cells. Furthermore, higher doses of calycosin were found to inhibit migration and invasion of the two cell lines in a dose-dependent manner. Additionally, treatment with a higher dose of calycosin significantly reduced the expression levels of Foxp3, followed by down-regulation of VEGF and MMP-9 in both MCF-7 and T47D breast cancer cells. CONCLUSION: Treatment with a higher dose of calycosin tends to reduce migration and invasion capacity of human breast cancer cells, by targeting Foxp3-mediated VEGF and MMP-9 expression.


Assuntos
Regulação para Baixo/efeitos dos fármacos , Fatores de Transcrição Forkhead/metabolismo , Isoflavonas/toxicidade , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/toxicidade , Feminino , Fatores de Transcrição Forkhead/genética , Humanos , Células MCF-7 , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
Med Sci Monit ; 23: 151-157, 2017 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-28074045

RESUMO

BACKGROUND SDF-1 and NF-κB are associated with the prognosis of a wide range of cancers, but their value in cervical cancer remains controversial. The aim of this study was to investigate the expression of SDF-1and NF-κB in cervical cancer and their significance in clinical prognosis. MATERIAL AND METHODS The expression of SDF-1and NF-κB in 105 formalin-fixed, paraffin-embedded cervical cancer tissues and the adjacent tissues was examined by immunohistochemistry (IHC). The results were semi-quantitatively scored and analyzed by chi-square test. The overall survival times (OS) were collected by follow-up and analyzed by Kaplan-Meier analysis. RESULTS The expression level of both SDF-1and NF-κB in cervical cancer are higher than that in the adjacent tissues (P<0.05). SDF-1 expression are correlated with tumor size and FIGO histology grade (P<0.05). NF-κB expression are correlated with tumor size and FIGO histology grade, and lymph node metastasis (LNM) status (P<0.05). The patients with a positive expression of SDF-1or NF-κB tended to have much shorter survival time than patients with negative expression. In addition, multivariate Cox regression analysis demonstrated that SDF-1 expression and lymph node metastasis are independent predictors of the OS in cervical cancer patients. CONCLUSIONS The expression of SDF-1 is significantly associated with tumor size and FIGO histology grade. The expression of NF-κB is significantly associated with tumor size, FIGO histology grade, and lymph node metastasis. The positive SDF-1or NF-κB expression is significantly correlated with poor prognosis. These may be valuable biomarkers for the prognosis and the potential therapeutic targets of cervical cancer.


Assuntos
Quimiocina CXCL12/metabolismo , NF-kappa B/metabolismo , Neoplasias do Colo do Útero/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Neoplasias do Colo do Útero/patologia
14.
Med Sci Monit ; 22: 4475-4481, 2016 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-27866212

RESUMO

BACKGROUND IL-1α and IL-6 are associated with the prognosis of a wide range of cancers, but their value in cervical cancer remains controversial. The aim of this study was to investigate the expression of IL-1α and IL-6 in cervical cancer and their significance in clinical prognosis. MATERIAL AND METHODS The expression of IL-1α and IL-6 in 105 formalin-fixed, paraffin-embedded cervical cancer tissues and adjacent non-tumor tissues was examined by immunohistochemistry. The results were semi-quantitatively scored and analyzed by chi-square test. Patient overall survival (OS) data was collected by follow-up and analyzed by Kaplan-Meier analysis. RESULTS The expression level of both IL-1α and IL-6 in cervical cancer tissue was higher than in adjacent non-tumor tissues (p<0.05). IL-1α expression was shown to be correlated with tumor size, FIGO histology grade, lymph node metastasis, stromal invasion, and tumor differentiation (p<0.05). IL-6 expression was shown to be correlated with tumor size, FIGO histology grade, and tumor differentiation (p<0.05). Patients with positive expression of IL-1α or IL-6 tended to have much shorter survival times than patients with negative expression. In addition, a multivariate Cox regression analysis demonstrated that IL-1α expression and lymph node metastasis were independent predictors of OS in cervical cancer patients. CONCLUSIONS The expression of IL-1α was significantly associated with tumor size, FIGO histology grade, lymph node metastasis, stromal invasion, and tumor differentiation. The expression of IL-6 was significantly associated with tumor size, FIGO histology grade, and tumor differentiation. Positive IL-1α and IL-6 expression was significantly correlated with poor prognosis. They may be considered valuable biomarkers for prognosis and potential therapeutic targets for cervical cancer.


