Publications by authors named "Lixin Li"

183 Publications

Mitochondrial DNA variants modulate N-formylmethionine, proteostasis and risk of late-onset human diseases.

Nat Med 2021 Sep 23;27(9):1564-1575. Epub 2021 Aug 23.

Human Genetics Department, Wellcome Sanger Institute (WT), Hinxton, UK.

Mitochondrial DNA (mtDNA) variants influence the risk of late-onset human diseases, but the reasons for this are poorly understood. Undertaking a hypothesis-free analysis of 5,689 blood-derived biomarkers with mtDNA variants in 16,220 healthy donors, here we show that variants defining mtDNA haplogroups Uk and H4 modulate the level of circulating N-formylmethionine (fMet), which initiates mitochondrial protein translation. In human cytoplasmic hybrid (cybrid) lines, fMet modulated both mitochondrial and cytosolic proteins on multiple levels, through transcription, post-translational modification and proteolysis by an N-degron pathway, abolishing known differences between mtDNA haplogroups. In a further 11,966 individuals, fMet levels contributed to all-cause mortality and the disease risk of several common cardiovascular disorders. Together, these findings indicate that fMet plays a key role in common age-related disease through pleiotropic effects on cell proteostasis.
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http://dx.doi.org/10.1038/s41591-021-01441-3DOI Listing
September 2021

Genetic Polymorphisms in CD35 Gene Contribute to the Susceptibility and Prognosis of Hepatocellular Carcinoma.

Front Oncol 2021 5;11:700711. Epub 2021 Aug 5.

Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China.

CD35, an important molecule implicated in inflammation and immunity, is reportedly associated with several cancers. However, very few studies have investigated the relationship between polymorphisms and hepatocellular carcinoma (HCC). The current study was conducted to investigate the association between tag SNPs in and HCC susceptibility and postoperative recurrence, in an attempt to elucidate the gene-environment interactions in HCC. A total of 1233 Chinese Han people, including 647 healthy controls and 586 HCC cases, were sampled in this study. Six Tag SNPs (rs10494885, rs2296160, rs3737002, rs3849266, rs669117, and rs7525160) of were selected using the HaploView 4.2 program and genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Overall, the mutation genotypes CC/CG of rs7525160 significantly increased the risk of HCC. Stratification analysis indicated that rs7525160 CC/CG genotypes increased HCC risk in patients younger than 65 years and were closely related to the pathological type of poor prognosis of HCC. Cox proportional hazard ratio model analysis revealed that the rs7525160 CC/CG genotype remains a significant independent risk factor for postoperative recurrence of HCC. In conclusion, rs7525160 polymorphism may contribute to the susceptibility and prognosis of HCC in the Chinese Han population.
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http://dx.doi.org/10.3389/fonc.2021.700711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374953PMC
August 2021

Single-cell transcriptomics reveals heterogeneous progression and EGFR activation in pancreatic adenosquamous carcinoma.

Int J Biol Sci 2021 22;17(10):2590-2605. Epub 2021 Jun 22.

Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital affiliated to Capital Medical University, Beijing 100020, China.

Pancreatic adenosquamous carcinoma (PASC) - a rare pathological pancreatic cancer (PC) type - has a poor prognosis due to high malignancy. To examine the heterogeneity of PASC, we performed single-cell RNA sequencing (scRNA-seq) profiling with sample tissues from a healthy donor pancreas, an intraductal papillary mucinous neoplasm, and a patient with PASC. Of 9,887 individual cells, ten cell subpopulations were identified, including myeloid, immune, ductal, fibroblast, acinar, stellate, endothelial, and cancer cells. Cancer cells were divided into five clusters. Notably, cluster 1 exhibited stem-like phenotypes expressing UBE2C, ASPM, and TOP2A. We found that S100A2 is a potential biomarker for cancer cells. LGALS1, NPM1, RACK1, and PERP were upregulated from ductal to cancer cells. Furthermore, the copy number variations in ductal and cancer cells were greater than in the reference cells. The expression of EREG, FCGR2A, CCL4L2, and CTSC increased in myeloid cells from the normal pancreas to PASC. The gene sets expressed by cancer-associated fibroblasts were enriched in the immunosuppressive pathways. We demonstrate that EGFR-associated ligand-receptor pairs are activated in ductal-stromal cell communications. Hence, this study revealed the heterogeneous variations of ductal and stromal cells, defined cancer-associated signaling pathways, and deciphered intercellular interactions following PASC progression.
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http://dx.doi.org/10.7150/ijbs.58886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315026PMC
June 2021

