Publications by authors named "Xiaohua Lu"

156 Publications

A novel moniliformin derivative as pan-inhibitor of histone deacetylases triggering apoptosis of leukemia cells.

Biochem Pharmacol 2021 Jul 13:114677. Epub 2021 Jul 13.

Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany. Electronic address:

New and potent agents that evade multidrug resistance (MDR) and inhibit epigenetic modifications are of great interest in cancer drug development. Here, we describe that a moniliformin derivative (IUPAC name: 3-(naphthalen-2-ylsulfanyl)-4-{[(2Z)-1,3,3-trimethyl-2,3-dihydro-1H-indol-2-ylidene]methyl}cyclobut-3-ene-1,2-dione; code: MCC1381) bypasses P-gp-mediated MDR. Using transcriptomics, we identified a large number of genes significantly regulated in response to MCC1381, which affected the cell cycle and disturbed cellular death and survival. The potential targets of MCC1381 might be histone deacetylases (HDACs) as predicted by SwissTargetPrediction. In silico studies confirmed that MCC1381 presented comparable affinity with HDAC1, 2, 3, 6, 8 and 11. Besides, the inhibition activity of HDACs was dose-dependently inhibited by MCC1381. Particularly, a strong binding affinity was observed between MCC1381 and HDAC6 by microscale thermophoresis analysis. MCC1381 decreased the expression of HDAC6, inversely correlated with the increase of acetylated HDAC6 substrates, acetylation p53 and α-tubulin. Furthermore, MCC1381 arrested the cell cycle at the G/M phase, induced the generation of reactive oxygen species and collapse of the mitochondrial membrane potential. MCC1381 exhibited in vivo anti-cancer activity in xenografted zebrafish. Collectively, MCC1381 extended cytotoxicity towards P-gp-resistant leukemia cancer cells and may act as a pan-HDACs inhibitor, indicating that MCC1381 is a novel candidate for cancer therapy.
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http://dx.doi.org/10.1016/j.bcp.2021.114677DOI Listing
July 2021

Fusion proteins of biologic agents in the treatment of rheumatoid arthritis (RA): A network meta-analysis.

Medicine (Baltimore) 2021 Jun;100(24):e26350

Department of Epidemiology and Biostatistics.

Background: To evaluate the efficacy of fusion proteins biologics (Etanercept (ETN), Anakinra (ANA), and Abatacept) combinations in the treatment of rheumatoid arthritis (RA) using network meta-analysis to rank those according to their performance medicines. The performance of these processes is ranked according to the results of the analysis and an explanatory study of the possible results is carried out.

Methods: Multiple databases including PubMed, EMBASE, and Cochrane Library were used to identify applicable articles and collect relevant data to analyze using STATA (14.0) software. The literature included in this study was divided into a combination of a placebo, methotrexate (MTX), and an observation group (1 of the 3 drugs). The last search date was December 12, 2019.

Results: A total of 19 eligible randomized controlled trials of fusion proteins biologics were identified, a total of 1109 papers were included, and the results showed that the ETN + MTX had the highest probability of being the most clinically efficacious intervention, with a surface under the cumulative ranking curve of 91.6, was significantly superior (P < .05). Patients who had received ETN or ETN + MTX or ANA had effective compared with patients who had received placebo (95% CI 1.28%-8.47%; 1.92%-19.18%; 1.06%-10.45%).

Conclusions: 1. The combination of ETN and MTX had the highest probability of optimal treatment compared to other drugs and 2. ENT, ENT + MTX, and ANA were effective in the treatment of RA compared to placebo.
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http://dx.doi.org/10.1097/MD.0000000000026350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213327PMC
June 2021

The influence mechanism of the molecular structure on the peak current and peak potential in electrochemical detection of typical quinolone antibiotics.

Phys Chem Chem Phys 2021 Jun;23(25):13873-13877

Saitama Institute of Technology, 1690, Fusaiji, Fukaya, Saitama 369-0293, Japan.

Antibiotic pollution in water has become an increasingly serious problem, posing a potentially huge threat to human health. Ofloxacin (OFL), norfloxacin (NOR), and enoxacin (ENX) are typical broad-spectrum quinolone antibiotics, which are frequently detected in various water environments. An electrochemical sensor is a rapid and effective tool to detect antibiotics in the aquatic environment. The molecular structure of target pollutants is an important factor affecting the detection performance of electrochemical sensors. Based on the electrochemical detection results of antibiotics (OFL, NOR, and ENX), we first used the molecular structure analysis method based on quantum chemistry to accurately identify the electronegativity and the electrocatalytic degree of the oxidizable (and non-oxidizable) functional groups of pollutants. We also clarified the influence mechanism of the molecular structure on the peak current and peak potential. These results can provide theoretical support for rapidly selecting electrodes with a suitable electrochemical window to efficiently detect trace organic pollutants (such as antibiotics) in water based on the molecular structure of the target pollutant.
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http://dx.doi.org/10.1039/d1cp01358kDOI Listing
June 2021

Overexpression of Cassava Enhances the Salt and IAA Tolerance of Transgenic .

Plants (Basel) 2021 May 8;10(5). Epub 2021 May 8.

College of Tropical Crops, Hainan University, Haikou 570228, China.

Annexins are a superfamily of soluble calcium-dependent phospholipid-binding proteins that have considerable regulatory effects in plants, especially in response to adversity and stress. The gene has been reported to play a significant role in various abiotic stress responses. In our study, the cDNA of an annexin gene highly similar to was isolated from the cassava genome and named . It contains domains specific to annexins, including four annexin repeat sequences (I-IV), a Ca-binding sequence, Ca-independent membrane-binding-related tryptophan residues, and a salt bridge-related domain. is localized in the cell membrane and cytoplasm, and it was found to be preferentially expressed in the storage roots of cassava. The overexpression of reduced the sensitivity of transgenic to various Ca, NaCl, and indole-3-acetic acid (IAA) concentrations. The expression of the stress resistance-related gene and auxin signaling pathway-related genes and in transgenic was significantly increased under salt stress, while the Malondialdehyde (MDA) content was significantly lower than that of the control. These results indicate that the gene may increase the salt tolerance of transgenic via the IAA signaling pathway.
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http://dx.doi.org/10.3390/plants10050941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150822PMC
May 2021

PACAP ameliorates the fertility of obese mice through PAC1/PKA/ERK/Nrf2 signal axis.

