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1.
BMC Med Genomics ; 17(1): 99, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38650009

RESUMO

RESEARCH BACKGROUND AND PURPOSE: Osteoporosis (OP) is one of the most common bone diseases worldwide, characterized by low bone mineral density and susceptibility to pathological fractures, especially in postmenopausal women and elderly men. Ferroptosis is one of the newly discovered forms of cell death regulated by genes in recent years. Many studies have shown that ferroptosis is closely related to many diseases. However, there are few studies on ferroptosis in osteoporosis, and the mechanism of ferroptosis in osteoporosis is still unclear. This study aims to identify biomarkers related to osteoporosis ferroptosis from the GEO (Gene Expression Omnibus) database through bioinformatics technology, and to mine potential therapeutic small molecule compounds through molecular docking technology, trying to provide a basis for the diagnosis and treatment of osteoporosis in the future. MATERIALS AND METHODS: We downloaded the ferroptosis-related gene set from the FerrDb database ( http://www.zhounan.org/ferrdb/index.html ), downloaded the data sets GSE56815 and GSE7429 from the GEO database, and used the R software "limma" package to screen differentially expressed genes (DEGs) from GSE56815, and intersected with the ferroptosis gene set to obtain ferroptosis-related DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed by the R software "clusterProfiler" package. The random forest model was further screened to obtain essential ferroptosis genes. R software "corrplot" package was used for correlation analysis of essential ferroptosis genes, and the Wilcox test was used for significance analysis. The lncRNA-miRNA-mRNA-TF regulatory network was constructed using Cytoscape software. The least absolute shrinkage and selection operator (LASSO) was used to construct a disease diagnosis model, and a Receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic performance, and then GSE7429 was used to verify the reliability of the diagnosis model. Molecular docking technology was used to screen potential small molecule compounds from the Drugbank database. Finally, a rat osteoporosis model was constructed, and peripheral blood mononuclear cells were extracted for qRT-PCR detection to verify the mRNA expression levels of crucial ferroptosis genes. RESULT: Six DEGs related to ferroptosis were initially screened out. GO function and KEGG pathway enrichment analysis showed that ferroptosis-related DEGs were mainly enriched in signaling pathways such as maintenance of iron ion homeostasis, copper ion binding function, and ferroptosis. The random forest model identified five key ferroptosis genes, including CP, FLT3, HAMP, HMOX1, and SLC2A3. Gene correlation analysis found a relatively low correlation between these five key ferroptosis genes. The lncRNA-miRNA-mRNA-TF regulatory network shows that BAZ1B and STAT3 may also be potential molecules. The ROC curve of the disease diagnosis model shows that the model has a good diagnostic performance. Molecular docking technology screened out three small molecule compounds, including NADH, Midostaurin, and Nintedanib small molecule compounds. qRT-PCR detection confirmed the differential expression of CP, FLT3, HAMP, HMOX1 and SLC2A3 between OP and normal control group. CONCLUSION: This study identified five key ferroptosis genes (CP, FLT3, HAMP, HMOX1, and SLC2A3), they were most likely related to OP ferroptosis. In addition, we found that the small molecule compounds of NADH, Midostaurin, and Nintedanib had good docking scores with these five key ferroptosis genes. These findings may provide new clues for the early diagnosis and treatment of osteoporosis in the future.


Assuntos
Biologia Computacional , Ferroptose , Simulação de Acoplamento Molecular , Osteoporose , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Osteoporose/tratamento farmacológico , Osteoporose/genética , Biologia Computacional/métodos , Humanos , Animais , Biomarcadores/metabolismo , Ratos , Ontologia Genética , Perfilação da Expressão Gênica
2.
J Hazard Mater ; 470: 134269, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38613952

