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1.
J Cell Mol Med ; 28(8): e18292, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38652116

RESUMO

Foodborne illnesses, particularly those caused by Salmonella enterica with its extensive array of over 2600 serovars, present a significant public health challenge. Therefore, prompt and precise identification of S. enterica serovars is essential for clinical relevance, which facilitates the understanding of S. enterica transmission routes and the determination of outbreak sources. Classical serotyping methods via molecular subtyping and genomic markers currently suffer from various limitations, such as labour intensiveness, time consumption, etc. Therefore, there is a pressing need to develop new diagnostic techniques. Surface-enhanced Raman spectroscopy (SERS) is a non-invasive diagnostic technique that can generate Raman spectra, based on which rapid and accurate discrimination of bacterial pathogens could be achieved. To generate SERS spectra, a Raman spectrometer is needed to detect and collect signals, which are divided into two types: the expensive benchtop spectrometer and the inexpensive handheld spectrometer. In this study, we compared the performance of two Raman spectrometers to discriminate four closely associated S. enterica serovars, that is, S. enterica subsp. enterica serovar dublin, enteritidis, typhi and typhimurium. Six machine learning algorithms were applied to analyse these SERS spectra. The support vector machine (SVM) model showed the highest accuracy for both handheld (99.97%) and benchtop (99.38%) Raman spectrometers. This study demonstrated that handheld Raman spectrometers achieved similar prediction accuracy as benchtop spectrometers when combined with machine learning models, providing an effective solution for rapid, accurate and cost-effective identification of closely associated S. enterica serovars.


Assuntos
Salmonella enterica , Sorogrupo , Análise Espectral Raman , Máquina de Vetores de Suporte , Análise Espectral Raman/métodos , Salmonella enterica/isolamento & purificação , Humanos , Algoritmos
2.
Small ; 20(16): e2307786, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38161248

RESUMO

To date, transforming environmental energy into electricity through a non-mechanical way is challenging. Herein, a series of photomechaelectric (PME) polyurethanes containing azobenzene-based photoisomer units and ionic liquid-based dipole units are synthesized, and corresponding PME nanogenerators (PME-NGs) to harvest electricity are fabricated. The dependence of the output performance of PME-NGs on the structure of the polyurethane is evaluated. The results show that the UV light energy can directly transduce into alternating-current (AC) electricity by PME-NGs via a non-mechanical way. The optimal open-circuit voltage and short-circuit current of PME-NGs under UV illumination reach 17.4 V and 696 µA, respectively. After rectification, the AC electricity can be further transformed into direct-current (DC) electricity and stored in a capacitor to serve as a power system to actuate typical microelectronics. The output performance of PME-NGs is closely related to the hard segment content of the PME polyurethane and the radius of counter anions in the dipole units. Kelvin probe force microscopy is used to confirm the existence of the PME effect and the detailed mechanism about the generation of AC electricity in PME-NGs is proposed, referring to the back and forth drift of induced electrons on the two electrodes in contact with the PME polyurethanes.

3.
J Transl Med ; 22(1): 86, 2024 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-38246999

RESUMO

BACKGROUND: Obesity, a condition associated with the development of widespread cardiovascular disease, metabolic disorders, and other health complications, has emerged as a significant global health issue. Oleanolic acid (OA), a pentacyclic triterpenoid compound that is widely distributed in various natural plants, has demonstrated potential anti-inflammatory and anti-atherosclerotic properties. However, the mechanism by which OA fights obesity has not been well studied. METHOD: Network pharmacology was utilized to search for potential targets and pathways of OA against obesity. Molecular docking and molecular dynamics simulations were utilized to validate the interaction of OA with core targets, and an animal model of obesity induced by high-fat eating was then employed to confirm the most central of these targets. RESULTS: The network pharmacology study thoroughly examined 42 important OA targets for the treatment of obesity. The key biological processes (BP), cellular components (CC), and molecular functions (MF) of OA for anti-obesity were identified using GO enrichment analysis, including intracellular receptor signaling, intracellular steroid hormone receptor signaling, chromatin, nucleoplasm, receptor complex, endoplasmic reticulum membrane, and RNA polymerase II transcription Factor Activity. The KEGG/DAVID database enrichment study found that metabolic pathways, PPAR signaling pathways, cancer pathways/PPAR signaling pathways, insulin resistance, and ovarian steroidogenesis all play essential roles in the treatment of obesity and OA. The protein-protein interaction (PPI) network was used to screen nine main targets: PPARG, PPARA, MAPK3, NR3C1, PTGS2, CYP19A1, CNR1, HSD11B1, and AGTR1. Using molecular docking technology, the possible binding mechanism and degree of binding between OA and each important target were validated, demonstrating that OA has a good binding potential with each target. The molecular dynamics simulation's Root Mean Square Deviation (RMSD), and Radius of Gyration (Rg) further demonstrated that OA has strong binding stability with each target. Additional animal studies confirmed the significance of the core target PPARG and the core pathway PPAR signaling pathway in OA anti-obesity. CONCLUSION: Overall, our study utilized a multifaceted approach to investigate the value and mechanisms of OA in treating obesity, thereby providing a novel foundation for the identification and development of natural drug treatments.