J Endocrinol 2021 03;248(3):337-354

Institute of Biomedicine, Department of Cellular Biology, Jinan University, Guangzhou, China.

Obesity is strongly linked to male infertility. Apoptotic inflammatory response caused by oxidative stress in testicular spermatogenic cells is one of the important causes of obesity-related male infertility. As bioactive peptide is secreted by the pituitary gland, pituitary adenylate cyclase activating polypeptide (PACAP) has a powerful triple role of anti-oxidation, anti-apoptosis, and anti-inflammation, and it is involved in the male reproduction regulation, but the specific mechanism remains unknown. The purpose of this study is to explore the role of PACAP in obesity-related male infertility. In cellular level experiments, mouse spermatocytes (GC-2) were treated with palmitate (PA) to establish an high-fat injury cell model in vitro and then treated with PACAP. In animal-level experiments, C57BL/6 male mice were fed with a high-fat diet (HFD) to induce obesity and subsequently treated with PACAP. The cell mechanism studies show that PACAP selectively binded to the PAC1 receptor to attenuate palmitic acid-induced mouse spermatogenic cell (GC-2) oxidative damage and apoptotic inflammatory response via the PKA/ERK/Nrf2 signaling axis. However, this mechanism was inhibited in GC-2 cells inhibiting the activity of Nrf2. The animal experiment studies show that PACAP treatment ameliorated obesity characteristics, including body weight, epididymal adipose weight, testes/body weight, serum lipids levels, and reproductive hormone levels in vivo. Additionally, PACAP was shown to improve the reproductive function of the obese mice, which was characterized by improved testis morphology and sperm parameters via Keap1/Nrf2/ARE pathway. These beneficial effects of PACAP were abolished in obese mice with testes-specific knockdown of Nrf2. Our data suggested that PACAP could ameliorate fertility in obese male mice and may be a promising candidate drug for obesity-induced male infertility.
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http://dx.doi.org/10.1530/JOE-20-0316DOI Listing
March 2021

[Designment and application of a novel device for microcirculation viviperception].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Jan;33(1):109-110

School of Preclinical Medicine, Wannan Medical College, Wuhu 241002, Anhui, China.

The key technology of the device for the viviperception of the animal mesenteric microcirculation is to simulate the celiac environment in the device. The technical requirements of the device for microcirculation viviperception are that the observation box should be able to "keep warm, preserve moisture, continually perfuse, and fix the sample"; and the lighting should be "intense", "convergence", and "cool". After actual application, it was found that the newly designed and developed the device by research personnel of Wannan Medical College for the viviperception of the animal mesenteric microcirculation can meet the technical requirements, which is able to "keep warm, preserve moisture, continually perfuse, and fix the sample", and using LED lamp as the microscope light source is "intense", "convergence", and "cool". This device is ingenious and reasonable in design, stable in technology, convenient in operation, and competent in microcirculation viviperception. It solves the technical problem to simulate the celiac environment for mesenteric microcirculation viviperception. The device provides convenience to observe and study the microcirculation, which is worth to be applicated widely.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200817-00582DOI Listing
January 2021

High nuclear expression of APE1 correlates with unfavorable prognosis and promotes tumor growth in hepatocellular carcinoma.

J Mol Histol 2021 Apr 4;52(2):219-231. Epub 2021 Jan 4.

Department of Interventional Radiology, Affiliated Hospital of Nantong University, Nantong, 226001, China.

APE1 is a multifunctional protein that plays important roles in cancer development. However, the association between APE1 expression and the clinicopathological parameters of HCC patients has not been fully characterized. In this study, bioinformatics analysis of APE1 was performed in several databases, including the TCGA, GeneCard, Human Protein Atlas and Ualcan databases. The relationship between APE1 mRNA expression and several attributes of liver cancer patients in TCGA was investigated. Then, the protein expression of APE1 was detected by IHC analysis in 95 HCC samples and the association between APE1 expression and the clinicopathological parameters of HCC patients was explored. GSEA-KEGG analysis was performed to predict the potential signaling pathways that associated with APE1 expression. Then the siRNA-mediated knockdown model of APE1 was constructed in HCC cell line to further detect the detailed function of APE1 in HCC development in vitro and in vivo. The results of the bioinformatics analysis showed that APE1 expression was primarily located in the cell nucleus. APE1 mRNA expression was substantially correlated with pathological grade and T status in TCGA database. Elevated APE1 expression was observed in HCC samples and was associated with unfavorable survival time in liver cancer patients. IHC data demonstrated that the nuclear expression of APE1 in HCC tissues was significantly higher than that in noncancerous tissues. The expression level of the APE1 protein in HCC was strongly associated with tumor diameter and overall survival. Survival analysis indicated that APE1 nuclear expression is an independent prognostic marker for the overall survival of HCC patients. GSEA-KEGG results confirmed that APE1 associated with the base excision repair signaling pathway. The data of phenotypic experiments indicated that APE1 remarkably promoted tumor growth both in HCC cells and xenografts. The findings firstly imply that nuclear expression of APE1 is a valuable prognostic marker for HCC. APE1 significantly facilitate HCC development and targeting APE1 may be a promising strategy for HCC treatment.
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http://dx.doi.org/10.1007/s10735-020-09939-9DOI Listing
April 2021

Remediation of hexachlorobenzene-contaminated soils with alkyl glycoside-enhanced desorption and zero-valent iron-EDTA-air treatment.

J Environ Qual 2020 Mar 4;49(2):358-367. Epub 2020 Mar 4.

Environmental Science Research Institute, School of Environmental Science and Engineering, Huazhong Univ. of Science and Technology, Wuhan, 430074, PR China.

