Publications by authors named "Jian Guan"

551 Publications

T MRI at 3T of cartilage and menisci in patients with hyperuricemia: initial findings.

Skeletal Radiol 2021 Jul 21. Epub 2021 Jul 21.

Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions; School of Radiation Medicine and Protection, Medical College of Soochow University; School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou, 215123, Jiangsu, China.

Objective: To compare and evaluate T values of compartmental femorotibial cartilage and subregional menisci in patients with hyperuricemia at 3T.

Materials And Methods: Thirty-two subjects were included in this study and subdivided into two subgroups: 15 healthy controls (3 females, 12 males; mean age = 45.3 ± 10.9 years), 17 patients with hyperuricemia (2 females, 15 males; mean age = 44.4 ± 12.7 years). All subjects were assessed on a 3T MR scanner using an 8-channel phased-array knee coil (transmit-receive). Wilcoxon rank sum test and analysis of covariance (ANCOVA) were performed to determine whether there were any statistically significant differences in T values of compartmental femorotibial cartilage and subregional menisci between the two subgroups.

Results: Lateral tibial cartilage (48.6 ± 3.5 ms) in healthy subgroup had significantly lower (p < 0.05) T values than all subcompartments of femorotibial cartilage in hyperuricemia subgroup. Medial tibial cartilage (56.5 ± 4.3 ms) in hyperuricemia subgroup had significantly higher (p < 0.05) T values than all subcompartments of femorotibial cartilage except medial tibial cartilage in healthy subgroup. Medial anterior horn of meniscus (39.4 ± 2.9 ms) in healthy subgroup had significantly lower (p < 0.05) T values than all subregional menisci except both medial anterior horn and medial body segment of meniscus in hyperuricemia subgroup.

Conclusion: T values in certain compartmental femorotibial cartilage and subregional menisci in patients with hyperuricemia are evidently and abnormally heightened compared with those in healthy subjects, to which special attention should be paid when diagnosing and treating the patients with hyperuricemia in the clinical setting. The LT cartilage had significantly lower T values (48.6 ± 3.5 ms) in healthy subgroup compared to all compartmental femorotibial cartilage in cohort with HU. MF cartilage had significantly lower T values (51.6 ± 2.9 ms) in healthy subgroup compared to both LF (54.4 ± 4.1 ms) and MT (56.5 ± 4.3 ms) in cohort with HU. MT cartilage had significantly higher T values (56.5 ± 4.3 ms) in cohort with HU subgroup compared to LF (52.5 ± 3.0 ms) in healthy subgroup. T mapping may be promising and potential sensitive discriminator of understanding and examining the early compositional and structural change in proteoglycan-collagen matrix of human femorotibial cartilage in patients with hyperuricemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00256-021-03861-1DOI Listing
July 2021

Risk factors for non-positional obstructive sleep apnea-hypopnea syndrome.

Sleep Breath 2021 Jul 19. Epub 2021 Jul 19.

Department of Otolaryngology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Otolaryngology Institute of Shanghai Jiao Tong University, 600 Yishan Road, Shanghai, 200233, China.

Objective: To explore the main risk factors for non-positional obstructive sleep apnea (NPOSA).

Methods: A total of 560 patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) were divided into non-positional obstructive sleep apnea (NPOSA) and positional obstructive sleep apnea (POSA) groups. All patients were assessed by the Friedman staging system and anthropometry before overnight polysomnography. Blood tests were performed to determine the fasting blood glucose level and lipid profile. Forward logistic regression analysis was performed to evaluate the effects of all parameters on positional dependency.

Results: The study sample consisted of 318 NPOSA patients and 242 POSA patients (88% and 85% were men, respectively). The mean apnea-hypopnea index (AHI) was 57.0 events/h in the NPOSA group, compared with 25.7 events/h in the POSA group. The POSA group had a significantly smaller neck circumference (NC), waist circumference (WC), hip circumference (HC), lower body mass index (BMI), AHI, fasting blood glucose, and apolipoprotein-B (apoB) levels than did the NPOSA group (all, P < 0.01). The minimal nocturnal oxyhemoglobin saturation (minSpO) and apoB/apoA ratio were higher in the POSA group than in the NPOSA group (both, P < 0.001). The AHI, minSpO, WC, and fasting blood glucose level were included in the logistic regression models.

Conclusion: The AHI, WC, minSpO, and fasting blood glucose level are the main independent risk factors for NPOSA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11325-021-02430-zDOI Listing
July 2021

Exploring the potential of functional polymer-lipid hybrid nanoparticles for enhanced oral delivery of paclitaxel.

Asian J Pharm Sci 2021 May 2;16(3):387-395. Epub 2021 Mar 2.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.

Most biopharmaceutics classification system (BCS) class IV drugs, with poor solubility and inferior permeability, are also substrates of P-glycoprotein (P-gp) and cytochrome P450 (CYP450), leading to their low oral bioavailability. The objective of this study is to explore the potential of using functional polymer-lipid hybrid nanoparticles (PLHNs) to enhance the oral absorption of BCS IV drugs. In this paper, taking paclitaxel (PTX) as a drug model, PTX-loaded PLHNs were prepared by a self-assembly method. Chitosan was selected to modify the PLHN to enhance its mucoadhesion and stability. Three P-gp inhibitors (D-α-tocopherol polyethylene glycol 1000 succinate, pluronic P123 and Solutol HS15) were incorporated into selected PLHNs, and a CYP450 inhibitor (the extract of VBRB, BC0) was utilized to jointly promote the drug absorption. Properties of all the PLHNs were characterized systemically, including particle size, zeta potential, encapsulation efficiency, morphology, stability, drug release, mucoadhesion, intestinal permeability and systemic exposure. It was found mucoadhesion of the CS-modified PLHNs was the strongest among all the formulations tested, with absolute bioavailability 21.95%. P-gp and CYP450 inhibitors incorporation further improved the oral bioavailability of PTX to 42.60%, 8-fold increase compared with that of PTX itself (4.75%). Taken together, our study might shed light on constructing multifunctional PLHNs based on drug delivery barriers for better oral absorption, especially for BCS IV drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajps.2021.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261254PMC
May 2021

LACTB2 renders radioresistance by activating PINK1/Parkin-dependent mitophagy in nasopharyngeal carcinoma.

