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1.
Biomater Sci ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32211626

RESUMO

Theranostics is a new trend integrating diagnostic and therapeutic functions in tumour research. Theranostic nanoparticles enabling both tumour imaging and drug delivery are a promising platform for image-guided cancer therapy. Photodynamic therapy (PDT) has great potential in synergy with traditional chemotherapy but faces great challenges due to hypoxia, poor targeting ability and the limited penetration depth of visible light. To solve these problems, we presented a novel nanosystem of FA/UCNPs-RB/HCPT/PFH@lipid (denoted as FURH-PFH-NPs), with a perfluorohexane (PFH) carrying rich oxygen core and a folic acid-modified lipid shell. The shell contains 10-hydroxycamptothecin (HCPT) and self-fluorescing photosensitizer compounds, namely, upconversion nanoparticles and rose bengal (UCNPs-RB). In this study, FURH-PFH-NPs aggregated in SKOV3 cells (in vitro) and the nude xenograft tumour region when combined with folic acid receptors. When triggered by low-intensity focused ultrasound (LIFU), FURH-PFH-NPs released PFH, UCNPs-RB and HCPT. The above procedure was monitored through multimodal imaging, which simultaneously guided the tumour therapy. UCNPs-RB and PFH promoted the PDT effect under LIFU. Through PDT and HCPT, we obtained better therapeutic effects and good biosafety against SKOV3 nude xenograft tumours. FURH-PFH-NPs combined with LIFU and laser irradiation might be a promising strategy for ovarian cancer.

2.
J Vasc Access ; : 1129729820904866, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32114875

RESUMO

BACKGROUND: Ultrasound-guided axillary vein catheterization is now widely used in hospital, but it remains uncertain whether the distal axillary vein approach is more beneficial for seniors than the proximal axillary vein approach. This study aims to compare the puncture success rate and anatomical characteristics between these two approaches. METHODS: Senior patients requiring central venous catheterization were enrolled and randomized to the proximal axillary vein group (n = 49) or the distal axillary vein group (n = 50). Proximal axillary vein and distal axillary vein location time, venous depth, maximum diameter, and collapse index (defined as the percentage change in vein width caused by respiration) were recorded for all patients. The rate of puncture success and operation time were compared between groups. RESULTS: Mean venous depth was 1.93 ± 0.45 cm for proximal axillary vein and 1.79 ± 0.46 cm for distal axillary vein (p < 0.001). Maximum diameter was 0.80 ± 0.33 cm for proximal axillary vein and 0.61 ± 0.33 cm for distal axillary vein (p < 0.001). Collapse indices were 20% ± 27% and 56% ± 34%, respectively (p < 0.001). Also, location time was significantly shorter for proximal axillary vein than for distal axillary vein (p < 0.001). One attempt and overall success rates were significantly higher in the proximal axillary vein group, compared with the distal axillary vein group (71.4% vs 42.0%, p = 0.003; 79.6% vs 54.0%, p = 0.007). CONCLUSION: For catheterization under ultrasound guidance in elderly patients, the proximal axillary vein approach is superior to the distal axillary vein approach.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32124537

RESUMO

Aqueous zinc-ion batteries have been developed rapidly recently as promising energy storage devices in large-scale energy storage systems owing to their low cost and high safety. The research on suppressing zinc dendrite growth has meanwhile attracted widespread attention in order to improve the lifespan and reversibility of batteries. Herein, design methods for dendrite-free zinc anodes and their internal mechanisms are reviewed from the perspective of optimizing host-zinc interface and zinc-electrolyte interface. Furthermore, we propose a design strategy to homogenize zinc deposition by regulating the interfacial electric field and ion distribution during zinc nucleation and growth. This Minireview can offer potential directions for the rational design of dendrite-free zinc anodes employed in aqueous zinc-ion batteries.