In this work, the use of a coupled process, alkyl glycoside (APG) enhanced soil desorption followed by the zero-valent iron-ethylenediaminetetraacetic acid (EDTA)-air (ZEA) Fenton-like system, was investigated for the remediation of a simulated hexachlorobenzene (HCB)-contaminated diatomite soil and a real HCB-contaminated soil. Three surfactants with different concentrations were studied to obtain the suitable soil desorption agent. Compared with APG0810 and Triton x-100, APG0814 showed a better solubilization effect due to its lower critical micelle concentration. With addition of 3000 mg L APG0814, 35% of HCB was removed from contaminated diatomite soil, and a small amount of residual APG in diatomite soil was found to be beneficial for the soil dispersion. After treatment with the ZEA system, the removal efficiency of HCB in the diatomite soil desorption solution reached 76% in 2 h; we observed that a small amount of APG retained in the desorption solution accelerated the HCB removal. A real HCB-contaminated soil was used to verify the remediation effects. This study demonstrates that our approach is a feasible alternative for remediating soil contaminated with hydrophobic organic compounds.
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http://dx.doi.org/10.1002/jeq2.20057DOI Listing
March 2020

Techno-economic analysis of biomass processing with dual outputs of energy and activated carbon.

Bioresour Technol 2021 Jan 11;319:124108. Epub 2020 Sep 11.

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, Nanjing 211816, China. Electronic address:

Biomass utilization is facing great challenge mainly due to the low profit margin of biomass products. Bio-energy plants using gasification and liquefaction technologies are barely surviving, while biomass to activated carbon (AC) route has been demonstrated economically successful. In this work, spent mushroom substrate was used to produce AC and fuel gas with two different processes using internal flue gas and external air as activation agents, respectively. Experimental work was conducted to produce input data for Aspen Plus simulation including processing temperature, flue gas composition, AC yield, etc. Techno-economic analysis was performed, which reveals a great economic potential of integrating AC production in biomass processing. Air activation has obvious advantage in economic benefits, while the risk of precise temperature control and operation stability needs to be carefully evaluated in large-scale production. Flue gas activation is more reliable and it also generates less CO that is beneficial for the long-term operation.
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http://dx.doi.org/10.1016/j.biortech.2020.124108DOI Listing
January 2021

Knockdown of Ror2 suppresses TNF‑α‑induced inflammation and apoptosis in vascular endothelial cells.

Mol Med Rep 2020 Oct 28;22(4):2981-2989. Epub 2020 Jul 28.

Department of Intervention Radiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China.

Wnt family member 5a (Wnt5a) is a noncanonical member of the Wnt family that is highly expressed in atherosclerosis. Studies have shown that Wnt5a/receptor tyrosine kinase‑like orphan receptors 2 (Ror2) signaling can participate in the formation of foam cells; however, the role of Ror2 in vascular endothelial cells during atherosclerotic injury is unknown. Therefore, the present study aimed to investigate the role of Ror2 in tumor necrosis factor (TNF)‑α‑induced vascular endothelial cell injury and investigate whether it could be regulated by Wnt5a. Human umbilical vein endothelial cells were transfected with short hairpin RNA specific against Ror2 in the absence or presence of TNF‑α. The alteration of inflammatory cytokine levels was detected, and the expression of adhesion molecules was assessed. Western blot and flow cytometry analyses were used to detect the activation of nuclear factor‑κB (NF‑κB) signaling and cell apoptosis. The interaction between Ror2 and Wnt5a was confirmed by immunoprecipitation. Ror2 was upregulated upon TNF‑α stimulation. Knockdown of Ror2 inhibited the TNF‑α‑induced release of inflammatory cytokines, the expression of intercellular adhesion molecule‑1 and vascular cell adhesion molecule‑1 and the activation of NF‑κB signaling. Furthermore, cell apoptosis induced by TNF‑α was rescued by Ror2 silencing. In addition, Wnt5a expression was increased by TNF‑α, and Ror2 could bind to Wnt5a, the knockdown of which could downregulate the levels of Ror2. In conclusion, it was demonstrated that Ror2 was upregulated upon TNF‑α stimuli, and interference of Ror2 regulated by Wnt5a could suppress TNF‑α‑induced inflammation and apoptosis in vascular endothelial cells.
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http://dx.doi.org/10.3892/mmr.2020.11377DOI Listing
October 2020

Excellent Protein Immobilization and Stability on Heterogeneous C-TiO Hybrid Nanostructures: A Single Protein AFM Study.

Langmuir 2020 08 29;36(31):9323-9332. Epub 2020 Jul 29.

State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing 210009, P.R. China.

Enhancing molecular interaction is critical for improving the immobilization and stability of proteins on TiO surfaces. In this work, mesoporous TiO materials with varied pore geometries were decorated with phenyl phosphoric acid (PPA), followed by a thermal treatment to obtain chemically heterogeneous C-TiO samples without changing the geometry and crystalline structure, which can keep the advantages of both carbon and TiO. The molecular interaction force between the protein and the surfaces was measured using atomic force microscopy by decomposing from the total adhesion forces, showing that the surface chemistry determines the interaction strength and depends on the amount of partial carbon coverage on the TiO surface (∼40-80%). Samples with 58.3% carbon coverage provide the strongest molecular interaction force, consistent with the observation from the detected friction force. Surface-enhanced Raman scattering and electrochemical biosensor measurements for these C-TiO materials were further conducted to illustrate their practical implications, implying their promising applications such as in protein detection and biosensing.
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http://dx.doi.org/10.1021/acs.langmuir.0c01942DOI Listing
August 2020

Chemopreventive Property of Sencha Tea Extracts towards Sensitive and Multidrug-Resistant Leukemia and Multiple Myeloma Cells.

Biomolecules 2020 07 4;10(7). Epub 2020 Jul 4.

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.