Cancer Lett 2021 Jul 13;518:127-139. Epub 2021 Jul 13.

Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, China. Electronic address:

Radiotherapy is a standard and conventional treatment strategy for nasopharyngeal carcinoma (NPC); however, radioresistance remains refractory to clinical outcomes. Understanding the molecular mechanism of radioresistance is crucial for advancing the efficacy of radiotherapy and improving the prognosis of NPC. In this study, β-lactamase-like-protein 2 (LACTB2) was identified as a potential biomarker for radioresistance using tandem mass tag proteomic analysis of NPC cells, gene chip analysis of NPC tissues, and differential gene analysis between NPC and normal nasopharyngeal tissues from the Gene Expression Omnibus database GSE68799. Meanwhile, LACTB2 levels were elevated in the serum of patients with NPC after radiotherapy. Inhibiting LACTB2 levels and mitophagy can sensitize NPC cells to ionizing radiation. In NPC cells, LACTB2 was augmented at the transcription and protein levels after radiation rather than nucleus-cytoplasm-mitochondria transposition to activate PTEN-induced kinase 1 (PINK1) and mitophagy. In addition, LACTB2 was first authenticated to co-locate with PINK1 by interacting with its N-terminal domain. Together, our findings indicate that overexpressed LACTB2 provoked PINK1-dependent mitophagy to promote radioresistance and thus might serve as a prognostic biomarker for NPC radiotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2021.07.019DOI Listing
July 2021

Correction to Cedrol from Ginger Ameliorates Rheumatoid Arthritis via Reducing Inflammation and Selectively Inhibiting JAK3 Phosphorylation.

J Agric Food Chem 2021 Jul 12;69(28):8063. Epub 2021 Jul 12.

Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, People's Republic of China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.1c03690DOI Listing
July 2021

An 18.3 MJ charging and discharging pulsed power supply system for the Space Plasma Environment Research Facility (SPERF): The subsystem for the magnetopause shape control coils.

Rev Sci Instrum 2021 Jun;92(6):064709

Key Laboratory of Pulsed Power, Institute of Fluid Physics, CAEP, Mianyang 621900, Sichuan, China.

The Space Plasma Environment Research Facility currently under construction at the Harbin Institute of Technology in China uses four magnetosheath coils (flux cores) and a dipole coil to generate the magnetic field required for the study on the magnetopause magnetic reconnection. Two groups of magnetopause shape control coils (labeled CK coils) are used to slightly adjust the magnetic field distribution on the magnetopause. A capacitive pulsed power supply (PPS) system with a modular design is developed to excite CK coils. The PPS system consists of six sets of PPS with the same principle and structure, which are used to excite six sub-coils of the CK coils, respectively. Each set of PPS consists of ten modules and one local controller, and each module consists of a charger and discharge unit. Each set of PPS can provide a pulsed current of no less than 400 kA for the corresponding sub-coil at 0.11 ms when the charging voltage is 20 kV, and the duration of the pulsed current from the peak to 10% of the peak is no more than 0.6 ms. The detailed design of the PPS is discussed in this paper, and the discharge test of the PPS is carried out to verify the design of the PPS. Because there are acquisition and control devices in the discharge unit, the electromagnetic interference immunity design is also discussed to ensure the normal operation of the PPS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1063/5.0052725DOI Listing
June 2021

An 18.3 MJ charging and discharging pulsed power supply system for the Space Plasma Environment Research Facility (SPERF): The subsystem for the dipole coil.

Rev Sci Instrum 2021 Apr;92(4):044706

Key Laboratory of Pulsed Power, Institute of Fluid Physics, CAEP, Mianyang 621900, Sichuan, China.

The Space Plasma Environment Research Facility (SPERF) currently under construction at the Harbin Institute of Technology in China is a user facility dedicated to studying space plasma physics on the ground. A coil system of the SPERF consists of seven types of coils, which are used to generate the magnetic fields and plasma required by the physical experiments. A dipole coil of the coil system works with four magnetosheath coils (flux cores) to build the magnetic fields resembling that of the Earth and solar wind. A capacitor-based pulsed power supply (PPS) system with a modular design is developed to excite the dipole coil to generate a magnetosphere-like magnetic field required by the magnetopause magnetic reconnection experiment. The PPS of the dipole coil has a longer pulse duration and more energy than that of other coils in the coil system, it delivers a pulsed current with a peak of more than 18 kA, and the duration of the current is not less than 95% of the peak over 10 ms to the dipole coil when the charging voltage is not less than 20 kV. The detailed design of the PPS is discussed in this paper, and the discharge test of the PPS is carried out to verify the design of the PPS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1063/5.0043730DOI Listing
April 2021

Plasma Kallikrein Contributes to Intracerebral Hemorrhage and Hypertension in Stroke-Prone Spontaneously Hypertensive Rats.

Transl Stroke Res 2021 Jul 9. Epub 2021 Jul 9.

Research Division, Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA, 02215, USA.

