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1.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(3): 193-197, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32389165

RESUMO

Objective To investigate the role of Ras homolog gene (Rho) A/Rho-associated coiled-coil containing protein kinase (ROCK) signaling pathway in tumor necrosis factor α (TNF-α) promoting hyper-permeability of vascular endothelial cells infected by Listeria monocytogenes (Lm) . Methods The cultured human umbilical vein endothelial cells (HUVECs) were divided into a control group (uninfected cells), TNF-α treatment group (100 ng/mL TNF-α, for 2 hours), Lm infection group (infected with MOI=10 Lm for 2 hours, then added gentamicin for 0.5 hour), Lm infection and TNF-α treatment group (infected with Lm and then treated with 100 ng/mL TNF-α for 2 hours), and Y-27632 inhibitor group combined with Lm infection and TNF-α treatment (treated with 50 µmol/L ROCK inhibitor Y-27632 for 30 minutes, and then Lm infection and TNF-α treatment as above). The protein levels of RhoA, zonula occluden-1 (ZO-1), occludin and ROCK in HUVECs were detected by Western blot analysis; the permeability of HUVECs was analyzed by the horseradish peroxidase (HRP) leakage; and the distribution of F-actin in HUVECs was detected by fluorescein isothiocyanate (FITC)-labeled phalloidine staining. Results TNF-α reduced the expression of tight junction protein ZO-1 and occludin in Lm-infected HUVECs, promoted its hyper-permeability and cytoskeletal rearrangement, and up-regulated the expression of RhoA and ROCK. ROCK inhibitor Y-27632 obviously inhibited the cytoskeleton rearrangement and hyper-permeability of HUVECs induced by TNF-α. Conclusion TNF-α can enhance hyper-permeability of HUVECs infected by Lm, which may be regulated by RhoA/Rock signaling pathway.

2.
FASEB J ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32367591

RESUMO

Bone loss is a severe complication of primary biliary cirrhosis (PBC). Trehalose was intermittently administered in bile duct-ligated (BDL) male rats, a PBC-related osteoporosis model, for 4 weeks to reduce osteoporosis. Femoral bones were assessed ex vivo by micro computed tomography (CT) and histomorphometry. The potential mechanisms related to the reduction of osteoporosis were explored by evaluating the effect of trehalose on osteoblast autophagy, osteogenesis, osteoclastogenesis, and ERK phosphorylation. The results demonstrated that trehalose reduced osteoporosis of BDL rats and decreased osteoblast-mediated osteoclast differentiation by enhancing osteoblast autophagy to regulate osteoprotegerin (OPG) secretion. Hydroxychloroquine (HCQ) increased the expression of OPG and OPG/receptor activator genes for nuclear factor-κB ligand (RANKL) ratio, and reduced osteoblast-mediated osteoclastogenesis by inhibiting autophagy flux and inducing autophagosome formation. Furthermore, trehalose increased the phosphorylation of ERK1/2 in MC3T3-E1 cells, and the ERK inhibitor PD98059 reversed the upregulation of OPG gene and reduction of trehalose-induced osteoclastogeneis. The treatment with HCQ markedly increased the ERK phosphorylation. The correlation between autophagosome formation and ERK phosphorylation was confirmed in autophagy proteins (ATG) 4B or ATG5-deficient cells. Thus, trehalose could decrease osteoblast-mediated osteoclastogenesis and reduce PBC-related bone loss by regulating ERK phosphorylation via autophagosome formation.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32407165