The popular beverage green tea possesses chemopreventive activity against various types of tumors. However, the effects of its chemopreventive effect on hematological malignancies have not been defined. In the present study, we evaluated antitumor efficacies of a specific green tea, sencha tea, on sensitive and multidrug-resistant leukemia and a panel of nine multiple myelomas (MM) cell lines. We found that sencha extracts induced cytotoxicity in leukemic cells and MM cells to different extents, yet its effect on normal cells was limited. Furthermore, sencha extracts caused G2/M and G0/G1 phase arrest during cell cycle progression in CCRF/CEM and KMS-12-BM cells, respectively. Specifically, sencha-MeOH/HO extracts induced apoptosis, ROS, and MMP collapse on both CCRF/CEM and KMS-12-BM cells. The analysis with microarray and COMPARE in 53 cell lines of the NCI panel revealed diverse functional groups, including cell morphology, cellular growth and proliferation, cell cycle, cell death, and survival, which were closely associated with anti-tumor effects of sencha tea. It is important to note that PI3K/Akt and NF-κB pathways were the top two dominant networks by ingenuity pathway analysis. We demonstrate here the multifactorial modes of action of sencha tea leading to chemopreventive effects of sencha tea against cancer.
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http://dx.doi.org/10.3390/biom10071000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407630PMC
July 2020

Repurposing of artemisinin-type drugs for the treatment of acute leukemia.

Semin Cancer Biol 2021 Jan 30;68:291-312. Epub 2020 May 30.

Department of Pharmaceutical Biology, Institute of Pharmacy and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany. Electronic address:

Cancer treatment represents an unmet challenge due to the development of drug resistance and severe side effects of chemotherapy. Artemisinin (ARS)-type compounds exhibit excellent antimalarial effects with few side effects and drug-resistance. ARS and its derivatives were also reported to act against various tumor types in vitro and in vivo, including acute leukemia. Therefore, ARS-type compounds may be exquisitely suitable for repurposing in leukemia treatment. To provide comprehensive clues of ARS and its derivatives for acute leukemia treatment, their molecular mechanisms are discussed in this review. Five monomeric molecules and 72 dimers, trimers and hybrids based on the ARS scaffold have been described against acute leukemia. The modes of action involve anti-angiogenic, anti-metastatic and growth inhibitory effects. These properties make ARS-type compounds as potential candidates for the treatment of acute leukemia. Still, more potent and target-selective ARS-type compounds need to be developed.
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http://dx.doi.org/10.1016/j.semcancer.2020.05.016DOI Listing
January 2021

Relationship of ankle-brachial index, vibration perception threshold, and current perception threshold to glycemic variability in type 2 diabetes.

Medicine (Baltimore) 2020 Mar;99(12):e19374

Department of Endocrinology, Qingyuan People's Hospital, Qingyuan, Guangdong Province, China.

To explore the relationship of glycemic variability with lower extremity arterial disease (LEAD) and diabetic peripheral neuropathy (DPN).Seventy-eight patients with type 2 diabetes were enrolled. All patients underwent 72-hour dynamic blood glucose monitoring and obtained mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), standard deviation of blood glucose (SD), largest amplitude of glycemic excursion (LAGE), mean blood glucose (MBG), T≥10.0 (percentage of time for blood glucose levels ≥10.0 mmol/L), T≤3.9 (percentage of time for blood glucose levels ≤3.9 mmol/L), and other glycemic variability parameters. In the meanwhile, in order to explore the correlation of glycemic variability parameters with ankle-brachial index (ABI), vibration perception threshold (VPT), and current perception threshold (CPT), all patients underwent quantitative diabetic foot screening, including ABI for quantitative assessment of lower extremity arterial lesions and VPT and CPT for quantitative assessment of peripheral neuropathy.Patients were divided into abnormal CPT group (n = 21) and normal CPT group (n = 57) according to the CPT values. Compared with the normal CPT group, abnormal CPT group showed significantly higher levels of HbA1c, longer duration of diabetes, and higher levels of T≤3.9 (P < .05). However, there was no significant difference of MAGE, SD, LAGE, MODD, and other glycemic variability parameters between abnormal CPT group and normal CPT group (P > .05). Pearson correlation analysis or Spearman correlation analysis showed that ABI negatively correlated with MBG, T≥10.0, SD, LAGE, and MAGE (P < .05), but no correlation of ABI with T≤3.9 and MODD (P > .05) was shown. VPT showed a positive correlation with T≥10.0 (P < .05), but no correlation with other glycemic variability parameters (P > .05). There was no correlation between the other CPT values and the glycemic variability parameters (P > .05), except that the left and right 250 Hz CPT values were positively correlated with T≤3.9 (P > .05).The higher the blood glucose levels, the severer the degree of LEAD and DPN lesions; the higher the incidence of hypoglycemia, the severer the degree of DPN lesions; the greater the fluctuation of blood glucose, the severer the degree of LEAD lesions. However, the glycemic variability was not significantly correlated with DPN.
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http://dx.doi.org/10.1097/MD.0000000000019374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220673PMC
March 2020

Successful management and treatment of SLE-associated hypophysitis.

Immunol Res 2020 04;68(2):107-109

Department of Oncology, First Affiliated Hospital of Jinan University, Guangzhou, 510632, China.

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http://dx.doi.org/10.1007/s12026-020-09118-8DOI Listing
April 2020

A Pandas complex adapted for piRNA-guided transcriptional silencing and heterochromatin formation.

Nat Cell Biol 2019 10 30;21(10):1261-1272. Epub 2019 Sep 30.

Key Laboratory of RNA Biology, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

The repression of transposons by the Piwi-interacting RNA (piRNA) pathway is essential to protect animal germ cells. In Drosophila, Panoramix enforces transcriptional silencing by binding to the target-engaged Piwi-piRNA complex, although the precise mechanisms by which this occurs remain elusive. Here, we show that Panoramix functions together with a germline-specific paralogue of a nuclear export factor, dNxf2, and its cofactor dNxt1 (p15), to suppress transposon expression. The transposon RNA-binding protein dNxf2 is required for animal fertility and Panoramix-mediated silencing. Transient tethering of dNxf2 to nascent transcripts leads to their nuclear retention. The NTF2 domain of dNxf2 competes dNxf1 (TAP) off nucleoporins, a process required for proper RNA export. Thus, dNxf2 functions in a Panoramix-dNxf2-dependent TAP/p15 silencing (Pandas) complex that counteracts the canonical RNA exporting machinery and restricts transposons to the nuclear peripheries. Our findings may have broader implications for understanding how RNA metabolism modulates heterochromatin formation.
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http://dx.doi.org/10.1038/s41556-019-0396-0DOI Listing
October 2019

Mechanistic Study of Protein Adsorption on Mesoporous TiO in Aqueous Buffer Solutions.