Plasma kallikrein (PKa) has been implicated in contributing to hemorrhage following thrombolytic therapy; however, its role in spontaneous intracerebral hemorrhage is currently not available. This report investigates the role of PKa on hemorrhage and hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were fed with a high salt-containing stroke-prone diet to increase blood pressure and induce intracerebral hemorrhage. The roles of PKa on blood pressure, hemorrhage, and survival in SHRSP were examined in rats receiving a PKa inhibitor or plasma prekallikrein antisense oligonucleotide (PK ASO) compared with rats receiving control ASO. Effects on PKa on the proteolytic cleavage of atrial natriuretic peptide (ANP) were analyzed by tandem mass spectrometry. We show that SHRSP on high-salt diet displayed increased levels of PKa activity compared with control rats. Cleaved kininogen was increased in plasma during stroke compared to SHRSP without stroke. Systemic administration of a PKa inhibitor or PK ASO to SHRSP reduced hemorrhage and blood pressure, and improved neurological function and survival compared with SHRSP receiving control ASO. Since PKa inhibition was associated with reduced blood pressure in hypertensive rats, we investigated the effects of PKa on the cleavage of ANP. Incubation of PKa with ANP resulted in the generation fragment ANP, which displayed reduced effects on blood pressure lowering compared with full length ANP. PKa contributes to increased blood pressure in SHRSP, which is associated with hemorrhage and reduced survival. PKa-mediated cleavage of ANP reduces its blood pressure lowering effects and thereby may contribute to hypertension-induced intracerebral hemorrhage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12975-021-00929-xDOI Listing
July 2021

Fabrication of 3D-Printed Interpenetrating Hydrogel Scaffolds for Promoting Chondrogenic Differentiation.

Polymers (Basel) 2021 Jun 29;13(13). Epub 2021 Jun 29.

Beijing Key Laboratory of Sports Injuries, Sports Medicine Department, Peking University Third Hospital, Beijing 100191, China.

The limited self-healing ability of cartilage necessitates the application of alternative tissue engineering strategies for repairing the damaged tissue and restoring its normal function. Compared to conventional tissue engineering strategies, three-dimensional (3D) printing offers a greater potential for developing tissue-engineered scaffolds. Herein, we prepared a novel photocrosslinked printable cartilage ink comprising of polyethylene glycol diacrylate (PEGDA), gelatin methacryloyl (GelMA), and chondroitin sulfate methacrylate (CSMA). The PEGDA-GelMA-CSMA scaffolds possessed favorable compressive elastic modulus and degradation rate. In vitro experiments showed good adhesion, proliferation, and F-actin and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the scaffolds. When the CSMA concentration was increased, the compressive elastic modulus, GAG production, and expression of F-actin and cartilage-specific genes (COL2, ACAN, SOX9, PRG4) were significantly improved while the osteogenic marker genes of COL1 and ALP were decreased. The findings of the study indicate that the 3D-printed PEGDA-GelMA-CSMA scaffolds possessed not only adequate mechanical strength but also maintained a suitable 3D microenvironment for differentiation, proliferation, and extracellular matrix production of BMSCs, which suggested this customizable 3D-printed PEGDA-GelMA-CSMA scaffold may have great potential for cartilage repair and regeneration in vivo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym13132146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271621PMC
June 2021

SFTPA1 is a potential prognostic biomarker correlated with immune cell infiltration and response to immunotherapy in lung adenocarcinoma.

Cancer Immunol Immunother 2021 Jun 28. Epub 2021 Jun 28.

Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Pulmonary surfactant protein A1 (SFTPA1) is a member of the C-type lectin subfamily that plays a critical role in maintaining lung tissue homeostasis and the innate immune response. SFTPA1 disruption can cause several acute or chronic lung diseases, including lung cancer. However, little research has been performed to associate SFTPA1 with immune cell infiltration and the response to immunotherapy in lung cancer. The findings of our study describe the SFTPA1 expression profile in multiple databases and was validated in BALB/c mice, human tumor tissues, and paired normal tissues using an immunohistochemistry assay. High SFTPA1 mRNA expression was associated with a favorable prognosis through a survival analysis in lung adenocarcinoma (LUAD) samples from TCGA. Further GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that SFTPA1 was involved in the toll-like receptor signaling pathway. An immune infiltration analysis clarified that high SFTPA1 expression was associated with an increased number of M1 macrophages, CD8 T cells, memory activated CD4 T cells, regulatory T cells, as well as a reduced number of M2 macrophages. Our clinical data suggest that SFTPA1 may serve as a biomarker for predicting a favorable response to immunotherapy for patients with LUAD. Collectively, our study extends the expression profile and potential regulatory pathways of SFTPA1 and may provide a potential biomarker for establishing novel preventive and therapeutic strategies for lung adenocarcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-021-02995-4DOI Listing
June 2021

Effect of Interaction Between Slow Wave Sleep and Obstructive Sleep Apnea on Insulin Resistance: A Large-Scale Study.

Nat Sci Sleep 2021 4;13:739-749. Epub 2021 Jun 4.

Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.

Objective: Slow-wave sleep (SWS) and obstructive sleep apnea (OSA) have attracted recent research attention. However, their joint effects on insulin resistance (IR) remain unclear. This study explored whether SWS influences the relationship between OSA and IR.

Methods: We enrolled potential participants in our sleep center from 2007 to 2019. We collected demographic and clinical characteristics and determined IR status. SWS was derived from polysomnography data. Logistic regression analysis was used to reveal the associations between SWS and IR.

Results: In all, 6966 participants (5709 OSA and 1257 primary snoring [PS] subjects) were enrolled. Less SWS increased the risk of IR in OSA patients but not in PS patients. OSA patients with SWS <6.5% were more likely to have IR than were those with SWS >21.3%. OSA was an independent risk factor for IR after adjusting for potential confounding factors. In stratified analyses according to the percentage of SWS, OSA patients with SWS <6.5% had an odds ratio for IR of 2.461 (95% CI, 2.018-3.002) compared to the PS group after adjusting for potential confounders.

