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1.
J Basic Microbiol ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31588591

RESUMO

As a homo-oligomeric protein, the disassembly of Escherichia coli RbsD decamer produces a urea-unfolded oligomeric intermediate structure, as the dissociation speed of the protein is lower than that of the unfolding process. There are five Lys2-Cl- -Lys2 salt linkages to connect these subunits. To explore the role of the salt linkages in these oligomeric intermediates, the Lys2Ala mutated in the N-terminal of E. coli RbsD protein subunit was designed. It was found that the RbsD mutation protein (RbsD:K2A) loses its minor larger oligomers, which exist in RbsD, and displays other several oligomeric states (less than decamers), meanwhile the state of the oligomers depends on the protein concentration. It was also found that compared with RbsD, the crosslinking capability of the subunits of RbsD:K2A is weaker, while the crosslinking rate of dimers is higher, RbsD:K2A needs to substantially adjust its conformation to meet the space requirements when combined with d-ribose. On the basis of these results, we suggest that Lys2-Cl- -Lys2 salt linkages in E. coli RbsD protein play an important role in stabilizing the intermediate products of oligomers and maintaining interaction between the intermediate products of oligomers, which may shed light on the study of these oligomeric proteins.

2.
J Coll Physicians Surg Pak ; 29(10): 942-945, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31564266

RESUMO

OBJECTIVE: To compare the efficacy of intramedullary nailing (IMN) and minimally invasive percutaneous plate osteosynthesis (MIPO) in treatment of humeral shaft fractures. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Orthopedics, Zhejiang Hospital, China, during March 2010 to December 2016. METHODOLOGY: The study included patients with humeral shaft fractures who received surgery by IMN or MIPO. The intraoperative outcomes including operation time, bleeding volume, and the postoperative outcomes were also recorded. The Constant-Murley scores were used for assessment of function of shoulder joint and Mayo score was used for measurement of elbow joint function. RESULTS: Among a total of 436 patients with humeral shaft fractures, 204 cases received MIPO and 232 cases received IMN. The follow-up duration ranged from 16~36 months with a mean duration of 25.8 ±6.1 months. The mean operation time, mean bleeding volume, mean hospitalisation time and mean healing time showed no significant difference between MIPO and IMN groups. No significant difference was observed in Mayo scores, but the Constant-Murley scores of MIPO group was significantly higher that the IMN group. Fracture nonunion was observed for 15 (6.5%) cases in IMN group; however, only 1 (0.5%) case was found to be nonunion in MIPO group. Meanwhile, 9 (4.4%) cases showed radial nerve injury in the MIPO group, with no significant difference compared to the IMN group of 15 (6.5%) cases. CONCLUSION: Both the two methods were effective; however, MIPO method might be better for recovery of shoulder function and might reduce the nonunion rate.

3.
Langmuir ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578065

RESUMO

Diverse chains and cross-linking density of polymers are important for cell proliferation, aging and death. In this study, by controlling component ratio of N, N'- methylene - bis - acrylamide (Bis) / acrylamide (Acr), we prepared polyacrylamide (PAM) hydrogels with three different polymer structures using ultraviolet (UV) irradiation. Moreover, we quantified their Flory's cross-linking densities, gel concentrations, mechanical properties, and evaluated their influence to HL-7702 liver cells behavior and metabolism. Results showed that PAM hydrogel at ratio of Bis/Acr = 1:50 (Acr-50) owned the highest cross-linking density (0.04), which provided abundant binding sites for cell adhesion and be allowed rapid cell proliferation. Based on the binding sites cells have strong traction interaction from fibrillate adhesion with the polymers and be allowed easy cell migration and induced the living cells aggregations with diameter of 800 µm. Cells in aggregation exhibited healthy cell phenotypes and functions also the mitosis of the cells in aggregation are exactly the same with the cells in tissue. It is concluded that cell proliferation, aging and death can be controlled by adjusting the cross-linking density and diverse chains of matrix hydrogels. This work will be helpful to design new functional soft biomaterials for tissue regeneration in future.

