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1.
Cell Biochem Funct ; 42(1): e3929, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38269504

RESUMO

Myeloid-derived suppressor cells (MDSC) are a group of immature inhibitory cells of bone marrow origin. Human γδ T cells (mainly Vγ9Vδ2 T cells) have emerged as dominant candidates for cancer immunotherapy because of their unique recognition pattern and broad killing activity against tumor cells. Intestinal mucosal intraepithelial lymphocytes are almost exclusively γδ T cells, so it plays an important role in inhibiting the development of colorectal cancer. In this study, we investigated the effects and molecular mechanism of human MDSC on anticolorectal cancer cells activity of Vγ9Vδ2 T cells. Our results suggested that MDSC can reduce the NKG2D expression of Vγ9Vδ2 T cells through direct cell-cell contact, which is associated with membrane-type transforming growth factor-ß. In contrast, MDSC can increase Vγ9Vδ2 T cells activation and production of IFN-γ, perforin, Granzyme B through direct cell-cell contact. This may be related to the upregulation of T-bet in Vγ9Vδ2 T cells by MDSC. However, MDSC had a dominant negative regulatory effect on the anticolorectal cancer cells activity of Vγ9Vδ2 T cells. Our study provides a theoretical basis for the immune regulatory function of human MDSC on γδ T cells. This will be conducive to the clinical development of a new antitumor therapy strategy.


Assuntos
Células Supressoras Mieloides , Neoplasias , Humanos , Linfócitos T , Ativação Linfocitária , Fator de Crescimento Transformador beta , Regulação para Cima
2.
Molecules ; 28(12)2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37375195

RESUMO

p-coumaric acid (p-CA), a common plant phenolic acid with multiple bioactivities, has a lipid-lowering effect. As a dietary polyphenol, its low toxicity, with the advantages of prophylactic and long-term administration, makes it a potential drug for prophylaxis and the treatment of nonalcoholic fatty liver disease (NAFLD). However, the mechanism by which it regulates lipid metabolism is still unclear. In this study, we studied the effect of p-CA on the down-regulation of accumulated lipids in vivo and in vitro. p-CA increased a number of lipase expressions, including hormone-sensitive lipase (HSL), monoacylglycerol lipase (MGL) and hepatic triglyceride lipase (HTGL), as well as the expression of genes related to fatty acid oxidation, including long-chain fatty acyl-CoA synthetase 1 (ACSL1), carnitine palmitoyltransferase-1 (CPT1), by activating peroxisome proliferator-activated receptor α, and γ (PPARα and γ). Furthermore, p-CA promoted adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and enhanced the expression of the mammalian suppressor of Sec4 (MSS4), a critical protein that can inhibit lipid droplet growth. Thus, p-CA can decrease lipid accumulation and inhibit lipid droplet fusion, which are correlated with the enhancement of liver lipases and genes related to fatty acid oxidation as an activator of PPARs. Therefore, p-CA is capable of regulating lipid metabolism and is a potential therapeutic drug or health care product for hyperlipidemia and fatty liver.


Assuntos
Lipólise , Hepatopatia Gordurosa não Alcoólica , Animais , Gotículas Lipídicas/metabolismo , Fígado/metabolismo , Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácidos Graxos/metabolismo , Lipídeos , Proteínas Quinases Ativadas por AMP/metabolismo , PPAR alfa/metabolismo , Mamíferos/metabolismo
3.
Fa Yi Xue Za Zhi ; 39(4): 393-398, 2023 Aug 25.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-37859479