Assuntos
Doenças Cardiovasculares , Ácido Oleanólico , Animais , Simulação de Acoplamento Molecular , Farmacologia em Rede , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , PPAR gama
4.
BMC Cancer ; 22(1): 643, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35690752

RESUMO

BACKGROUND: Hepato-pulmonary metastasis of colorectal cancer (CRC) is a rare disease with poor prognosis. This study aims to establish a highly efficient nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with colorectal cancer hepato-pulmonary metastasis (CRCHPM). METHODS: We retrospectively analyzed the data of patients with CRCHPM from SEER database and Wuhan Union Hospital Cancer Center (WUHCC). A total of 1250 CRCHPM patients were randomly assigned to the training, internal validation, and external validation cohorts from 2010 to 2016.Univariate and multivariate cox analysis were performed to identify independent clinicopathological predictors of OS and CSS, and a nomogram was constructed to predict OS and CSS in CRCHPM patients. RESULTS: A nomogram of OS was constructed based on seven independent predictors of age, degree of differentiation, T stage, chemotherapy, number of lsampled lymph nodes, number of positive lymph nodes, and tumor size. Nomogram showed favorable sensitivity in predicting OS at 1, 3 and 5 years, with area under the receiver operating characteristic curve (AUROC) values of 0.802, 0.759 and 0.752 in the training cohort;0.814, 0.769 and 0.716 in the internal validation cohort;0.778, 0.756 and 0.753 in the external validation cohort, respectively. A nomogram of CSS was constructed based on three independent predictors of T stage, chemotherapy, and tumor size. The AUROC values of 1, 3 and 5 years were 0.709,0.588,0.686 in the training cohort; 0.751, 0.648,0.666 in the internal validation cohort;0.781,0.588,0.645 in the external validation cohort, respectively. Calibration curves, Concordance index (C-index), and decision curve analysis (DCA) results revealed that using our model to predict OS and CSS is more efficient than other single clinicopathological characteristics. CONCLUSION: A nomogram of OS and CSS based on clinicopathological characteristics can be conveniently used to predict the prognosis of CRCHPM patients.


Assuntos
Neoplasias Colorretais , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/terapia , Estadiamento de Neoplasias , Nomogramas , Prognóstico , Estudos Retrospectivos , Programa de SEER
5.
Biotechnol Lett ; 44(3): 367-386, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35294695

RESUMO

Drought stress is one of the major abiotic stresses that limit growth, development and yield of maize crops. To better understand the responses of maize inbred lines with different levels of drought resistance and the molecular mechanism of exogenous glycine betaine (GB) in alleviating drought stress, the responses of two maize inbred lines to drought stress and to the stress-mitigating effects of exogenous GB were investigated. Seedling morphology, physiological and biochemical indexes, root cell morphology and root transcriptome expression profiles were compared between a drought-tolerant inbred line Chang 7-2 and drought-sensitive inbred line TS141. Plants of both lines were subjected to treatments of drought stress alone and drought stress with application of exogenous GB. The results showed that with the increase of drought treatment time, the growth and development of TS141 were inhibited, while those of Chang 7-2 were not significantly different from those of the control (no drought stress and GB). Compared with the corresponding data of the drought-stress group, every index measured from the two inbred lines indicated mitigating effects from exogenous GB, and TS141 produced stronger mitigating responses due to the GB. Transcriptome analysis showed that 562 differentially expressed genes (DEGs) were up-regulated and 824 DEGs were down-regulated in both inbred lines under drought stress. Due to the exogenous GB, 1061 DEGs were up-regulated and 424 DEGs were down-regulated in both lines. In addition, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify 10 DEGs screened from the different treatments. These results showed that the expression of 9 DEGs were basically consistent with their respective transcriptome expression profiles. The results of this study provide models of potential mechanisms of drought tolerance in maize as well as potential mechanisms of how exogenous GB may regulate drought tolerance.


