Cartilage
·
2021
·
IF 4.634
Yunliang Lei,Jiabin Peng,Zhu Dai,Ying Liao,Quanhui Liu,Jian Li,Yonghui Jiang
ObjectiveThis study was undertaken to elucidate the mechanism of improved chondrocyte migration after juvenile articular cartilage fragmentation.DesignIn vitro organ culture with rabbit cartilage fragments and cell culture with rabbit chondrocytes were performed. In part A, minced juvenile cartilage fragments (~0.5 × 0.5 × 0.5 mm) from rabbits, planted in gelatin sponge and fibrin glue, were cultured for 2, 4, or 6 weeks in vitro and compared with the cartilage chunks (~4 × 4 × 1 mm) and membrane type 1 matrix metalloprotease (MT1-MMP) inhibitor groups. Chondrocyte outgrowth was evaluated on histology and confocal laser scanning microscopy. MT1-MMP expression was compared between the cartilage fragment group and the cartilage chunks group. In part B, articular chondrocytes were harvested from juvenile rabbits, MT1-MMP was transfected into the cells, and cell migration was evaluated using the Transwell and wound healing tests.ResultsThe histology and confocal microscopy results revealed that cell accumulation occurred at the edge of cartilage fragments, and outgrowth was better in the cartilage fragment group than those in the cartilage chunks group. Similar results were observed for MT1-MMP expression. After MT1-MMP inhibition, cells did not accumulate at the edge of the cartilage fragments, and chondrocyte outgrowth did not occur. Furthermore, overexpression of MT1-MMP enhanced the migration of articular chondrocytes.ConclusionsJuvenile articular cartilage fragmentation improved chondrocyte migration by upregulating MT1-MMP.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF CHEMICAL KINETICS
·
2021
·Vol. 54
·期 2
·71-80
·
IF 1.462
Yufei Yang,Yadong Zhang
In this work, a HPW/ZSM-5 catalyst was prepared by impregnating phosphotungstic acid (HPW) with carrier ZSM-5 zeolite and characterized by XRD, SEM, N 2 adsorption/desorption isotherm, NH 3 -TPD, and FT-IR techniques. The catalytic performance of HPW/ZSM-5 was investigated by using the decomposition reaction of cyclohexylbenzene-1-hydroperoxide (CHBHP) to phenol and cyclohexanone. The conversion rate of CHBHP was up to 97.28%. In addition, the reusability test exhibited that the high durability HPW/ZSM-5 as the conversion rate of CHBHP only decreased by 3.11% after five runs. The kinetic study of the decomposition reaction indicated it was a primary reaction. The apparent activation energy of the decomposition reaction was 102.39 kJ·mol –1 in the temperature range of 45–60℃. All results indicate that the HPW/ZSM-5 catalyst has good performance and promising applications in acid catalyzed organic chemistry.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Mengshi Jiang,Bing Qin,Lihua Luo,Xiang Li,Yingying Shi,Junlei Zhang,Zhenyu Luo,Chunqi Zhu,Guannan Guan,Yongzhong Du,Jian You
The hypoxic tumor microenvironment (TME) hinders the effectiveness of immunotherapy . Alleviating tumor hypoxia to improve the efficacy of immune checkpoint inhibitors (ICIs) represented by programmed cell death protein 1 (PD-1) antibody has become a meaningful strategy. In this study, we adopted three methods to alleviate hypoxia, including direct oxygen delivery using two different carriers and an indirect way involving HIF-1α inhibition. Both in vivo and in vitro experiments showed that liposomes modified with perfluorocarbon or hemoglobin ( [email protected] or [email protected] ) were able to efficiently load and release oxygen, relieving tumor hypoxia. However, the gas release behavior of [email protected] was uncontrollable, which might induce acute hyperoxia side effects during intravenous injection and reduce its biosafety. In contrast, whether administered locally or systemically, [email protected] revealed high animal tolerance, and was much safer than commercial HIF-1α inhibitor (PX-478), displaying prospects as a promising oxygen carrier for clinical practice. Pharmacodynamic experiments