Langmuir 2019 08 16;35(34):11037-11047. Epub 2019 Aug 16.

State Key Laboratory of Materials-Oriented and Chemical Engineering , Nanjing Tech University , Nanjing 210009 , China.

Protein adsorption is of fundamental importance for bioseparation engineering applications. In this work, a series of mesoporous TiO with various geometric structures and different aqueous buffer solutions were prepared as platforms to investigate the effects of the surface geometry and ionic strength on the protein adsorptive behavior. The surface geometry of the TiO was found to play a dominant role in the protein adsorption capacity when the ionic strength of buffer solutions is very low. With the increase in ionic strength, the effect of the geometric structure on the protein adsorption capacity reduced greatly. The change of ionic strength has the highest significant effect on the mesoporous TiO with large pore size compared with that with small pore size. The interaction between the protein and TiO measured with atomic force microscopy further demonstrated that the adhesion force induced by the surface geometry reduced with the increase in the ionic strength. These findings were used to guide the detection of the retention behavior of protein by high-performance liquid chromatography, providing a step forward toward understanding the protein adsorption for predicting and controlling the chromatographic separation of proteins.
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http://dx.doi.org/10.1021/acs.langmuir.9b01354DOI Listing
August 2019

Atomistic Insights into the Layered Microstructure and Time-Dependent Stability of [BMIM][PF] Confined within the Meso-Slit of Carbon.

J Phys Chem B 2019 Aug 29;123(31):6857-6869. Epub 2019 Jul 29.

College of Chemical Engineering, State Key Laboratory of Materials-Oriented Chemical Engineering , Nanjing Tech University , 30# Puzhu South Road , Nanjing 211816 , P.R. China.

Clarifying the microstructures and time-dependent stability of ionic liquids (ILs) within the confinement of the meso-slit of carbon is the first step to understand the intrinsic synergy effect between ILs and a promising mesoporous carbon electrode. In this work, we adopted molecular dynamics to systematically investigate the behavior of [BMIM][PF] in the 2.8 nm-wide meso-slit of carbon. The confined ILs formed a pronounced layered spatial distribution and can be divided into three distinct regions, namely, com-, sub-, and cen-layer, according to valley coordinates in the number density profiles. In the com-layer region, the imidazolium rings of ILs possess two dominant orientations, namely, "parallel" and "tilted standing". The rotation ability of all the ions is highly restrained. In the sub-layer and cen-layer regions, a part of the [BMIM] imidazolium ring has a preferred "tilted standing" orientation. The [BMIM] cations are still in a rotational restrain state and show a preferred rotation motion along the - plane. The hydrogen bond between [BMIM] cations and [PF] anions play a crucial role in determining the confined multilayered spatial distribution and distinctive orientation properties of ILs.
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http://dx.doi.org/10.1021/acs.jpcb.9b02682DOI Listing
August 2019

Cytotoxicity and antimitotic activity of Rhinella schneideri and Rhinella marina venoms.

J Ethnopharmacol 2019 Oct 29;242:112049. Epub 2019 Jun 29.

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, 55128, Germany. Electronic address:

Ethnopharmacological Relevance: Rhinella schneideri and Rhinella marina are toad venoms distributed in different parts of the world, including Brazil, Columbia and amazon. Venoms extracted from different species have many clinical applications such as antimicrobial cardiotonics and treatment of cancer. Aim of the study; In this study, we aim to investigate the effect of venoms extracted from R. schneideri and R. marina on cancer cells and verify possible mechanism of action.

Material And Method: Cytotoxicity analyses was performed using the resazurin reduction assay, where different concentrations of venoms were tested against sensitive CCRF-CEM and P-gp overexpressing ADR/CEM5000 leukemia cells. Programmed cell death was investigated using the flow cytometric annexin V/propidium iodide apoptosis assay. Furthermore, we analyzed flow cytometric cell cycle analyses of CCRF-CEM cells. Effect on tubulin formation was tested using molecular docking and fluorescence microscopy of U2OS-GFP-α-tubulin osteosarcoma cells treated for 24 h with venoms.

Results: Cytotoxicity assays revealed a strong activity towards wild-type CCRF-CEM cells (IC values of 0.202 ± 0.005 μg/ml and 0.18 ± 0.007 μg/ml for R. schneideri and R. marina, respectively) and multidrug-resistant CEM/ADR5000 cells (IC 0.403 ± 0.084 μg/ml and 0.32 ± 0.077 μg/ml for R. schneideri and R. marina, respectively). The venoms induced apoptosis as major mechanism of cell death. The venoms induced strong G2/M cell arrest in CCRF-CEM cells. We suggested tubulin as a major target for the venoms. In silico molecular docking of the major constituents of the venoms, i.e. bufalin, marinobufagin, telocinbufagin, hellebrigenin, showed strong binding affinities to tubulin. This result was verified in vitro. The venoms dysregulated microtubule arrangement of U2OS cells expressing GFP-labeled tubulin. Toxicity predictions by QSAR methodology highlighted the toxic features of bufadienolides.

Conclusion: Our study demonstrated the importance of toad venoms as source of cytotoxic compounds that may serve as lead compounds for the development of novel anticancer drugs.
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http://dx.doi.org/10.1016/j.jep.2019.112049DOI Listing
October 2019

[Prevalence and influencing factors of hyperuricemia among natural gas drilling workers in Northwest Sichuan gas field in 2016].

Wei Sheng Yan Jiu 2019 Jan;48(1):70-75

Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health, Sichuan University, Chengdu 610041, China.

Objective: To investigate the prevalence and influencing factors of hyperuricemia among natural gas drilling workers in Northwest Sichuan gas field.

Methods: A census of 1051 natural gas drilling workers in Northwest Sichuan gas field at an average altitude of 2552 meters was conducted in the survey, the serum uric acid, fasting blood glucose, blood lipid, creatinine and hemoglobin were detected. A staff canteen was randomly selected and the method of weighing and 24-hour dietary review were used for dietary survey. The blood biochemical level and dietary intake of subjects with different blood uric acid levels were compared, and the influencing factors of hyperuricemia were analyzed by Logistic regression model.