AtSEC22 Regulates Cell Morphogenesis via Affecting Cytoskeleton Organization and Stabilities.

Front Plant Sci 2021 4;12:635732. Epub 2021 Jun 4.

Key Laboratory of Saline-Alkali Vegetation Ecology Restoration, Ministry of Education, College of Life Sciences, Northeast Forestry University, Harbin, China.

The plant cytoskeleton forms a stereoscopic network that regulates cell morphogenesis. The cytoskeleton also provides tracks for trafficking of vesicles to the target membrane. Fusion of vesicles with the target membrane is promoted by SNARE proteins, etc. The vesicle-SNARE, Sec22, regulates membrane trafficking between the ER and Golgi in yeast and mammals. AtSEC22 might also regulate early secretion and is essential for gametophyte development. However, the role of AtSEC22 in plant development is unclear. To clarify the role of AtSEC22 in the regulation of plant development, we isolated an knock-down mutant, , and found that cell morphogenesis and development were seriously disturbed. exhibited shorter primary roots (PRs), dwarf plants, and partial abortion. More interestingly, the mutant had less trichomes with altered morphology, irregular stomata, and pavement cells, suggesting that cell morphogenesis was perturbed. Further analyses revealed that in , vesicle trafficking was blocked, resulting in the trapping of proteins in the ER and collapse of structures of the ER and Golgi apparatus. Furthermore, AtSEC22 defects resulted in impaired organization and stability of the cytoskeleton in . Our findings revealed essential roles of AtSEC22 in membrane trafficking and cytoskeleton dynamics during plant development.
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http://dx.doi.org/10.3389/fpls.2021.635732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211912PMC
June 2021

Corrigendum: Genetic Variation in an Experimental Goldfish Derived From Hybridization.

Front Genet 2021 5;12:645346. Epub 2021 May 5.

State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, China.

[This corrects the article DOI: 10.3389/fgene.2020.595959.].
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http://dx.doi.org/10.3389/fgene.2021.645346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132942PMC
May 2021

Liraglutide Has Anti-Inflammatory and Anti-Amyloid Properties in Streptozotocin-Induced and 5xFAD Mouse Models of Alzheimer's Disease.

Int J Mol Sci 2021 Jan 16;22(2). Epub 2021 Jan 16.

Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI 48859, USA.

Recent clinical and epidemiological studies support the contention that diabetes mellitus (DM) is a strong risk factor for the development of Alzheimer's disease (AD). The use of insulin cell toxin, streptozotocin (STZ), when injected into the lateral ventricles, develops an insulin resistant brain state (IRBS) and represents a non-transgenic, or sporadic AD model (SAD), with several AD-like neuropathological features. The present study explored the effects of an anti-diabetic drug, liraglutide (LIR), in reversing major pathological hallmarks in the prodromal disease stage of both the 5xFAD transgenic and SAD mouse models of AD. Three-month-old 5xFAD and age-matched wild type mice were given a single intracerebroventricular (i.c.v) injection of STZ or vehicle (saline) and were subsequently treated with LIR, intraperitoneally (IP), once a day for 30 days. The extent of neurodegeneration, Aβ plaque load, and key proteins associated with the insulin signaling pathways were measured using Western blot and neuroinflammation (via immunohistological assays) in the cortical and hippocampal regions of the brain were assessed following a series of behavioral tests used to measure cognitive function after LIR or vehicle treatments. Our results indicated that STZ significantly increased neuroinflammation, Aβ plaque deposition and disrupted insulin signaling pathway, while 25 nmol/kg LIR, when injected IP, significantly decreased neuroinflammatory responses in both SAD and 5xFAD mice before significant cognitive changes were observed, suggesting LIR can reduce early neuropathology markers prior to the emergence of overt memory deficits. Our results indicate that LIR has neuroprotective effects and has the potential to serve as an anti-inflammatory and anti-amyloid prophylactic therapy in the prodromal stages of AD.
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http://dx.doi.org/10.3390/ijms22020860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829894PMC
January 2021