4.
Theranostics ; 10(4): 1833-1848, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32042339

RESUMO

Purpose: To determine the role of UCH-L1 in regulating ERα expression, and to evaluate whether therapeutic targeting of UCH-L1 can enhance the efficacy of anti-estrogen therapy against breast cancer with loss or reduction of ERα. Methods: Expressions of UCH-L1 and ERα were examined in breast cancer cells and patient specimens. The associations between UCH-L1 and ERα, therapeutic response and prognosis in breast cancer patients were analyzed using multiple databases. The molecular pathways by which UCH-L1 regulates ERα were analyzed using immunoblotting, qRT-PCR, immunoprecipitation, ubiquitination, luciferase and ChIP assays. The effects of UCH-L1 inhibition on the efficacy of tamoxifen in ERα (-) breast cancer cells were tested both in vivo and in vitro. Results: UCH-L1 expression was conversely correlated with ERα status in breast cancer, and the negative regulatory effect of UCH-L1 on ERα was mediated by the deubiquitinase-mediated stability of EGFR, which suppresses ERα transcription. High expression of UCH-L1 was associated with poor therapeutic response and prognosis in patients with breast cancer. Up-regulation of ERα caused by UCH-L1 inhibition could significantly enhance the efficacy of tamoxifen and fulvestrant in ERα (-) breast cancer both in vivo and in vitro. Conclusions: Our results reveal an important role of UCH-L1 in modulating ERα status and demonstrate the involvement of UCH-L1-EGFR signaling pathway, suggesting that UCH-L1 may serve as a novel adjuvant target for treatment of hormone therapy-insensitive breast cancers. Targeting UCH-L1 to sensitize ER negative breast cancer to anti-estrogen therapy might represent a new therapeutic strategy that warrants further exploration.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32108468

RESUMO

Despite the fact that lithium-sulfur batteries are regarded as promising next-generation rechargeable battery systems owning to high theoretical specific capacity (1675 mA h g-1) and energy density (2600 W h kg-1), several issues such as poor electrical conductivity, sluggish redox kinetics, and severe "shuttle effect" in electrodes still hinder their practical application. MXenes, novel two-dimensional materials with high conductivity, regulable interlayer spacing, and abundant functional groups, are widely applied in energy storage and conversion fields. In this work, a Ti3C2/carbon hybrid with expanded interlayer spacing is synthesized by one-step heat treatment in molten potassium hydroxide. The subsequent experiments indicate that the as-prepared Ti3C2/carbon hybrid can effectively regulate polysulfide redox conversion and has strong chemisorption interaction to polysulfides. Consequently, the Ti3C2/carbon-based sulfur cathode boosts the performance in working lithium-sulfur batteries, in terms of an ultrahigh initial discharge capacity (1668 mA h g-1 at 0.1 C), an excellent rate performance (520 mA h g-1 at 5 C), and an outstanding capacity retention of 530 mA h g-1 after 500 cycles at 1 C with a low capacity fade rate of 0.05% per cycle and stable Coulombic efficiency (nearly 99%). The above results indicate that this composite with high catalytic activity is a potential host material for further high-performance lithium-sulfur batteries.

6.
Int J Biol Macromol ; 146: 588-595, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31923493

RESUMO

The dissolution of silk fibroin in highly concentrated neutral salt solution and the subsequent long time-costing desalination have long inhibited silk regeneration. Here, a 4-fold volume of acetone was first added into a silk fibroin of 9.3 M LiBr solution (SF-LBS) to extract the dissolved silk protein. In fact, acetone extracted the salt and water from SF-LBS rather than silk protein. The extracted protein has less than half of the original amount of LiBr and could be redissolved easily in water. The dialysis time of the extracted protein could reduce the original dialysis time by approximately half. SDS-PAGE revealed that acetone extraction didn't induce any breakage to the peptide chains of the extracted silk fibroin. FTIR indicated that the structure of the extracted fibroin was very similar to that of the unextracted fibroin, and displayed predominantly a mixture of random coil and α-helices. X-ray diffraction also showed that acetone extraction had no effect on the crystal structure of the fibroin. In addition, both acetone and LiBr from the processing waste could easily be recycled for silk regeneration. This novel method can significantly enhance the desalination efficiency of highly concentrated LiBr solution containing silk protein without affecting its structure.