RESUMO

Objective: To compare the surgical feasibility, oncological and functional results between sutureless and suture techniques in retroperitoneal laparoscopic nephron-sparing surgery (LNSS). Materials and Methods: This retrospective study collected consecutive patients with a renal mass who underwent retroperitoneal LNSS in two high-volume centers. Propensity score matching (PSM) analysis was conducted to select two baseline homogeneous cohorts. Descriptive statistics was performed both before and after PSM. Moreover, univariate and multivariate logistic analyses were carried out to identify the risk factors of postoperative acute kidney injury (AKI), whereas Kaplan-Meier analysis for functional deterioration (new-onset stage 3 chronic kidney disease [CKD], estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2, or CKD upstaging after surgery) was utilized to compare the two cohorts. Results: After PSM at a ratio of 1:3, the sutureless group (n = 65) was compared with the suture group (n = 152) with no remaining statistically significant differences in baseline characteristics. With regard to patient outcomes, differences in warm ischemia time (WIT) (P < .001), estimated blood loss (P < .001), AKI (P = .002), length of hospital stay (P = .020), and eGFR at discharge (P < .001) were statistically significant. Meanwhile, the postoperative complication rates (9.2% versus 13.8%, P = .378) and positive surgical margins (0% versus 2.0%, P = .556) were not statistically different. At the last follow-up, the eGFR decline percent was the same (-1.5% versus -2.2%, P = .192). No difference was detected on Kaplan-Meier analysis for functional deterioration (log-rank test, P = .304). Conclusions: Sutureless technique in LNSS is safe and feasible, compared with the traditional suture method, with shorter WIT, lower AKI rate, and comparable long-term oncological and functional outcomes.

5.
Acta Biomater ; 2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32434079

RESUMO

Injectable hydrogels have attracted increasing attention because of convenient clinical operation, non-invasive surgical procedure and seamless filling of irregular defects. Here, injectable di-self-crosslinking HSMSSA hydrogel was formed via fast thiol/maleimide click chemistry reaction and thiol oxidation reaction as primary and secondary self-crosslinking network, respectively. Molecular weight and precursor concentration significantly affected physichemical properties and biological functions of hydrogels. Although single HSMSSA gel (0.1M Da, 10 mg/mL) had moderate injectability, preferable mechanical properties and good proliferative ability of chondrocytes in vitro, and could greatly promote cartilaginous tissue formation in vivo, the lack of adhesion sites resulted in an untenable situation in maintaining effective connections among newborn cell clusters. However, the biomimetic injectable di-self-crosslinking blend hydrogel by combing injectable HSMSSA and bioactive Col I had improved resistance to degradation, chondrocytes adhesion and proliferation, especially for multiples ascending genes expression level associated with hyaline cartilage formation and polyproteoglycan secretion, which might be a potential clinical treatment strategy for constructing injectable cartilage repair filler by combining expanded autologous chondrocytes.

6.
J Appl Clin Med Phys ; 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32436351

RESUMO

PURPOSE: To accomplish the 3D dose verification to IMRT plan by incorporating DVH information and gamma passing rates (GPs) (DVH_GPs) so as to better correlate the patient-specific quality assurance (QA) results with clinically relevant metrics. MATERIALS AND METHODS: DVH_GPs analysis was performed to specific structures of 51 intensity-modulated radiotherapy (IMRT) treatment plans (17 plans each for oropharyngeal neoplasm, esophageal neoplasm, and cervical neoplasm) with Delta4 3D dose verification system. Based on the DVH action levels of 5% and GPs action levels of 90% (3%/2 mm), the evaluation results of DVH_GPs analysis were categorized into four regions as follows: the true positive (TP) (%DE> 5%, GPs < 90%), the false positive (FP) (%DE ≤ 5%, GPs < 90%), the false negative (FN) (%DE> 5%, GPs ≥ 90%), and the true negative (TN) (%DE ≤ 5%, GPs ≥ 90%). Considering the actual situation, the final patient-specific QA determination was made based on the DVH_GPs evaluation results. In order to exclude the impact of Delta4 phantom on the DVH_GPs evaluation results, 5 cm phantom shift verification was carried out to structures with abnormal results (femoral heads, lung, heart). RESULTS: In DVH_GPs evaluation, 58 cases with FN, 5 cases with FP, and 2 cases with TP were observed. After the phantom shift verification, the extremely abnormal FN of both lung (%DE = 21.52%±8.20%) and heart (%DE = 19.76%) in the oropharyngeal neoplasm plans and of the bilateral formal heads (%DE = 26.41%±13.45%) in cervical neoplasm plans disappeared dramatically. DVH_GPs analysis was performed to all evaluation results in combination with clinical treatment criteria. Finally, only one TP case from the oropharyngeal neoplasm plans and one FN case from the esophageal neoplasm plans did not meet the treatment requirements, so they needed to be replanned. CONCLUSION: The proposed DVH_GPs evaluation method first make up the deficiency of conventional gamma analysis regarding intensity information and space information. Moreover, it improves the correlation between the patient-specific QA results and clinically relevant metrics. Finally, it can distinguish the TP, TN, FP, and FN in the evaluation results. They are affected by many factors such as the action levels of DVH and GPs, the feature of the specific structure, the QA device, etc. Therefore, medical physicist should make final patient-specific QA decision not only by taking into account the information of DVH and GPs, but also the practical situation.