Assuntos
Biomarcadores Tumorais/biossíntese , Interleucina-1alfa/biossíntese , Interleucina-6/biossíntese , Neoplasias do Colo do Útero/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Interleucina-1alfa/genética , Interleucina-6/genética , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
15.
Hepatogastroenterology ; 61(131): 628-32, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-26176047

RESUMO

BACKGROUND/AIMS: Hemorrhage after abdominal surgery remains a frequent clinical complication, and associated with prolonged length of stay, increased complications and mortality. Indication of blood product requirements accurately and promptly is very important for recovery of patients. Thrombelastography (TEG) as a tool for evaluation of bleeding and effects of blood components and blood products is increasing. We investigated that whether TEG can identify postoperative active bleeding and evaluate blood product requirements in abdominal surgery. METHODOLOGY: Between June to December in 2012, there were 55 patients who had bleeding after operation in SICU of Jinling Hospital. Recorded data included vital signs (MAP, heart rate, respiratory rate, blood oxygen saturation), urine volume per hour, blood routine (Hb, Hct, Plt), the coagulation tests (Fib, PT, aPTT, INR), TEG parameters (R, K, Angle, MA, Cl) and blood product requirements within 24h. Patients were divided into active bleeding group and non-active bleeding group based on the findings of reoperation or digital subtraction angiography (DSA). To compare vital signs, laboratory values, TEG values and blood product requirements in two groups. RESULTS: Vital signs (MAP, heart rate, respiratory rate, blood oxygen saturation), urine volume per hour and the coagulation tests (Fib, PT, INR) showed no significant correlations with subsequent blood product requirements, but aPTT (R = 0.546, P = 0.000) and MA (R = 0.665, P = 0.000) correlated with the blood products use. MA values of patients had more blood loss was significantly lower and had a descending tendency which did not showed in aPTT values. 25 patients had postoperative active bleeding confirmed by reoperation or DSA. They had significantly increased use of blood products, and significantly lower MA, Hb, Hct, and Fib values, whereas aPTT exhibited no significant differences. CONCLUSION: MA can not only identify postoperative active bleeding together with hemoglobin, hematocrit, and fibrinogen, but also evaluate blood product requirements in abdominal surgery.


Assuntos
Abdome/cirurgia , Transfusão de Sangue/métodos , Hemorragia Pós-Operatória/diagnóstico , Hemorragia Pós-Operatória/terapia , Tromboelastografia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Digital , Biomarcadores/sangue , China , Feminino , Fibrinogênio/metabolismo , Hematócrito , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/sangue , Hemorragia Pós-Operatória/etiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
16.
Hepatogastroenterology ; 60(127): 1653-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24627921

RESUMO

BACKGROUND/AIMS: Recent studies indicate that perioperative fluid restriction leads to better preserved clinical data as well as reduced complication rates. This study aimed to determine the probable mechanism of fluid restriction influence on the complication rate of patients undergoing gastrointestinal surgery for malignancy. METHODOLOGY: Patients (n = 174) undergoing restricted fluid regimen (R group) or standard fluid regimen (S group) were included in this prospective, randomized trial over 16 months. Fluid distribution was determined by Bioelectrical Impedance Analyzer (BIA) and the difference between two groups was compared regarding complications and the relationship between complications and fluid distribution changes. RESULTS: The restricted intravenous fluid regimen significantly reduced perioperative intravenous fluid volume. Weight gained in S group and was not significantly changed in R group after surgery, especially in POD2 (media; R vs. S; 61.17 vs. 65.40 kg, p = 0.017). The number of patients with postoperative complications was reduced in R group compared with in S group (34.5% vs. 47.8%, p = 0.076). Systemic complications were significantly reduced in R group (t = -5.895, p = 0.000). Patients with complications had an average of 1.6 complications in R group vs. 2.0 in S group (t = -1.345, p = 0.183). The multivariate analysis suggested that perioperative fluid distribution changes were associated with the development of postoperative complications. CONCLUSIONS: Perioperative fluid restriction could effect on fluid distribution and reduce tissue and cellular edema, and further, could reduce postoperative complication rates.


Assuntos
Neoplasias Abdominais/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório , Deslocamentos de Líquidos Corporais , Hidratação/métodos , Idoso , Distribuição de Qui-Quadrado , China , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Impedância Elétrica , Feminino , Hidratação/efeitos adversos , Humanos , Infusões Intravenosas , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Aumento de Peso
17.
STAR Protoc ; 4(1): 102138, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36861826

RESUMO

Efficient gene delivery in an integrated drug delivery system is urgent for multimodal antitumor therapy. Herein, we describe a protocol for constructing a peptide-based siRNA delivery system to achieve tumor vascular normalization and gene silencing in 4T1 cells. We highlighted four major steps, including (1) synthesis of the chimeric peptide, (2) preparation and characterization of PA7R@siRNA micelleplexes, (3) in vitro tube formation assay and transwell cell migration assay, and (4) siRNA transfection in 4T1 cells. This delivery system is expected to be used to silence gene expression, normalize tumor vasculature, and perform other treatments based on the different peptide segments. For complete details on the use and execution of this protocol, please refer to Yi et al. (2022).1.