Results: (1)There were 513 hyperuricemia patients in natural gas drilling workers, with a detection rate of 48. 8%. (2)The levels of fasting blood glucose, total cholesterol, triglyceride, creatinine and hemoglobin in the hyperuricemia group were higher than those in the normouricemia group. The risk of hyperuricemia in patients with diabetes, hypercholesterolemia, hypertriglyceridemia, elevated serum creatinine and hemoglobin were 3. 57(95%CI 2. 45-4. 67), 2. 88(95%CI 1. 99-4. 16), 1. 93(95%CI 1. 30-2. 86), 1. 61(95%CI 1. 01-2. 51)and 2. 54(95%CI 2. 11-3. 36)times of normal fasting blood glucose, blood lipid, serum creatinine and hemoglobin, respectively(P<0. 05). (3)The intakes of meat, oil and salt in the hyperuricemia group were higher than those in the normouricemia group, while the intakes of vegetables, milk products and vitamin B were lower than those in the normouricemia group(P<0. 05). Intake of vegetable is a protective factor for hyperuricemia(0. 82(95%CI 0. 65-0. 93)), and intakes of protein(1. 47(95%CI 1. 16-2. 28))and fat(2. 34(95%CI 2. 01-3. 22)) are the risk factors.

Conclusion: Drilling workers in Northwest Sichuan gas field have a high prevalence of hyperuricemia and are related to diabetes, hypercholesterolemia, hypertriglyceridemia, elevated creatinine and hemoglobin, and too much protein, fat intake and too little vegetable intake.
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January 2019

[Effect of nocturnal sleep duration and daytime napping on overweight/obesity among adults in Chengdu City].

Wei Sheng Yan Jiu 2018 Nov;47(6):918-923

Department of Nutrition, Food Safety and Toxicology, West China School of Public Health, Sichuan University, Chengdu 610041, China.

Objective: To examine whether nocturnal sleep duration and daytime napping are related to overweight/obesity among adults in Chengdu City.

Methods: A total of 1276 adults( women 823, men 453) aged 20-70 years were selected by randomized cluster sampling in 2015. The sleep duration rounded up to the hour was determined according to the answer to the question, "How much time do you usually sleep per night?", the nap time of subjects were collected according to the answer by the question, "How many days do you have a nap in a week?". Height and weight were measured to calculate body massindex. Logistic regression models were used to estimate the odd ratio( OR) and 95%confidence interval( 95% CI) of overweight/obesity.

Results: Approximately 66. 38% of subjects had daytime napping habit. After adjustment for potential confounders, OR( 95% CI) of overweight/obesity was 0. 69( 0. 54 - 0. 88) for nap takers compared with individuals without daytime napping habit. One nap increase in a week was associated with-0. 20, -0. 13 BMI in young adults and middle-aged adults. Very short nocturnal sleep duration( < 6 hours) and short nocturnal sleep duration( 6-6. 9 hours) was significantly associated with an increased risk of overweight/obesity among middle-aged adults OR = 2. 11( 95% CI 1. 20-3. 76), OR = 1. 93( 95% CI 1. 13-3. 34).

Conclusion: The frequency of daytime napping was negative associated with BMI among young and middle-aged adults. Short nocturnal sleep duration was associated with higher risk of overweight/obesity among middle-aged adults in Chengdu.
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November 2018

Therapeutic efficacy and safety of Shexiang Baoxin Pill combined with trimetazidine in elderly patients with heart failure secondary to ischaemic cardiomyopathy: A systematic review and meta-analysis.

Medicine (Baltimore) 2018 Dec;97(51):e13580

Department of Pharmacy, 302 Military Hospital of People's Liberation Army, Beijing.

Background: Shexiang Baoxin Pill (SBP) is one of the most commonly used traditional Chinese patent medicines for cardiovascular diseases. This systematic review was designed to provide rigorous therapeutic efficacy and safety evidence on the use of SBP combined with trimetazidine in elderly patients with heart failure (HF) secondary to ischaemic cardiomyopathy (ICM).

Methods: Relevant randomized controlled trials (RCTs) investigating the clinical efficacy of SBP combined with trimetazidine in treating ICM-associated HF were widely searched in electronic databases, including PubMed, Cochrane library, EMBASE, CBM, CNKI, VMIS, and Wanfang up to January 1, 2018. The methodological quality of each trial was assessed according to the Cochrane Reviewers' Handbook 5.0. Meta-analysis was performed by using Review Manager 5.3.

Results: Eighteen RCTs (N = 1532) that met the criteria were included in the review for the assessment of methodological quality. Meta-analysis showed that, when compared with conventional therapy, SBP combined with trimetazidine significantly improved the clinical efficacy and indices of cardiac function (including increasing left ventricular ejection fraction [LVEF] and 6-minute walk distance [6-MWD], decreasing left ventricular end-diastolic diameter [LVEDD] and left ventricular end-systolic diameter [LVESD]) without serious adverse reactions.

Conclusion: This work provides evidence of the benefit of SBP combined with trimetazidine for the treatment of HF secondary to ICM. More high quality and well-designed RCTs are needed to confirm these findings.
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http://dx.doi.org/10.1097/MD.0000000000013580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320128PMC
December 2018

Anti-Inflammatory Effect of a TCM Formula Li-Ru-Kang in Rats With Hyperplasia of Mammary Gland and the Underlying Biological Mechanisms.

Front Pharmacol 2018 20;9:1318. Epub 2018 Nov 20.