suggested that [email protected] helped PD-1 antibody break the therapeutic bottleneck and significantly inhibited the progression of 4 T1 breast cancer. But in CT26 colon cancer , the combination therapy failed to suppress tumor growth. After in-depth analysis and comparison, we found that the ratio of M1/M2 tumor associated macrophages (TAMs) between these two tumor models were dramatically different. And the lower M1/M2 ratio in CT26 tumors limited the anti-tumor effect of combination therapy. In this study, three methods for alleviating tumor hypoxia were compared from the perspectives of biosafety, efficacy and clinical applicability. Among them, [email protected] stood out, and its combined use with PD-1 antibody exhibit a distinct synergistic suppression effect on tumors with more M1 macrophages presented in the microenvironment. Our work provided a good reference for improving the efficacy of PD-1 antibody by alleviating tumor hypoxia.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Sida Ruan,Guiying Yang,Yuanzhen Dong,Wenwen Shangguan,Weigen Lu
Hypoparathyroidism (HP) is a rare disease with clinical manifestations of hypocalcemia and hyperphosphatemia, resulting from deficient or absent parathyroid hormone (PTH) secretion. Conventional treatment for patients with HP involves extensive calcium and vitamin D supplementation. In 2015, PTH1–84 was approved by the United States Food and Drug Administration as an adjunct for HP patients who cannot be well-controlled on conventional treatment. However, PTH1–84 therapy requires a daily injection, leading to poor patient compliance. The purpose of this study was to develop a long-acting PTH1–34 analogue by increasing its affinity to albumin. Three PTH1–34 variants were generated by substituting two of the three lysine (Lys) residues with arginine, reserving a single Lys as the modification site in each sequence. A series of side chains, containing fatty acid, deoxycholic acid, or biotin groups, were synthesized to modify these PTH1–34 variants by using a solid–liquid phase synthesis approach. In vitro bioactivity and albumin affinity tests were used to screen these new PTH1–34 analogues. Finally, Lys27-AAPC was selected from 69 synthesized analogues as a candidate therapeutic compound because it retained potency and exhibited a high albumin-binding capacity. In pharmacodynamic experiments, Lys27-AAPC demonstrated enhanced and prolonged efficacy in serum calcium elevating relative to PTH1–84. Moreover, a lyophilized powder for injection containing Lys27-AAPC was developed for further testing and represented a potential long-acting HP treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Catalysis
·
2021
·
IF 5.062
Mengzhe Li,Xiaohua Shen,Miaoqing Liu,Jianjun Lu
L-lysine is used as a crystallization regulator, and a two-step synthesis method is adopted in a concentrated gel system, which provides a new route to synthesize of nano-sized TS-1 zeolite. The new synthesis strategy was used to successfully synthesize TS-1 zeolite with a particle size less than 100 nm. The rate of crystal nucleation is faster than the crystal growth at the low temperature in the first step. Introduction of L-lysine can prevent crystal growth to form nano-sized TS-1 zeolite at the high temperature in the second step. Meanwhile, L-lysine decrease the pH value of the gel system, which is favorable for Ti atoms to incorporate the TS-1 framework. TS-1 nanozeolite can effectively reduce the diffusion resistance, and nanozeolite has a large specific surface area and high stability. Therefore, TS-1 nanozeolite exhibits the excellent catalytic performance during the hydroxylation of benzene. The conversion of benzene has been greatly improved and the types of by-products are effectively reduced. The conversion of benzene reached 50.2%, and the yield of phenol was 30.8% without by-product benzoquinone. TS-1 nano-zeolite as a catalyst for benzene hydroxylation shows great potential in industrial application.