Assuntos
Secas , Zea mays , Betaína/metabolismo , Betaína/farmacologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genética , Transcriptoma , Zea mays/metabolismo
6.
FASEB J ; 34(5): 6198-6214, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32162746

RESUMO

Mitochondrial dysfunction is the leading cause of reactive oxygen species (ROS) burst and apoptosis in hepatic ischemia/reperfusion (I/R) injury. Ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE) is a hepatotargeted agent that exerts hepatoprotective roles by regulating lipid metabolism. Our previous studies have shown that UDCA-LPE improves hepatic I/R injury by inhibiting apoptosis and inflammation. However, the role of UDCA-LPE in lipid metabolism and mitochondrial function in hepatic I/R remains unknown. In the present study, we investigated the role of UDCA-LPE in hepatic I/R by focusing on the interface of phospholipid metabolism and mitochondrial homeostasis. Livers from 28-week-old mice, primary hepatocytes and HepG2 cells were subjected to in vivo and in vitro I/R, respectively. Analyses of oxidative stress, imaging, ATP generation, genetics, and lipidomics showed that I/R was associated with mitochondrial dysfunction and a reduction in phospholipids. UDCA-LPE alleviated mitochondria-dependent oxidative stress and apoptosis and prevented the decrease of phospholipid levels. Our study found that cytosolic phospholipase A2 (cPLA2 ), a phospholipase that is activated during I/R, hydrolyzed mitochondrial membrane phospholipids and led to mitochondria-mediated oxidative stress and apoptosis. UDCA-LPE inhibited the interaction between cPLA2 and mitochondria and reduced phospholipid hydrolysis-mediated injury. UDCA-LPE might regulate the crosstalk between the phospholipid metabolism and the mitochondria, restore mitochondrial function and ameliorate I/R injury.


Assuntos
Transtornos do Metabolismo dos Lipídeos/prevenção & controle , Hepatopatias/prevenção & controle , Lisofosfolipídeos/farmacologia , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosfolipídeos/metabolismo , Traumatismo por Reperfusão/complicações , Ácido Ursodesoxicólico/análogos & derivados , Animais , Apoptose , Células Hep G2 , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Transtornos do Metabolismo dos Lipídeos/etiologia , Transtornos do Metabolismo dos Lipídeos/metabolismo , Hepatopatias/etiologia , Hepatopatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio , Ácido Ursodesoxicólico/farmacologia
7.
Macromol Rapid Commun ; 42(19): e2100318, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34347335

RESUMO

Owing to deep activation in biotissues and enhanced targeting efficiency, developing photoresponsive polymer-upconversion nanoparticles (PP-UCNPs) nanovectors has witnessed rapid growth in the past decade. However, up to date, all developed nanovectors require high-order photon processes to initiate the release of cargos. The photodamage caused by high-power near-infrared laser light may be a critical obstacle to their clinical application. Here, for the first time, by leveraging absorption-emission spectral matching between donor-acceptor Stenhouse adducts (DASA) PP and UCNPs (λex , 808 nm) in the green region (≈530 nm), the designed nanovector is capable of releasing cargos at a low-power 808 nm excitation (0.2 W). Considering the high molar absorptivity, biobenign, and synthetic tunability of DASA, DASA PP can be utilized as an up-and-coming candidate to design and synthesize the next generation of upconversion nanovectors without photodamage.