RESUMO

OBJECTIVES: To explore the characteristics of postmortem examination, chemical examination and scene investigation of deaths caused by oral diphenidol hydrochloride poisoning, and so as to provide a reference for proper settlement and prevention of such deaths. METHODS: The data of 22 deaths caused by oral diphenidol hydrochloride poisoning in a city from January 2018 to August 2020 were collected, including case details, scene investigations, autopsies, chemical examinations and digital evidence. Thirty-one cases of deaths caused by oral diphenidol hydrochloride poisoning reported in previous literature were also collected. RESULTS: In the 53 oral diphenidol hydrochloride poisoning death cases, 50 cases were suicide, 2 cases were accidental, while 1 case was undetermined. Fifty-two cases were found in the medical records or crime scene investigation reports with doses ranging from 775 mg to 12 500 mg, and 23 deceased were detected with postmortem blood concentrations ranging from 2.71 mg/L to 83.1 mg/L. Clinical symptoms were recorded in 6 patients, including conscious disturbance and convulsion. Among the 45 cases which were performed with external examination, 23 cases autopsied. CONCLUSIONS: Most of the deceased of oral diphenidol hydrochloride poisoning were suicide. No significant correlation was found between dose and blood concentration through the retrospective analysis of cases.


Assuntos
Intoxicação , Suicídio , Humanos , Estudos Retrospectivos , Piperidinas , Autopsia
4.
Zhongguo Zhong Yao Za Zhi ; 47(3): 701-712, 2022 Feb.
Artigo em Zh | MEDLINE | ID: mdl-35178953

RESUMO

The effects of Jingui Shenqi Pills(Jingui) and Liuwei Dihuang Pills(Liuwei) which respectively tonify kidney Yang and kidney Yin on brain function have attracted great attention, while the differences of protein expression regulated by Jingui and Liuwei remain to be studied. This study explored the difference of protein expression profiles in the hippocampi of mice orally administrated with the two drugs for 7 days. The protein expression was quantified using LC-MS/MS. The results showed that among the 5 860 proteins tested, 151, 282 and 75 proteins responded to Jingui alone, Liuwei alone, and both drugs, respectively. The ratio of up-regulated proteins to down-regulated proteins was 1.627 in Jingui group while only 0.56 in Liuwei group. The proteins up-regulated by Jingui were mainly involved in membrane transport, synaptic vesicle cycle, serotonergic synapse, dopaminergic synapse and so on, suggesting that Jingui may play a role in promoting the transport of neurotransmitter in the nervous system. The proteins down-regulated by Liuwei were mainly involved in membrane transport, synapse, ion transport(potassium and sodium transport), neurotransmitter transport, innate and acquired immune responses, complement activation, inflammatory response, etc. In particular, Liuwei showed obvious down-regulation effect on the members of solute carrier(SLC) superfamily, which suggested that Liuwei had potential inhibitory effect on membrane excitation and transport. Finally, consistent results were obtained in the normal mouse and the mouse model with corticosterone-induced depressive-like behavior. This study provides an experimental basis for understanding the effect of Jingui and Liuwei on brain function from protein network.


Assuntos
Medicamentos de Ervas Chinesas , Hipocampo/efeitos dos fármacos , Proteoma/metabolismo , Animais , Cromatografia Líquida , Medicamentos de Ervas Chinesas/farmacologia , Hipocampo/metabolismo , Camundongos , Proteômica , Espectrometria de Massas em Tandem
5.
Fa Yi Xue Za Zhi ; 38(5): 625-639, 2022 Oct 25.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-36727180

RESUMO

The succession of microbiota is closely associated with several essential factors, including race, sex, health condition, lifestyle, postmortem interval, etc., and it has great potential application value in forensic medicine. This paper summarizes recent studies on the forensic applications of the microbiome, including individual identification, geographical feature identification, origin identification of the tissue or body fluid, and postmortem interval estimation, and introduces the current machine learning algorithms for microbiology research based on next-generation sequencing data. In addition, the current problems facing forensic microbiomics such as the extraction and preservation of samples, construction of standardization and database, ethical review and practical applicability are discussed. Future multi-omics studies are expected to explore micro ecosystems from a comprehensive and dynamic perspective, to promote the development of forensic microbiomics application.