RESUMO

Mercury (Hg) is one of the most widespread pollutants that pose serious threats to public health and the environment. People are inevitably exposed to Hg via different routes, such as respiration, dermal contact, drinking or diet. Hg poisoning could cause gingivitis, inflammation, vomiting and diarrhea, respiratory distress or even death. Especially during the developmental stage, there is considerable harm to the brain development of young children, causing serious symptoms such as intellectual disability and motor impairments, and delayed neural development. Therefore, it's of great significance to develop a specific, quick, practical and labor-saving assay for monitoring Hg2+. Herein, a mitochondria-targeted dual (excitation 700 nm and emission 728 nm) near-infrared (NIR) fluorescent probe JZ-1 was synthesized to detect Hg2+, which is a turn-on fluorescent probe designed based on the rhodamine fluorophore thiolactone, with advantages of swift response, great selectivity, and robust anti-interference capability. Cell fluorescence imaging results showed that JZ-1 could selectively target mitochondria in HeLa cells and monitor exogenous Hg2+. More importantly, JZ-1 has been successfully used to monitor gastrointestinal damage of acute mercury poisoning in a drug-induced mouse model, which provided a great method for sensing Hg species in living subjects, as well as for prenatal diagnosis.


Assuntos
Corantes Fluorescentes , Intoxicação por Mercúrio , Mercúrio , Mitocôndrias , Corantes Fluorescentes/química , Mitocôndrias/efeitos dos fármacos , Humanos , Animais , Células HeLa , Intoxicação por Mercúrio/diagnóstico por imagem , Mercúrio/toxicidade , Imagem Óptica , Camundongos , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/diagnóstico por imagem , Trato Gastrointestinal/metabolismo , Feminino , Gastroenteropatias/diagnóstico por imagem , Gastroenteropatias/induzido quimicamente , Rodaminas/química , Rodaminas/toxicidade
3.
Eur J Pharmacol ; 966: 176352, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38290567

RESUMO

BACKGROUND: Curcumin nicotinate (Curtn), derived from curcumin and niacin, reduces serum LDL-C levels, partly due to its influence on PCSK9. This study investigates IDOL's role in Curtn's lipid-lowering effects. OBJECTIVE: To elucidate Curtn's regulation of the IDOL/LDLR pathway and potential molecular mechanisms in hepatocytes. METHODS: Differential metabolites in Curtn-treated HepG2 cells were identified via LC-MS. Molecular docking assessed Curtn's affinity with IDOL. Cholesterol content and LDLR expression effects were studied in high-fat diet Wistar rats. In vitro evaluations determined Curtn's influence on IDOL overexpression's LDL-C uptake and LDLR expression in hepatocytes. RESULTS: Lipids were the main differential metabolites in Curtn-treated HepG2 cells. Docking showed Curtn's higher affinity to IDOL's FERM domain compared to curcumin, suggesting potential competitive inhibition of IDOL's binding to LDLR. Curtn decreased liver cholesterol in Wistar rats and elevated LDLR expression. During in vitro experiments, Curtn significantly enhanced the effects of IDOL overexpression in HepG2 cells, leading to increased LDL-C uptake and elevated expression of LDL receptors. CONCLUSION: Curtn modulates the IDOL/LDLR pathway, enhancing LDL cholesterol uptake in hepatocytes. Combined with its PCSK9 influence, Curtn emerges as a potential hyperlipidemia therapy.


Assuntos
Curcumina , Curcumina/análogos & derivados , Niacina/análogos & derivados , Pró-Proteína Convertase 9 , Ratos , Animais , LDL-Colesterol , Curcumina/farmacologia , Ratos Wistar , Simulação de Acoplamento Molecular , Ubiquitina-Proteína Ligases/metabolismo , Hepatócitos/metabolismo , Receptores de LDL/metabolismo , Colesterol , Lipoproteínas LDL/metabolismo
4.
Food Chem ; 440: 138240, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38150907