Conclusion: Less SWS is associated with higher odds for IR in OSA patients but not in PS patients. OSA is independently associated with IR. In addition, OSA combined with an extreme lack of SWS has a more harmful effect on the status of IR than OSA itself.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/NSS.S311130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187030PMC
June 2021

The nonclassical immune surveillance for ERAAP function.

Curr Opin Immunol 2021 Jun 4;70:105-111. Epub 2021 Jun 4.

Department of Pathology and Institute of Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.

The peptide repertoire presented by MHC class I molecules on the cell surface is essential for the immune surveillance of intracellular pathogens and transformed cells. The generation of this peptide repertoire is critically dependent on the endoplasmic reticulum aminopeptidase associated with antigen processing (ERAAP). Loss of ERAAP function leads to the generation of a profoundly disrupted peptide repertoire including many novel and immunogenic peptides. Strikingly, a large fraction of these novel peptides on ERAAP-KO cells are presented by the nonclassical MHC Ib molecule, Qa-1. One immunodominant Qa-1-restricted novel peptide is recognized by a unique CD8 T cell population showing features of both conventional cytotoxic T cells and unconventional innate-like T cells. While much remains to be uncovered, here we summarize the latest discoveries of our lab on the important immune surveillance of ERAAP function mediated by nonclassical MHC Ib molecules and their unusual cognate T cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.coi.2021.05.008DOI Listing
June 2021

Construction of autophagy prognostic signature and analysis of prospective molecular mechanisms in skin cutaneous melanoma patients.

Medicine (Baltimore) 2021 Jun;100(22):e26219

Spine and Osteopathy Ward, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi.

Background: Autophagy is closely related to skin cutaneous melanoma (SKCM), but the mechanism involved is unclear. Therefore, exploration of the role of autophagy-related genes (ARGs) in SKCM is necessary.

Materials And Methods: Differential expression autophagy-related genes (DEARGs) were first analysed. Univariate and multivariate Cox regression analyses were used to evaluate the expression of DEARGs and prognosis of SKCM. Further, the expression levels of prognosis-related DEARGs were verified by immunohistochemical (IHC) staining. Finally, gene set enrichment analysis (GSEA) was used to explore the underlying molecular mechanisms of SKCM.

Results: Five ARGs (APOL1, BIRC5, EGFR, TP63, and SPNS1) were positively correlated with the prognosis of SKCM. IHC verified the results of the differential expression of these 5 ARGs in the bioinformatics analysis. According to the receiver operating characteristic curve, the signature had a good performance at predicting overall survival in SKCM. The signature could classify SKCM patients into high-risk or low-risk groups according to distinct overall survival. The nomogram confirmed that the risk score has a particularly large impact on the prognosis of SKCM. Calibration plot displayed excellent agreement between nomogram predictions and actual observations. Principal component analysis indicated that patients in the high-risk group could be distinguished from those in low-risk group. Results of GSEA indicated that the low-risk group is enriched with aggressiveness-related pathways such as phosphatidylinositol-3-kinase/protein kinase B and mitogen-activated protein kinase signalling pathways.

Conclusion: Our study identified a 5-gene signature. It revealed the mechanisms of autophagy that lead to the progression of SKCM and established a prognostic nomogram that can predict overall survival of patients with SKCM. The findings of this study provide novel insights into the relationship between ARGs and prognosis of SKCM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000026219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183723PMC
June 2021

COMMD10 inhibits tumor progression and induces apoptosis by blocking NF-κB signal and values up BCLC staging in predicting overall survival in hepatocellular carcinoma.

Clin Transl Med 2021 May;11(5):e403

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Currently, there is limited knowledge of dysregulation of cellular proliferation and apoptosis that contribute to the malignant phenotype in HCC. Copper metabolism gene MURR1 domain 10 (COMMD10) is initially identified as a suppressor gene in the pathogenesis of HCC in our observations. Here we aimed to explore its function and prognostic value in the progression of HCC.

Methods: Functional experiments were performed to explore the role of COMMD10 in HCC. The molecular mechanisms of COMMD10 were determined by luciferase assay, immunofluorescence, and immunoprecipitation. The nomogram was based on a retrospective and multicenter study of 516 patients who were pathologically diagnosed with HCC from three Chinese hospitals. The predictive accuracy and discriminative ability of the nomogram were determined by a C-index and calibration curve and were compared with COMMD10 and the Barcelona Clinic Liver Cancer (BCLC) staging system. The primary endpoint was overall survival (OS).

Results: COMMD10 expression was significantly lower in HCC than that in normal liver tissues. In vitro and in vivo experiments revealed that COMMD10 suppressed cell proliferation and induced apoptosis in HCC. Mechanistically, COMMD10 inhibits TNFα mediated ubiquitination of IκBα and p65 nuclear translocation through the combination of COMMD10-N terminal to the Rel homology domain of p65, which inhibited NF-κB activity and increased expression of cleaved caspase9/3 in HCC. Clinically, COMMD10 stratifies early-stage HCC patients into two risk groups with significantly different OS. Additionally, the nomogram based on COMMD10 and BCLC stage yielded more accuracy than BCLC stage alone for predicting OS of HCC patients in three cohorts.

Conclusions: COMMD10 suppresses proliferation and promotes apoptosis by inhibiting NF-κB signaling and values up BCLC staging in predicting OS, which provides evidence for the identification of potential therapeutic targets and the accurate prediction of prognosis for patients with HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ctm2.403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093973PMC
May 2021

Large Recurrent Mediastinal Abscess Presenting With Cardiopulmonary Collapse.

Cureus 2021 Apr 23;13(4):e14653. Epub 2021 Apr 23.

Internal Medicine, AdventHealth Orlando, Orlando, USA.