Assuntos
Medicina Legal , Microbiota , Humanos , Autopsia , Microbiota/genética , Algoritmos , Sequenciamento de Nucleotídeos em Larga Escala , Mudanças Depois da Morte
6.
Pharm Biol ; 58(1): 1252-1262, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33332210

RESUMO

CONTEXT: Dexamethasone (DXM) has an anti-immunoinflammatory effect, and is often used in acute kidney injury (AKI). However, the effects of DXM on albumin (ALB) have not been fully studied. OBJECTIVE: To investigate the effects of DXM on ALB production and renal function. MATERIALS AND METHODS: Male Wistar rats were divided into normal and DXM groups (0.25, 0.5, 1 mg/kg for 5 days) (n = 15) for a dose-dependent study. Rats were divided into normal group and DXM groups (0.5 mg/kg for 3, 5, 7 days) (n = 9) for a time-dependent study. In AKI experiment, rats were divided into normal (saline), cisplatin (CP, 5 mg/kg, i.v.), CP + DXM groups (0.25, 0.5 and 1 mg/kg, i.m.) (n = 16). The blood and the organs were isolated for analysis. RESULTS: In normal, serum ALB (sALB) and serum total protein (sTP) increased in DXM group with sALB increased 19.8-32.2% (from small to large dosages); and 30.2-32.5.6% (from 3 to 7 days of DXM); sTP 15.7-22.6% and 14.2-24.3%; urine ALB (uALB) 31.5-392.3%, and 1047.2-1390.8%; urine TP (uTP) 0.68-173.1% and 98.0-504.9%, compared with normal groups. DXM increased the mRNA expression of Cebp and Hnf, suppressing podocin. In AKI, DXM decreased serum BUN (53.7%), serum Cre (73.4%), sALB (30.0%), sTP (18.7%), uALB (74.5%), uTP (449.3%), rescuing the suppressed podocin in kidney. CONCLUSIONS: DXM acts on Cebp and Hnf and promotes ALB production. This finding helps to evaluate the rationale of DXM for kidney injury.


Assuntos
Injúria Renal Aguda/metabolismo , Dexametasona/farmacologia , Albumina Sérica/biossíntese , Animais , Proteínas Sanguíneas/análise , Cisplatino/toxicidade , Relação Dose-Resposta a Droga , Elementos Facilitadores Genéticos/fisiologia , Rim/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
7.
Zhongguo Zhong Yao Za Zhi ; 45(20): 4909-4917, 2020 Oct.
Artigo em Zh | MEDLINE | ID: mdl-33350264

RESUMO

To establish the quantitative analysis multi-components with a single-marker(QAMS) method for six components and fingerprint of standard decoction of Gastrodiae Rhizoma, verify the accuracy and feasibility of the method, and evaluate the quality of standard decoction. Based on UPLC with gastrodin as the internal standard, relative correction factors of p-hydroxybenzyl alcohol, parishin E, parishin B, parishin C, parishin A and gastrodin were determined by investigating the column temperature, flow rate, chromatographic columns and multi-point concentration correction. The total contents in 18 batches of standard decoction of Gastrodiae Rhizoma and the similarity were determined to calculate the similarity. The results of standard curve method, external standard one-point method and quantitative analysis multi-components with a single-marker(QAMS) were compared, and the results showed that there was no significant difference among these three methods. By analyzing the results of standard decoctions from different origins, it can be seen that the quality of Gastrodia standard decoctions derived from Anhui and Yunnan was better, followed by Shaanxi and Hubei, and relatively poor in Gansu, with similarities all above 0.90 in the fingerprints. Therefore, the QAMS method that can measure the contents of gastrodin, p-hydroxybenzyl alcohol, parishin E, parishin B, parishin C and parishin A in standard decoction of Gastrodiae Rhizoma combined with fingerprint is accurate, feasible and fast, which can be used to evaluate the quality of standard decoction of Gastrodiae Rhizoma, and also provide a reference for the research on the quality standards of raw materials for Gastrodiae Rhizoma prepared slices and alike.