RESUMO

As ubiquitous components among fruits, polyphenols, including flavonoids and phenolic acids, are somewhat embarrassed on their health benefits but low bioavailability, triggering a hotspot on their interaction with microbiota. Due to its structural characteristics similar to flavonoids and phenolic acids, dihydrochalcone phlorizin (PHZ) was selected as a reference, to illustrate its step-by-step metabolic fate associated with microbiota. The results confirmed that the metabolic flux of PHZ starts with its conversion to phloretin (PHT), sequentially followed by the formation of 3-(4-hydroxyphenyl) propionic acid (PHA), and 4-hydroxyphenylacetic acid (4-HPAA). Catabolic characteristics was comparatively elucidated by introducing apparent and potential kinetics. Besides, coupling catabolic processes with microbial changes suggested several potential bacteria involving in PHZ metabolism, as well as those regulated by PHZ and its metabolites. In particular, seven strains from Lactobacillus were selectively isolated and confirmed to be essential for deglycosylation of PHZ, implying a potential synergistic effect between PHZ and Lactobacillus.


Assuntos
Microbioma Gastrointestinal , Hidroxibenzoatos , Florizina , Prebióticos , Polifenóis/metabolismo , Flavonoides/metabolismo
5.
Org Biomol Chem ; 21(45): 8975-8978, 2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-37933470

RESUMO

Laccase from Trametes versicolor was found to oxidize non-phenolic arenes and enable the trifluoromethylation of arenes in the presence of in situ generated CF3 radicals at a catalyst loading as low as 0.0034%. The biocatalytic trifluoromethylation proceeded under mild conditions and could increase the yield by up to 12 fold, compared to the control.


Assuntos
Lacase , Trametes , Lacase/metabolismo , Trametes/metabolismo , Catálise , Biocatálise
6.
Huan Jing Ke Xue ; 44(10): 5727-5736, 2023 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-37827788

RESUMO

Cadmium (Cd) contamination of paddy fields is a global concern, as it can cause the accumulation of Cd in food. To explore the effects of equal application of silicon fertilizers on the bioavailability of cadmium and soil Cd uptake at different growth stages of rice, a field experiment was conducted with five silicon fertilizers under the same silicon dose (225 kg·hm-2). The results revealed that the Cd contents in roots, stems, and leaves increased with the extension of the rice growth stage. The application of silicon fertilizers reduced the Cd contents in roots, stems, and leaves in brown rice by 14.9%, 28.2%, and 12.2%, respectively. Compared with that in the control, the Cd content of brown rice in the SiCaMgFe and SiW treatments was decreased by 21.1% (P<0.05) and 21.2% (P<0.05), respectively. Similarly, Cd content in iron plaque (DCB-Cd) increased with the extension of the rice growth period, which accounted for 15.8%-42.8% of the total Cd content in roots, and the DCB-Cd content was different in each stage of rice. The content of exchangeable Cd (Exc-Cd) in soil at the mature stage of rice decreased by 36.4%, and the other fractions increased by 12.5%-48.2%. The results showed significant negative correlations between the Cd contents and Si in roots, DCB-Cd and soil available Cd and available Si, Exc-Cd and Car-Cd, and soil available Cd and pH value. Cd content in roots was positively correlated with DCB-Cd. With the equal dose of silicon fertilizer, the treatments of SiCaMgFe and SiW could effectively reduce the Cd content in rice. The application of silicon fertilizer promoted the transfer of Exc-Cd to Carb-Cd by increasing the soil pH value and the soil available Si content, meanwhile reducing the soil available Cd, Exc-Cd contents, the adsorption of Cd by the iron film on the root surface, and the adsorption capacity of iron plaque and root, thereby reducing the absorption of Cd by rice.