Assuntos
Nanopartículas , Polímeros , Raios Infravermelhos
8.
BMC Surg ; 21(1): 201, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879122

RESUMO

BACKGROUND: Anastomosis-related complications are common after the radical resection of colon cancer. Among such complications, severe stenosis or completely occluded anastomosis (COA) are uncommon in clinical practice, and the separation of the anastomosis is even rarer. For such difficult problems as COA or anastomotic separation, clinicians tend to adopt surgical interventions, and few clinicians try to solve them through endoscopic operations. CASE PRESENTATION: In this article, we present a case of endoscopic treatment of anastomotic closure and separation after radical resection for sigmoid carcinoma. After imaging examination and endoscopic evaluation, we found that the patient had a COA accompanied by a 3-4 cm anastomotic separation. With the aid of fluoroscopy, we attempted to use the titanium clip marker as a guide to perform an endoscopic incision and successfully achieved recanalization. We used a self-expanding covered metal stent to bridge the intestinal canal to resolve the anastomotic separation. Finally, the patient underwent ileostomy takedown, and the postoperative recovery was smooth. The follow-up evaluation results showed that the anastomotic stoma was unobstructed. CONCLUSIONS: We reported the successful application of endoscopic technique in a rare case of COA and separation after colon cancer surgery, which is worth exploring and verifying through more clinical studies in the future.


Assuntos
Anastomose Cirúrgica/efeitos adversos , Colectomia/efeitos adversos , Colonoscopia/métodos , Constrição Patológica/cirurgia , Neoplasias do Colo Sigmoide/cirurgia , Deiscência da Ferida Operatória/cirurgia , Colo/diagnóstico por imagem , Colo/patologia , Colo/cirurgia , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/etiologia , Fluoroscopia , Humanos , Ileostomia , Laparoscopia , Masculino , Pessoa de Meia-Idade , Implantação de Prótese , Stents Metálicos Autoexpansíveis , Neoplasias do Colo Sigmoide/tratamento farmacológico , Deiscência da Ferida Operatória/diagnóstico por imagem , Deiscência da Ferida Operatória/etiologia
9.
Cancer Sci ; 111(5): 1582-1595, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32129914

RESUMO

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an oncogenic long noncoding RNA that has been found to promote carcinogenesis and metastasis in many tumors. However, the underlying role of MALAT1 in the progression and metastasis of hepatocellular carcinoma (HCC) remains unclear. In this study, aberrantly elevated levels of MALAT1 were detected in both HCC specimens and cell lines. We found that knockdown of MALAT1 caused retardation in proliferation, migration, and invasion both in vivo and in vitro. Mechanistic investigations showed that Snail family transcriptional repressor 1 (SNAI1) is a direct target of microRNA (miR)-22 and that MALAT1 modulates SNAI1 expression by acting as a competing endogenous RNA for miR-22. Inhibition of miR-22 restored SNAI1 expression suppressed by MALAT1 knockdown. Furthermore, MALAT1 facilitated the enrichment of enhancer of zeste homolog 2 (EZH2) at the promoter region of miR-22 and E-cadherin, which was repressed by MALAT1 knockdown. Cooperating with EZH2, MALAT1 positively regulated SNAI1 by repressing miR-22 and inhibiting E-cadherin expression, playing a vital role in epithelial to mesenchymal transition. In conclusion, our results reveal a mechanism by which MALAT1 promotes HCC progression and provides a potential target for HCC therapy.


Assuntos
Carcinoma Hepatocelular/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Fatores de Transcrição da Família Snail/genética , Animais , Antígenos CD/genética , Sítios de Ligação , Caderinas/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Transição Epitelial-Mesenquimal/genética , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Regiões Promotoras Genéticas , Fatores de Transcrição da Família Snail/metabolismo
10.
BMC Cancer ; 20(1): 1099, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33183271

RESUMO

BACKGROUND: Identifying the mutation status of KRAS is important for optimizing treatment in patients with colorectal cancer (CRC). The aim of this study was to investigate the predictive value of haematological parameters and serum tumour markers (STMs) for KRAS gene mutations. METHODS: The clinical data of patients with colorectal cancer from January 2014 to December 2018 were retrospectively collected, and the associations between KRAS mutations and other indicators were analysed. Receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors. Univariate and multivariate logistic regression models were applied to identify predictors of KRAS mutations by calculating the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). RESULTS: KRAS mutations were identified in 276 patients (35.2%). ROC analysis revealed that age, CA12-5, AFP, SCC, CA72-4, CA15-3, FERR, CYFRA21-1, MCHC, and tumor location could not predict KRAS mutations (P = 0.154, 0.177, 0.277, 0.350, 0.864, 0.941, 0.066, 0.279, 0.293, and 0.053 respectively), although CEA, CA19-9, NSE and haematological parameter values showed significant predictive value (P = 0.001, < 0.001, 0.043 and P = 0.003, < 0.001, 0.001, 0.031, 0.030, 0.016, 0.015, 0.019, and 0.006, respectively) but without large areas under the curve. Multivariate logistic regression analysis showed that CA19-9 was significantly associated with KRAS mutations and was the only independent predictor of KRAS positivity (P = 0.016). CONCLUSIONS: Haematological parameters and STMs were related to KRAS mutation status, and CA19-9 was an independent predictive factor for KRAS gene mutations. The combination of these clinical factors can improve the ability to identify KRAS mutations in CRC patients.