✓ 已验证
产品关联
DOI
高影响因子
BMC Complementary Medicine and Therapies
·
2020
·Vol. 20
·期 1
·1-10
·
IF 0
Liu Shou Gang,Luo Guang Pu,Qu Yong Bin,Chen Yong Feng
Background Psoriasis is a common inflammatory skin disease. Abnormal proliferation of keratinocytes is one of the psoriatic histopathological features. Indirubin has an essential effect on the proliferation and activation of keratinocytes; however, in psoriasis, the specific mechanism of action of indirubin on keratinocytes is unclear. In the present study, we revealed the effects of indirubin on DNA methyltransferase 1 (DNMT1), wnt inhibitory factor 1 (wif-1), and wnt/β-catenin signal pathway, in the meantime, we explored the effects of indirubin on proliferation, cell cycle and the apoptosis of HaCaT cells.Methods The expression of DNMT1, wif-1, Frizzled2, Frizzled5, and β-catenin in HaCaT cells treated with different concentrations of indirubin were detected by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). The expression levels of DNMT1 and wif-1 were observed after treated with different concentrations of indirubin by enzyme-linked immunosorbent assay (ELISA). The wif-1 promoter methylation status was detected by DNA methylation-specific PCR (MSP). The transcriptional activities of wif-1 and β-catenin were discovered by a luciferase reporter gene system. Cell viability was determined by Cell Counting Kit-8 (CCK8) method. The cell cycle was detected by flow cytometry. The apoptotic cells were surveyed by the apoptosis kit. The expression of Inolucrin, Loricrin, Filaggrin, Keratin 17, and transcriptional activation of transglutaminase 1(TGase1) were detected by Western blotting.Results Indirubin inhibited the expression of DNMT1 and the methylation of the wif-1 promoter. In the wnt signal pathway, indirubin restored the protein expression of wif-1 and inhibited expression of Frizzled2, Frizzled5, and β-catenin. Besides, indirubin inhibited the proliferation of HaCaT cells, induced apoptosis, and arrest cell cycle. We also reported that indirubin could down-regulate the expression of Involucrin, TGase 1, and keratin 17, but the expression of Filaggrin and Loricrin had no significant effect.Conclusion Our research showed that indirubin promoted the demethylation of wif-1 and suppressed the wnt/β-catenin signal pathway, thereby exerted an anti-proliferative effect. This study reveals the anti-proliferation mechanism of indirubin, which may provide an effective option for the treatment of proliferative diseases.
✓ 已验证
产品关联
DOI
PubMed
CANCER LETTERS
·
2020
·
IF 7.36
Huimin Tao,Lu Cheng,Lihua Liu,Hong Wang,Zhijie Jiang,Xu Qiang,Lijun Xing,Yifeng Xu,Xinying Cai,Jing Yao,Min Wang,Zheng Qiu
Antibodies blocking the PD-1/PD-L1 pathway have achieved great success. However, some disadvantages of antibodies have been found, which limit their clinical applications. Peptide antagonists are alternatives to antibodies in PD-1/PD-L1 blockage, but successful studies in this area are limited. A PD-1 targeting peptide, P–F4, was identified using phage display. P–F4 bound PD-1 with an affinity of 0.119 μM, inhibited PD-1/PD-L1 interaction at the cellular level and modulated T cell activity in vitro . We have overcome the poor solubility and rapid degradation problems of this peptide by packaging P–F4 in nanoparticles. In vivo experiments demonstrated that P–F4 nanoparticles could strongly inhibit tumor growth in a CT26 mouse model. Further research revealed that treatment of P–F4 nanoparticles increased CD8+T cells and reduced Tregs in the tumor microenvironment and tumor-draining lymph nodes. It was shown that treatment of P–F4 nanoparticles also increased lymphocytic activities, including proliferation, cytokine secretion and cytolytic activity. Moreover, computer modeling suggested that the P–F4 binding site to PD-1 overlaps with the PD-L1 binding surface. In this study, a peptide candidate for cancer immunotherapy was provided, and its working mechanisms were studied.