7.
Int J Biol Macromol ; 143: 594-601, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31836392

RESUMO

The dissolution and regeneration of silk fibre have long been an issue for producers of silk. The high solubility of silk fibroin (SF) in ionic liquids (ILs) is a promising new avenue in silk dissolution and regeneration as it may allow for a significant reduction in operational steps required for SF regeneration and the subsequent formation of SF biomaterials. The regenerated SF solution can be prepared by dissolving directly SF in ILs without the tedious steps of degumming, dissolution and dialysis. Besides, the regenerated SF solution can simply form different SF biomaterials with the help of coagulant, and ILs can be separated from SF biomaterials easily during SF solidification. The goal of this work is to summarize the commonly used ILs for dissolving silk protein and their dissolution methods and to present the potential application of SF/ILs mixed solution in medical biomaterials.

8.
Huan Jing Ke Xue ; 41(1): 232-241, 2020 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854924

RESUMO

This study assesses the spatial distribution characteristics and ecological risk of phthalate esters (PAEs) in the surface sediments of the mainstream and tributaries of the Songhua River, China, using concentrations and composition of six PAEs, which were analyzed using gas chromatography-mass spectrometery (GC-MS). We assess the ∑6PAEs ecological risk using the hazard quotient (HQ) method and environmental risk levels (ERL). The results were as follows. ① It was found that the total concentrations of ∑6PAEs ranged from 6832.5 to 36298.9 ng·g-1 dry weight (average 18388.6 ng·g-1), with the main contributions coming from di-(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP). The difference between the main stream ∑6PAEs (6832.5-36298.9 ng·g-1, average 18616.9 ng·g-1) and the tributary ∑6PAEs (10367.6-26593.3 ng·g-1, average 18264.1 ng·g-1) was not significant (P >0.05). The mean concentrations of individual PAEs in the tributary stream differed little from that of the main stream. The ∑6PAEs concentration of the Songhua River decreased initially but then increased from the upstream to the downstream. The average ∑6PAEs concentration in natural agricultural areas (18677.5 ng·g-1) was similar to that found in urban industrial areas (18063.7 ng·g-1), and DBP and DEHP contributed 98% of ∑6PAEs. ② The main sources of ∑6PAEs were domestic, agricultural production, and industrial production using plasticizers. ③ The ecological risk assessment indicated that DMP and BBP in the surface sediments of the Songhua River did not pose an ecological risk for aquatic organisms, and that DEP was associated with a low ecological risk, whereas DEHP and DBP posed a high ecological risk for aquatic organisms.


Assuntos
Ésteres/análise , Sedimentos Geológicos/química , Ácidos Ftálicos/análise , Rios/química , Poluentes Químicos da Água/análise , China , Dibutilftalato , Medição de Risco
9.
Neurochem Res ; 44(12): 2765-2775, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31701381