Assuntos
Povo Asiático/genética , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Hematócrito , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos
11.
J Clin Lab Anal ; 34(5): e23197, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31912542

RESUMO

BACKGROUND: To calculate the reference intervals for thyroid-stimulating hormone (TSH) and thyroid hormones using the Access TSH 3rd IS method and evaluate the differences between age and genders in Chinese populations. METHODS: This study collected 349 serum samples of healthy subjects were from Shengli Oilfield Central Hospital in China. Subjects who tested positive for thyroid peroxidase antibody or thyroglobulin antibody were excluded. Accordingly, 313 subjects were included for establishing reference intervals for the thyroid hormones. The serum concentrations of TSH, total and free thyroxine (TT4 and FT4), and total and free triiodothyronine (TT3 and FT3) were measured using the Access TSH 3rd IS method. The 2.5th and 97.5th percentiles or mean with standard deviation were calculated as the reference interval as appropriate. RESULTS: The reference intervals for TSH, FT4, FT3, TT4, and TT3 calculated in present study were 0.61-4.16 mIU/L, 0.67-1.11 ng/dL, 2.63-4.33 pg/mL, 5.56-11.33 µg/dL, and 0.72-1.32 ng/mL, respectively. The FT3, TT4, and TT3 levels in males were significantly higher than in females (P < .05), while TSH levels in males were significantly lower than in females (P < .05). The levels of FT3 in subjects with the age of less than 30 years were significantly higher than other groups (P < .05). CONCLUSION: The present study provided a valid basis for the reference intervals for TSH, FT4, FT3, TT4, and TT3 in Chinese populations. In addition, this present study indicated that age and gender should be considered in diagnostic evaluation of thyroid diseases.


Assuntos
Hormônios Tireóideos/sangue , Tireotropina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , China , Feminino , Humanos , Imunoensaio/métodos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto Jovem
12.
Int J Colorectal Dis ; 34(3): 545-547, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30091011

RESUMO

PURPOSE: Colonic perforation is a life-threatening complication after colonic stent insertion as a bridge to surgery for acute obstruction caused by colorectal cancer. The oncological consequence of colonic perforation after emergent surgical intervention was unknown. The aim of this short communication was to investigate whether or not the perforation and emergent surgery had obviously impact on the peritoneal recurrence and long-term survival of patients. METHODS: Data of the patients who underwent colorectal stenting as a bridge to surgery in 5 years from 2012 to 2017 was collected by the Endoscopical Surgery Group of Hubei. The perforated cases treated by emergent operation were retrospectively analyzed. RESULTS: During 5 years from 2012 to 2017, 116 cases of colorectal stenting as a bridge to surgery had been performed, and 7 patients had perforation after stent placement and treated by emergent surgery, including 1 case of synchronic liver metastasis treated by one-stage metastasectomy. One of the 7 patients died of septic shock after operation, and the remaining patients were followed up for 6-60 months. There was no evidence of abdominal implantation or extra-abdominal metastasis. CONCLUSION: This small case series implicated that colonic perforation after stent insertion for malignant colorectal obstruction treated by emergent surgery might not obviously increase the peritoneal implantation and metastasis.


Assuntos
Neoplasias do Colo/cirurgia , Obstrução Intestinal/etiologia , Perfuração Intestinal/complicações , Perfuração Intestinal/cirurgia , Stents/efeitos adversos , Idoso , Neoplasias do Colo/diagnóstico por imagem , Feminino , Humanos , Obstrução Intestinal/diagnóstico por imagem , Perfuração Intestinal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade
13.
Biochim Biophys Acta ; 1861(5): 449-61, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26873633

