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Article ; Online: Assessing the structural stability and drug encapsulation efficiency of poly(ethylene glycol)-poly(L-lactic acid) nanoparticles loaded with atorvastatin calcium: Based on dissipative particle dynamics.

Feng, Yun Hao / Guo, Wei Xin / Li, Zhuo Lin / Hu, Liu Fu / Liu, Yue / Jing, Li Yue / Wang, Jianhao / Shahbazi, Mohammad-Ali / Chen, Bo Zhi / Guo, Xin Dong

International journal of biological macromolecules

2024 Volume 267, Issue Pt 1, Page(s) 131436

Abstract: Block polymer micelles have been proven highly biocompatible and effective in improving drug utilization for delivering atorvastatin calcium. Therefore, it is of great significance to measure the stability of drug-loading nano micelles from the ... ...

Abstract	Block polymer micelles have been proven highly biocompatible and effective in improving drug utilization for delivering atorvastatin calcium. Therefore, it is of great significance to measure the stability of drug-loading nano micelles from the perspective of block polymer molecular sequence design, which would provide theoretical guidance for subsequent clinical applications. This study aims to investigate the structural stability of drug-loading micelles formed by two diblock/triblock polymers with various block sequences through coarse-grained dissipative particle dynamics (DPD) simulations. From the perspectives of the binding strength of poly(L-lactic acid) (PLLA) and polyethylene glycol (PEG) in nanoparticles, hydrophilic bead surface coverage, and the morphological alteration of nanoparticles induced by shear force, the ratio of hydrophilic/hydrophobic sequence length has been observed to affect the stability of nanoparticles. We have found that for diblock polymers, PEG3kda-PLLA2kda has the best stability (corresponding hydrophilic coverage ratio is 0.832), while PEG4kda-PLLA5kda has the worst (coverage ratio 0.578). For triblock polymers, PEG4kda-PLLA2kda-PEG4kda has the best stability (0.838), while PEG4kda-PLLA5kda-PEG4kda possesses the worst performance (0.731), and the average performance on stability is better than nanoparticles composed of diblock polymers.
MeSH term(s)	Atorvastatin/chemistry ; Polyethylene Glycols/chemistry ; Nanoparticles/chemistry ; Hydrophobic and Hydrophilic Interactions ; Drug Carriers/chemistry ; Micelles ; Polyesters/chemistry ; Drug Compounding ; Molecular Dynamics Simulation ; Lactates
Chemical Substances	Atorvastatin (A0JWA85V8F) ; Polyethylene Glycols (3WJQ0SDW1A) ; Drug Carriers ; Micelles ; Polyesters ; poly(lactic acid-ethylene glycol) ; poly(lactide) (459TN2L5F5) ; Lactates
Language	English
Publishing date	2024-04-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2024.131436
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Article ; Online: Functional insulin aspart/insulin degludec-based microneedles for promoting postprandial glycemic control.

Chen, Bo Zhi / Li, Wen Xuan / Feng, Yun Hao / Zhang, Xiao Peng / Jiao, Jie / Li, Zhuo Lin / Nosrati-Siahmazgi, Vahideh / Shahbazi, Mohammad-Ali / Guo, Xin Dong

Acta biomaterialia

2023 Volume 171, Page(s) 350–362

Abstract: Insulin aspart (IAsp) and insulin degludec (IDeg), as the third generation of insulin, have a faster onset time or a more durable action period, which may simulate the secretion of insulin under physiological conditions. Microneedles (MNs) are ... ...