RESUMO

Transplantation of neural stem cells (NSCs) may be a potential strategy for traumatic brain injury treatment (TBI) due to their intrinsic advantages, such as cell replacement, secretion of neurotrophins and formation of functional synapses with host. However the underlying effects of transplanted NSCs on host micro-environment still need to be further elucidated. In this manuscript the effects of NSCs on release of neurotransmitter, survival of hippocampal neurons, reactivity of astrocytes and recovery of cognitive function after TBI were observed. The NSCs were isolated from cortex of neonatal Sprague-Dawley rat and then transplanted into injured brain regions caused by free-weight drop. The proliferation of astrocytes around injured sites were examined by GFAP immunofluorescent staining on 3, 7, 14 days after injury. The survival of neurons at CA1 regions of hippocampus toward contused regions was observed by HE staining on 3 and 14 days post-injury. The content of glutamic acid (Glu) and GABA in hippocampal tissues was examined on 1, 3, 7, 14, 28 days after injury by ELISA. On third day post-injury, hippocampal-dependent spatial memory was measured for 5 days without intermittent. NSCs in culture have the ability to proliferate and differentiate into different phenotypes of neural cells. After transplantation of NSCs, the proliferation of astrocytes around injured site was significantly inhibited compared to the injured group. At the same time the survival of neurons in hippocampal CA1 region were much more than those in injured group on 14 days post-injury. Meanwhile, the cognitive functions in NSC transplanted group was remarkably improved compared with injured group (p < 0.05). Furthermore, NSCs transplantation dramatically inhibited the release of Glu and maintained the content of GABA in injured hippocampal tissues on 1, 3, 7, 14, 28 days post-injury, which was of difference in statistics (p < 0.05). NSCs transplantation can effectively alleviate the formation of glial scar, enhance the survival of hippocampal neurons and improve cognitive function defects in rats with TBI. The underlying mechanism may be related to their effects on inhibiting the release of Glu and maintaining the content of GABA, so as to down-regulate excitotoxicity of neurotransmitter and improve the micro-environment in injured sites.

10.
Int J Biol Macromol ; 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31743716

RESUMO

The sericin protein from silk-processing waste added to the normal diet at 0.8% (g%) level was administered orally to type 2 diabetic (T2D) mice to investigate its hypoglycaemic effects and mechanism. The oral protein is in the form of silk sericin hydrolysate, obtained from a boiling treatment of 0.025% calcium hydroxide solution. The protein significantly decreased fasting blood glucose, fasting plasma insulin, and glycosylated serum protein levels; improved oral glucose tolerance and insulin tolerance, and enhanced antioxidative activities. The protein could ameliorate the pathological damage in pancreatic ß-cells and the liver tissue. It enhanced the expression of key proteins and enzymes, including insulin receptor, insulin receptor substrate, PI3K, phosphorylated-AKT, hepatic kinase, GLUT4, glycogen synthase, GSK3ß, GLK, PFK1, PKM2, and AMPKα, which are related to insulin metabolism and glycolysis. The protein also reduced the expression of G6Pase, PCK, and ACC, which are related to gluconeogenesis and lipid metabolism in the liver, and decreased the expression of TNF-α, IL-6, P65, and IKKß related to inflammation. In general, sericin could maintain normal glucose levels and regulate insulin secretion, insulin and lipid metabolism, and inhibition of inflammation. Therefore, sericin protein could be developed into a novel functional health food with significantly hypoglycaemic effect.

11.
Nanoscale ; 11(36): 17018-17030, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31502627

RESUMO

Targeting is vital for precise positioning and efficient therapy, and integrated platforms for diagnosis and therapy have attracted more and more attention. Herein, we established dual-template molecularly imprinted polymer (MIP) coated fluorescent silicon nanoparticles (Si NPs) by using the linear peptide of the extracellular region of human epidermal growth factor receptor-2 (HER2) and adopting doxorubicin (DOX) as templates for targeted imaging and targeted therapy. Benefiting from the epitope imprinting approach, the imprinted sites generated by peptides on the MIP surface can be employed for recognizing the corresponding protein, which allowed the MIP to specifically and actively target HER2-positive breast cancer cells. Because of its ability to identify breast cancer cells, the MIP was applied for targeted fluorescence imaging by taking advantage of the excellent fluorescence properties of Si NPs, and the DOX-loaded MIP (MIP@DOX) can act as a therapeutic probe to effectively target and kill breast cancer cells. In fluorescence images, the targeting of the MIP promoted more uptake of the nanoparticles by cells than the non-imprinted polymer (NIP), so HER2-positive breast cancer cells incubated with the MIP exhibited stronger fluorescence, and there was no significant difference in fluorescence when HER2-negative cells and normal cells were respectively hatched with the MIP and NIP. Importantly, the cell viability was evaluated to demonstrate targeted accumulation and therapy of MIP@DOX for breast cancer cells. The nanoplatform for diagnosis and therapy combined the high sensitivity of fluorescence with the high selectivity of the molecular imprinting technique, which holds vital potential in targeted imaging and targeted therapy in vitro.