Mediastinal abscesses are rarely encountered but pose a potential threat for cardiopulmonary collapse given the close proximity of vital structures. Our focus is to illustrate a case of a mediastinal abscess that was promptly diagnosed and treated, leading to complete resolution of the airway and circulatory compromise. The proposed pathogeneses behind mediastinal abscesses are discussed at length.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7759/cureus.14653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141383PMC
April 2021

The effect of local intraoperative corticosteroid application on postoperative dysphagia following anterior cervical spine surgery.

Neurosurg Rev 2021 May 12. Epub 2021 May 12.

Department of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, 45 Changchun Street, Beijing, 100053, China.

Dysphagia is a common complication following anterior cervical spine surgery (ACSS). Although several literatures have reported the potential benefit of local corticosteroid application on dysphagia, its safety and efficacy are still unclear. A systematic review was performed aiming to evaluate the evidence of local corticosteroid application in prevention or treatment of postoperative dysphagia following ACSS. A systematic search was performed in September 2018 in PubMed and Embase database. The following information was extracted: study investigator, year of publication, number of patients, study design, inclusion/exclusion criteria, administration protocol of steroid, type of surgical procedure, number of levels performed, assessment methodology of dysphagia, radiologic assessment of prevertebral soft tissue swelling (PSTS), follow-up time points, outcome of dysphagia, and corticosteroid-related complications. Qualitative synthesis was performed. Finally, 5 studies met the inclusion/exclusion criteria. Four studies found that local corticosteroid application could decrease the incidence and magnitude of postoperative dysphagia while 1 study showed no effect on dysphagia significantly at 6 weeks and 3 months follow-up time. A total of 2325 patients received local corticosteroid intraoperatively; no early corticosteroid-related complication was reported. Totally, 4 adverse events occurred in long-term follow-up time, including 2 bone nonunion at 1.5 and 2.5 years postoperatively, 2 esophageal perforation at 2 months and 11 months of follow-up, respectively. Local corticosteroid application can reduce the incidence and severity of dysphagia following ACSS without increasing early corticosteroid-related complications. But further high-quality study is necessary to analyze potential delayed complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10143-019-01207-zDOI Listing
May 2021

Metabolomics and microbiome profiling as biomarkers in obstructive sleep apnoea: a comprehensive review.

Eur Respir Rev 2021 Jun 11;30(160). Epub 2021 May 11.

Dept of Otolaryngology Head and Neck Surgery & Center of Sleep Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Introduction: Obstructive sleep apnoea (OSA) is a common sleep disorder with a high social and economic burden. Thus, early prediction and diagnosis of OSA are important. Changes in metabolism and the microbiome may serve as biomarkers for OSA. Herein, we review the literature on the metabolomic and microbiome changes associated with OSA, and identify the metabolites and microorganisms involved.

Methods: We searched the PUBMED and EMBASE electronic databases using the following terms: "obstructive sleep apnea", "OSA", "sleep disordered breathing", "SDB", "intermittent hypoxia", "sleep fragmentation", and either "metabolomics" or "microbiome". In total, 273 papers were identified, of which 28 were included in our study.

Results: Changes in the levels of certain metabolites related to fatty acid, carbohydrate and amino acid metabolism were associated with the incidence of OSA. The diversity and abundance of microflora, particularly Firmicutes and Bacteroidetes, were altered in humans and rodents with OSA.

Conclusions: Certain changes in metabolism and the microbiota play an integral role in the pathophysiology of OSA and OSA-induced cardiovascular complications. Metabolomic and microbiome biomarkers shed light on the pathogenesis of OSA, and facilitate early diagnosis and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/16000617.0220-2020DOI Listing
June 2021

Effect of simple-bundles management vs. guideline-bundles management on elderly patients with septic shock: a retrospective study.

Ann Palliat Med 2021 May 10;10(5):5198-5204. Epub 2021 May 10.

Emergency Department, First Hospital of Tsinghua University, Beijing, China.

Background: The objective of this study was to compare the effects of simple-bundles management and guideline-bundles management on elderly patients with severe sepsis and septic shock.

Methods: This was a single-center retrospective observational study of elderly patients with a hospital discharge diagnosis of severe sepsis or septic shock from First Hospital of Tsinghua University from January 2014 to December 2018. Management for patients from emergency ward adhered to the simple bundles. Management for patients from intensive care unit adhered to Surviving Sepsis Campaign Guidelines 2012. Data of the two groups were collected to determine the demographic, the source of infection, the baseline physiology, the Acute Physiology and Chronic Health Evaluation (APACHE) II Scores and the serum lactate concentration during the in-hospital period and were compared. The 30-, 60-, and 90-day mortality were compared between the two groups.

Results: One hundred patients came from emergency ward and ninety-eight patients came from intensive care unit met the inclusion criteria. There were no significant differences between the two groups in demographic and clinical characteristics at baseline (P>0.05). There were no significant differences between the two groups in the APACHE-II scores and the lactate concentration at 6, 24, 72 hours after management and before management (P>0.05). There were also no significant differences between the two groups in the 30-, 60- and 90-day mortality (P>0.05).

Conclusions: The level of improvement achieved in the simple-bundles group was similar with that achieved in the guideline-bundles group. Guideline-bundles management, compared with simple-bundles management, might not decrease mortality among elderly patients with severe sepsis and septic shock.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-20-2320DOI Listing
May 2021

Tongue swelling as a manifestation of tongue metastasis from pulmonary sarcomatoid carcinoma: A case report.

World J Clin Oncol 2021 Apr;12(4):282-289

Department of Internal Medicine, AdventHealth Orlando, Orlando, FL 32804, United States.

Background: Sarcomatoid carcinoma is a rare subtype of non-small-cell lung cancer, commonly associated with locally advanced disease, early metastasis, and poor prognosis. Tongue metastasis from lung cancer is a rare condition that may occur in advanced stage of the disease.