Abstract	Insulin aspart (IAsp) and insulin degludec (IDeg), as the third generation of insulin, have a faster onset time or a more durable action period, which may simulate the secretion of insulin under physiological conditions. Microneedles (MNs) are transdermal delivery devices that may allow diabetic patients to easily deploy transdermal insulin therapy while considerably reducing injection pain. In this study, we investigated the combination of dissolving MNs with IAsp or IDeg therapy as an alternative to daily multiple insulin injections, aiming to improve glycemic control and patient compliance. Mechanical properties of the MNs, structural stability of insulin encapsulated in the MNs, and transdermal application characteristics were studied to assess the practicality of insulin-loaded MNs for diabetes therapy. In vivo experiments conducted on diabetic rats demonstrated that the IAsp- and IDeg-loaded MNs have comparable blood glucose control abilities to that of subcutaneous injections. In addition, the therapeutic properties of insulin-loaded MNs under diverse dietary conditions and application strategies were further investigated to provide new information to support future clinical trials. Taken together, the proposed MNs have the potential to improve balances between glycemic control, hypoglycemia risk, and convenience, providing patients with simpler regimens. STATEMENT OF SIGNIFICANCE: 1. The fabricated functional insulin-loaded dissolving microneedles closely matched the glucose rise that occurs in response to meals, demonstrating promising alternatives for multiple daily insulin injections. 2. The hypoglycemic properties of insulin microneedles were investigated under diverse dietary conditions and application strategies, yielding new information to support future clinical trials. 3. Molecular dynamics simulations were utilized to study the interactions between the insulin and microneedle matrix materials, providing a strategy for theoretically understanding drug stability as well as the release mechanism of drug-loaded microneedles.
MeSH term(s)	Humans ; Rats ; Animals ; Insulin Aspart/therapeutic use ; Glycemic Control ; Diabetes Mellitus, Experimental/drug therapy ; Hypoglycemic Agents ; Insulin/pharmacology ; Blood Glucose
Chemical Substances	insulin degludec (54Q18076QB) ; Insulin Aspart (D933668QVX) ; Hypoglycemic Agents ; Insulin ; Blood Glucose
Language	English
Publishing date	2023-09-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2023.09.010
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Article ; Online: Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice.

Ma, Zhen-Rong / Li, Zhuo-Lin / Zhang, Ni / Lu, Bin / Li, Xuan-Wu / Huang, Ye-Hong / Nouhoum, Dibo / Liu, Xian-Shu / Xiao, Ke-Chun / Cai, Li-Ting / Xu, Shao-Rui / Yang, Xue-Xian O / Huang, Shuai-Qin / Wu, Xiang

Parasites & vectors

2023 Volume 16, Issue 1, Page(s) 280

Abstract: Background: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. Although there is currently no completely curative treatment, helminthic therapy shows certain therapeutic potential for ... ...

Abstract	Background: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. Although there is currently no completely curative treatment, helminthic therapy shows certain therapeutic potential for UC. Many studies have found that Trichinella spiralis (T.s) has a protective effect on UC, but the specific mechanism is still unclear. Methods: Balb/c mice drank dextran sulfate sodium (DSS) to induce acute colitis and then were treated with T.s. In vitro experiments, the LPS combination with ATP was used to induce the pyroptosis model, followed by intervention with crude protein from T.s (T.s cp). Additionally, the pyroptosis agonist of NSC or the pyroptosis inhibitor vx-765 was added to intervene to explore the role of pyroptosis in DSS-induced acute colitis. The degree of pyroptosis was evaluated by western blot, qPCR and IHC, etc., in vivo and in vitro. Results: T.s intervention significantly inhibited NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by downregulating the expression of pyroptosis-related signatures in vitro (cellular inflammatory model) and in vivo (DSS-induced UC mice model). Furthermore, blockade of GSDMD-mediated pyroptosis by the caspase-1 inhibitor vx-765 has a similar therapeutic effect on DSS-induced UC mice with T.s intervention, thus indicating that T.s intervention alleviated DSS-induced UC in mice by inhibiting GSDMD-mediated pyroptosis. Conclusion: This study showed that T.s could alleviate the pathological severity UC via GSDMD-mediated pyroptosis, and it provides new insight into the mechanistic study and application of helminths in treating colitis.
MeSH term(s)	Animals ; Mice ; Colitis/chemically induced ; Colitis, Ulcerative/chemically induced ; Colitis, Ulcerative/drug therapy ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Inflammatory Bowel Diseases ; Mice, Inbred C57BL ; Pyroptosis ; Trichinella spiralis ; Gasdermins
Chemical Substances	Dextran Sulfate (9042-14-2) ; Gsdmd protein, mouse ; Gasdermins
Language	English
Publishing date	2023-08-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2409480-8
ISSN	1756-3305 ; 1756-3305
ISSN (online)	1756-3305
ISSN	1756-3305
DOI	10.1186/s13071-023-05857-3
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Article ; Online: Epitope vaccine design for Toxoplasma gondii based on a genome-wide database of membrane proteins.