Ethnic disparities in stillbirth risk in Yunnan, China: a prospective cohort study, 2010-2018.

BMC Public Health 2021 01 14;21(1):136. Epub 2021 Jan 14.

State Key Laboratory of Organ Failure Research, Department of Biostatistics, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China.

Background: Racial and ethnic disparities in stillbirth risk had been documented in most western countries, but it remains unknown in China. This study was to determine whether exist ethnic disparities in stillbirth risk in mainland China.

Methods: Pregnancy outcomes and ethnicity data were obtained from the National Free Preconception Health Examination Project (NEPHEP), a nationwide prospective population-based cohort study conducted in Yunnan China from 2010-2018. The Han majority and other four main minorities including Yi, Dai, Miao, Hani were investigated in the analysis. The stillbirth hazards were estimated by life-table analysis. The excess stillbirth risk (ESR) was computed for Chinese minorities using multivariable logistic regression.

Results: Compared with other four minorities, women in Han majority were more likely to more educated, less multiparous, and less occupied in agriculture. The pattern of stillbirth hazard of Dai women across different gestation intervals were found to be different from other ethnic groups, especially in 20-23 weeks with 3.2 times higher than Han women. The ESR of the Dai, Hani, Miao, and Yi were 45.05, 18.70, -4.17 and 12.28%, respectively. Adjusted for maternal age, education, birth order and other general risk factors, the ethnic disparity still persisted between Dai women and Han women. Adjusted for preterm birth further (gestation age <37 weeks) can reduce 16.91% ESR of Dai women and made the disparity insignificant. Maternal diseases and congenital anomalies explained little for ethnic disparities.

Conclusions: We identified the ethnic disparity in stillbirth risk between Dai women and Han women. General risk factors including sociodemographic factors and maternal diseases explained little. Considerable ethnic disparities can be attributed to preterm birth.
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http://dx.doi.org/10.1186/s12889-020-10102-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807874PMC
January 2021

Genetic Variation in an Experimental Goldfish Derived From Hybridization.

Front Genet 2020 15;11:595959. Epub 2020 Dec 15.

State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, China.

Owning to the extreme difficulty in identifying the primary generation (G), the common ancestor of various twin-tail goldfish strains remains unclear. However, several authors have hypothesized that this ancestor may have been the crucian carp (). Previously, we generated an experimental hybrid goldfish (EG) from the interspecific hybridization of red crucian carp ( ♀, RCC) × common carp ( ♂, CC). Unlike either parent, EG possessed twin caudal fins similar to those of natural goldfish (, NG). The genetic characteristics of EG, as well as the mechanisms underlying its formation, are largely unknown. Here, we identified the genetic variation in the gene that was associated with the formation of the twin-tail phenotype in EG: a stop codon mutation at the 127 amino acid. Furthermore, simple sequence repeat (SSR) genotyping indicated that, among the six alleles, all of the EG alleles were also present in female parent (RCC), but alleles specific to the male parent (CC) were completely lost. At some loci, EG and NG alleles differed, showing that these morphologically similar goldfish were genetically dissimilar. Collectively, our results demonstrated that genetic variations and differentiation contributed to the changes of morphological characteristics in hybrid offspring. This analysis of genetic variation in EG sheds new light on the common ancestor of NG, as well as on the role of hybridization and artificial breeding in NG speciation.
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http://dx.doi.org/10.3389/fgene.2020.595959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770164PMC
December 2020

Cocrystallization-Promoted Charge Mobility in All-Conjugated Diblock Copolymers for High-Performance Field-Effect Transistors.