7.
Stem Cell Res Ther ; 11(1): 180, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32430067

RESUMO

BACKGROUND: The dedifferentiation of chondrocytes and the unstable chondrogenic differentiation status of pluripotent mesenchymal stem cells (MSCs) are immense issues in cell-based articular cartilage repair and regenerative strategies. Here, to improve the cartilage characteristics of seed cells, a double biomimetic acellular cartilage extracellular matrix (ACECM)-oriented scaffold was used to mimic the cartilage microenvironment for human umbilical cord Wharton's jelly-derived MSCs (hWJMSCs) and primary cartilage cells (pACs) to regenerate hyaline cartilage. METHODS: A double biomimetic ACECM-oriented scaffold was created from the cartilage extracellular matrix of pig articular cartilage using pulverization decellularization freeze-drying procedures. hWJMSCs and pACs were co-cultured at ratios of 50:50 (co-culture group, ACCC), 0:100 (ACAC group) and 100:0 (ACWJ group) in the ACECM-oriented scaffold, and the co-culture system was implanted in a caprine model for 6 months or 9 months to repair full-thickness articular cartilage defects. The control groups, which had no cells, comprised the blank control (BC) group and the ACECM-oriented scaffold (AC) group. Gross morphology and magnetic resonance imaging (MRI) as well as histological and biomechanical evaluations were used to characterize the cartilage of the repair area. RESULTS: Relative to the control groups, both the gross morphology and histological staining results demonstrated that the neotissue of the ACCC group was more similar to native cartilage and better integrated with the surrounding tissue. Measurements of glycosaminoglycan content and Young's modulus showed that the repair areas had more abundant cartilage-specific content and significantly higher mechanical strength in the ACCC group than in the control groups, especially at 9 months. On MRI, the T2-weighted signal of the repair area was homogeneous, and the oedema signal disappeared almost completely in the ACCC group at 9 months. HLA-ABC immunofluorescence staining demonstrated that hWJMSCs participated in the repair and regeneration of articular cartilage and escaped surveillance and clearance by the caprine immune system. CONCLUSION: The structure and components of double biomimetic ACECM-oriented scaffolds provided a cartilage-like microenvironment for co-cultured seed cells and enhanced the biomechanics and compositions of neotissue. This co-culture system has the potential to overcome the dedifferentiation of passage chondrocytes and the unstable chondrogenic differentiation status of MSCs.

8.
Yi Chuan ; 42(5): 483-492, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32431299

RESUMO

In recent years, it has been demonstrated that some susceptible gene loci of type 2 diabetes mellitus (T2DM) are not only associated with the susceptibility risk of T2DM, but also the modifying effects of lifestyle interventions. To further explore the modifying effects of the single nucleotide polymorphism (SNP) on the onset of T2DM and the reduction of blood glucose in response to lifestyle interventions among the high-risk population, we performed a lifestyle intervention study in two Deqing rural communities during the period from June to December in 2017. The intensive lifestyle interventions were conducted among the study subjects of the intervention group while those in the control group only received conventional and general health education. All participants were genotyped by the MassARRY system. This study showed that for SNP rs9502570, fasting blood glucose showed a significantly greater reduction for individuals with CC + CT genotype than those with TT genotype (P=0.031). In the intervention group, the glycated hemoglobin A1C (HbA1C) decreased by 0.03% for those with CC+CT genotype, while HbA1C increased by 0.27% for those with TT genotype (P=0.012). The difference in the reduction of fasting blood glucose and HbA1c between the intervention and control groups was also statistically significant between individuals with TT and those with CC+CT genotype. For SNP rs10811661, the reduction of fasting blood glucose was significantly higher in people with TT genotype than those with CC + CT genotype (0.44 mmol/L vs 0.12 mmol/L, P=0.021). The difference in reduction of fasting blood glucose between the intervention group and control group was also statistically significant between TT and CC+CT genotype (P<0.001). In summary, the SNP genotypes of both rs9502570 and rs10811661 could modify the effects of lifestyle interventions on reducing fasting blood glucose and HbA1C among the high risk rural population for T2DM. The present study has provided supporting evidence for future development of individualized intervention measures for high-risk population of T2DM.