4.
J Transl Med ; 17(1): 320, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547815

RESUMO

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the leading cause of end-stage kidney disease. Previous mRNA microarray profiling studies of IgAN revealed inconsistent data. We sought to identify the aberrantly expressed genes and biological pathways by integrating IgAN gene expression datasets in blood cells and performing systematically experimental validation. We also explored the relationship between target genes and galactose-deficient IgA1 (Gd-IgA1) in IgAN. METHODS: We retrieved Gene Expression Omnibus (GEO) datasets of IgAN. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for functional analysis. Deep sequencing on RNA isolated from B cells was used for microarray validation. The relationship between target mRNA expressions and Gd-IgA1 levels in serum were also studied. RESULTS: Three studies with microarray expression profiling datasets met our inclusion criteria. We identified 655 dyregulated genes, including 319 up-regulated and 336 down-regulated genes in three GEO datasets with a total of 35 patients of IgAN and 19 healthy controls. Based on biological process in GO term, these dyregulated genes are mainly related to pentose-phosphate shunt, non-oxidative branch, post-embryonic camera-type eye development and leukocyte activation. KEGG pathway analysis of microarray data revealed that these aberrantly expressed genes were enriched in human T-cell leukemia virus 1 infection, proteoglycans in cancer, intestinal immune network for IgA production and autophagy. We further performed deep sequencing on mRNAs isolated from B cells of an independent set of five patients with IgAN and three healthy persons with the same clinical and demographic characteristics. Seventy-seven genes overlapped with 655 differentially regulated genes mentioned above, including 43 up-regulated and thirty-four down-regulated genes. We next investigated whether these genes expression correlated with Gd-IgA1 levels in IgAN patients. Pearson correlation analyses showed PTEN (phosphatase and tensin homolog) was the most powerful gene negatively correlated with Gd-IgA1 levels. CONCLUSIONS: These results demonstrated that dyregulated genes in patients with IgAN were enriched in intestinal immune network for IgA production and autophagy process, and PTEN in B cells might be involved in the mechanism of Gd-IgA1 production.

5.
Curr Gene Ther ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31549954

RESUMO

Novel gene therapy strategies have changed the prognosis of many inherited diseases in recent years. New development in genetic tools and study models has brought us closer to a complete cure for hemophilia. This review will address the latest gene therapy research in hemophilia A and B including gene therapy tools, genetic strategies and animal models, and summarizes results of recent clinical trials. We will also discuss potential solutions to the current barriers in gene therapy for hemophilia.

6.
ACS Appl Mater Interfaces ; 11(39): 36286-36295, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31491081

RESUMO

A novel dimercaptosuccinic acid-functionalized mesoporous alumina (DMSA-MA) is synthesized by the dicarboxylic acid groups of dimercaptosuccinic acid molecules coordinating to the Al3+ ions located in the mesostructure. The as-prepared DMSA-MA composites possess a large surface area of 91.17 m2/g as well as a uniform pore size and a high pore volume of 17.22 nm and 0.23 cm3/g, respectively. DMSA coating of mesostructures significantly enhanced their selectivity for glycoprotein adsorption through a powerful hydrophilic binding force, and the maximum adsorption capacity of immunoglobulin G (IgG) can reach 2298.6 mg g-1. The captured IgG could be lightly stripped from the DMSA-MA composites with an elution rate of 98.3% by using 0.5 wt % CTAB solution as the elution reagent. DMSA-MA is further employed as a sorbent for the enrichment of IgG heavy chain and light chain from human serum sample. SDS-PAGE assay results showed the obtained IgG with high purity compared to that of the standard solution of IgG.