Assuntos
Sistemas de Liberação de Medicamentos , Peptídeos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Linhagem Celular Tumoral , Peptídeos/química , Sistemas de Liberação de Medicamentos/métodos , Inativação Gênica
18.
World J Surg ; 36(5): 993-1002, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22402971

RESUMO

BACKGROUND: Perioperative fluid restriction can lead to better clinical outcomes and reduced complications. However, whether perioperative fluid restriction can alter the patient's postoperative cellular immunity is unknown. Therefore, a randomized, prospective clinical study was designed to determine whether fluid restriction improves immunological outcome in elderly patients who undergo gastrointestinal surgery for cancer removal. METHODS: A total of 179 patients aged 65 years or older were recruited for the study and were randomly assigned to receive the restricted fluid regimen (R group) or the standard fluid regimen (S group). Postoperative T-lymphocyte subpopulations (CD3(+), CD4(+), and CD8(+)) frequencies and monocyte HLA-DR expression was investigated. Perioperative complications and cellular immunity changes were analyzed comparatively between the two groups. RESULTS: The restricted intravenous fluid regimen was associated with significantly less postoperative complications (1.5 complications/patient vs. S group: 2.2 complications/patient), especially for infection complications (15% vs. S group: 27%, p = 0.04). Circulating CD3(+) T-cells were suppressed after surgery in both treatment groups, but the cell frequency (cell/µL) was higher in the R group (746 vs. S group: 480 at postoperative day (POD) 2, p = 0.022; 878 vs. 502 at POD 3, p = 0.005; 892 vs. 674 at POD 5, p = 0.042). Similarly, the HLA-DR expression (% of all T cells) in monocytes were decreased in both groups, but the expression remained higher in the R group (66.20 vs. S group: 51.97 at POD 1, p = 0.029; 68.19 vs. 51.26 at POD 2, p = 0.039; 72.19 vs. 57.45 at POD 3, p = 0.014; 73.92 vs. 60.46 at POD 5, p = 0.036). Multivariate analysis suggested that perioperative CD3(+) T cell changes were associated with the development of postoperative complications [odds ratio (OR) = 1.963; 95% confidence interval (CI) 1.019-3.782; p = 0.044] and postoperative infections (OR = 3.106; 95% CI 1.302-7.406; p = 0.011). CONCLUSIONS: In elderly gastrointestinal cancer patients, cellular immunity is better preserved by the perioperative fluid restriction regimen. The better preserved cellular immunological function is correlated with a reduced perioperative complications rate.


Assuntos
Hidratação/métodos , Neoplasias Gastrointestinais/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Feminino , Antígenos HLA-DR/metabolismo , Humanos , Imunidade Celular , Infusões Intravenosas , Modelos Logísticos , Masculino , Monócitos/metabolismo , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/imunologia , Estudos Prospectivos , Método Simples-Cego , Subpopulações de Linfócitos T/metabolismo , Resultado do Tratamento
19.
Bioact Mater ; 13: 96-104, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35224294

RESUMO

The emerging two-dimensional monoelemental materials (2D Xenes) have been commonly supposed as promising drug delivery carriers, photothermal and photodynamic therapeutic agents, biosensors, theranostics, and some other candidates for biomedical applications. Here, high-performance and bioactive ultrathin 2D Tellurium nanosheets (Te NSs) are prepared by a simple but efficient liquid-phase exfoliation approach. The as-obtained Te NSs possess a mean size of ∼90 nm and a mean thickness of ∼5.43 nm. The pegylation Te NSs (Te-PEG NSs) possess excellent biocompatibility and stability. The Te-PEG NSs could generate local hyperthermia with a remarkable photothermal conversion efficiency of about 55% under 808 nm laser irradiation. Additionally, Te-PEG NSs exhibit an extremely high loading capacity of chemo drug (∼162%) owing to their ultra-high surface area and tumor microenvironment-triggered drug release superiority. The results of in vivo experiments show that the Te-PEG NSs have higher tumor elimination efficiency via the combination of photothermal and chemotherapy, comparing to any other single therapeutic modalities. Therefore, our work not only highlights the promising potentials of tellurene as an ideal anti-cancer platform but also expands the application of 2D Te for cancer nanomedicine.

20.
Acta Pharm Sin B ; 12(5): 2206-2223, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35013704

RESUMO

Looking retrospectively at the development of humanity, vaccination is an unprecedented medical landmark that saves lives by harnessing the human immune system. During the ongoing coronavirus disease 2019 (COVID-19) pandemic, vaccination is still the most effective defense modality. The successful clinical application of the lipid nanoparticle-based Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines highlights promising future of nanotechnology in vaccine development. Compared with conventional vaccines, nanovaccines are supposed to have advantages in lymph node accumulation, antigen assembly, and antigen presentation; they also have, unique pathogen biomimicry properties because of well-organized combination of multiple immune factors. Beyond infectious diseases, vaccine nanotechnology also exhibits considerable potential for cancer treatment. The ultimate goal of cancer vaccines is to fully mobilize the potency of the immune system as a living therapeutic to recognize tumor antigens and eliminate tumor cells, and nanotechnologies have the requisite properties to realize this goal. In this review, we summarize the recent advances in vaccine nanotechnology from infectious disease prevention to cancer immunotherapy and highlight the different types of materials, mechanisms, administration methods, as well as future perspectives.

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