College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Li-Ru-Kang (LRK), a formula of eight traditional Chinese medicines (TCM), has been used to treat hyperplasia of mammary gland (HMG) in TCM clinics. However, how LRK works in HMG patients is unclear. To explore the possible mechanisms of LRK against HMG, the network pharmacology was used to screen the potential targets and possible pathways that involved in LRK treated HMG. Rat HMG model induced by estrogen and progesterone was used to further verify the effects of the key molecules of LRK selected from the enriched pathways on HMG. Nipple heights and diameters were measured and uterus index was calculated. The histopathological changes of mammary gland tissue were detected by hematoxylin-eosin (H&E) staining. Western blot was used to detect the phosphorylation of ERK, JNK, and P38. And immunohistochemistry staining was performed to evaluate the levels of estrogen receptor α (ERα), progesterone receptor (PR), nuclear factor-(NF-)κB (p65), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), cyclooxygenases 2 (COX-2), inducible nitric oxide synthase (iNOS), 8-hydroxy-2'deoxyguanosine (8-OHdG), and nitrotyrosine (NT). Our results indicate that LRK treatment rescues significantly nipples height and diameter, decreases uterus index and ameliorates HMG. LRK treatment also markedly attenuates the over-expression of IL-1β, TNF-α, COX-2, and iNOS, and suppressed the formation of 8-OHdG and NT. Furthermore, LRK treatment significantly inhibits the phosphorylation of JNK, ERK, and p38 and expression of NF-κB (p65), interestingly, LRK treatment has no effect on the expression of ERα and PR. Our data suggest that the LRK treatment protects the mammary glands from the damage of oxidative stress and inflammation induced by estrogen and progesterone, via suppresses of MAPK/NF-κB signaling pathways without affecting on the expression of ERα and PR.
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http://dx.doi.org/10.3389/fphar.2018.01318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262177PMC
November 2018

Determination of the small amount of proteins interacting with TiO nanotubes by AFM-measurement.

Biomaterials 2019 02 20;192:368-376. Epub 2018 Nov 20.

State Key Laboratory of Materials-Oriented and Chemical Engineering and Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, Nanjing 210009, China. Electronic address:

Detecting the small amounts of proteins interacting effectively with the solid film electrodes surface still remains a challenge. To address this, in this work, a new approach was proposed by the combination of the adhesion forces and the molecular interaction measured with AFM. Cytochrome c (Cyt C) interacting effectively with TiO nanotube arrays (TNAs) was chosen as a probe. The amounts of Cyt C molecules interacting effectively on TNAs surface (C) range from 5.5×10 to 7.0×10 mol/cm (68.2-86.8 ng/cm) and they are comparable with the values obtained by the electrochemistry method in the literature, in evidence of the accuracy of this AFM-based approach. The reliability of the proposed approach was further verified by conducting Surface Enhanced Raman Scattering (SERS) measurements and estimating the enhancement factor (EF). This interaction-based AFM approach can be used to accurately obtain the small amounts of adsorbed substances on the solid film electrodes surface in the applications such as biosensors, biocatalysis, and drug delivery, etc.
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http://dx.doi.org/10.1016/j.biomaterials.2018.11.013DOI Listing
February 2019

Adjusting the rheological properties of corn-straw slurry to reduce the agitation power consumption in anaerobic digestion.

Bioresour Technol 2019 Jan 22;272:360-369. Epub 2018 Oct 22.

State Key Laboratory of Material-Oriented Chemical Engineering, Nanjing Tech University, Nanjing 210009, PR China. Electronic address:

Agitation power consumption (P) in the anaerobic digestion of biogas plants is a major consumer of electric energy. To reduce P by adjusting the rheological properties, in this work, the rheological properties of the corn-straw slurry were studied systematically considering the effects of TS, temperature and particle-size, and P was calculated based on the rheological behavior of the corn-straw slurry. The investigation shows that the corn-straw slurry is a non-Newtonian fluid and exhibit shear-thinning behavior, and the rheological properties can be well described with the power law model. The size-reduction is more effective compared to the option of temperature-increase to improve the agitation power efficiency, and the value of P can be reduced by up to 48.11%. Since the size-reduction can also increase the methane yield, the reduction of the particle-size is a promising option to save P, especially at relatively high TSs and for the thermophilic AD process.
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http://dx.doi.org/10.1016/j.biortech.2018.10.050DOI Listing
January 2019

Construction of Hierarchically Porous [email protected] Frameworks Composites by Inherent Defects for the Enhancement of Catalytic Efficiency.

Adv Mater 2018 Dec 10;30(49):e1803263. Epub 2018 Oct 10.

Chemical Sciences and Engineering Division, Argonne National Laboratory, Argonne, IL, 60439, USA.

[email protected] frameworks (MOFs) composites have attracted considerable attention in recent years due to the prominent selective catalytic activity. However, it is highly desirable to develop a simple and universal way to settle the trade-off between the catalytic efficiency and selectivity. Herein, by employing the thermal instability of inherent defects, hierarchically porous [email protected] , [email protected], [email protected], and [email protected] are successfully constructed after annealing at an appropriate temperature, respectively. The generated mesopores in the MOFs can be located around the external nanoparticle to retain the MOF shell for catalytic selectivity. Finally, when tested in olefin hydrogenation, [email protected] shows significantly improved catalytic rate and enhanced dynamic selectivity.
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http://dx.doi.org/10.1002/adma.201803263DOI Listing
December 2018

Unique Structures and Vibrational Spectra of Protic Ionic Liquids Confined in TiO Slits: The Role of Interfacial Hydrogen Bonds.

Langmuir 2018 11 26;34(44):13449-13458. Epub 2018 Oct 26.

College of Chemical Engineering, State Key Laboratory of Materials-Oriented Chemical Engineering , Nanjing Tech University , 5 Xinmofan Road , Nanjing 210009 , P. R. China.

The ionic liquid (IL)/titanium dioxide (TiO) interface exists in many application systems, such as nanomaterial synthesis, catalysis, and electrochemistry systems. The nanoscale interfacial properties in the above systems are a common issue. However, directly detecting the interfacial properties of nanoconfined ILs by experimental methods is still challenging. To help better learn about the interfacial issue, molecular dynamics simulations have been performed to explore the structures, vibration spectra, and hydrogen bond (HB) properties at the IL/TiO interface. Ethylammonium nitrate (EAN) ILs confined in TiO slit pores with different pore widths were studied. A unique vibrational spectrum appeared for EAN ILs confined in a 0.7 nm TiO slit, and this phenomenon is related to interfacial hydrogen bonds (HBs). An analysis of the HB types indicated that the interfacial NH group of the cations was in an asymmetric HB environment in the 0.7 nm TiO slit, which led to the disappearance of the symmetric N-H stretching mode. In addition, the significant increase in the HB strength between NH groups and the TiO surface slowed down the stretching vibration of the N-H bond, resulting in one peak in the vibrational spectra at a lower frequency. For the first time, our simulation work establishes a molecular-level relationship between the vibrational spectrum and the local HB environment of nanoconfined ILs at the IL/TiO interface, and this relationship is helpful for interface design in related systems.
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http://dx.doi.org/10.1021/acs.langmuir.8b02527DOI Listing
November 2018

The peculiar effect of water on ionic liquids and deep eutectic solvents.