Assuntos
Oryza , Poluentes do Solo , Cádmio/análise , Fertilizantes/análise , Solo/química , Silício , Disponibilidade Biológica , Poluentes do Solo/análise , Ferro
7.
Nutrients ; 15(17)2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37686740

RESUMO

Unhealthy diets rich in fats and/or sugar are considered as the major external cause of the obesity epidemic, which is often accompanied by a significant decrease in gut hormone glucagon-like peptide-1 (GLP1) levels. Numerous studies have demonstrated notable contributions of the gut microbiota in this process. Nevertheless, the underlying mechanism still needs further investigation. The role of epigenetic modifications in gene expression and metabolism has been well demonstrated, with m6A methylation on RNAs being the most prevalent modification throughout their metabolism. In the present study, we found that the expressions of small intestinal Gcg and Pc3, two key genes regulating GLP1 expression, were significantly downregulated in obese mice, associated with reduced GLP1 level. Immunohistochemistry analysis indicated that a high-fat diet slightly increased the density of enteroendocrine L cells in the small intestine, implying that decreased GLP1 levels were not caused by the changes in L cell intensity. Instead, the small intestinal m6A level as well as the expression of known "writers", mettl3/14 and wtap, were found to be positively correlated with the expression of Gcg and Pc3. Fecal microbiota transplantation with feces from normal and obese mice daily to antibiotic-treated mice revealed that dysbiosis in diet-induced obesity was sufficient to reduce serum GLP1, small intestinal m6A level, and intestinal expressions of Gcg, Pc3, and writer genes (mettl3/14, wtap). However, as the most direct and universal methyl donor, the production of fecal S-adenosylmethionine was neither affected by the different dietary patterns nor their shaped microbiota. These results suggested that microbial modulation of the epitranscriptome may be involved in regulating GLP1 expression, and highlighted epitranscriptomic modifications as an additional level of interaction between diet and individual health.


Assuntos
Dieta Hiperlipídica , Hormônios Gastrointestinais , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Peptídeo 1 Semelhante ao Glucagon , Camundongos Obesos , Intestino Delgado
8.
J Vis Exp ; (183)2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35695535

RESUMO

The epididymis is a common site of obstruction in obstructive azoospermia (OA). Vasoepididymostomy has become an important method for the treatment of epididymal OA since 2000. There are two challenges in classic microscopic vasoepididymostomy. First, anastomosis of the vas deferens and epididymis is performed with double-needle sutures. However, there is a lack of good-quality and cost-effective double-needle sutures in China, which leads to increased difficulty and poor success rates of anastomosis. Second, the separation of the vas deferens does not retain vasculature, although the vas deferens vasculature plays an important role in the blood supply to the vas deferens, epididymis, and testis. This affects the blood supply to the anastomotic area and epididymis. Therefore, this team has made innovative improvements to address these problems. Good-quality, cost-effective, single-needle sutures, which are easy to purchase in China and other countries, were used in microsurgical longitudinal intussusception vasoepididymostomy. This can optimize the operation procedure and shorten the operation time while ensuring the success rate of the anastomosis. The surgical method of preserving the vas deferens vessels was innovatively proposed because the etiology of epididymal OA is mostly inflammatory in China. The protection of the blood supply to the vas deferens and epididymis is maximized using microsurgical forceps to separate and protect the vasculature. Patency reached 81.7% in the postoperative follow-up, indicating a better surgical treatment effect.


Assuntos
Azoospermia , Intussuscepção , Azoospermia/etiologia , Azoospermia/cirurgia , Epididimo/cirurgia , Humanos , Intussuscepção/cirurgia , Masculino , Microcirurgia/métodos , Ducto Deferente/cirurgia
9.
Zhongguo Zhong Yao Za Zhi ; 45(21): 5273-5279, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33350245