9.
Nanoscale ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32363363

RESUMO

The search for a one-dimensional (1D) system with purely 1D bands and strong Rashba spin splitting is essential for the realization of Majorana fermions and spin transport but presents a fundamental challenge to date. Herein, using first-principles calculations, we demonstrated that atomic Tellurium (Te) chains exhibit purely 1D bands and giant Rashba spin splitting, and their splitting parameters depend strongly on strain and structure distortion. This phenomenon stems from the helical structure of atomic Te chains, which can not only sustain significant strain but also realize the synergy of orbital angular momentum and in-chain potential gradient in enhancing spin splitting. The structure distortion of stretched helical Te chains is critical to execute this synergy, generating a large Rashba spin splitting among the known systems. Our findings proposed a potential 1D giant Rashba splitting system for exploring spintronics and Majorana fermions, and provide routes for engineering spin splitting in other materials.

10.
mBio ; 11(2)2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32317327

RESUMO

Reversible repression of HIV-1 5' long terminal repeat (5'-LTR)-mediated transcription represents the main mechanism for HIV-1 to maintain latency. Identification of host factors that modulate LTR activity and viral latency may help develop new antiretroviral therapies. The heterogeneous nuclear ribonucleoproteins (hnRNPs) are known to regulate gene expression and possess multiple physiological functions. hnRNP family members have recently been identified as the sensors for viral nucleic acids to induce antiviral responses, highlighting the crucial roles of hnRNPs in regulating viral infection. A member of the hnRNP family, X-linked RNA-binding motif protein (RBMX), has been identified in this study as a novel HIV-1 restriction factor that modulates HIV-1 5'-LTR-driven transcription of viral genome in CD4+ T cells. Mechanistically, RBMX binds to HIV-1 proviral DNA at the LTR downstream region and maintains the repressive trimethylation of histone H3 lysine 9 (H3K9me3), leading to a blockage of the recruitment of the positive transcription factor phosphorylated RNA polymerase II (RNA pol II) and consequential impediment of transcription elongation. This RBMX-mediated modulation of HIV-1 transcription maintains viral latency by inhibiting viral reactivation from an integrated proviral DNA. Our findings provide a new understanding of how host factors modulate HIV-1 infection and latency and suggest a potential new target for the development of HIV-1 therapies.IMPORTANCE HIV-1 latency featuring silence of transcription from HIV-1 proviral DNA represents a major obstacle for HIV-1 eradication. Reversible repression of HIV-1 5'-LTR-mediated transcription represents the main mechanism for HIV-1 to maintain latency. The 5'-LTR-driven HIV gene transcription can be modulated by multiple host factors and mechanisms. The hnRNPs are known to regulate gene expression. A member of the hnRNP family, RBMX, has been identified in this study as a novel HIV-1 restriction factor that modulates HIV-1 5'-LTR-driven transcription of viral genome in CD4+ T cells and maintains viral latency. These findings provide a new understanding of how host factors modulate HIV-1 infection and latency and suggest a potential new target for the development of HIV-1 therapies.

11.
Int J Mol Sci ; 21(7)2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32244499

RESUMO

Antxr1/Tem8 is highly expressed in tumor endothelial cells and is a receptor for anthrax toxin. Mutation of Antxr1 causes GAPO syndrome, which is characterized by growth retardation, alopecia, pseudo-anodontia, and optic atrophy. However, the mechanism underlying the growth retardation remains to be clarified. Runx2 is essential for osteoblast differentiation and chondrocyte maturation and regulates chondrocyte proliferation through Ihh induction. In the search of Runx2 target genes in chondrocytes, we found that Antxr1 expression is upregulated by Runx2. Antxr1 was highly expressed in cartilaginous tissues and was directly regulated by Runx2. In skeletal development, the process of endochondral ossification proceeded similarly in wild-type and Antxr1-/- mice. However, the limbs of Antxr1-/- mice were shorter than those of wild-type mice from embryonic day 16.5 due to the reduced chondrocyte proliferation. Chondrocyte-specific Antxr1 transgenic mice exhibited shortened limbs, although the process of endochondral ossification proceeded as in wild-type mice. BrdU-uptake and apoptosis were both increased in chondrocytes, and the apoptosis-high regions were mineralized. These findings indicated that Antxr1, of which the expression is regulated by Runx2, plays an important role in chondrocyte proliferation and that overexpression of Antxr1 causes chondrocyte apoptosis accompanied by matrix mineralization.