Chem Soc Rev 2018 Nov;47(23):8685-8720

Energy Engineering, Division of Energy Science, Luleå University of Technology, Luleå, 971 87, Sweden.

Ionic liquids (ILs) and deep eutectic solvents (DESs) have been suggested as eco-friendly alternatives to organic solvents. A trace amount of water is often unavoidable as impurity, and water is also added on purpose to reduce their problematically high viscosity and lower their high price. Understanding the distinct effects of water on the properties of ILs/DESs is highly important. In this review, we collect published experimental and theoretical results for IL/DES-H2O systems at varied water concentrations and analyze them. Results from mechanistic studies, thermodynamic modelling and advanced experiments are collected and critically discussed. Six commonly studied IL/DES-H2O systems were selected to map experimental observations onto microscopic results obtained in mechanistic studies. A great variety of distinct contours of the excess properties can be observed over the entire compositional range, indicating that the properties of IL/DES-H2O systems are highly unpredictable. Mechanistic studies clearly demonstrate that the added H2O rapidly changes the heterogeneous 3D structures of pure ILs/DESs, leading to very different properties and behaviour. There are similarities between aqueous electrolytes and IL/DES solutions but the bulky and asymmetric organic cations in ILs/DESs do not conform to the standard salt dissolution and hydration concepts. Thermodynamic modelling previously assumes ILs/DESs to be either a neutral ion-pair or completely dissociated ions, neglecting specific ion hydration effects. A new conceptual framework is suggested for thermodynamic modelling of IL/DES-H2O binary systems to enable new technologies for their practical applications.
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http://dx.doi.org/10.1039/c8cs00325dDOI Listing
November 2018

Minimum structural requirements for BMP-2-binding of heparin oligosaccharides.

Biomaterials 2018 11 31;184:41-55. Epub 2018 Aug 31.

Glycotherapeutics Group, Institute of Medical Biology, 8A Biomedical Grove, #06-06 Immunos, 138648, Singapore; Dept. of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119074, Singapore. Electronic address:

Bone morphogenetic proteins (BMPs) are essential during tissue repair and remodeling after injury. Glycosaminoglycan (GAG) sugars are known to enhance BMP activity in vitro and in vivo; here the interactions of BMP-2 with various glycosaminoglycan classes were compared and shown to be selective for heparin over other comparable saccharides. The minimal chain lengths and specific sulfate moieties required for heparin-derived oligosaccharide binding to BMP-2, and the ability of such oligosaccharides to promote BMP-2-induced osteogenic differentiation in vitro were then determined. BMP-2 could bind to heparin hexasaccharides (dp6) and octasaccharides (dp8), but decasaccharides (dp10) were the minimum chain length required for both efficient binding of BMP-2 and consequent heparin-dependent cell responses. N-sulfation is the most important, and 6-O-sulfation moderately important for BMP-2 binding and activity, whereas 2-O-sulfation was much less critical. Bone formation assays in vivo further confirmed that dp10, N-sulfated heparin oligosaccharides were the minimal requirement for effective enhancement of BMP-2-induced bone formation. Such information is necessary for the rational design of the next generations of heparan-based devices for bone tissue repair.
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http://dx.doi.org/10.1016/j.biomaterials.2018.08.056DOI Listing
November 2018

Clinical Efficacy and Safety of Xinmailong Injection for the Treatment of Chronic Heart Failure: A Meta-Analysis.

Front Pharmacol 2018 27;9:810. Epub 2018 Jul 27.

China Military Institute of Chinese Medicine, 302 Military Hospital of China, Beijing, China.

Chronic heart failure (CHF) is one of the most stubborn cardiovascular disease. Xinmailong (XML), a bioactive fraction extracted from L., has been commonly used for CHF treatment in China. However, there is few comprehensive evaluation for the clinical efficacy and safety of XML for CHF. We aimed to evaluate the beneficial and adverse effects of Xinmailong Injection (XMLI) on CHF treatment with the use of meta-analysis. In accordance with the Cochrane Handbook and transparent reporting of systematic reviews and meta-analysis protocol (CRD42018087091), seven English and Chinese electronic databases, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wanfang database, VIP medicine information system and China Biomedical Literature Database (CBM), were searched to retrieve potential randomized controlled trials (RCTs) before November 2017. The eligible trials were evaluated for methodological quality. The main outcome measures were analyzed with RevMan 5.3 software. 26 RCTs involving 3447 participants were subjected to meta-analysis. The total effective rate was improved by XMLI plus conventional therapy (OR 3.10, 95% CI 2.47-3.90, < 0.00001). When compared to the conventional treatment alone, the combination of XMLI and conventional treatment increased left ventricular ejection fraction (LVEF, MD 4.93, 95% CI 3.96-5.89, < 0.00001) and 6-min walking distance (6-MWD, MD 46.76, 95% CI 32.51 to 61.01, < 0.00001), and decreased left ventricular end-diastolic diameter (LVEDD, MD -4.73, 95% CI-5.64 to-3.83, < 0.00001), serum brain natriuretic peptide (BNP, MD -149.59, 95% CI -211.31 to -87.88, < 0.00001) and N-terminal pro-brain natriuretic peptide (NT-proBNP, MD -322.35, 95% CI -517.87 to -126.83, = 0.001). However, the frequency and severity of adverse effects was similar between these two different medications. Poor methodological quality and the limitations also existed in this study. The combinational use of XMLI on conventional treatment may exert better therapeutic effects on improving cardiac function in CHF patients, indicating that XMLI was suggested to be considered during the conventional treatment of CHF. High-quality and large scale RCTs are still required to confirm the impacts of XMLI.
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http://dx.doi.org/10.3389/fphar.2018.00810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094981PMC
July 2018
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