RESUMO

PLA2G6 or GVIA calcium-independent PLA2 (iPLA2ß) is identified as one of the NAFLD modifier genes in humans, and thought to be a target for NAFLD therapy. iPLA2ß is known to play a house-keeping role in phospholipid metabolism and remodeling. However, its role in NAFLD pathogenesis has not been supported by results obtained from high-fat feeding of iPLA2ß-null (PKO) mice. Unlike livers of human NAFLD and genetically obese rodents, fatty liver induced by high-fat diet is not associated with depletion of hepatic phospholipids. We therefore tested whether iPLA2ß could regulate obesity and hepatic steatosis in leptin-deficient mice by cross-breeding PKO with ob/ob mice to generate ob/ob-PKO mice. Here we observed an improvement in ob/ob-PKO mice with significant reduction in serum enzymes, lipids, glucose, insulin as well as improved glucose tolerance, and reduction in islet hyperplasia. The improvement in hepatic steatosis measured by liver triglycerides, fatty acids and cholesterol esters was associated with decreased expression of PPARγ and de novo lipogenesis genes, and the reversal of ß-oxidation gene expression. Notably, ob/ob livers contained depleted levels of lysophospholipids and phospholipids, and iPLA2ß deficiency in ob/ob-PKO livers lowers the former, but replenished the latter particularly phosphatidylethanolamine (PE) and phosphatidylcholine (PC) that contained arachidonic (AA) and docosahexaenoic (DHA) acids. Compared with WT livers, PKO livers also contained increased PE and PC containing AA and DHA. Thus, iPLA2ß deficiency protected against obesity and ob/ob fatty liver which was associated with hepatic fatty-acyl phospholipid remodeling. Our results support the deleterious role of iPLA2ß in severe obesity associated NAFLD.


Assuntos
Ácidos Graxos/sangue , Fosfolipases A2 do Grupo VI/deficiência , Fígado/enzimologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Obesidade/prevenção & controle , Fosfolipídeos/sangue , Animais , Apoptose , Ácido Araquidônico/sangue , Glicemia/metabolismo , Ésteres do Colesterol/sangue , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/sangue , Regulação da Expressão Gênica , Genótipo , Fosfolipases A2 do Grupo VI/genética , Insulina/sangue , Resistência à Insulina , Fígado/patologia , Lisofosfolipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/enzimologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/sangue , Obesidade/enzimologia , Obesidade/genética , Obesidade/patologia , Oxirredução , PPAR gama/genética , PPAR gama/metabolismo , Fenótipo , Fosfatidilcolinas/sangue , Fosfatidiletanolaminas/sangue , Triglicerídeos/sangue
14.
Neurol Sci ; 38(6): 1087-1092, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28367610

RESUMO

Gliomas are the most common and aggressive brain tumors, and a poor prognosis is correlated with its World Health Organization (WHO) grade. MicroRNAs (miRNAs) may serve as diagnostic and prognostic biomarkers in gliomas. In the present study, we collected plasma samples from patients with gliomas to evaluate the expression of miR-122 and analyzed the role of miR-122 in the diagnosis and prognosis of gliomas. We found that the expression of miR-122 in the plasma of patients with gliomas was significantly down-regulated compared to that in healthy individuals. In addition, the expression of miR-122, which was significantly correlated with WHO grade, decreased along with the development of gliomas. A receiver operating characteristic curve analysis showed high sensitivity and specificity of miR-122 for diagnosing gliomas (sensitivity 91.9%; specificity 81.1%; area under the curve 0.939). Finally, we found that lower expression of miR-122 was correlated with poor prognosis, and miR-122 was an independent prognostic parameter indicating poor prognosis for gliomas. In conclusion, our results showed that plasma miR-122 expression might act as a diagnostic and prognostic biomarker for gliomas.


Assuntos
Neoplasias Encefálicas/sangue , Glioma/sangue , MicroRNAs/sangue , Área Sob a Curva , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Feminino , Glioma/patologia , Glioma/cirurgia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Carga Tumoral
15.
Bioorg Med Chem Lett ; 25(13): 2617-20, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25987374

RESUMO

A simple and practical procedure for the preparation of C5-(isoxazol-3-yl)-pyrimidine nucleosides through 1,3-dipolar cycloaddition of the in situ formed C5-nitrile oxide substituted pyrimidine nucleosides with various terminal alkynes is presented. Compared with literature procedures, this new method has advantageous features such as readily available and inexpensive starting materials, simple procedure without using expensive transition metal catalyst, and broad scope of substrates. By employing this method, 30 nucleoside analogues were prepared in moderate yields. Biological studies on these C5-(isoxazol-3-yl)-pyrimidine nucleosides showed that most of them exhibited significant in vitro antileishmanial activity.