RESUMO

This paper aimed to investigate the protective effect and mechanism of the Tibetan medicine Ershiwuwei Songshi Pills on α-naphthalene isothiocyanate(ANIT)-induced cholestatic liver injury in rats based on the farnesol X receptor(FXR) signaling pathway. SD rats were randomly divided into blank group, model group, ursodeoxycholic acid(UDCA) group, Tibetan medicine Ershiwuwei Songshi Pills low, medium and high dose groups(0.09, 0.18, 0.36 g·kg~(-1)). A prophylactic dosing regimen was used in the experiment. From the 1 st to 4 th days, the UDCA group and the Tibetan medicine Ershiwuwei Songshi Pills suspension groups received prophylactic gavage administration; on the 5 th day, the blank control group was given an equal volume of olive oil blank reagent, and the remaining groups were given ANIT modeling reagent. Administration was continued on day 5 to 6 in each administration group. Forty-eight hours after modeling on the 7 th day, blood was collected from the femoral artery of rats. Serum alkaline phosphatase(ALP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), direct bilirubin(DBIL), total bilirubin(TBIL), and total bile acid(TBA) levels were detected, and liver histopathological changes were observed. The relative expression changes of FXR, SHP, CYP7 A1, MRP2, MRP3, NTCP, BSEP mRNA in liver tissues were detected by Real-time fluorescence quantitative method, and the expression changes of FXR, SHP, UGT2 B4 protein in liver tissues were detected by Western blot. The results showed that the Tibetan medicine Ershiwuwei Songshi Pills significantly reduced the levels of ALT, ALP, DBIL, TBIL and TBA in the serum of the ANIT mo-del rats(P<0.01, P<0.05), significantly up-regulated the mRNA expressions of SHP and NTCP(P<0.01, P<0.05), significantly down-regulated the mRNA expression of CYP7 A1 and MRP3(P<0.01, P<0.05); and significantly up-regulated the protein expressions of FXR and SHP(P<0.01, P<0.05). The Tibetan medicine Ershiwuwei Songshi Pills have an obvious protective effect on ANIT-induced cholestatic liver injury in rats, and its mechanism may be related to the bile acid metabolism mediated by the FXR signaling pathway.


Assuntos
Colestase , Medicina Tradicional Tibetana , Animais , Colestase/tratamento farmacológico , Colestase/genética , Fígado , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
10.
Mol Med Rep ; 22(4): 2665-2672, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32945384

RESUMO

Oxidative stress induces the formation of oxidized low­density lipoprotein (ox­LDL), which accelerates the development of atherosclerosis and the rupture of atherosclerotic plaques by promoting lipid accumulation and inhibiting autophagy in vascular cells. Lipophagy is known to be involved in maintaining the balance of neutral lipid metabolism; however, the phenomenon of lipophagy deficiency in ox­LDL­treated endothelial cells (ECs) remains to be elucidated. It has been demonstrated that lipid accumulation caused by ox­LDL inhibits autophagy, which promotes apoptosis in ECs. The aim of the present study was to investigate the association between decreased autophagy and lipid accumulation in ECs treated with ox­LDL. Electron microscopy demonstrated that the formation of autolipophagosomes was decreased in ox­LDL­treated human umbilical vein ECs compared with that in the LDL­treated group and was accompanied by a decrease in the autophagy­associated proteins via western blotting analysis. Using laser focal colocalization detection, decreased lipid processing was observed in the lysosomes of ox­LDL­treated ECs, which indicated that lipophagy may be attenuated and subsequently result in lipid accumulation in ox­LDL­treated ECs.


Assuntos
Autofagia/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/citologia , Lipoproteínas LDL/efeitos adversos , Linhagem Celular , Sobrevivência Celular , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Metabolismo dos Lipídeos , Microscopia Eletrônica , Estresse Oxidativo/efeitos dos fármacos
11.
J Membr Biol ; 253(2): 101-108, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32140737

RESUMO

As a member of the kinesin-3 family, kinesin family member 16B (KIF16B) has a characteristic PhoX homology (PX) domain that binds to membranes containing phosphatidylinositol-3-phosphate (PI(3)P) and moves along microtubule filaments to the plus end via a process regulated by coiled coils in the stalk region in various cell types. The physiological function of KIF16B supports the transport of intracellular cargo and the formation of endosomal tubules. Ras-related protein (Rab) coordinates many steps of membrane transport and are involved in the regulation of KIF16B-mediated vesicle trafficking. Data obtained from clinical research suggest that KIF16B has a potential effect on the disease processes in intellectual disability, abnormal lipid metabolism, and tumor brain metastasis. In this review, we summarize recent advances in the structural and physiological characteristics of KIF16B as well as diseases associated with KIF16B disorders, and speculating its role as a potential adaptor for intracellular cholesterol trafficking.