Assuntos
Medicamentos de Ervas Chinesas , Gastrodia , China , Cromatografia Líquida de Alta Pressão , Padrões de Referência , Rizoma
8.
J Pharmacol Exp Ther ; 370(3): 682-694, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30796131

RESUMO

Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer-related death in the United States, is highly aggressive and resistant to both chemo- and radiotherapy. It remains one of the most difficult-to-treat cancers, not only due to its unique pathobiological features such as stroma-rich desmoplastic tumors surrounded by hypovascular and hypoperfused vessels limiting the transport of therapeutic agents, but also due to problematic early detection, which renders most treatment options largely ineffective, resulting in extensive metastasis. To elevate therapeutic effectiveness of treatments and overt their toxicity, significant enthusiasm was generated to exploit new strategies for combating PDAC. Combination therapy targeting different barriers to mitigate delivery issues and reduce tumor recurrence and metastasis has demonstrated optimal outcomes in patients' survival and quality of life, providing possible approaches to overcome therapeutic challenges. This paper aims to provide an overview of currently explored multimodal therapies using either conventional therapy or nanomedicines along with rationale, up-to-date progress, as well as the key challenges that must be overcome. Understanding the future directions of the field may assist in the successful development of novel treatment strategies for enhancing therapeutic efficacy in PDAC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada/métodos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Pancreáticas/terapia , Animais , Humanos , Nanomedicina/métodos , Nanomedicina/tendências , Metástase Neoplásica , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/tratamento farmacológico
9.
J Pharmacol Exp Ther ; 370(3): 894-901, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30683666

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. A combination of cisplatin (CDDP) and gemcitabine (Gem) treatment has shown favorable clinical results for metastatic disease; both are limited by toxicities and nontargeted delivery. More than 80% of PDAC aberrantly expresses the sialyl Tn (STn) antigen due to the loss of function of the core 1ß3-Gal-T-specific molecular chaperone, a specific chaperone for the activity of core 1 ß3-galactosyltransferase or C1GalT. Here, we report the development of polymeric nanogels (NGs) loaded with CDDP and coated with an anti-STn antigen-specific antibody (TKH2 monoclonal antibody) for the targeted treatment of PDAC. TKH2-functionalized, CDDP-loaded NGs delivered a significantly higher amount of platinum into the cells and tumors expressing STn antigens. We also confirmed that a synergistic cytotoxic effect of sequential exposure of pancreatic cancer cells to Gem followed by CDDP can be mimicked by the codelivery of CDDP-loaded NGs (NG/CDDP) and free Gem. In a murine orthotopic model of PDAC, combined simultaneous treatment with Gem and targeted NG/CDDP significantly attenuated tumor growth with no detectable acute toxicity. Altogether, these results suggest that combination therapy consisting of Gem followed by TKH2-conjugated CDDP NGs induces highly synergistic therapeutic efficacy against pancreatic cancer. Our results offer the basis for development of combination drug regimens using targeted nanomedicines to increase treatment effectiveness and improve outcomes of PDAC therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Sinergismo Farmacológico , Géis , Humanos , Camundongos , Camundongos Nus , Nanoestruturas , Platina/metabolismo , Polímeros/química , Gencitabina
10.
Toxicol Appl Pharmacol ; 368: 26-36, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30776389

RESUMO

Cardiac dysfunction is a vital complication during endotoxemia (ETM). Accumulating evidence suggests that enhanced glycolytic metabolism promotes inflammatory and myocardial diseases. In this study, we performed deep mRNA sequencing analysis on the hearts of control and lipopolysaccharide (LPS)-challenged mice (40 mg/kg, i.p.) and identified that the glycolytic enzyme, 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase 3 (PFKFB3) might play an indispensable role in ETM-induced cardiac damage. Quantitative real-time PCR validated the transcriptional upregulation of PFKFB3 in the myocardium of LPS-challenged mice and immunoblotting and immunostaining assays confirmed that LPS stimulation markedly increased the expression of PFKFB3 at the protein level both in vivo and in vitro. The potent antagonist 3-(3pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) was used to block PFKFB3 activity in vivo (50 mg/kg, i.p.) and in vitro (10 µM). Echocardiographic analysis and TUNEL staining showed that 3PO significantly alleviated LPS-induced cardiac dysfunction and apoptotic injury in vivo. 3PO also suppressed the LPS-induced secretion of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6 and lactate in the serum, in addition to lactate in the myocardium. PFKFB3 inhibition also diminished the nuclear translocation and phosphorylation of transcription factor nuclear factor-κB (NF-κB) in both adult cardiomyocytes and HL-1 cells. Furthermore, immunoblotting analysis showed that 3PO inhibited LPS-induced apoptotic induction in cardiomyocytes. Taken together, these findings demonstrate that PFKFB3 participates in LPS-induced cardiac dysfunction via mediating inflammatory and apoptotic signaling pathway.