Case Summary: The patient was a 70-year-old female with a history of resected pulmonary sarcomatoid carcinoma (PSC) who presented with subacute tongue swelling, imparting the clinical impression of a lingual abscess. However, histologic examination of the partial glossectomy revealed a high-grade, poorly differentiated spindle and epithelioid carcinoma consistent with metastatic PSC.

Conclusion: Although uncommon, clinicians should be cognizant of the possibility of a metastatic process to the tongue mimicking a benign or inflammatory process. A high index of suspicion for metastatic disease should be maintained when tongue swelling is observed in patients with a known history of PSC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5306/wjco.v12.i4.282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085509PMC
April 2021

Cedrol from Ginger Ameliorates Rheumatoid Arthritis via Reducing Inflammation and Selectively Inhibiting JAK3 Phosphorylation.

J Agric Food Chem 2021 May 28;69(18):5332-5343. Epub 2021 Apr 28.

Shenyang Pharmaceutical University, Shenyang 110016, China.

Ginger, as a food spice, is widely applied due to its extensive effects. Cedrol (CE) found in ginger is a sesquiterpene with anti-inflammatory activity. The objective of this research is to discuss the efficacy of CE on ameliorating rheumatoid arthritis (RA). CE inhibited chronic inflammation and pain in a dose-dependent manner accompanied by rapid onset and long duration. Besides, CE treatment effectively ameliorated the paw edema volume and arthritis score with no significant effect on body weight. Organ index, T-cell and B-cell proliferation, histopathology, and immunohistochemistry demonstrated that CE had immunological enhancement and attenuated RA effects. Remarkably, inhibition of phosphorylated-JAK3 protein, thereby abating the secretion of pro-inflammatory cytokines and inflammation-related mediators, was involved in the potential mechanism of CE efficiency through forming a hydrogen bond with ARG953 and ILE955 in the JAK3 active pocket. At the same time, the pharmacokinetic results showed that the absolute bioavailability of CE at 20, 40, and 80 mg/kg was 30.30, 23.68, and 16.11%, respectively. The current results offered clues for mastering the ameliorated RA of CE and further perfected the effective substance basis on the anti-inflammatory effect of ginger, which was beneficial for further applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.1c00284DOI Listing
May 2021

2D Metal-Organic Framework-Based Thin-Film Nanocomposite Membranes for Reverse Osmosis and Organic Solvent Nanofiltration.

ChemSusChem 2021 Jun 7;14(11):2452-2460. Epub 2021 May 7.

Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585, Singapore.

Metal-organic frameworks (MOFs) are promising candidates for membrane-based liquid separations due to their intrinsic microporosity, but many are limited by their insufficient stability. In this work, a copper-benzoquinoid (Cu-THQ) MOF was synthesized and demonstrated structural stability in water and organic solvents. After incorporation into the polyamide layer, the hydrophilicity of the membranes was enhanced. The resultant thin-film nanocomposite (TFN) membranes broke the permeability-selectivity tradeoff by showing 242 % increase in water permeance and slightly enhanced salt rejection at MOF loading of 0.0192 mg cm . The underlying mechanism was probed by different chemical and morphological characterizations. The membranes also showed improved tolerance to chlorine oxidation. With their excellent stability, the Cu-THQ MOF-based membranes further demonstrated impressive performance in organic solvent nanofiltration involving dimethylformamide.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cssc.202100335DOI Listing
June 2021

Patient-reported outcome improvements at 24-month follow-up after fusion added to decompression for grade I degenerative lumbar spondylolisthesis: a multicenter study using the Quality Outcomes Database.

J Neurosurg Spine 2021 Apr 16:1-10. Epub 2021 Apr 16.

16Department of Neurological Surgery, University of California, San Francisco, California.

Objective: The ideal surgical management of grade I lumbar spondylolisthesis has not been determined despite extensive prior investigations. In this cohort study, the authors used data from the large, multicenter, prospectively collected Quality Outcomes Database to bridge the gap between the findings in previous randomized trials and those in a more heterogeneous population treated in a typical practice. The objective was to assess the difference in patient-reported outcomes among patients undergoing decompression alone or decompression plus fusion.

Methods: The primary outcome measure was change in 24-month Oswestry Disability Index (ODI) scores. The minimal clinically important difference (MCID) in ODI score change and 30% change in ODI score at 24 months were also evaluated. After adjusting for patient-specific and clinical factors, multivariable linear and logistic regressions were employed to evaluate the impact of fusion on outcomes. To account for differences in age, sex, body mass index, and baseline listhesis, a sensitivity analysis was performed using propensity score analysis to match patients undergoing decompression only with those undergoing decompression and fusion.

Results: In total, 608 patients who had grade I lumbar spondylolisthesis were identified (85.5% with at least 24 months of follow-up); 140 (23.0%) underwent decompression alone and 468 (77.0%) underwent decompression and fusion. The 24-month change in ODI score was significantly greater in the fusion plus decompression group than in the decompression-only group (-25.8 ± 20.0 vs -15.2 ± 19.8, p < 0.001). Fusion remained independently associated with 24-month ODI score change (B = -7.05, 95% CI -10.70 to -3.39, p ≤ 0.001) in multivariable regression analysis, as well as with achieving the MCID for the ODI score (OR 1.767, 95% CI 1.058-2.944, p = 0.029) and 30% change in ODI score (OR 2.371, 95% CI 1.286-4.371, p = 0.005). Propensity score analysis resulted in 94 patients in the decompression-only group matched 1 to 1 with 94 patients in the fusion group. The addition of fusion to decompression remained a significant predictor of 24-month change in the ODI score (B = 2.796, 95% CI 2.228-13.275, p = 0.006) and of achieving the 24-month MCID ODI score (OR 2.898, 95% CI 1.214-6.914, p = 0.016) and 24-month 30% change in ODI score (OR 2.300, 95% CI 1.014-5.216, p = 0.046).