Assuntos
Cinesinas/química , Cinesinas/metabolismo , Microtúbulos/metabolismo , Domínios e Motivos de Interação entre Proteínas , Animais , Proteínas de Transporte/metabolismo , Membrana Celular/metabolismo , Suscetibilidade a Doenças , Humanos , Espaço Intracelular/metabolismo , Ligação Proteica , Transporte Proteico , Relação Estrutura-Atividade
12.
Med Hypotheses ; 136: 109524, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31862687

RESUMO

Human health is threatened by obesity which causes the increasing incidence of various diseases, especially stroke. Ischemic stroke (IS) is mostly caused by the rupture of arterial plaque, whose instability is positively associated with matrix metalloproteinases (MMPs) that degrades extracellular matrix components. Studies have shown that matrix metalloproteinase-12 (MMP-12) may be involved in the pathogenesis of IS. Because of the higher incidence of stroke in obese patients than that in normal weight people, it is urgent for obesity to forecast stroke early. Considering high levels MMP-12 in obesity, we put forward that MMP-12 may be a potential biomarker for IS in obese patients.


Assuntos
Isquemia Encefálica/diagnóstico , AVC Isquêmico/diagnóstico , Metaloproteinase 12 da Matriz/metabolismo , Obesidade/fisiopatologia , Animais , Apoptose , Biomarcadores/metabolismo , Isquemia Encefálica/complicações , Humanos , Incidência , Inflamação , AVC Isquêmico/complicações , Longevidade , Obesidade/complicações , Trombina/metabolismo
13.
Clin Chim Acta ; 500: 81-86, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31770510

RESUMO

The SREBP2/LDLR pathway is sensitive to cholesterol content in the endoplasmic reticulum (ER), while membrane low-density lipoprotein receptor (LDLR) is influenced by sterol response element binding protein 2 (SREBP2), pro-protein convertase subtilisin/kexin type 9 (PCSK9) and inducible degrader of LDLR (IDOL). LDL-C, one of the risk factors in cardiovascular disease, is cleared through endocytosis recycling of LDLR. Therefore, we propose that a balance between LDLR endocytosis recycling and PCSK9-mediated and IDOL-mediated lysosomal LDLR degradation is responsible for cholesterol homeostasis in the ER. For statins that decrease serum LDL-C levels via cholesterol synthesis inhibition, the mechanism by which the statins increase the membrane LDLR may be regulated by cholesterol homeostasis in the ER.


Assuntos
Colesterol/metabolismo , Receptores de LDL/metabolismo , Animais , Endocitose , Humanos , Receptores de LDL/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Transcrição Gênica
14.
Materials (Basel) ; 12(18)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31547280

RESUMO

The high-strength bolt shear connector in prefabricated concrete slab has advantages in applications as it reduces time during the construction of steel-concrete composite building structures and bridges. In this research, an innovative and advanced bolt shear connector in steel-concrete composite structures is proposed. To investigate the fundamental mechanical behavior and the damage form, 22 static push-off tests were conducted with consideration of different bolt dimensions, the reserved hole constraint condition, and the dimension of slab holes. A finite element (FE) model was established and verified by using test results, and then the model was utilized to investigate the influence of concrete strength, bolt dimension, yield strength, bolt pretension, as well as length-to-diameter ratio of high strength bolts on the performances of shear connectors. On the basis of FE simulation and test results, new design formulas for the calculation of shear resistance behavior were proposed, and comparisons were made with current standards, including AISC, EN 1994-1-1, GB 50017-2017, and relevant references, to check the calculation efficiency. It is confirmed that the proposed equation is in better agreement with the experimental results.