Assuntos
Neoplasias da Mama , Materiais Revestidos Biocompatíveis , Doxorrubicina , Sistemas de Liberação de Medicamentos , Epitopos , Nanopartículas , Imagem Óptica , Receptor ErbB-2/metabolismo , Silício , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Epitopos/química , Epitopos/farmacologia , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Silício/química , Silício/farmacologia
12.
Biomed Pharmacother ; 118: 109379, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545278

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is one of the major complications of diabetes. Sericin and flavonoids are two bioactive substances which have been demonstrated to have some therapeutical effect on diabetic nephropathy. The aim of this paper is to investigate the effect of ethanolic extract (EE) rich in quercetin and kaempferol and their glucosides from the green cocoon of silkworm Bombyx mori on DN in type 2 diabetic (T2D) mice induced by high-fat and streptozotocin (STZ). METHODS: Ethanolic extract from the green cocoon shell of silkworm Bombyx mori was used as material. Diabetic mice were orally treated with three doses (150, 250 and 350 mg/kg) of the extract for 7 weeks, then the levels of oxidases and related inflammatory factors were measured in kidneys. RESULTS: Compared with the negative control, EE administration resulted in an evident reduction in blood glucose levels and an improvement of the body weight in diabetic mice. Oral EE could inhibit the expressions of renal tumour necrosis factor TNF-α, monocyte chemoattractant protein-1 (MCP-1), fibronectin (FN) and P38 mitogen-activated protein kinase (p38 MAPK) in T2D mice. Moreover, the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) were significantly elevated in T2D mice treated with EE. CONCLUSIONS: The activities of anti-fibrosis and anti-inflammation contributed to the renal protective effects by reducing oxidative stress, which might be mediated by the inhibition of the TNF-α-p38 MAP kinase signalling pathway. It is suggested that the ethanolic extract from silkworm green cocoon might be potential as an herbal medicine for DN.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Flavonoides/uso terapêutico , Rim/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Administração Oral , Animais , Antioxidantes/metabolismo , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Bombyx , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/enzimologia , Etanol/química , Jejum/sangue , Fibronectinas/metabolismo , Flavonoides/química , Flavonoides/farmacologia , Mediadores da Inflamação/metabolismo , Rim/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia
13.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(3): 232-238, 2019 May 28.
Artigo em Chinês | MEDLINE | ID: mdl-31257805

RESUMO

OBJECTIVE: To quantitatively investigate the effects of Ringer's solution with different concentrations of alcohol (1%~80%) on biphasic compound action potentials (AP) from frog sciatic nerve trunk, and their recoveries from alcohol effects. METHODS: Individual segments of frog sciatic nerve trunk with a length of 6 to 8 cm were prepared. Ringer's solution with different concentrations of alcohol (0%, 1%, 2%, 4%, 8%, 16%, 32%, 48%, 64% and 80%) was applied onto the segment of the trunk between the stimulus and ground electrodes via an agent reservoir which was newly armed in a nerve trunk shielded chamber for 5 minutes. The nerve trunk was respectively electro-stimulated to generate the biphasic compound AP which was recorded using the experimental system of BL-420F. This was followed by 5 times washout plus 5 min administration with Ringer's solution before recovery recording of AP. RESULTS: Compared to normal Ringer's solution, Ringer's solution with alcohol at ≤4% did not have dramatic impacts on the AP amplitude and conduction velocity, while Ringer's solution with alcohol at ≥8% there was significant decrease in these two parameters. Ringer's solution with alcohol at the conentrations of 16%, 32% and ≥48% could prevent a small proportion (30%), a large proportion (90%) and all (100%) of sciatic nerve trunks, respectively, from generating AP. Washout with normal Ringer's solution after alcohol application at the concentration of ≤32%, AP could totally recover to normal status. While alcohol at the concentration of 48%, 64% and 80%, the probabilities to regenerate APs were 90%, 40% and 0%, and the AP amplitudes were decreased to 60%, 36% and 0%, respectively. After washout, AP conduction velocity showed no difference with alcohol at the concentration of ≤8% when compared with that before washout, while it could not be recovered to normal under alcohol at ≥16%. CONCLUSION: Ringer's solution with different concentrations of alcohol exerts different effects on biphasic compound AP amplitude and conduction velocity. Hopefully, our findings could be helpful for the alcoholic usage and its recovery from alcoholic damage.