✓ 已验证
DOI
PubMed
高影响因子
Iranian Journal of Biotechnology
·
2020
·
IF 0.973
Shuang Feng Li,Huai Wang,Jia Li Chen,Hui Xia Zhu,Ri-Sheng Yao,Huan Wu
Background: Lignin is the largest natural aromatic polymer in nature and is also a unique aromatic-based biopolymer, accountingfor nearly 30% of the earth’s organic carbon. Generally, lignin is regarded as waste and is mainly used as a low- valuefuel that is burned to generate heat and energy to solve the problem of biomass waste; for this obstacle of lignin,highly efficient biodegradation plays a critical role in developing an environmentally friendly technique for lignin biotransformation. Objectives: This study intends to isolate and purify several microbial strains from nature. It also explores how their lignin degradationis able to enhance the biodegradation and recycling of biomass and the reclamation of lignin in wastewater from pulp and paper mills. Materials and Methods: Lignin-degrading microbial strains were isolated from soil using medium containing sodium lignosulphonate as the sole carbonsource. They were then screened by aniline blue and guaiacol plate, and then the best strain was chosen and identified.The conventional one-factor method was used to optimize various parameters that affect lignin’s degradation ability. Results: The strain possessing the highest lignin biodegradation ability was identified and denominated as Aspergillus Flavus F-1. After optimization, the maximum degradation rate of lignin, 44.6% within 3 days, was obtained at pH 7.0, 30 ℃, 2.5 g·L -1 ammoniumsulfate, 2 g·L -1 lignin and 0.5 g·L -1 glucose. The results show the LiP and Lac secreted from Aspergillus Flavus F-1 played the main role in the degradation of lignin. Conclusion: One microbial strain, Aspergillus Flavus F-1, was successfully isolated with a lignin-degrading abilitythat can cut the lignin into fragments. This provides a promising candidate for the transformation and utilization of crop waste biomass for various industrial purposes.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ELECTROANALYTICAL CHEMISTRY
·
2020
·
IF 3.807
Lijun Zhou,Xueling Shan,Ding Jiang,Wenchang Wang,Zhidong Chen
Catechol (CC) exists a potential threat to human psychology and physiology. In this research, a novel ultra-sensitive electrochemiluminescence (ECL) sensor was established to detect CC based on carbon dots (CDs) and metal organic framework (HKUST-1) synergy system. The results showed good large specific surface area of HKUST-1 on CDs which could effectively improve the sensitivity of sensor. Under the optimal conditions, the as-fabricated sensor illustrated a wide linear range of 5.0 × 10 −9 –2.5 × 10 −5 mol/L with the detection limit of 3.8 × 10 −9 mol/L(S/N = 3). In addition, owning to its good reproducibility and stability, the sensor had been successfully applied to the actual sample. This work provides an important reference for the application of metal organic framework materials (MOFs) in ECL researches and a novel method for detecting catechol.
✓ 已验证
产品关联
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2020
·
IF 4.872
Yuliang Xu,Xiaozhou Wang,Na Geng,Yiran Zhu,Shuo Zhang,Yongxia Liu,Jianzhu Liu
Cr (VI), which is a common heavy metal pollutant with strong oxidizing property, exists widely in nature. Organisms can be exposed to Cr (VI) through various means. Cr (VI) causes mitochondrial dysfunction after being absorbed by cells. Whether Cr (VI) induces the selective autophagic degradation of mitochondria, which is a biological process called mitophagy, remains unclear. Mitophagy not only recycles intracellularly damaged mitochondria to compensate for nutrient deprivation but also is involved in mitochondria quality control. Thus, this study investigated whether Cr (VI) could induce mitophagy in DF-1 cells. Carbonyl cyanide m-chlorophenylhydrazone, which is a mitochondrial-uncoupling reagent that induces mitophagy, was used. DF-1 cells were incubated with different doses of Cr (VI) for varying durations. The autophagy-related proteins LC3-II and p62 levels decreased after 6 h of Cr (VI) treatment but recovered within 24 h. The mitochondrial membrane potential, which is an indicator of mitochondrial damage, was detected by flow cytometry. We found that different durations of Cr (VI) treatment induced mitochondrial mass decrease and depolarization. Furthermore, the expression of the protein translocase of outer mitochondrial membrane 20 (TOMM20), which is a mitochondrial outer membrane protein, was decreased significantly in the presence of Cr (VI). Our findings indicate that Cr (VI) may contribute to the mitochondrial morphology and function damage and may therefore lead to the autophagic clearance of mitochondria.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2020