15.
J Mater Chem B ; 7(39): 5966-5971, 2019 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-31524915

RESUMO

Effective photosensitizers (PSs) are highly desirable in many applications, such as photodynamic therapy and catalytic chemistry. Here, we demonstrated that vesicles of cucurbit[7]uril (Q[7] or CB[7])-anchored polymers enhanced photosensitization in the nucleus. The polyacrylic acid chain spacer triggered Q[7] polymers on the surfaces of the vesicles at a regular distance, thus not only leading to efficient inhibition of the aggregation induced self-quenching of the porphyrin based cationic PS in aqueous solution but also maintaining the PS at high concentration on the nanoscale via stable host-guest interactions. Further experiments indicated that Q[7] polymer based vesicles as a PS loading vehicle had a high penetration depth, entering the nuclei of cancer cells. Therefore, highly enhanced photosensitization and efficient anticancer effects were achieved.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/química , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/efeitos da radiação , Imidazóis/química , Imidazóis/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Linhagem Celular Tumoral , Humanos , Modelos Moleculares , Conformação Molecular , Relação Estrutura-Atividade
16.
Zhonghua Nan Ke Xue ; 25(5): 296-301, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32216209

RESUMO

OBJECTIVE: To explore the expression of the N-methyl-D-aspartate (NMDA) receptor in the rat model of orchialgia and its possible mechanisms. METHODS: According to Yoshioka's method, the male rats in the control group were injected with 0.2 ml saline, and those in the experimental group with 0.2 ml 2% acetic acid solution. Then we tested the behavioral responses of the rats and determined the expressions of the subunits NR1 and NR2B of the NMDA receptor in the dorsal root ganglion and spinal dorsal horn by Western blot, RT-qPCR and immunofluorescence staining. RESULTS: The withdrawal latency was decreased in the model rats, reaching the lowest value at 4 hours after modeling, significantly lower than in the controls (ï¼»4.15 ± 0.84ï¼½ vs ï¼»12.32 ± 1.05ï¼½, P < 0.05). Compared with the controls, the model rats showed remarkably increased mRNA and protein expressions of NR2B in the dorsal root ganglion (P < 0.05) but not in the spinal dorsal horn at 4 hours. However, no statistically significant difference was found in the expression of NR1 either in the dorsal root ganglion or in the spinal dorsal horn between the two groups (P > 0.05). CONCLUSIONS: The NMDA receptor plays an important role in pathogenesis of orchialgia in rats. In the early stage of pain, upregulating the expression of the subunit NR2B of the NMDA receptor can mediate peripheral hyperalgesia and consequently orchialgia.


Assuntos
Receptores de N-Metil-D-Aspartato/metabolismo , Doenças Testiculares/metabolismo , Animais , Gânglios Espinais/metabolismo , Hiperalgesia , Masculino , Dor , Ratos , Ratos Sprague-Dawley , Corno Dorsal da Medula Espinal/metabolismo
17.
Rev. bras. farmacogn ; 27(5): 557-563, Sept.-Oct. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-898714

RESUMO

Abstract Hu-Gu capsule is a traditional Chinese medical formula for preventing glucocorticoid-induced osteoporosis. In this work, an ultra-high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry was developed for chemical identification of the phytochemical compositions in positive ion mode. A total of 41 compounds were detected in Hu-Gu capsule, and 25 compounds were characterized and identified by retention time, accurate mass within 5 ppm error and characteristic fragment ions. Among of them, four major flavonoids were further quantified by high performance liquid chromatography diode array detection in the four batches. The method was validated in terms of calibration curve regression coefficient (r 2 > 0.9994), repeatability (RSD < 3.5%), intra- and inter-day precision (RSD < 1.1%), recovery (93.0-106.4%), limit of detection (0.1 µg/ml), and limit of quantification (1 µg/ml). The research could provide the analysis of chemical composition and be helpful to control the quality of HGC.