Assuntos
Potenciais de Ação , Anuros , Etanol/farmacologia , Solução de Ringer/farmacologia , Nervo Isquiático/efeitos dos fármacos , Animais
14.
Front Microbiol ; 10: 1399, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293544

RESUMO

Enterocytozoon bieneusi, an obligate intracellular pathogen, can infect various hosts. In this study, 3527 dairy cattle fecal specimens were collected from different geographic locations in China (including 673 from Shandong province, 1,440 from Guangdong province and 1,414 from Gansu province) and examined for the presence of E. bieneusi using polymerase chain reactions targeting the ribosomal internal transcribed spacer (ITS). The dominant genotypes identified were further subtyped by multilocus sequence typing. The overall prevalence of E. bieneusi was 14.2% (501/3527), with a significant difference in prevalence among the different geographical locations (P < 0.001). Our logistic regression analysis showed that all four variables (farming model, location, age, and clinical manifestations) had strong effects on the risk of contracting E. bieneusi. Sequence analysis revealed 11 genotypes: eight known genotypes (J, I, BEB4, BEB10, D, EbpC, CM19, and CM21) and three novel genotypes (named here as CGC1, CGC2, and CGC3). Genotypes J and I, the commonest, were found on all farms across the three provinces. Our linkage disequilibrium analysis showed a clonal population structure in the E. bieneusi dairy cattle population but the ITS genotypes had different population structures. Phylogenetic and haplotype network analysis showed the absence of geographical segregation in the E. bieneusi dairy cattle populations. Instead, they revealed the presence of host adaptation to the E. bieneusi populations in various animals. Our findings augment the current understanding of E. bieneusi transmission dynamics.

15.
Chin J Integr Med ; 25(12): 887-894, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31292845

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Tongxiening Granules (, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D). METHODS: A randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated. RESULTS: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05). CONCLUSION: Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415).

16.
Toxicol Res (Camb) ; 8(3): 407-420, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31160974

RESUMO

Diabetes mellitus is a clinically complex disease characterized by hyperglycaemia with disturbances in carbohydrate, fat and protein metabolism. The aim of this study was to determine the therapeutic effect of ethanolic extract (EE) from the green cocoon sericin layer of silkworm Bombyx mori on mice with type 2 diabetes mellitus (T2DM) and its hypoglycaemic mechanisms. The results showed that oral EE for 7 weeks had significant ameliorative effects on all the biochemical parameters studied in vivo. The levels of oral glucose tolerance and insulin tolerance were significantly improved. The hypoglycaemic rate in the 350 mg kg-1 high dosage group was 39.38%. The levels of nuclear factor kappa B (NFκB), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) in the high dosage EE-treated group were significantly reduced, while activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were obviously increased. The islet area and the number of insulin-positive beta cells increased significantly in the high dose group. Furthermore, expression levels of insulin receptor (IR), insulin receptor substrate (IRS), phosphatidylinositide 3-kinase (PI3K), p-Akt and phospho-glycogen synthase kinase-3ß (p-GSK3ß) involved in insulin signalling were increased. Adenosine 5'-monophosphate-activated protein kinase (AMPK) and glucose transporter 4 (GLUT4) also were activated to regulate glucose metabolism in EE-treated groups. The levels of glucose 6-phosphatase (G6pase) and phosphoenolpyruvate carboxykinase (PEPCK) decreased, while the glucokinase (GK) level increased to promote glycolysis. The results clearly indicated that oral EE, especially at a high dose, could improve the glucose metabolism of T2DM by reducing inflammatory reactions, enhancing the antioxidant capacity and insulin sensitivity, and regulating the balance between glycolysis and gluconeogenesis, which means that EE has potential ameliorative effects on T2DM mice.