7.
Anaerobe ; : 102094, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31499177

RESUMO

It is known that antibiotic usage is associated with the development of Clostridioides difficile infection (CDI), especially clindamycin, third-generation cephalosporins, and fuoroquinolones. Antibiotic resistance rates to many antibiotics varies a lot by study. We performed a study focused on antibiotic resistance in clinical isolates of C. difficile from more widespread geographic regions across China. Of 319 C. difficile isolates tested against 11 antibiotics, 313 (98.1%) were resistant to at least one antibiotic. The highest rate of resistance was to ciprofloxacin, clindamycin, and erythromycin across all age groups, similar to previous studies. However, all isolates were susceptible to metronidazole and vancomycin. Overall the resistance rate to tested antibiotics was lower than other reports in China except for chloramphenicol and meropenem. Genotype ST37/RT017 in clade 4 was resistant to more antibiotics than other types. Unexpectedly, RT078 isolates in this study were susceptible to almost all tested antibiotics. In addition, the proportion of multi-drug resistant (MDR) isolates observed (17%) in this study was much lower than several European studies (up to 55%) and a previous study in China (78%). Although isolates from patients aged between 65 and 85 were more resistant to antibiotics in comparison to other age groups, MDR isolates were still detected in children below 2-years of age. The highest percentage of MDR isolates was determined in South China, an area that is most developed economically. The clade 4, RT017 (ST37) has been associated with outbreaks in Europe and North America and is responsible for most C. difficile infections (CDIs) in Asia. In addition, RT017 is often clindamycin and fluoroquinolone resistant. This study provided a relatively comprehensive description of antibiotic resistance of C. difficile in China, and further elucidates the epidemiology and antibiotic resistance of clinical isolates of C. difficile in China at a national level.

8.
J Environ Manage ; 250: 109506, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31499468

RESUMO

Community-based ecotourism (CBET) is considered an efficient mechanism for alleviating conflicts between conservation and development. It is particularly important in the conservation of the giant panda population, which faces the primary threat of habitat fragmentation. Although studies have assessed livelihood changes of households participating in CBET, research on ecological effects is lacking. To address the gaps in the literature, we conducted propensity score matching on data from households at different altitudes in giant panda habitats in Sichuan Province, China. The results show that CBET has achieved desirable social outcomes, significantly increasing local households' income and well-being, especially for those at high altitudes. With respect to ecological impacts, CBET has significantly raised households' conservation attitudes, but has also increased natural resource extraction, especially at high altitudes. Overall, CBET in the giant panda habitat has not led to a win-win situation between social and ecological outcomes, especially at high altitudes. Our results indicate that the ecological impact of CBET is significant, and policies aimed at promoting the conservation of natural resources should account for this effect.

9.
Environ Int ; 132: 105115, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31473411

RESUMO

BACKGROUND: Nephrotoxic metals of arsenic, cadmium, lead and mercury exposures are common environmental pollutants. The associations between arsenic, cadmium, lead and mercury exposures and the risk of kidney stones are unclear. OBJECTIVE: To explore the associations between biomarkers of arsenic, cadmium, lead and mercury exposures and the odds of kidney stones. METHODS: Adult participants (≥20 years) from the 2007-2016 NHANES were included. Restricted cubic splines were adopted. RESULTS: The odds ratio (95% confidence interval) of kidney stones increased with increasing blood cadmium and reached the maximum at 1.00 µg/L [1.38 (1.02-1.88) overall, 1.62 (1.11-2.32) for women and 1.53 (1.06-2.22) for non-Hispanic white]. The odds of kidney stones increased with increasing urinary cadmium and reached the maximum at 1.50 µg/L [2.56 (1.17-5.59) overall, 5.57 (1.88-16.49) for women, 4.31 (1.75-10.63) for obese individuals and 3.75 (1.60-8.78) for non-Hispanic white]. The odds of kidney stones increased with increasing total urinary arsenic and urinary dimethylarsinic acid in women, and reached the maximum of 1.69 (1.08-2.67) at 40 µg/L and 1.71 (1.07-2.72) at 10.00 µg/L, respectively. Inverse associations were found between the odds of kidney stones and blood lead within 5.00 µg/dL [0.64 (0.46-0.90) overall, 0.53 (0.33-0.84) for men and 0.58 (0.37-0.92) for non-Hispanic white], methyl mercury within 3.00 µg/L [non-obese individuals: 0.71 (0.51-0.99)] and urinary arsenous acid within 1.20 µg/L [individuals other than non-Hispanic white: 0.63 (0.41-0.95)]. No association was found with other biomarkers. CONCLUSIONS: Several biomarkers of arsenic, cadmium, lead and mercury exposures were associated with the odds of kidney stones in adults.