ACS Appl Mater Interfaces 2020 Dec 17;12(52):58094-58104. Epub 2020 Dec 17.

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China.

The cocrystallization method that combines various constituents into cocrystals yields the newly formed materials with significantly enhanced charge transport properties. However, this strategy has not been greatly utilized in all-conjugated block copolymers (BCPs). Herein, we scrutinize the relationship between cocrystals and charge mobilities in all-conjugated BCPs (i.e., poly(3-butylthiophene)--poly(3-hexylthiophene); denoted P3BT--P3HT) by tuning their molecular weights and thermal annealing process. All the rod-rod BCPs form cocrystals with high charge mobilities than P3BT and P3HT homopolymers and P3BT/P3HT blend, imparting the cocrystal-facilitated charge transport because of the synergy of two conjugated components. Upon 150 °C treatment, their crystallinities increase and their charge mobilities at 15k, 18k, and 28k increase slightly. In contrast, P3BT--P3HT-12k shows decreased charge mobilities. It is due to the preferential increase of crystal size and order through the π-π stacking direction in the former while through the alkyl stacking direction in the latter. Intriguingly, when these P3BT--P3HT cocrystals experience two-step thermal treatment, P3BT--P3HT-12k retains its cocrystalline structure, while microphase separation of P3BT and P3HT occurs in P3BT--P3HT-15k, 18k, and 28k with different degrees. All P3BT--P3HT BCPs exhibit decreased charge mobilities. This study demonstrates the cocrystallization-promoted charge mobility in all-conjugated BCPs, which may facilitate their application in a wide range of optoelectronic devices.
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http://dx.doi.org/10.1021/acsami.0c17671DOI Listing
December 2020

AtNSF regulates leaf serration by modulating intracellular trafficking of PIN1 in Arabidopsis thaliana.

J Integr Plant Biol 2020 Dec 2. Epub 2020 Dec 2.

State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Daizong Street 61, Tai'an, 271018, China.

In eukaryotes, N-ethylmaleimide-sensitive factor (NSF) is a conserved AAA+ ATPase and a key component of the membrane trafficking machinery that promotes the fusion of secretory vesicles with target membranes. Here, we demonstrate that the Arabidopsis thaliana genome contains a single copy of NSF, AtNSF, which plays an essential role in the regulation of leaf serration. The AtNSF knock-down mutant, atnsf-1, exhibited more serrations in the leaf margin. Moreover, polar localization of the PIN-FORMED1 (PIN1) auxin efflux transporter was diffuse around the margins of atnsf-1 leaves and root growth was inhibited in the atnsf-1 mutant. More PIN1-GFP accumulated in the intracellular compartments of atnsf-1 plants, suggesting that AtNSF is required for intracellular trafficking of PIN between the endosome and plasma membrane. Furthermore, the serration phenotype was suppressed in the atnsf-1 pin1-8 double mutant, suggesting that AtNSF is required for PIN1-mediated polar auxin transport to regulate leaf serration. The CUP-SHAPED COTYLEDON2 (CUC2) transcription factor gene is up-regulated in atnsf-1 plants and the cuc2-3 single mutant exhibits smooth leaf margins, demonstrating that AtNSF also functions in the CUC2 pathway. Our results reveal that AtNSF regulates the PIN1-generated auxin maxima with a CUC2-mediated feedback loop to control leaf serration. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/jipb.13043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151873PMC
December 2020

Comprehensive circular RNA expression profiling constructs a ceRNA network and identifies hsa_circ_0000673 as a novel oncogene in distal cholangiocarcinoma.

Aging (Albany NY) 2020 11 18;12(22):23251-23274. Epub 2020 Nov 18.

Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated with Capital Medical University, Beijing, China.