Li, Xuan-Wu / Zhang, Ni / Li, Zhuo-Lin / Dibo, Nouhoum / Ma, Zhen-Rong / Lu, Bin / Huang, Ye-Hong / Chang, Yun-Feng / Chen, Hong-Zhi / Wu, Xiang

Parasites & vectors

2022 Volume 15, Issue 1, Page(s) 364

Abstract: Background: There is presently no effective and safe vaccine for Toxoplasma gondii for humans. The study described here was designed to search for a novel group of optimal B cell and T cell epitopes from Toxoplasma membrane proteins using genome-wide ... ...

Abstract	Background: There is presently no effective and safe vaccine for Toxoplasma gondii for humans. The study described here was designed to search for a novel group of optimal B cell and T cell epitopes from Toxoplasma membrane proteins using genome-wide comprehensive screening. Methods: The amino acid sequences of membrane proteins of T. gondii were obtained from the UniProt database. The ABCPred and BepiPred servers were employed to predict the linear B cell epitopes. The Immune Epitope Database (IEDB) online service was utilized to forecast T cell epitopes within T. gondii membrane proteins that bind to human leukocyte antigen (HLA) class I (HLA-I) or HLA-II molecules. Results: From the 314 membrane proteins of T. gondii, a total of 14 linear B cell epitopes embedded in 12 membrane proteins were identified. Eight epitopes for major histocompatibility complex (MHC) class I (MHC-I) molecules and 18 epitopes for MHC-II molecules were ultimately selected, for which world population coverage percentiles were 71.94% and 99.76%, respectively. The top rated combinations of linear B cell epitopes and T cell epitopes covering both BALB/c mice and a majority of the human population were identified for the development of a protective vaccine. Conclusions: The ultimate vaccine construct described here, which comprises B cells, MHC-I and MHC-II epitopes, might protect individuals against T. gondii infection by inducing humoral and cellular immune responses.
MeSH term(s)	Animals ; Epitopes, B-Lymphocyte/genetics ; Epitopes, T-Lymphocyte/genetics ; Histocompatibility Antigens Class II ; Humans ; Membrane Proteins/genetics ; Mice ; Mice, Inbred BALB C ; Toxoplasma/genetics ; Vaccines
Chemical Substances	Epitopes, B-Lymphocyte ; Epitopes, T-Lymphocyte ; Histocompatibility Antigens Class II ; Membrane Proteins ; Vaccines
Language	English
Publishing date	2022-10-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2409480-8
ISSN	1756-3305 ; 1756-3305
ISSN (online)	1756-3305
ISSN	1756-3305
DOI	10.1186/s13071-022-05497-z
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Article ; Online: Contribution of central sensitization to stress-induced spreading hyperalgesia in rats with orofacial inflammation.

Li, Jia-Heng / Yang, Jia-Le / Wei, Si-Qi / Li, Zhuo-Lin / Collins, Anna A / Zou, Min / Wei, Feng / Cao, Dong-Yuan

Molecular brain

2020 Volume 13, Issue 1, Page(s) 106

Abstract: Temporomandibular disorder (TMD) is commonly comorbid with fibromyalgia syndrome (FMS). The incidence of these pain conditions is prevalent in women and prone to mental stress. Chronic pain symptoms in patients with FMS and myofascial TMD (mTMD) are ... ...