10.
Am J Orthod Dentofacial Orthop ; 156(3): 412-419, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31474271

RESUMO

An 8-day-old male infant with unilateral cleft lip, alveolus, and palate had a wide alveolar defect, soft tissue deformity, and a markedly sunken nasal wing at the cleft side. The patient was treated with a series of 3D-printed molding plates and synchronously with a nasal hook. The cleft edges moved closer by 9 mm at the alveolar ridge and the nasal wing was lifted considerably. Split-type 3D printing of presurgical nasoalveolar molding helped to reduce the cleft gap, improve the arch form, approximate lip segments, and distinctly improve the morphology of the nose by correcting the flattened nasal wings.


Assuntos
Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Impressão Tridimensional , Procedimentos Cirúrgicos Reconstrutivos/métodos , Processo Alveolar/cirurgia , Fenda Labial/diagnóstico por imagem , Fissura Palatina/diagnóstico por imagem , Projeto Auxiliado por Computador , Técnica de Moldagem Odontológica , Modelos Dentários , Humanos , Recém-Nascido , Masculino , Nariz/cirurgia , Procedimentos Cirúrgicos Ortognáticos/métodos , Palato/cirurgia , Resultado do Tratamento
11.
J Cell Physiol ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541463

RESUMO

Growing evidence confirms that ferroptosis plays an important role in tumor growth inhibition. However, some non-small-cell lung cancer (NSCLC) cell lines are less sensitive to erastin-induced ferroptotic cell death. Elucidating the mechanism of resistance of cancer cells to erastin-induced ferroptosis and increasing the sensitivity of cancer cells to erastin need to be addressed. In our experiment, erastin and acetaminophen (APAP) cotreatment inhibited NSCLC cell viability and promoted ferroptosis and apoptosis, accompanied with attenuation of glutathione and ectopic increases in lipid peroxides. Erastin and APAP promoted NSCLC cell death by regulating nucleus translocation of nuclear factor erythroid 2-related factor 2 (Nrf2); and the ferroptosis induced by erastin and APAP was abrogated by bardoxolone methyl (BM) with less generation of reactive oxygen species and malondialdehyde. As a downstream gene of Nrf2, heme oxygenase-1 expression decreased significantly with the cotreatment of erastin and APAP, which could be rescued by BM. In vivo experiment showed that the combination of erastin and APAP had a synergic therapeutic effect on xenograft of lung cancer. In short, the present study develops a new effective treatment for NSCLC by synergizing erastin and APAP to induce ferroptosis.

12.
BMJ Open ; 9(9): e027964, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31492778

RESUMO

INTRODUCTION: Acute coronary syndrome (ACS) is one of the leading causes of death. Depression and/or anxiety after ACS is common. Studies from developed countries have reported that the occurrence of anxiety or depression after ACS might increase the risk of cardiovascular events and mortality. However, the results varied, and are limited in developing countries. Therefore, well designed large-scale real-world study is needed to make further clarification. The main objective of this study is to evaluate whether depression or anxiety could affect the prognosis of patients with percutaneous coronary intervention (PCI) post-ACS. METHOD AND ANALYSIS: The study is a prospective, multicentre, cohort study, which will be performed at 12 large hospitals in northwest China and led by the First Affiliated Hospital of Xi'an Jiaotong University. A total of 5000 patients with PCI post-ACS will be enrolled and followed up for 2 years. Their depression and anxiety status will be evaluated with the Patient Health Questionnaire-9 or Generalised Anxiety Disorder-7 Assessment scales during the follow-up. A Cox proportional hazard model will be used to determine if depression/anxiety after PCI increase the risk of cardiovascular events. The impact of antidepression or antianxiety treatment on the cardiac prognosis will be explored as well among the patients with ACS who received the treatment after PCI. ETHICS AND DISSEMINATION: This study has been approved by the ethics committee of the First Affiliated Hospital of Xi'an Jiaotong University (approval number: XJTU1AF2016LSL-036). The results will be published in research articles or conference papers. TRIAL REGISTRATION NUMBER: NCT03057691.