Circular RNAs (circRNAs) play an important role in cholangiocarcinoma (CCA) development; however, the expression and functions of circRNAs in distal CCA (dCCA) remain unknown. Herein, we explored the expression profile of circRNAs in six paired dCCA tumor and adjacent normal tissue samples using microarray. A total of 171 differentially expressed (DE) circRNAs were identified in dCCA tissues. Host genes of DE circRNAs were enriched in the cellular cytoskeleton and adheren junction. Bioinformatics analyses were used to establish a circRNA-microRNA-mRNA network for dCCA. Protein-protein interaction networks were constructed, and five hub genes were associated with the regulation of the cell cycle based on gene set enrichment analyses. Five DE circRNAs were validated with qRT-PCR in 40 pairs of dCCA tissues, and hsa_circ_0000673 showed promising diagnostic performance in distinguishing dCCA from normal tissues (AUC = 0.85, 0.01). Overexpression of hsa_circ_0000673 was associated with tumor invasion ( = 0.001), poor differentiation ( = 0.041), and residual tumor ( = 0.044). experiments indicated that inhibition of hsa_circ_0000673 suppressed the proliferation, migration, and invasion of CCA cells. This research provided a landscape of dysregulated circRNAs in dCCA and identified hsa_circ_0000673 as a potential biomarker and therapeutic target for dCCA.
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http://dx.doi.org/10.18632/aging.104099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746367PMC
November 2020

Coral-like CoMoO hierarchical structure uniformly encapsulated by graphene-like N-doped carbon network as an anode for high-performance lithium-ion batteries.

J Colloid Interface Sci 2021 Mar 21;586:11-19. Epub 2020 Oct 21.

Key Laboratory of Functional Inorganic Material Chemistry, Ministry of Education, School of Chemistry and Materials Science, Heilongjiang University, Harbin 150080, PR China. Electronic address:

Encapsulation of metal oxide anode material with hierarchical structure in graphene-like high conductivity carbon network is conducive to improving the lithium storage performance of the anode material. However, it is very challenging to rational synthesizing anode materials with such structure. Herein, a mesoporous spiny coral-like CoMoO (SCL-CMO) self-assembled from the mesoporous nanorods made of nanoparticles is prepared by a simple one-step solvothermal method. The layered coral-like [email protected] Carbon ([email protected]) composite is synthesized by polymerization of DA on the surface of SCL-CMO at room temperature and the subsequent sintering treatment. This [email protected] composite perfectly combines the comprehensive advantages of the spiny coral-like hierarchical architecture and the N-doped graphene-like carbon coating, which not only effectively improve the electron and Li ion transport dynamics and accommodate the large volume changes, but also prevent hierarchical structure aggregation and pulverization during cycle process. Therefore, [email protected] composite exhibits superior electrochemical kinetics and stability. The reversible specific capacity remained 1321.6 and 132 mA h g after 900 and 10,000 cycles at 0.4 and 5 A g, respectively.
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http://dx.doi.org/10.1016/j.jcis.2020.10.063DOI Listing
March 2021

Prognostic impact of lymph node parameters in distal cholangiocarcinoma after pancreaticoduodenectomy.

World J Surg Oncol 2020 Oct 8;18(1):262. Epub 2020 Oct 8.

Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, 8 Gongtinan Road, Chaoyang District, Beijing, 100020, China.

Background: Pancreaticoduodenectomy is the only definitively curative therapy for the long-term survival of distal cholangiocarcinoma patients. Lymph node metastasis is widely accepted as an important prognostic factor for distal cholangiocarcinoma. The latest American Joint Committee on Cancer (AJCC) TNM classification system for distal cholangiocarcinoma has divided the lymph node metastasis patients into N1 and N2 by lymph node metastasis number. However, some studies suggested that the lymph node metastasis ratio may be better than the lymph node metastasis number. Therefore, we develop a program to analyze the correlation between lymph node parameters (lymph node dissection number, lymph node metastasis number, and lymph node metastasis rate) and long-term prognosis.

Methods: We retrospectively reviewed 123 distal cholangiocarcinoma patients after pancreatoduodenectomy from January 2011 to December 2019. The patients were grouped according to lymph node metastases and tumor-free and overall survival rates which were investigated with the Kaplan-Meier analysis. The logistic regression models were used for multivariate analysis to determine the risk factors for lymph node metastases. And the X-tile program was used to calculate the cutoff values for the lymph node parameters that discriminated survival.