Assuntos
Apoptose , Endotoxemia/enzimologia , Cardiopatias/enzimologia , Mediadores da Inflamação/metabolismo , Miócitos Cardíacos/enzimologia , Fosfofrutoquinase-2/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Endotoxemia/induzido quimicamente , Endotoxemia/patologia , Endotoxemia/prevenção & controle , Inibidores Enzimáticos/farmacologia , Regulação Enzimológica da Expressão Gênica , Cardiopatias/induzido quimicamente , Cardiopatias/patologia , Cardiopatias/prevenção & controle , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Fosfofrutoquinase-2/antagonistas & inibidores , Fosfofrutoquinase-2/genética , Piridinas/farmacologia , Transdução de Sinais
11.
Cell Mol Life Sci ; 75(21): 4021-4040, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29916093

RESUMO

Mitochondrial intracrines are extracellular signaling proteins, targeted to the mitochondria. The pathway for mitochondrial targeting of mitochondrial intracrines and actions in the mitochondria remains unknown. Megalin/LRP2 mediates the uptake of vitamins and proteins, and is critical for clearance of amyloid-ß protein from the brain. Megalin mutations underlie the pathogenesis of Donnai-Barrow and Lowe syndromes, characterized by brain defects and kidney dysfunction; megalin was not previously known to reside in the mitochondria. Here, we show megalin is present in the mitochondria and associates with mitochondrial anti-oxidant proteins SIRT3 and stanniocalcin-1 (STC1). Megalin shuttles extracellularly-applied STC1, angiotensin II and TGF-ß to the mitochondria through the retrograde early endosome-to-Golgi transport pathway and Rab32. Megalin knockout in cultured cells impairs glycolytic and respiratory capacities. Thus, megalin is critical for mitochondrial biology; mitochondrial intracrine signaling is a continuum of the retrograde early endosome-to-Golgi-Rab32 pathway and defects in this pathway may underlie disease processes in many systems.


Assuntos
Peptídeos beta-Amiloides/genética , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Mitocôndrias/genética , Proteínas rab de Ligação ao GTP/genética , Agenesia do Corpo Caloso/genética , Agenesia do Corpo Caloso/metabolismo , Agenesia do Corpo Caloso/patologia , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Membrana Celular/genética , Glicoproteínas/genética , Células HEK293 , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/metabolismo , Perda Auditiva Neurossensorial/patologia , Hérnias Diafragmáticas Congênitas/genética , Hérnias Diafragmáticas Congênitas/metabolismo , Hérnias Diafragmáticas Congênitas/patologia , Humanos , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Camundongos , Mitocôndrias/metabolismo , Miopia/genética , Miopia/metabolismo , Miopia/patologia , Síndrome Oculocerebrorrenal/genética , Síndrome Oculocerebrorrenal/metabolismo , Síndrome Oculocerebrorrenal/patologia , Proteinúria/genética , Proteinúria/metabolismo , Proteinúria/patologia , Células RAW 264.7 , Erros Inatos do Transporte Tubular Renal/genética , Erros Inatos do Transporte Tubular Renal/metabolismo , Erros Inatos do Transporte Tubular Renal/patologia , Transdução de Sinais , Sirtuína 3/genética , Fator de Crescimento Transformador beta/genética , Proteínas rab de Ligação ao GTP/metabolismo
12.
Cell Mol Life Sci ; 74(6): 1117-1131, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27783096