13.
J Invest Dermatol ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31476317

RESUMO

Pemphigus is an organ-specific autoimmune disease targeting skin and/or mucous membranes. Our previous study showed that infiltrating lymphocytes in pemphigus vulgaris (PV) lesions produce anti-desmoglein (Dsg) 1/3 antibodies after in vitro culture. In this study, we found diffuse ectopic lymphoid-like structures (ELSs) commonly present in lesions of both PV and pemphigus foliaceus (PF). Notably, pemphigus lesions contained centroblasts, plasmablasts and plasma cells, which recapitulated the different stages of B cell differentiation. Elevated mRNA expression levels of the differentiation-related transcription factors BLIMP-1, IRF4 and BCL-6 were observed in pemphigus lesions. Moreover, B cell receptor (BCR) repertoire analysis revealed the clonal expansion of lesional B cells. Lesional B cells might recirculate among lesions, lymph nodes and peripheral blood. Increased mRNA expression levels of multiple chemokines in pemphigus lesions and elevated expression levels of chemokine receptors on lesional B cells were also observed. Collectively, these results show that ELSs in pemphigus lesions might act as a niche, supporting in situ B cell differentiation and clonal expansion.

14.
Psychiatr Genet ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31490346

RESUMO

Intellectual disability refers to significantly subaverage intellectual function (intelligence quotient < 70) with impairment of adaptive function. The IQSEC2 gene is one of the pathogenic genes located on chromosome Xp11.22. IQSEC2 is an X-linked gene correlated with intellectual disability and epilepsy. In this study, we reported a 2-year-old male patient presented with reacting sluggishly with people and surroungdings. Active electroencephalogram showed the background of epileptic activity. Brain MRI revealed patchy hyperintensity of bilateral parietal lobe white matter on fluid-attenuated inversion recovery image and widened ventricle, cistern and sulci on T2-weighted image. Delayed myelination was considered. The diagnosis of intellectual disability and epilepsy was made. Whole exome-sequencing was conducted and identified a novel frameshift mutation in exon 15 of IQSEC2 (NM_001111125.2: c.4164dupC: p.Ile1389 Hisfs*218). The variant resulted in the deletion of termination codon, and the protein was extended to termination after stretch of 218 amino acids.This study expands the mutation spectrum of IQSEC2. It supports the published data suggesting that IQSEC2 plays a significant part in patients with intellectual disability and epilepsy. IQSEC2 should be detected in patients with intellectual disability and epilepsy.

15.
J Am Geriatr Soc ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31490547

RESUMO

BACKGROUND/OBJECTIVES: Bundled payments are an alternative payment model in which a hospital takes accountability for the costs of a 90-day episode of care. Such models are meant to improve care through better coordination across care settings, but could have adverse consequences for frail adults if they lead to inappropriate cuts in necessary post-acute care. DESIGN: Retrospective claims-based analysis of hospitals' first year of participation in Medicare's Bundled Payments for Care Improvement (BPCI) program. SETTING: US hospitals. PARTICIPANTS: A total of 641 146 Medicare beneficiaries admitted to 688 BPCI programs and 1276 matched control hospitals for myocardial infarction, heart failure, pneumonia, sepsis, chronic obstructive pulmonary disease, or major joint replacement of the lower extremity in 2012 to 2016. INTERVENTION: Participation in BPCI. MEASUREMENTS: Proportion of patients in each quartile of a validated claims-based frailty index, total and setting-specific standardized Medicare payments per episode, days at home, 90-day readmissions, and 90-day mortality. RESULTS: Higher levels of frailty were associated with higher Medicare payments and worse clinical outcomes (for the medical composite, costs per episode were $11 921, $17 348, $22 828, and $29 157 across frailty quartiles; days at home were 70.1, 60.4, 54.3, and 51.5; 90-day readmission rates were 16.0%, 27.0%, 38.2%, and 50.9%; and 90-day mortality rates were 15.4%, 22.5%, 25.1%, 21.3%); patterns were similar for joint replacement. Under the BPCI program, there was no differential change in the proportion of highly frail patients at BPCI vs control hospitals. There were also no differential deleterious changes in payments or clinical outcomes for frail relative to nonfrail patients at BPCI vs non-BPCI hospitals. CONCLUSION: While frail patients had higher costs and worse outcomes in general, there was no evidence of changes in access or worsening clinical outcomes in BPCI hospitals for frail patients relative to the nonfrail in hospitals' first year of participation in the program. These findings may be reassuring for policy makers and clinical leaders.