18.
Nanoscale ; 9(20): 6649-6657, 2017 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-28261713

RESUMO

Resistive random access memory (RRAM) based reconfigurable logic provides a temporal programmable dimension to realize Boolean logic functions and is regarded as a promising route to build non-von Neumann computing architecture. In this work, a reconfigurable operation method is proposed to perform nonvolatile sequential logic in a HfO2-based RRAM array. Eight kinds of Boolean logic functions can be implemented within the same hardware fabrics. During the logic computing processes, the RRAM devices in an array are flexibly configured in a bipolar or complementary structure. The validity was demonstrated by experimentally implemented NAND and XOR logic functions and a theoretically designed 1-bit full adder. With the trade-off between temporal and spatial computing complexity, our method makes better use of limited computing resources, thus provides an attractive scheme for the construction of logic-in-memory systems.

19.
J Asian Nat Prod Res ; 19(9): 869-876, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28357881

RESUMO

A phytochemical study on the whole plant of Spermacoce latifolia led to the isolation of a new anthraquinone, 1,2,6-trihydroxy-5-methoxy-9,10-anthraquinone (1), and a new naphthoquinone, (2R)-6-hydroxy-7-methoxy-dehydroiso-α-lapachone (2), together with three known anthraquinones (3-5). Their structures were established on the basis of detailed spectroscopic analysis, including one- and two-dimensional NMR, ESI-MS, and HR-ESI-MS techniques. All the compounds were isolated from S. latifolia for the first time. Compounds 1, 2, 4, and 5 showed significant antibacterial activity toward Bacillus subtilis with MIC values ranging from 0.9 to 31.2 µg/ml, and compound 4 aslo exhibited antibacterial activity against Bacillus cereus with a MIC value 62.5 µg/ml. Compound 1 was further revealed to show significant in vitro α-glucosidase inhibitory activity with IC50 value of 0.653 mM.


Assuntos
Antraquinonas/isolamento & purificação , Antibacterianos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Naftoquinonas/isolamento & purificação , Rubiaceae/química , Antraquinonas/química , Antraquinonas/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Bacillus cereus/efeitos dos fármacos , Bacillus subtilis/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Escherichia coli/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Concentração Inibidora 50 , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Naftoquinonas/química , Naftoquinonas/farmacologia , Salmonella typhimurium/efeitos dos fármacos , Shigella dysenteriae/efeitos dos fármacos , alfa-Glucosidases/efeitos dos fármacos
20.
Sci Rep ; 6: 21805, 2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26892768

RESUMO

A greenhouse pot experiment was conducted to study the impact of arbuscular mycorrhizal fungi--Glomus versiforme (Gv) and Rhizophagus intraradices (Ri) on the growth, Cd uptake, antioxidant indices [glutathione reductase (GR), ascorbate peroxidase (APX), superoxide dismutase (SOD), catalase (CAT), ascorbate (ASA), glutathione (GSH) and malonaldehyde (MDA)] and phytochelatins (PCs) production of Lonicera japonica in Cd-amended soils. Gv and Ri significantly increased P acquisition, biomass of shoots and roots at all Cd treatments. Gv significantly decreased Cd concentrations in shoots and roots, and Ri also obviously reduced Cd concentrations in shoots but increased Cd concentrations in roots. Meanwhile, activities of CAT, APX and GR, and contents of ASA and PCs were remarkably higher in Gv/Ri-inoculated plants than those of uninoculated plants, but lower MDA and GSH contents in Gv/Ri-inoculated plants were found. In conclusion, Gv and Ri symbiosis alleviated Cd toxicity of L. japonica through the decline of shoot Cd concentrations and the improvement of P nutrition, PCs content and activities of GR, CAT, APX in inoculated plants, and then improved plant growth. The decrease of shoot Cd concentrations in L. japonica inoculated with Gv/Ri would provide a clue for safe production of this plant from Cd-contaminated soils.


Assuntos
Cádmio/metabolismo , Glomeromycota/fisiologia , Lonicera/crescimento & desenvolvimento , Micorrizas/fisiologia , Poluentes do Solo/metabolismo , Cádmio/análise , Cádmio/toxicidade , Peroxidação de Lipídeos , Lonicera/efeitos dos fármacos , Lonicera/metabolismo , Lonicera/microbiologia , Estresse Oxidativo , Fitoquelatinas/metabolismo , Solo/química , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
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