12.
J Biomed Inform ; 105: 103418, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32298846

RESUMO

OBJECTIVE: This study aims to develop and evaluate effective methods that can normalize diagnosis and procedure terms written by physicians to standard concepts in International Classification of Diseases(ICD) in Chinese, with the goal to facilitate automated medical coding in China. METHODS: We applied the entity-linking framework to normalize Chinese diagnosis and procedure terms, which consists of two steps - candidate concept generation and candidate concept ranking. For candidate concept generation, we implemented both the traditional BM25 algorithm and an extended version that integrates a synonym knowledgebase. For candidate concept ranking, we investigated a number of different algorithms: (1) the BM25 algorithm, (2) ranking support vector machines (RankSVM), (3) a previously reported Convolutional Neural Network (CNN) approach, (4) 11 deep ranking-based methods from the MatchZoo toolkit, and (5) a new BERT (Bidirectional Encoder Representations from Transformers) based ranking method. Using two manually annotated datasets (8,547 diagnoses and 8,282 procedures) collected from a Tier 3A hospital in China, we evaluated above methods and reported their performance (i.e., accuracy) at different cutoffs. RESULTS: The coverage of candidate concept generation was greatly improved after integrating the synonym knowledgebase, achieving 97.9% for diagnoses and 93.4% for procedures respectively. Overall the new BERT-based ranking method achieved the best performance on both diagnosis and procedure normalization, with the best accuracy of 92.1% for diagnosis and 80.1% for procedure, when the top one concept and exact match criteria were used. CONCLUSIONS: This study developed and compared diverse entity-linking methods to normalize clinical terms in Chinese and our evaluation shows good performance on mapping disease terms to ICD codes, demonstrating the feasibility of automated encoding of clinical terms in Chinese.

13.
Proc Natl Acad Sci U S A ; 117(19): 10378-10387, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32332162

RESUMO

Barrier-to-autointegration factor (BAF) is a highly conserved protein in metazoans that has multiple functions during the cell cycle. We found that BAF is SUMOylated at K6, and that this modification is essential for its nuclear localization and function, including nuclear integrity maintenance and DNA replication. K6-linked SUMOylation of BAF promotes binding and interaction with lamin A/C to regulate nuclear integrity. K6-linked SUMOylation of BAF also supports BAF binding to DNA and proliferating cell nuclear antigen and regulates DNA replication. SENP1 and SENP2 catalyze the de-SUMOylation of BAF at K6. Disrupting the SUMOylation and de-SUMOylation cycle of BAF at K6 not only disturbs nuclear integrity, but also induces DNA replication failure. Taken together, our findings demonstrate that SUMOylation at K6 is an important regulatory mechanism that governs the nuclear functions of BAF in mammalian cells.

14.
Int J Mol Sci ; 21(8)2020 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-32290615

RESUMO

Runx2 is required for chondrocyte proliferation and maturation. In the search of Runx2 target genes in chondrocytes, we found that Runx2 up-regulated the expression of hematopoietic cell kinase (Hck), which is a member of the Src tyrosine kinase family, in chondrocytes, that Hck expression was high in cartilaginous limb skeletons of wild-type mice but low in those of Runx2-/- mice, and that Runx2 bound the promoter region of Hck. To investigate the functions of Hck in chondrocytes, transgenic mice expressing a constitutively active form of Hck (HckCA) were generated using the Col2a1 promoter/enhancer. The hind limb skeletons were fused, the tibia became a large, round mass, and the growth plate was markedly disorganized. Chondrocyte maturation was delayed until E16.5 but accelerated thereafter. BrdU-labeled, but not terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive, chondrocytes were increased. Furthermore, Hck knock-down reduced the proliferation of primary chondrocytes. In microarray and real-time RT-PCR analyses using hind limb RNA from HckCA transgenic mice, the expression of Wnt (Wnt10b, Tcf7, Lef1, Dkk1) and hedgehog (Ihh, Ptch1, and Gli1) signaling pathway genes was upregulated. These findings indicated that Hck, whose expression is regulated by Runx2, is highly expressed in chondrocytes, and that HckCA activates Wnt and hedgehog signaling pathways, and promotes chondrocyte proliferation without increasing apoptosis.