RESUMO

Nuclear paraspeckle assembly transcript 1 (NEAT1) is the crucial structural platform of paraspeckles, which is one type of nuclear bodies. As a stress-induced lncRNA, the expression of NEAT1 increases in response to viral infection, but little is known about the role of NEAT1 or paraspeckles in the replication of herpes simplex virus-1 (HSV-1). Here, we demonstrate that HSV-1 infection increases NEAT1 expression and paraspeckle formation in a STAT3-dependent manner. NEAT1 and other paraspeckle protein components, P54nrb and PSPC1, can associate with HSV-1 genomic DNA. By binding with STAT3, PSPC1 is required for the recruitment of STAT3 to paraspeckles and facilitates the interaction between STAT3 and viral gene promoters, finally increasing viral gene expression and viral replication. Furthermore, thermosensitive gel containing NEAT1 siRNA or STAT3 siRNA effectively healed the skin lesions caused by HSV-1 infection in mice. Our results provide insight into the roles of lncRNAs in the epigenetic control of viral genes and into the function of paraspeckles.


Assuntos
Genes Virais , Herpesvirus Humano 1/fisiologia , RNA Longo não Codificante/metabolismo , Transcrição Gênica , Replicação Viral/genética , Animais , Sequência de Bases , Proteínas de Ligação a DNA , Regulação Viral da Expressão Gênica , Células HeLa , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Humanos , Corpos de Inclusão Intranuclear/metabolismo , Camundongos , Proteínas Associadas à Matriz Nuclear/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição de Octâmero/metabolismo , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/metabolismo , Fator de Transcrição STAT3/metabolismo
13.
Molecules ; 23(11)2018 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-30423891

RESUMO

Insulin injection relies on strict blood glucose monitoring. However, existing techniques and algorithms for blood glucose monitoring cannot be completed in a timely way. In this study, we have developed a new intelligent glucose-sensitive insulin delivery system to stabilize blood glucose levels in the body. This system does not require real-time detection of blood glucose. First, we successfully synthesized a nanoscale material called PAM-PAspPBA-b-PEG by using chemical methods. We then conducted TEM, DLS, and ¹H-NMR analyses to characterize the physicochemical properties, such as size, molecular composition, and configuration of the nanomaterial. We verified the glucose responsibility of the insulin loading nanoscale material in vitro and evaluated its safety and effect on mice in vivo. Results showed that insulin-loaded PAM-PAspPBA-b-PEG is glucose-sensitive, safer and more effective than regular insulin injection. This study provides a basis for future development of smart insulin delivery systems.


Assuntos
Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Insulina/administração & dosagem , Nanopartículas , Glicemia/efeitos dos fármacos , Ácidos Borônicos/química , Dendrímeros , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Insulina/química , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Peptídeos/química , Poliaminas/química
14.
Molecules ; 23(8)2018 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-30060618

RESUMO

Obesity and nonalcoholic fatty liver disease (NAFLD) are highly prevalent and cause numerous metabolic diseases. However, drugs for the prevention and treatment of obesity and NAFLD remain unavailable. In this study, we investigated the effects of mogrosides (luo han guo, LH) in Siraitia grosvenorii saponins on high-fat-diet-induced obesity and NAFLD in mice. We found that compared with the negative control, LH reduced body and liver weight. LH also decreased fat accumulation and increased AMP-activated protein kinase (AMPK) phosphorylation (pAMPK) levels in mouse livers. We also found that high-purity mogroside V upregulated pAMPK expression in HepG2 cells. In addition, high-purity mogroside V inhibited reactive oxygen species production and upregulated sequestosome-1 (SQSTM1, p62) expression in THP-1 cells. These results suggest that LH may affect obesity and NAFLD by enhancing fat metabolism and antioxidative defenses. Mogroside V may be a main component of LH. However, the exact molecular mechanisms and active components responsible for the inhibitory effects of LH on obesity and NAFLD require further investigation.