Conclusions: These results suggest that decompression plus fusion in patients with grade I lumbar spondylolisthesis may be associated with superior outcomes at 24 months compared with decompression alone, both in reduction of disability and in achieving clinically meaningful improvement. Longer-term follow-up is warranted to assess whether this effect is sustained.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2020.9.SPINE201082DOI Listing
April 2021

Elucidating the Effect of Fine Lactose Ratio on the Rheological Properties and Aerodynamic Behavior of Dry Powder for Inhalation.

AAPS J 2021 04 15;23(3):55. Epub 2021 Apr 15.

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.

Dry powder inhaler (DPI) is recognized as the first choice for lung diseases' treatment. However, it lacks a universal way for DPI formulation development. Fine lactose is commonly added in DPIs to improve delivery performance; however, the fine ratio-dependent mechanism is unclear. Therefore, the objective of this study is to explore the influence of fine lactose ratio on DPI powder properties and aerodynamic behavior, and the fine lactose ratio-dependent mechanism involved during powder fluidization and lung deposition. Here salbutamol sulfate was used as a model drug, Lactohale® 206 as coarse carrier, and Lactohale® 300 as fine component; the mixtures were prepared at 1% drug content, with fine content up to 20%. It was shown that with the fine addition, flowability of the mixtures was improved, interaction among particles was increased, and the presence of fines could help to improve DPI's aerosolization performance. When the fines added were less than 3%, the "active site" hypothesis played a leading role. When the added fines were over 3% but less than 10%, fluidization enhancement mechanism was more important. After the added fines reaching 10%, aggregate mechanism started to dominate. However, FPF cannot be further increased once the fines reached 20%. Moreover, the correlations between FPF and dynamic powder parameters were verified in ternary mixtures, and cohesion had a greater impact on FPF than that of flowability. In conclusion, adding lactose fines is an effective way to improve lung deposition of DPI, with the concrete mechanism lactose fine ratio dependent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1208/s12248-021-00582-0DOI Listing
April 2021

USP18-deficiency in cervical carcinoma is crucial for the malignant behavior of tumor cells in an ERK signal-dependent manner.

Oncol Lett 2021 May 29;21(5):421. Epub 2021 Mar 29.

Department of Human Anatomy, Basic Medical College, Jiamusi University, Jiamusi, Heilongjiang 154007, P.R. China.

Ubiquitin-specific peptidase (USP)18 belongs to the USP family, and is involved in cleaving and removing ubiquitin or ubiquitin-like molecules from their target molecules. Recently, increasing evidence has suggested that USP18 is constitutively expressed in different types of human tumors, and ectopic expression or downregulation of USP18 expression may contribute to tumorigenesis. However, the role of USP18 in uterine cervical cancer (UCC) remains unclear. Thus, the present study aimed to investigate USP18 expression in a human tissue microarray constructed using UCC and non-cancer cervical tissues, and to determine the potential role and molecular mechanism by which USP18 is implicated in the tumor biology of human UCC HeLa cells. Microarray analysis demonstrated that USP18 protein expression was downregulated in tumor tissues compared with in normal tissues. In addition, analysis revealed that USP18-knockdown markedly promoted the proliferation, colony formation, migration and aggressiveness of HeLa cells. Mechanistic analysis demonstrated that USP18-knockdown increased the levels of Bcl-2, STAT3 and phosphorylated-ERK in HeLa cells. Notably, USP18 silencing-induced malignant phenotypes were interrupted following exogenous administration of the ERK1/2 inhibitor PD98059. Overall, the results of the present study suggested that USP18 may be a potent inhibitor involved in UCC tumor-associated biological behaviors, which are associated with the ERK signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2021.12682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025074PMC
May 2021

Correction to: A novel classification and its clinical significance in Chiari I malformation with syringomyelia based on high‑resolution MRI.

Eur Spine J 2021 Jun;30(6):1794-1796

Department of Neurosurgery, Division of Spine, China, International Neurological Institute, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, People's Republic of China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00586-021-06787-3DOI Listing
June 2021

A novel tumor suppressor CECR2 down regulation links glutamine metabolism contributes tumor growth in laryngeal squamous cell carcinoma.

Clin Transl Oncol 2021 Sep 7;23(9):1942-1954. Epub 2021 Apr 7.

Department of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui, 200233, Shanghai, China.

Purpose: Glutamine plays an important role in tumor metabolism and progression. This research aimed to find out how Gln exert their effects on laryngeal squamous cell carcinoma (LSCC).

Methods: Cell proliferation was measured by CCK8 and EdU assay, mitochondrial bioenergetic activity was measured by mitochondrial stress tests. Gene expression profiling was revealed by RNA sequencing and validated by RT-qPCR. In LSCC patients, protein expression in tumor and adjacent tissues was examined and scored by IHC staining. RNAi was performed by stably expressed shRNA in TU177 cells. In vivo tumor growth analysis was performed using a nude mouse tumorigenicity model.

Results: Gln deprivation suppressed TU177 cell proliferation, which was restored by αKG supplementation. By transcriptomic analysis, we identified CECR2, which encodes a histone acetyl-lysine reader, as the downstream target gene for Gln and αKG. In LSCC patients, the expression of CECR2 in tumors was lower than adjacent tissues. Furthermore, deficiency of CECR2 promoted tumor cell growth both in vitro and in vivo, suggesting it has tumor suppressor effects. Besides, cell proliferation inhibited by Gln withdrawal could be restored by CECR2 depletion, and the proliferation boosted by αKG supplementation could be magnified either, suggested that CECR2 feedback suppressed Gln and αKG's effect on tumor growth. Transcriptomic profiling revealed CECR2 regulated the expression of a series of genes involved in tumor progression.