·
IF 4.96
Yue Liu,Zhuang-Zhuang Tang,Yu-Meng Zhang,Li Kong,Wei-Fen Xiao,Teng-Fei Ma,Yao-Wu Liu
Gestational diabetes mellitus (GDM) is associated with an increased risk of progressing to type 2 DM and cardiovascular disease; however, the pathogenesis is still poorly understood. This study was to investigate roles of thrombin and its receptor protease-activated receptor 1 (PAR-1) and NLRP1 inflammasome in endothelial injury in GDM condition. Umbilical cord and plasma of GDM patients and high glucose (HG) cultured human umbilical vein endothelial cells (HUVECs) were used to examine the pathological changes of these pathways. Meanwhile, ameliorative effects and potential mechanisms of a natural product sarsasapogenin (Sar) were investigated in HUVECs. Thrombin/PAR-1 pathway, advanced glycation endproducts (AGEs) and their receptor (RAGE) axis, and the nucleotide-binding domain and leucine-rich repeat containing protein 1 (NLRP1) inflammasome were activated in GDM condition and HG-cultured HUVECs, accompanied by endothelial injury (decreased cell viability and increased lactate dehydrogenase release). Nevertheless, thrombin inhibition or PAR-1 antagonism caused decreases in AGEs formation and RAGE expression in HG-cultured HUVECs, while AGEs inhibition or RAGE antagonism declined PAR-1 expression not thrombin activity. Furthermore, thrombin inhibition or PAR-1 antagonism restrained NLRP1 inflammasome activation in HG-cultured HUVECs; meanwhile, NLRP1 expression and interleukin 18 levels were remarkably reduced in HG-cultured HUVECs after PAR-1 knockdown. Interestingly, Sar co-treatment could suppress thrombin/PAR-1 pathway, NLRP1 inflammasome, and AGEs/RAGE axis. Together, endothelial damages in GDM were likely due to enhanced interaction between AGEs/RAGE axis and thrombin/PAR-1 pathway, followed by NLRP1 inflammasome activation. Moreover, Sar may act as a protective agent against endothelial injury in chronic HG condition.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEMBRANE SCIENCE
·
2020
·
IF 7.183
Jiaqi Li,Mengxiao Zhang,Weilin Feng,Liping Zhu,Lin Zhang
Herein, a novel thin film composite (TFC) membrane pore-filled with polymer of intrinsic microporosity, PIM-1, has been developed for organic solvent nanofiltration (OSN). The TFC membranes were facilely prepared by dip-coating of PIM-1/chloroform solution onto polyacrylonitrile support membranes followed by a solvent vapor annealing (SVA) process. The relationship between preparation conditions, selective layer morphologies and OSN performances of the prepared TFC membranes were studied systematically. It was found PIM-1 was evidently filled into the near surface pores of support membranes due to the infiltration of PIM-1 solution. With the elongation of SVA time, the thickness of the PIM-1 layer decreased and the PIM-1/PAN interface gradually disappeared, which is advantageous to enhance the interfacial bonding. The prepared TFC membranes were used to reject organic molecules in organic solvents and exhibited tunable solvent permeability and solute rejection. Especially, the membranes were suitable for the removal of neutral molecules and anionic dyes from ethanol. The typical membrane demonstrated an ethanol permeance of 4.3 L m −2 h −1 bar −1 with a rejection of 93.7% towards Methyl Orange (327 Da). By comparing the permeance of various solvents, it is found that the closer the Hansen solubility parameter of solvent is to that of PIM-1, the higher the solvent permeance. This indicates the affinity between solvent and membrane plays an important role in solvent permeability. This work offers a novel and convenient strategy to prepare highly permeable membranes with controllable microstructures and tunable permselectivity to meet the diverse demands of molecular separation in organic solvents.
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）