15.
Biol Trace Elem Res ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32236846

RESUMO

To study responses of Procapra przewalskii to zinc (Zn) nutrition in physical habitat, we analyzed the content of mineral elements in soil, forage, and animal tissues. Physiological and biochemical indexes were also determined. The results showed that Zn contents in the soil and forage from affected pasture were significantly lower (P < 0.01) than those in unaffected areas. Zn concentrations in the blood, liver, and hair from affected P. przewalskii were also significantly lower (P < 0.01) than those in healthy animals. The levels of hemoglobin, erythrocyte count, and packed cell volume from affected P. przewalskii were significantly lower (P < 0.01) than those in healthy animals. Serum aspartate aminotransferase and alanine transaminase activities were significantly lower (P < 0.01) in affected P. przewalskii than in healthy animals, while serum lactate dehydrogenase and alkaline phosphatase levels were significantly higher (P < 0.01) in affected compared with healthy animals. The activities of superoxide dismutase, glutathione peroxidase, and catalase in serum were significantly lower and the malondialdehyde content was significantly higher (all P < 0.01) in affected compared with healthy animals. Affected P. przewalskii were treated orally with ZnSO4. The Zn content in the blood increased gradually and serum antioxidant indexes gradually returned to within the healthy range. Zn deprivation in forage thus not only influenced the blood mineral content but also severely disrupted blood parameters and antioxidant function in P. przewalskii.

16.
J Mater Chem B ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32242608

RESUMO

The injectable composite hydrogel based on collagen and hyaluronic acid provided a bionic three-dimensional microenvironment and mimetic natural extracellular matrix (ECM) for the growth of cells in vivo and has been widely researched and developed for cartilage tissue engineering. Here, a novel injectable bionic hydrogel with hybrid covalent/noncovalent network derived from covalent conjugation of HA-SH and noncovalent supramolecular self-assembly of BPAA-AFF-OH short peptide was fabricated to overcome the collagen immunogenicity of animal origin and effectively maintain its biological function. Moreover, through optimizing the network structure and polymer composition, the bionic HS5FFAB5 hydrogel presented a reliable mechanical strength which depended on the highly integrated fiber structure between HA-SH and FFAB-AFF-OH molecules. The results in vitro and in vivo proved that HA-SH could provide a fundamental frame structure, while the supramolecular hydrogels could reinforce this structure via hydrogen bonds and hydrophilic/hydrophobic interactions, and endow bionic hydrogels with more abundant cell adhesion sites. The bionic composite hydrogel could improve the cell adhesion and proliferation when compared to HA-SH hydrogel, and enhanced chondrogenic related gene expression and matrix secretion by three-dimensional co-cultured in vitro and subcutaneous implantation in vivo, which further promoted phenotypic maintenance of hyaline cartilage. This bionic hydrogel with a hybrid covalent/noncovalent network is supposed to have potential application prospects in cartilage regeneration.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32187780

RESUMO

Synthesis of fully conjugated cyclophanes containing large-size polycyclic aromatics is challenging. Now, three benzidine-linked, hexa-peri-hexabenzocoronene (superbenzene)-based ortho-, para-, and meta-cyclophanes are synthesized through intermolecular Yamamoto coupling reaction of structurally pre-organized precursors. Subsequent oxidative dehydrogenation gave the corresponding quinoidal benzidine-linked cyclophanes. Their geometries were confirmed by X-ray crystallographic analysis and their electronic properties were investigated by electronic absorption, cyclic voltammetry, and DFT calculations. The quinoidal benzidine-linked cyclophanes show thermally populated paramagnetic activity with a relatively large singlet-triplet energy gap. Two enantiomers for the ortho-cyclophanes (1-NH and 1-N) were isolated and their chiral figure-of-eight macrocyclic structures were identified. The cage-like cyclophanes 2-NH and 3-NH with concave surface can selectively encapsulate fullerene C70 .