Results: The 1-year, 3-year, and 5-year overall survival rates of patients with distal cholangiocarcinoma after pancreatoduodenectomy were 75.2%, 37.1%, and 31.5%, respectively. And the 1-year, 3-year, and 5-year overall survival rates of patients without and with lymph node metastasis were 83.0%, 50.7%, and 42.5% and 63.5%, 19.0%, and 19.0% (p = 0.000), respectively. Logistic regression showed CA19-9 and portal vein system invasion as independent risk factors for lymph node metastases. The receiver operating characteristic curve showed the optimal cutoff value of CA19-9 to predict the lymph node metastases was 75.5 U/mL. Determined by the X-tile software, the optimal cutoff values of the lymph node dissection number were 24 (p = 0.021), the lymph node metastasis number were 1 and 7 (p = 0.504), and the lymph node metastasis rate were 0.13 (p = 0.002).

Conclusion: Lymph node metastasis is an important factor affecting the long-term survival of distal cholangiocarcinoma patients.CA19-9 and portal vein system invasion are independent risk factors for lymph node metastasis. Besides, the lymph node dissection number and lymph node metastasis rate can predict the long-term survival better than lymph node metastasis number.
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http://dx.doi.org/10.1186/s12957-020-02040-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545845PMC
October 2020

Synthesis of Phenanthridines through Iodine-Supported Intramolecular C-H Amination and Oxidation under Visible Light.

J Org Chem 2020 Oct 11;85(19):12187-12198. Epub 2020 Sep 11.

School of Chemistry and Chemical Engineering, Henan Key Laboratory of Boron Chemistry and Advanced Energy Materials, Henan Normal University, Xinxiang, Henan 453007, China.

Herein, we report a metal-free and step-economic synthesis of phenanthridines from 2-biarylmethanamines under mild conditions. The reaction involves iodine-supported intramolecular C-H amination and oxidation of 5,6-dihydrophenanthridine under air and benign visible light. The mechanism study reveals that visible light plays a key role in both these steps.
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http://dx.doi.org/10.1021/acs.joc.0c01390DOI Listing
October 2020

The adsorption mechanisms of algae-bacteria symbiotic system and its fast formation process.

Bioresour Technol 2020 Nov 16;315:123854. Epub 2020 Jul 16.

State Key Lab of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150080, People's Republic of China. Electronic address:

The formation process of the algae-bacteria symbiotic system (ABSS) was analyzed, and the formation adsorption conditions were optimized. The role of extracellular polymeric substances (EPS), specific surface area and zeta potential in adsorption mechanisms were assessed and proposed. The results showed the dry weight of the ABSS and adsorption efficiency of microalgae reached the highest under the conditions of 25 °C, pH 6.0, 160 rpm and CaCl 2.0 mg/mL. The process of the ABSS formation could be mainly divided into the fast stage and slow stage. The roles of EPS, specific surface area and zeta potential accounted for 84.22%, 5.17% and 10.61% of the adsorption capacity, respectively. EPS dominated the formation of the ABSS. The results indicated that mycelial pellets were biosorption materials and had the characteristics of chemical materials.
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http://dx.doi.org/10.1016/j.biortech.2020.123854DOI Listing
November 2020

Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma.

Biosci Rep 2020 07;40(7)

Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China.

Background: Hypermethylation of gene promoters plays an important role in tumorigenesis. The present study aimed to identify and validate promoter methylation-driven genes (PMDGs) for pancreatic ductal adenocarcinoma (PDAC).

Methods: Based on GSE49149 and the PDAC cohort of The Cancer Genome Atlas (TCGA), differential analyses of promoter methylation, correlation analysis, and Cox regression analysis were performed to identify PMDGs. The promoter methylation level was assessed by bisulfite sequencing polymerase chain reaction (BSP) in paired tumor and normal tissues of 72 PDAC patients. Kaplan-Meier survival analyses were performed to evaluate the clinical value of PMDGs.