Assuntos
Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Leishmania donovani/efeitos dos fármacos , Nucleosídeos de Pirimidina/síntese química , Nucleosídeos de Pirimidina/farmacologia , Animais , Antiprotozoários/química , Desenho de Fármacos , Humanos , Isoxazóis/síntese química , Isoxazóis/química , Isoxazóis/farmacologia , Leishmaniose/tratamento farmacológico , Nucleosídeos de Pirimidina/química , Relação Estrutura-Atividade
16.
Wound Repair Regen ; 22(5): 631-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24898474

RESUMO

Peritoneal adhesions are fibrous tissues formed after surgery. Both cytokines and transforming growth factors (TGFs) are involved in this process. The objective of this study was to investigate the cross talk between these entities. Peritoneal drainage fluid after surgery from patients and rodent models was examined by enzyme-linked immunosorbent assay and fluorescence-activated cell sorter. Data showed that the concentrations of interferon (IFN)-γ and interleukin (IL)-17 reached their peaks 6-12 hours after surgery, whereas TGF-ß1 concentrations showed two postoperative peak time points at 2 and 72-96 hours. By neutralizing IFN-γ, IL-17 6-12 hours, and TGF-ß1 72-96 hours after surgery, the degree of adhesion reduced significantly. However, neutralizing TGF-ß1 2 hours after surgery did not affect adhesion formation. Furthermore, in vitro studies showed that compared with the fibroblasts that were directly stimulated with TGF-ß1, the prestimulation of IL-17 promoted plasminogen activator inhibitor-1 production while inhibiting tissue-type plasminogen activator production. Moreover, additional stimulation with IFN-γ enhanced this effect. Together, these data indicate that IL-17 may promote adhesion formation by increasing the reaction of fibroblasts against TGF-ß1. Blocking IL-17 might have a therapeutic potential in preventing adhesion formation after surgery.


Assuntos
Interferon gama/imunologia , Interleucina-17/imunologia , Doenças Peritoneais/imunologia , Linfócitos T/imunologia , Fator de Crescimento Transformador beta1/imunologia , Adulto , Idoso , Animais , Colectomia/efeitos adversos , Feminino , Fibroblastos/metabolismo , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Células NIH 3T3 , Doenças Peritoneais/etiologia , Serpina E2/metabolismo , Transdução de Sinais/imunologia , Aderências Teciduais/etiologia , Aderências Teciduais/imunologia , Ativador de Plasminogênio Tecidual/metabolismo
17.
Anal Chim Acta ; 1309: 342699, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38772652

RESUMO

Extracellular vesicles (EVs) are cell-released, nucleus-free particles with a double-membrane structure that effectively prevents degradation of internal components by a variety of salivary enzymes. Saliva is an easily accessible biofluid that contains a wealth of valuable information for disease diagnosis and monitoring and especially reflect respiratory and digestive tract diseases. However, the lack of efficient and high-throughput methods for proteomic analysis of salivary biomarkers poses a significant challenge. Herein, we designed a salivary EV amphiphile-dendrimer supramolecular probe (SEASP) array which enables efficient enrichment and in situ detection of EVs protein biomarkers. Detergent Tween-20 washing of SEASP arrays removes high abundance of heteroproteins from saliva well. This array shows good analytical performance in the linear range of 10 µL-150 µL (LOD = 0.4 µg protein, or 10 µL saliva), exhibiting a good recovery (80.0 %). Compared to ultracentrifugation (UC), this procedure provides simple and convenient access to high-purity EVs (1.3 × 109 particles per mg protein) with good physiological status and structure. Coupling with mass spectrometry based proteomic analysis, differentially expressed proteins as selected asthma biomarkers have been screened. Then, we validated the proteomics primary screening results through clinical samples (100 µL each) using the SEASP array. Utilizing the dual antibody fluorescence technology, SEASP enables the simultaneous high-throughput detection of two proteins. Therefore, the EVs marker protein CD81 could be used as an internal standard to normalize the number of EVs, which was stably expressed in EVs. Proteomics and array results suggested that HNRNPU (P = 4.9 * 10-6) and MUC5B (P = 4.7 * 10-11) are promising protein biomarkers for infantile asthma. HNRNPU and MUC5B may be associated with disease onset and subtypes. The SEASP arrays provide a significant advancement in the field of salivary biomarker. The array enables high-throughput in situ protein detection for highly viscous and complex biological samples. It provides a rapid, low-cost, highly specific screening procedure and experimental basis for early disease screening and diagnosis in the field of liquid biopsy.