Abstract	Temporomandibular disorder (TMD) is commonly comorbid with fibromyalgia syndrome (FMS). The incidence of these pain conditions is prevalent in women and prone to mental stress. Chronic pain symptoms in patients with FMS and myofascial TMD (mTMD) are severe and debilitating. In the present study, we developed a new animal model to mimic the comorbidity of TMD and FMS. In ovariectomized female rats, repeated forced swim (FS) stress induced mechanical allodynia and thermal hyperalgesia in the hindpaws of the 17β-estradiol (E2) treated rats with orofacial inflammation. Subcutaneous injection of E2, injection of complete Freund's adjuvant (CFA) into masseter muscles or FS alone did not induce somatic hyperalgesia. We also found that the somatic hyperalgesia was accompanied by upregulation of GluN1 receptor and serotonin (5-hydroxytryptamine, 5-HT)
MeSH term(s)	Animals ; Central Nervous System Sensitization ; Face/pathology ; Female ; Hyperalgesia/etiology ; Hyperalgesia/physiopathology ; Inflammation/pathology ; Inflammation/physiopathology ; Mouth/pathology ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism ; Receptors, Serotonin, 5-HT3/metabolism ; Stress, Psychological/complications ; Swimming ; Temperature
Chemical Substances	Receptors, N-Methyl-D-Aspartate ; Receptors, Serotonin, 5-HT3
Language	English
Publishing date	2020-07-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2436057-0
ISSN	1756-6606 ; 1756-6606
ISSN (online)	1756-6606
ISSN	1756-6606
DOI	10.1186/s13041-020-00645-x
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Article ; Online: Spinal 5-HT

Li, Zhuo-Lin / Xue, Yang / Tao, Zhuo-Ying / Du, Wen-Zhi / Jiang, Yue-Gui / Cao, Dong-Yuan

Molecular pain

2019 Volume 15, Page(s) 1744806919859723

MeSH term(s)	Animals ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use ; Female ; Hyperalgesia/drug therapy ; Hyperalgesia/etiology ; Hyperalgesia/metabolism ; Male ; Neuralgia/drug therapy ; Neuralgia/etiology ; Neuralgia/metabolism ; Ovariectomy ; Oxazines/therapeutic use ; Pain/drug therapy ; Pain/etiology ; Pain/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin, 5-HT3/metabolism ; Serotonin 5-HT3 Receptor Antagonists/therapeutic use ; Spinal Cord/drug effects ; Spinal Cord/metabolism ; Stress, Physiological
Chemical Substances	Bridged Bicyclo Compounds, Heterocyclic ; Oxazines ; Receptors, Serotonin, 5-HT3 ; Serotonin 5-HT3 Receptor Antagonists ; azasetron (77HC7URR9Z)
Language	English
Publishing date	2019-06-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2174252-2
ISSN	1744-8069 ; 1744-8069
ISSN (online)	1744-8069
ISSN	1744-8069
DOI	10.1177/1744806919859723
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Article ; Online: Schistosoma japonicum

Ma, Zhen Rong / Sun, Xi / Zheng, Wen Xiao / Li, Xuan Wu / Zhang, Ni / Huang, Ye Hong / Lu, Bin / Li, Zhuo Lin / Nouhoum, Di Bo / Yu, Xin Ling / Zhou, Jie / Chen, Hong Zhi / Yang, Xue Xian / Wu, Xiang

Biomedical and environmental sciences : BES

2022 Volume 35, Issue 11, Page(s) 1085–1089

MeSH term(s)	Animals ; Schistosoma japonicum ; Colitis, Ulcerative
Language	English
Publishing date	2022-11-25
Publishing country	China
Document type	Letter
ZDB-ID	645083-0
ISSN	2214-0190 ; 0895-3988
ISSN (online)	2214-0190
ISSN	0895-3988
DOI	10.3967/bes2022.138
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Article: [Diagnostic Application of Invasive Cardiopulmonary Exercise Test in Patients with Unexplained Dyspnea].

Li, Zhuo-Lin / He, Yang-Ke / Xiang, Ya-Jie / Yi, Xin / Zhu, Zhong-Kai / Li, Ai-Ling / Xiang, Rui / Han, Xiao-Li / Wang, Pu / Huang, Wei

Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition

2021 Volume 52, Issue 1, Page(s) 142–148

Abstract: Objective: To explore the clinical diagnostic application of invasive cardiopulmonary exercise test (iCPET) in patients with unexplained dyspnea.: Methods: A retrospective analysis was conducted, covering patients with a chief complaint of exertional ...