Assuntos
Fármacos Antiobesidade/farmacologia , Anticolesterolemiantes/farmacologia , Momordica/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Triterpenos/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Anticolesterolemiantes/química , Anticolesterolemiantes/isolamento & purificação , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/patologia , Tamanho do Órgão/efeitos dos fármacos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Saponinas/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Proteína Sequestossoma-1/agonistas , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Células THP-1 , Triterpenos/química , Triterpenos/isolamento & purificação
15.
Zhongguo Zhong Yao Za Zhi ; 39(19): 3876-80, 2014 Oct.
Artigo em Zh | MEDLINE | ID: mdl-25612458

RESUMO

Rheum franzenbachii (called Tudahuang in local) has some similarities with R. palmatum (rhubarb) collected by "China Pharmacopoeia" and is often used as a substitute of rhubarb. Can Tudahuang simply replace rhubarb in the application or whether is there difference between Tudahuang and rhubarb, and what is the difference it is important to verify the difference and understand its proper application in the field of clinical practice. In this paper, we discussed the differences of the two herbs from the views of chemistry, efficacy and toxicity based on the author's previous research work as well as literatures, by using the major role of the rhubarb "diarrhea" as the basic point. The analysis result showed that the role of diarrhea Tudahuang was much weaker than that of rhubarb. The reason lies in the difference between the contents of combined anthraquinones component. While acute toxicity in mice of Tudahuang is stronger than that of rhubarb. Thus, Tudahuang should not simply replace rhubarb in practice.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/toxicidade , Rheum/química , Animais , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Camundongos , Rheum/efeitos adversos
16.
Zhongguo Zhong Yao Za Zhi ; 39(16): 3142-7, 2014 Aug.
Artigo em Zh | MEDLINE | ID: mdl-25509303

RESUMO

Pineapple (Ananas comosus) leaves contain mainly phenolic components with antioxidant and hypolipidemic effects. One of the principle components is p-coumaric acid. In this study, the transport behavior of p-coumaric acid, was observed after the administration of pineapple leaf phenols in vitro. Simultaneously, the effect of the phenols on glucose, total cholesterol and triglycerides transportation and metabolism in HepG2 cells was also observed. The results showed that the phenols had good transport characteristics. 5 min after the administration, p-coumaric acid of the phenols could be detected, and the content of p-coumaric acid reached the peak concentration after 60 min of the administration. p-coumaric acid of phenols have time-and dose-dependent manner. While promoting glucose transporter (GLUT4) and low density lipoprotein receptor (LDLR) expression, the phenols decreased intracellular lipid content. This reduction of intracellular lipid content was highly correlated with the promotion of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) expression, while the reduction of intracellular glucose levels was correlated with glycogen synthesis in the cells.


Assuntos
Glucose/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Ananas/química , Transporte Biológico/efeitos dos fármacos , Colesterol/metabolismo , Células Hep G2 , Humanos
17.
IEEE Trans Vis Comput Graph ; 30(2): 1592-1607, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37801373

RESUMO

Visualization linting is a proven effective tool in assisting users to follow established visualization guidelines. Despite its success, visualization linting for choropleth maps, one of the most popular visualizations on the internet, has yet to be investigated. In this paper, we present GeoLinter, a linting framework for choropleth maps that assists in creating accurate and robust maps. Based on a set of design guidelines and metrics drawing upon a collection of best practices from the cartographic literature, GeoLinter detects potentially suboptimal design decisions and provides further recommendations on design improvement with explanations at each step of the design process. We perform a validation study to evaluate the proposed framework's functionality with respect to identifying and fixing errors and apply its results to improve the robustness of GeoLinter. Finally, we demonstrate the effectiveness of the GeoLinter - validated through empirical studies - by applying it to a series of case studies using real-world datasets.