Assuntos
Vesículas Extracelulares , Proteômica , Saliva , Saliva/química , Humanos , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Proteômica/métodos , Biomarcadores/análise , Ensaios de Triagem em Larga Escala , Asma/diagnóstico , Asma/metabolismo
18.
J Vis Exp ; (205)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38619279

RESUMO

Respiratory tract infections (RTIs) are among the most common problems in clinical settings. Rapid and accurate identification of bacterial pathogens will provide practical guidelines for managing and treating RTIs. This study describes a method for rapidly detecting bacterial pathogens that cause respiratory tract infections via multi-channel loop-mediated isothermal amplification (LAMP). LAMP is a sensitive and specific diagnostic tool that rapidly detects bacterial nucleic acids with high accuracy and reliability. The proposed method offers a significant advantage over traditional bacterial culturing methods, which are time-consuming and often require greater sensitivity for detecting low levels of bacterial nucleic acids. This article presents representative results of K. pneumoniae infection and its multiple co-infections using LAMP to detect samples (sputum, bronchial lavage fluid, and alveolar lavage fluid) from the lower respiratory tract. In summary, the multi-channel LAMP method provides a rapid and efficient means of identifying single and multiple bacterial pathogens in clinical samples, which can help prevent the spread of bacterial pathogens and aid in the appropriate treatment of RTIs.


Assuntos
Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Ácidos Nucleicos , Infecções Respiratórias , Humanos , Microfluídica , Reprodutibilidade dos Testes , Infecções Respiratórias/diagnóstico , Klebsiella pneumoniae
19.
Int J Biol Macromol ; 261(Pt 2): 129789, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38296127

RESUMO

Interactions between polysaccharides and ionic liquids (ILs) at the molecular level are essential to elucidate the dissolution and/or plasticization mechanism of polysaccharides. Herein, saccharide-based ILs (SILs) were synthesized, and cellulose membrane was soaked in different SILs to evaluate the interactions between SILs and cellulose macromolecules. The relevant results showed that the addition of SILs into cellulose can effectively reduce the intra- and/or inter-molecular hydrogen bonds of polysaccharides. Glucose-based IL showed the intensest supramolecular interactions with cellulose macromolecules compared to sucrose- and raffinose-based ILs. Two-dimensional correlation and perturbation-correlation moving window Fourier transform infrared techniques were for the first time used to reveal the dynamic variation of the supramolecular interactions between SILs and cellulose macromolecules. Except for the typical HO⋯H interactions of cellulose itself, stronger -Cl⋯HO hydrogen bonding interactions were detected in the specimen of SILs-modified cellulose membranes. Supramolecular interactions of -Cl⋯H, HO⋯H, C-Cl⋯H, and -C=O⋯H between SILs and cellulose macromolecules sequentially responded to the stimuli of temperature. This work provides a new perspective to understanding the interaction mechanism between polysaccharides and ILs, and an avenue to develop the next-generation ILs for dissolving or thermoplasticizing polysaccharide materials.


Assuntos
Líquidos Iônicos , Líquidos Iônicos/química , Imidazóis/química , Celulose/química , Polissacarídeos , Temperatura
20.
J Org Chem ; 78(7): 3262-70, 2013 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-23485094

RESUMO

A practical and efficient synthesis of pyrazolo[1,5-c]quinazolines and 5,6-dihydropyrazolo[1,5-c]quinazolines, including several spiro compounds, through copper-catalyzed tandem reaction of 5-(2-bromoaryl)-1H-pyrazoles with carbonyl compounds and aqueous ammonia under air has been developed. Compared with literature methods toward pyrazolo[1,5-c]quinazoline derivatives, the synthetic method reported in this paper has the advantages of readily available and inexpensive starting materials and reagents, broad scope of substrates, and mild reaction conditions.


Assuntos
Amônia/química , Cobre/química , Cetonas/química , Pirazóis/química , Quinazolinas/síntese química , Catálise , Estrutura Molecular , Pirazóis/síntese química , Quinazolinas/química , Água/química
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