17.
Biosens Bioelectron ; 140: 111349, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31150983

RESUMO

In this report, enhanced organic-inorganic heterojunction of polypyrrole@Bi2WO6 was fabricated and applied for sensitive photoelectrochemical (PEC) immunoassay of creatine kinase-MB (CK-MB). Specifically, heterostructured polypyrrole@Bi2WO6 photoelectrode was prepared and sandwich immunorecognition were integrated for the CK-MB immunoassay. In the detection, with the aid of alkaline phosphate (ALP)-induced biocatalytic precipitation (BCP), the precipitation-dependent suppression of the photocurrent can be recorded due to the impediment of the interfacial mass and electron transfer. On the basis of target-controlled BCP formation, a novel PEC immunoassay could be developed for the sensitive and specific CK-MB detection. This work manifested the great potential of polypyrrole@Bi2WO6 heterojunction as a novel platform for PEC bioanalysis development and also a PEC method for CK-MB detection. This work is expected to stimulate more interest in the design and implementation of numerous other organic-inorganic heterojunction for advanced PEC bioanalysis development.


Assuntos
Bismuto/química , Creatina Quinase Forma MB/análise , Polímeros/química , Pirróis/química , Compostos de Tungstênio/química , Animais , Anticorpos Imobilizados/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Humanos , Imunoensaio/métodos
18.
BMC Biotechnol ; 19(1): 23, 2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-31014302

RESUMO

BACKGROUND: The gene transduction efficiency of adenovirus to hematopoietic cells, especially T lymphocytes, is needed to be improved. The purpose of this study is to improve the transduction efficiency of T lymphocytes by using fiber-modified human adenovirus 5 (HAdV-5) vectors. RESULTS: Four fiber-modified human adenovirus 5 (HAdV-5) vectors were investigated to transduce hematopoietic cells. F35-EG or F11p-EG were HAdV-35 or HAdV-11p fiber pseudotyped HAdV-5, and HR-EG or CR-EG vectors were generated by incorporating RGD motif to the HI loop or to the C-terminus of F11p-EG fiber. All vectors could transduce more than 90% of K562 or Jurkat cells at an multiplicity of infection (MOI) of 500 viral particle per cell (vp/cell). All vectors except HR-EG could transduce nearly 90% cord blood CD34+ cells or 80% primary human T cells at the MOI of 1000, and F11p-EG showed slight superiority to F35-EG and CR-EG. Adenoviral vectors transduced CD4+ T cells a little more efficiently than they did to CD8+ T cells. These vectors showed no cytotoxicity at an MOI as high as 1000 vp/cell because the infected and uninfected T cells retained the same CD4/CD8 ratio and cell growth rate. CONCLUSIONS: HAdV-11p fiber pseudotyped HAdV-5 could effectively transduce human T cells when human EF1a promoter was used to control the expression of transgene, suggesting its possible application in T cell immunocellular therapy.