18.
Aging (Albany NY) ; 12(6): 5399-5410, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32203055

RESUMO

Sphingosine kinase 1 (SphK1) is a potential therapeutic target for human osteosarcoma (OS). SphK1-targeting microRNAs (miRNAs) could have important therapeutic value for OS. We discovered that micorRNA-3677 (miR-3677) is a SphK1-targeting miRNA, inhibiting OS cell progression. The results of RNA-Pull down assay confirmed direct binding between biotinylated-miR-3677 and SphK1 mRNA in primary human OS cells. In established and primary human OS cells forced overexpression of miR-3677, by a lentiviral construct, decreased SphK1 3'-UTR (untranslated region) activity and downregulated SphK1 expression. Both were however enhanced with miR-3677 inhibition in OS cells. Function studies demonstrated that OS cell growth, proliferation and migration were inhibited with miR-3677 overexpression, but augmented with miR-3677 inhibition. MiR-3677 overexpression-induced anti-OS cell activity was reversed with re-expression of the 3'-UTR-depleted SphK1. Additionally, in SphK1 knockout OS cells (by CRISPR/Cas9 strategy), altering miR-3677 expression failed to further alter cell functions. Finally, we show that miR-3677 expression was significantly downregulated in primary human OS tissues, correlating with SphK1 mRNA upregulation. We conclude that targeting SphK1 by miR-3677 inhibits human OS cell progression.

19.
Int J Mol Sci ; 21(5)2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32156008

RESUMO

Melanoma is the deadliest form of skin cancer, and its incidence has continuously increased over the past 20 years. Therefore, the discovery of a novel targeted therapeutic strategy for melanoma is urgently needed. In our study, MTT-based cell proliferation assay, cell cycle, and apoptosis assays through flow cytometry, protein immunoblotting, protein immunoprecipitation, designing of melanoma xenograft models, and immunohistochemical/immunofluorescent assays were carried out to determine the detailed molecular mechanisms of a novel HSP90-PI3K dual inhibitor. Our compound, named DHP1808, was found to suppress A375 cell proliferation through apoptosis induction by activating the Fas/FasL signaling pathway; it also induced cell-cycle arrest and inhibited the cell migration and invasion of A375 cells by interfering with Hsp90-EGFR interactions and downstream signaling pathways. Our results indicate that DHP1808 could be a promising lead compound for the Hsp90/PI3K dual inhibitor.

20.
BMC Musculoskelet Disord ; 21(1): 62, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005208

RESUMO

BACKGROUND: Decreasing the length of hospital stay is an ideal course of action to appropriately allocate medical resources. The aim of this retrospective study was to identify perioperative factors that may decrease the length of hospital stay (LOS). METHODS: In this study, we collected the data on 1112 patients who underwent primary total knee arthroplasty surgery (TKAs) at our institution from Jan 1, 2011 to Nov 31, 2017. Based on the published literature, 16 potential factors (12 preoperative variables, 1 intraoperative variable, and 3 postoperative variables) were investigated. The patients requiring a hospital stay longer than the mean LOS (8 days) were defined as patients with a prolonged LOS. The factors with a P value less than 0.1 in the univariate analysis were further analysed in a multivariate model. An ordinal regression was used to determine independent risk factors for a prolonged LOS. RESULTS: The mean LOS was 8.3 days (±4.3), with a range of 2 to 30 days. Sixteen variables were analysed by univariate analysis, and 11 of them had p < 0.1 and were included in the multivariable model. Finally, 9 factors were found to be associated with a prolonged LOS. Among the 9 variables, 2 were surgery-related factors (operative time and intraoperative blood loss), and 3 were patient-related factors (age, ASA classification and neurological comorbidities). CONCLUSION: In this study, we found that the clinical protocol, complications, the patient's age, the ASA classification, neurological comorbidities, the operative time, the ward, intraoperative blood loss and the surgeon were all factors contributing to a prolonged LOS. In clinical practice, these factors provide important information for the surgeon and are useful for identifying patients with a high risk of a prolonged LOS.

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