Abstract	Objective: To explore the clinical diagnostic application of invasive cardiopulmonary exercise test (iCPET) in patients with unexplained dyspnea. Methods: A retrospective analysis was conducted, covering patients with a chief complaint of exertional dyspnea between May 5, 2017 and October 1, 2020. Right cardiac catheterization examination was performed on patients whose cause had not been identified through routine examination, and further iCPET was performed on patients if no clear etiology was identified through right cardiac catheterization. According to the results and the diagnostic criteria of iCPET, patients showing no obvious abnormalities in the right cardiac catheterization examination were divided into four subgroups: exercise-induced pulmonary arterial hypertension (eiPAH), exercise-induced heart failure with preserved ejection fraction (eiHFpEF), preload failure, and oxidative myopathy. By comparing the lab test, echocardiography, right heart catheter and iCPET peak exercise data of the subgroups, the disease distribution and exercise hemodynamic characteristics of patients with unexplained dyspnea examined by iCPET were described. Results: Of the 1 046 patients with exertional dyspnea, 771 were diagnosed with routine examination, while among the remaining 275 patients, 131 (47.6%) were diagnosed with right cardiac catheterization and 144 (52.4%) showed no clear etiology after routine examination and right cardiac catheterization. Of these 144 patients, 49 (34.0%) received iCPET with a median exercise time of 375 s. A total of 47 patients completed the examination, with a male-to-female ratio of 0.27∶1 and an average age of (47.9±14.4) years old. Among the 47 patients, 76.6% (36/47) aged between 20 and 59 and 78.7% (36/47) lived in urban areas. The preload failure group (
MeSH term(s)	Adult ; Cardiac Catheterization ; Dyspnea/etiology ; Exercise Test ; Exercise Tolerance ; Female ; Heart Failure/diagnosis ; Heart Failure/diagnostic imaging ; Humans ; Male ; Middle Aged ; Pulmonary Wedge Pressure ; Retrospective Studies
Language	Chinese
Publishing date	2021-01-20
Publishing country	China
Document type	Journal Article
ZDB-ID	2106840-9
ISSN	1672-173X
ISSN	1672-173X
DOI	10.12182/20210160205
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Article ; Online: Single-cell transcriptome analysis of xenotransplanted human retinal organoids defines two migratory cell populations of nonretinal origin.

Stem cell reports

2023 Volume 18, Issue 5, Page(s) 1138–1154

Abstract: Human retinal organoid transplantation could potentially be a treatment for degenerative retinal diseases. How the recipient retina regulates the survival, maturation, and proliferation of transplanted organoid cells is unknown. We transplanted human ... ...

Abstract	Human retinal organoid transplantation could potentially be a treatment for degenerative retinal diseases. How the recipient retina regulates the survival, maturation, and proliferation of transplanted organoid cells is unknown. We transplanted human retinal organoid-derived cells into photoreceptor-deficient mice and conducted histology and single-cell RNA sequencing alongside time-matched cultured retinal organoids. Unexpectedly, we observed human cells that migrated into all recipient retinal layers and traveled long distances. Using an unbiased approach, we identified these cells as astrocytes and brain/spinal cord-like neural precursors that were absent or rare in stage-matched cultured organoids. In contrast, retinal progenitor-derived rods and cones remained in the subretinal space, maturing more rapidly than those in the cultured controls. These data suggest that recipient microenvironment promotes the maturation of transplanted photoreceptors while inducing or facilitating the survival of migratory cell populations that are not normally derived from retinal progenitors. These findings have important implications for potential cell-based treatments of retinal diseases.
MeSH term(s)	Humans ; Mice ; Animals ; Single-Cell Gene Expression Analysis ; Cell Differentiation/physiology ; Retina ; Retinal Cone Photoreceptor Cells ; Retinal Degeneration/therapy ; Organoids/transplantation
Language	English
Publishing date	2023-05-08
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2023.04.004
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