Conclusion: We confirmed the Gln-αKG-CECR2 axis contributes to tumor growth in LSCC. This finding provided a potential therapeutic opportunity for the use of associated metabolites as a potential treatment for LSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12094-021-02603-yDOI Listing
September 2021

An 18.3 MJ charging and discharging pulsed power supply system for the Space Plasma Environment Research Facility (SPERF): Modular design method and component selection.

Rev Sci Instrum 2021 Mar;92(3):034709

Key Laboratory of Pulsed Power, Institute of Fluid Physics, CAEP, Mianyang 621900, Sichuan, China.

The capacitor-based pulsed power supply (PPS) system is an important subsystem of the Space Plasma Environment Research Facility being built as a user facility at Harbin Institute of Technology in China. It has been developed with a modular design to drive magnetic coils to generate magnetic fields and plasma for the physical experiments. In this paper, the modular design and component selection are proposed based on a calculation of parameter ranges of components and the number of modules followed by a simulation and an engineering test. Both the simulation and test results show the feasibility of the selected components and the number of modules to meet the designing requirements of the PPS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1063/5.0036923DOI Listing
March 2021

A Systematic Review of Tissue Engineering Scaffold in Tendon Bone Healing .

Front Bioeng Biotechnol 2021 15;9:621483. Epub 2021 Mar 15.

Sports Medicine Department, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.

Tendon-bone healing is an important factor in determining the success of ligament reconstruction. With the development of biomaterials science, the tissue engineering scaffold plays an extremely important role in tendon-bone healing and bone tissue engineering. Electronic databases (PubMed, Embase, and the Web of Science) were systematically searched for relevant and qualitative studies published from 1 January 1990 to 31 December 2019. Only original articles that met eligibility criteria and evaluated the use of issue engineering scaffold especially biomaterials in tendon bone healing were selected for analysis. The search strategy identified 506 articles, and 27 studies were included for full review including two human trials and 25 animal studies. Fifteen studies only used biomaterials like PLGA, collage, PCL, PLA, and PET as scaffolds to repair the tendon-bone defect, on this basis, the rest of the 11 studies using biological interventions like cells or cell factors to enhance the healing. The adverse events hardly ever occurred, and the tendon bone healing with tissue engineering scaffold was effective and superior, which could be enhanced by biological interventions. Although a number of tissue engineering scaffolds have been developed and applied in tendon bone healing, the researches are mainly focused on animal models which are with limitations in clinical application. Since the efficacy and safety of tissue engineering scaffold has been proved, and can be enhanced by biological interventions, substantial clinical trials remain to be done, continued progress in overcoming current tissue engineering challenges should allow for successful clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fbioe.2021.621483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005599PMC
March 2021

Influence of drug-carrier compatibility and preparation method on the properties of paclitaxel-loaded lipid liquid crystalline nanoparticles.

J Pharm Sci 2021 Jul 28;110(7):2800-2807. Epub 2021 Mar 28.

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address:

The main objective of this paper is to elucidate the influence of drug-carrier compatibility and preparation method on the properties of Paclitaxel (PTX)-loaded lipid liquid crystalline nanoparticles (LLCNs). Here, glyceryl monooleate (GMO), glycerol monolinoleate (GML), glyceryl monolinolenate (GMLO) were selected as the lipids, and Soluplus, Poloxamer 407 (P407), Tween 80 were selected as the stabilizer to prepare LLCNs. First of all, PTX-carrier compatibility was screened by molecular dynamic simulation using Flory-Huggins interaction parameter as the criteria. Thereafter, PTX-loaded LLCNs were prepared under different energy input conditions and were characterized. Influence of lipid type, stabilizer type, drug-lipid ratio and preparation method on properties of the LLCNs was explored. It was found that both lipid and stabilizer type had significant influence on drug encapsulation efficiency. Compared to the LLCNs prepared under high energy condition, PTX-loaded LLCN prepared under low energy input had higher drug encapsulation efficiency, smaller particle size (211.6 nm versus 346.8 nm) and a sustained release behavior. In conclusion, molecular dynamic simulation is an effective tool to select the most appropriate composition of LLCNs for a specific drug substance, and LLCNs prepared using low energy input methods was particularly applicable for industrial manufacture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.xphs.2021.03.016DOI Listing
July 2021

Design of biotin decorated enterocyte targeting muco-inert nanocomplexes for enhanced oral insulin delivery.

Carbohydr Polym 2021 Jun 27;261:117873. Epub 2021 Feb 27.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

The natural mucus cover has been a major obstacle to prevent enterocyte targeting particles from contact with the receptors. Thus, mucus penetration and intestinal targeting should be designed into one system. Based on the concept that biotin specifically recognizes epithelium receptors, enterocyte targeting muco-inert nanocomplexes were designed. Firstly, biotinylated chitosan (CS-Biotin) copolymers with different degree of substitution were synthesized and characterized. The nanocomplexes between CS-Biotin and insulin were prepared via self-assembly method. Thereafter, the nanocomplexes were fabricated by coating with various molecular weight hyaluronic acid (HA), which improved penetration efficiency in the mucus layer and small intestine in a HA molecular weight dependent manner. In vivo study indicated that hypoglycemic effect of the nanocomplexes was biotin modification degree and HA molecular weight dependent, with HA (200)-coated CS-Biotin21.8%/Insulin polyelectrolyte complex presenting the best performance. In conclusion, biotin decorated muco-inert nanocomplexes with HA coating are a promising platform for oral insulin delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carbpol.2021.117873DOI Listing
June 2021