Assuntos
Adenovírus Humanos/genética , Técnicas de Transferência de Genes/normas , Vetores Genéticos/genética , Linfócitos T/metabolismo , Proteínas da Cauda Viral/genética , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , Proliferação de Células/genética , Terapia Genética/métodos , Células HL-60 , Humanos , Células Jurkat , Células K562 , Linfócitos T/virologia , Transdução Genética/normas , Transgenes/genética , Células U937 , Proteínas da Cauda Viral/metabolismo
19.
Orthop Surg ; 11(1): 143-150, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30834706

RESUMO

OBJECTIVES: To explore the effects of acupoint application therapy (AAT) with TianGui Powder (TGP) on the expressions of the transforming growth factor ß1 (TGF-ß1) and Smad-2/3 signaling pathway in ovariectomized osteoporosis rats. METHODS: Sixty rats were randomly divided into four groups: normal group (group A), model group (group B), TGP group (group C), and Western medicine group (group D). Group A had only the corresponding amount of adipose tissue around the ovary removed; rats in the other groups had bilateral ovariectomies. After 1 week, groups A and B were given 1 mL/100 mg normal saline solution by gavage, group C was treated with AAT with TGP on ShenQue acupoint (0.2 piece/rat, 6 h/time, 1 time/d) and group D was given calcium carbonate vitamin D3 (36 mg/kg/d) and alfacalcidol (0.05 µg/kg/d) tablet suspension. In this study, the bone mineral density (BMD) , the levels of BALP, TRAP-5b, and BGP in serum and the changes in bone histomorphology was detected. For acquiring lumbar experimental data, the expression of TGF-ß1, Smad-2/3 proteins and mRNA of TGF-ß1and Smad-2/3 were assessed. After 12 weeks, the data were collected for analysis. RESULTS: Compared with group A, the bone trabecula was thinner and significantly reduced in other groups. The result of BMD improved significantly in both groups C and D compared to group B after intervention (P < 0.05). In contrast, compared to group B, the levels of BALP, TRAP-5b, and BGP significantly declined in both groups C and D. In group C, the results of protein expressions in TGF-ß1, Smad-2/3 were 2.870 ± 0.270, 1.552 ± 0.111, and 1.420 ± 0.079, respectively. In groups C and D, those indications significantly declined compared to group B (P < 0.01). In group C, the level of mRNA expressions of TGF-ß1, Smad-2/3 were 1.872 ± 0.177, 1.672 ± 0.086, and 1.790 ± 0.136, respectively. Compared with group B, those indications had significant difference in groups C and D (P < 0.05). CONCLUSION: Acupoint application therapy with TGP could significantly improve the BMD. The TGF-ß1 and Smad-2/3 signaling pathway could be a therapeutic target of TGP in postmenopausal osteoporosis rats.


Assuntos
Pontos de Acupuntura , Conservadores da Densidade Óssea/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Osteoporose Pós-Menopausa/terapia , Animais , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Humanos , Osteoporose Pós-Menopausa/fisiopatologia , Ovariectomia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/fisiologia , Proteína Smad3/fisiologia , Fator de Crescimento Transformador beta1/fisiologia
20.
Front Pharmacol ; 10: 170, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30894816

RESUMO

The nuclear factor (NF)-κB signaling pathway plays an important role in the initialization and development phase of inflammatory injuries, including inflammatory bowel disease (IBD). Sishen Wan (SSW) is a classic Chinese patent medicine listed in the Chinese Pharmacopoeia, which is usually used to treat chronic colitis; however, it is unclear whether SSW can treat IBD via the NF-κB signaling pathway. In the present study, the therapeutic effect of SSW was demonstrated by the decreased index of colonic weight, macroscopic and microscopic score, and pathological observation in chronic colitis induced by trinitrobenzene sulfonic acid. In colonic mucosa of rats with chronic colitis, SSW reduced the levels of calprotectin and eliminated oxidative lesions; downregulated expression of interferon-γ, interleukin (IL)-1ß and IL-17; increased expression of IL-4; and suppressed expression of NF-κB p65, and NF-κB essential modulator (NEMO)-like kinase (NLK). Furthermore, SSW inhibited ubiquitinated NEMO, ubiquitin-activated enzyme, and E2i activation, and phosphorylation of downstream proteins (cylindromatosis protein, transforming growth factor-ß-activated kinase and P38). These results show that the therapeutic effects of SSW in chronic colitis were mediated by inhibiting the NEMO/NLK signaling pathway to suppress NF-κB activation.

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