16.
Anal Chim Acta ; 1082: 106-115, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472699

RESUMO

Sphingoid bases (SBs) are one of important components of cell membranes, playing important roles in cellular biology. Meanwhile, SBs are associated with various metabolic diseases such as Type 2 Diabetes mellitus (T2DM). Therefore, simultaneous quantitation of multiple SBs in biological samples could provide crucial information for uncovering underlying mechanisms of SBs related functions and diseases. However, existing methods are difficult to achieve simultaneous quantitation for multiple SBs due to the lack of isotope internal standards (ISs) of corresponding SBs. In the current study, we developed a highly sensitive method for the simultaneous detection of 26 SBs in biological samples by stable isotope labeling coupled with ultra-high performance liquid chromatography tandem mass spectrometry (SIL-UHPLC-MS/MS) analysis. In this respect, a pair of isotope labeling reagents, 3-(N, N-dimethylamino)propyl isothiocyanate (DMPI) and d4-3-(N, N-dimethylamino)propyl isothiocyanate (d4-DMPI), were synthesized and utilized to label SBs in biological samples and SB standards, respectively. The d4-DMPI labeled SB standards were used as ISs to calibrate quantitation deviation in MS analysis from the biological matrix. Using the developed method, we successfully quantitated 19 SBs in cells, 20 SBs in mice feces and 18 SBs in human serum samples. Three C17-SBs used as ISs in many reported works were even found in all prepared samples. In summary, the developed SIL-UHPLC-MS/MS analysis was demonstrated to be a promising method for the simultaneous determination of multiple SBs, which could facilitate the investigation of cellular function of SBs and pathogenesis of related diseases.

17.
Behav Genet ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31493278

RESUMO

There is increasing interest within the genetics community in estimating the relative contribution of parental genetic effects on offspring phenotypes. Here we describe the user-friendly M-GCTA software package used to estimate the proportion of phenotypic variance explained by maternal (or alternatively paternal) and offspring genotypes on offspring phenotypes. The tool requires large studies where genome-wide genotype data are available on mother- (or alternatively father-) offspring pairs. The software includes several options for data cleaning and quality control, including the ability to detect and automatically remove cryptically related pairs of individuals. It also allows users to construct genetic relationship matrices indexing genetic similarity across the genome between parents and offspring, enabling the estimation of variance explained by maternal (or alternatively paternal) and offspring genetic effects. We evaluated the performance of the software using a range of data simulations and estimated the computing time and memory requirements. We demonstrate the use of M-GCTA on previously analyzed birth weight data from two large population based birth cohorts, the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Norwegian Mother and Child Cohort Study (MoBa). We show how genetic variation in birth weight is predominantly explained by fetal genetic rather than maternal genetic sources of variation.