18.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167158, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38588780

RESUMO

OBJECTIVES: Diabetic cardiomyopathy (DCM) is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients, with its underlying mechanisms still elusive. This study aims to investigate the role of cholesterol-25-monooxygenase (CH25H) in T2DM induced cardiomyopathy. METHODS: High fat diet combined with streptozotocin (HFD/STZ) were used to establish a T2DM model. CH25H and its product 25-hydroxycholesterol (25HC) were detected in the hearts of T2DM model. Gain- or loss-of-function of CH25H were performed by receiving AAV9-cTNT-CH25H or CH25H knockout (CH25H-/-) mice with HFD/STZ treatment. Cardiac function was evaluated using echocardiography, and cardiac tissues were collected for immunoblot analysis, histological assessment and quantitative polymerase chain reaction (qPCR). Mitochondrial morphology and function were evaluated using transmission electron microscopy (TEM) and Seahorse XF Cell Mito Stress Test Kit. RNA-sequence analysis was performed to determine the molecular changes associated with CH25H deletion. RESULTS: CH25H and 25HC were significantly decreased in the hearts of T2DM mice. CH25H-/- mice treated with HFD/STZ exhibited impaired mitochondrial function and structure, increased lipid accumulation, and aggregated cardiac dysfunction. Conversely, T2DM mice receiving AAV9-CH25H displayed cardioprotective effects. Mechanistically, RNA sequencing and qPCR analysis revealed that CH25H deficiency decreased peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and its target gene expression. Additionally, administration of ZLN005, a potent PGC-1α activator, partially protected against high glucose and palmitic acid induced mitochondria dysfunction and lipid accumulation in vitro. CONCLUSION: Our study provides compelling evidence supporting the protective role of CH25H in T2DM-induced cardiomyopathy. Furthermore, the regulation of PGC-1α may be intricately involved in this cardioprotective process.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Cardiomiopatias Diabéticas , Camundongos Knockout , Animais , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/prevenção & controle , Cardiomiopatias Diabéticas/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Camundongos , Masculino , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Esteroide Hidroxilases/metabolismo , Esteroide Hidroxilases/genética , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Hidroxicolesteróis/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética
19.
IEEE Trans Vis Comput Graph ; 30(1): 1391-1401, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37883268

RESUMO

Geographic regression models of various descriptions are often applied to identify patterns and anomalies in the determinants of spatially distributed observations. These types of analyses focus on answering why questions about underlying spatial phenomena, e.g., why is crime higher in this locale, why do children in one school district outperform those in another, etc.? Answers to these questions require explanations of the model structure, the choice of parameters, and contextualization of the findings with respect to their geographic context. This is particularly true for local forms of regression models which are focused on the role of locational context in determining human behavior. In this paper, we present GeoExplainer, a visual analytics framework designed to support analysts in creating explanative documentation that summarizes and contextualizes their spatial analyses. As analysts create their spatial models, our framework flags potential issues with model parameter selections, utilizes template-based text generation to summarize model outputs, and links with external knowledge repositories to provide annotations that help to explain the model results. As analysts explore the model results, all visualizations and annotations can be captured in an interactive report generation widget. We demonstrate our framework using a case study modeling the determinants of voting in the 2016 US Presidential Election.

20.
Zhongguo Zhong Yao Za Zhi ; 38(16): 2639-44, 2013 Aug.
Artigo em Zh | MEDLINE | ID: mdl-24228579

RESUMO

Activation pattern recognition receptors can cause the startup of downstream signaling pathways, the expression of inflammatory factors, and finally immunological inflammatory reaction. Either exogenous pathogenic microorganisms or endogenous tissue components can activate these pattern recognition receptors as ligands at varying degrees, and then cause the immunological inflammatory reaction. Therefore, it is of great significance to inhibit relevant receptors, as well as the immunological inflammatory reaction, in order to avoid tissue injury during the course of disease. Baicalin is able to specifically inhibit the expression of TLR2/4-NOD2, inhibit the expression of inflammatory factors IL-1beta, IL-6 and TNF-alpha, and thereby reducing the injury of the tissue cells during the course of disease. This effect is non-specific with tissues, which is of great theoretical and practical significance in druggability. In addition, the drug metabolism and toxicity of baicalin are also discussed for its druggability in this article.


Assuntos
Flavonoides/farmacologia , Proteína Adaptadora de Sinalização NOD2/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Humanos
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