18.
Mater Sci Eng C Mater Biol Appl ; 104: 110001, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31500023

RESUMO

Paclitaxel is broad-spectrum anticancer drug which has been widely used in clinic. However, traditional drug delivery often suffers from the scarcity of resources and systemic toxic side effects caused by the localization to non-tumor areas, rendering cancer treatment extremely challenging. To address this problem, we developed a novel multifunctional drug delivery system of a poly(lactic-co-glycolic acid) (PLGA) drug-loaded magnetic Janus particles (DMJPs) using electrohydrodynamic (EDH) co-jetting. The DMJPs were loaded with three compartments each with distinct function, i.e. paclitaxel for killing cancer cell, Fe3O4 nanoparticles for target location, and rhodamine B for fluorescence tracing, respectively. The Janus structure of the DMJPs, as demonstrated by the loaded nano-quantum dots CdS/ZnS and CdSe/ZnS in different compartments, enhanced not only the drug loading and encapsulation efficiency but also the cumulative release rate of the loaded drugs from DMJPs in different media. More importantly, DMJPs exhibited specific and high toxicity only to human breast cancer cells (MDA-MB-231), but not to mouse embryonic fibroblasts (NIH-3 T3). Consistently, DMJPs induced the higher lethal effect on cancer cells than paclitaxel suspension of high concentrations. Under guidance of external magnetic field, DMJPs can readily target and accumulate on and inside cancer cells for cell elimination. The specific targetability, selectivity, and toxicity of DMJPs on cancer cells would greatly avoid any potential side effects and reduce the overdose of drugs for conventional drug delivery. This work hopefully provides a new drug delivery system for the development of anticancer drug systems for clinical and precision medicine treatment.

19.
J Cell Biochem ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31502329

RESUMO

It is well characterized that activated hepatic stellate cells (HSCs) exert critical functions in accelerating the progression of liver fibrosis. Previous studies have indicated that Dahuang Zhechong pill (DHZCP), a traditional Chinese herbal medicine, is capable of inactivating HSCs and thus attenuate the formation of liver fibrosis in rats. However, pharmacological mechanisms of DHZCP in alleviating liver fibrosis remain unclear. This study aims to investigate the antifibrotic role of DHZCP through inhibiting the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) pathway. DHZCP was found to significantly suppresses extracellular matrix formation and immune cell infiltration, thus alleviating liver fibrosis symptoms in the in vivo model. Moreover, DHZCP reduced serum levels of transforming growth factor ß1 and tumor necrosis factor-α in rats with liver fibrosis. DHZCP treatment remarkably downregulated protein levels of PI3K and phosphorylated Akt, as well as fibrosis markers. In vitro experiments further demonstrated that DHZCP markedly suppressed HSCs proliferation by downregulating PI3K/Akt, which exerted a synergistic effect with the PI3K inhibitor LY294002. To sum up, our results confirmed that DHZCP exerted an antifibrotic effect in the animal model through inactivating the PI3K/Akt pathway, thus protecting rats from liver injury.

20.
Chin J Nat Med ; 17(7): 525-534, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31514984

RESUMO

This study aimed to investigate the mechanisms of Yu-Ping-Feng-San (YPFS) on attenuating allergic inflammation in the initial stage of atopic dermatitis (AD). AD mouse model was established with fluorescein isothiocyanate (FITC) sensitization and elicitation. Epithelial barrier structure was observed with transmission electron microscope. The populations of dendritic cells (DCs) and group 2 innate lymphoid cells (ILC2s) were detected by flow cytometry. Human immortalized keratinocyte (HaCaT) cells were stimulated with Poly(I:C)/TNF-α in vitro to assessthymic stromal lymphopoietin (TSLP), interleukin (IL)-33 and nuclear factor-κB (NF-κB) levels or expressions by immunofluorescence, enzyme linked immunosorbent assay (ELISA) and western blot. In the initial stage of AD, ear swelling and infiltration of inflammatory cells in ear tissues were markedly attenuated with YPFS treatments. The damaged structures of ear epithelium and the increased levels of Th2-cytokines induced by FITC were significantly rescued in YPFS-treated mice. The production of pro-allergic cytokines, TSLP and IL-33, as well as the cell populations of their target cells DCs and ILC2s were decreased in AD model, respectively. Likewise, the levels of TSLP and IL-33 in Poly(I:C)/TNF-α-stimulated HaCaT cells showed the same results. Lower levels of p-NF-κB were detected with YPFS treatment, and the expressions of TSLP and IL-33 could be further decreased with inhibiting of NF-κB. Therefore, YPFS attenuates allergic inflammation in the initial stage of AD probably through regulating NF-κB-TSLP/IL-33 pathway, which may provide a novel effective target for the prevention and treatment of allergic diseases.

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