Results: In GSE49149, the β-value of the dipeptidyl peptidase like 6 (DPP6) promoter was significantly higher in tumor compared with normal samples (0.50 vs. 0.24, P<0.001). In the PDAC cohort of TCGA, the methylation level of the DPP6 promoter was negatively correlated with mRNA expression (r = -0.54, P<0.001). In a multivariate Cox regression analysis, hypermethylation of the DPP6 promoter was an independent risk factor for PDAC (hazard ratio (HR) = 543.91, P=0.002). The results of BSP revealed that the number of methylated CG sites in the DPP6 promoter was greater in tumor samples than in normal samples (7.43 vs. 2.78, P<0.001). The methylation level of the DPP6 promoter was moderately effective at distinguishing tumor from normal samples (area under ROC curve (AUC) = 0.74, P<0.001). Hypermethylation of the DPP6 promoter was associated with poor overall (HR = 3.61, P<0.001) and disease-free (HR = 2.01, P=0.016) survivals for PDAC patients.

Conclusion: These results indicate that DPP6 promoter methylation is a potential prognostic biomarker for PDAC.
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http://dx.doi.org/10.1042/BSR20200214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396423PMC
July 2020

Internally controlled recombinase-aided amplification (IC-RAA) assays for the detection of human papillomavirus genotypes 16 and 18 using extracted DNA and samples treated with nucleic acid releasing agent.

Arch Virol 2020 Oct 17;165(10):2241-2247. Epub 2020 Jul 17.

NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, No. 155, Changbai Street, Changping District, Beijing, 102206, China.

Cervical cancer is primarily caused by persistent infection with high-risk human papillomavirus (HPV), and 70% of cases are associated with HPV16 and 18 infections. The objective of this study was to establish rapid, simple, and sensitive internally controlled recombinase-aided amplification (IC-RAA) assays for the detection of HPV16 and 18. The assays were performed at 39 ℃ and were completed within 30 min. A total of 277 clinical samples of exfoliated cervical cells were tested by IC-RAA assays and commercial HPV real-time fluorescent PCR kits using extracted DNA and samples treated with nucleic acid releasing agent. The analytical sensitivity of the IC-RAA assay was found to be 10 copies/μL for the detection of HPV16 and 18 when using recombinant plasmids as targets. The optimal concentration of the internal control (IC) plasmid and 18 was 1000 copies/μL for HPV16 and 100 copies/μL for HPV18. The clinical sensitivity of the IC-RAA assays for HPV16 using extracted DNA and samples treated with nucleic acid releasing agent was 98.73% and 97.47%, respectively, with kappa values of 0.977 (P < 0.01) and 0.955 (P < 0.01), respectively, and 100% The specificity in both cases. For HPV18, the sensitivity and specificity were 100%, and the kappa value was 1 for both samples (P < 0.01). The IC-RAA assay is a promising tool for the detection of HPV16 and HPV18, especially in resource-constrained settings.
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http://dx.doi.org/10.1007/s00705-020-04722-3DOI Listing
October 2020

Synthesis of remote fluoroalkylated alkenes by a palladium-catalyzed relay Heck-type reaction.

Chem Commun (Camb) 2020 Aug 16;56(65):9384-9387. Epub 2020 Jul 16.

College of Chemistry and Chemical Engineering, Xinyang Normal University, Xinyang, Henan 464000, China.

Herein, we report a palladium-catalyzed relay Heck-type reaction of fluoroalkyl bromide and terminal alkenes. The reaction involves fluoroalkylation of alkenes and migration of double bonds via a 1,5-hydrogen atom transfer strategy. Through this method, a series of remote fluoroalkylated alkenes was obtained under mild conditions.
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http://dx.doi.org/10.1039/c9cc10048bDOI Listing
August 2020

LZP02 Promotes Rice Root Growth by Improving Carbohydrate Metabolism and Phenylpropanoid Biosynthesis.

Mol Plant Microbe Interact 2020 Oct 11;33(10):1222-1231. Epub 2020 Aug 11.

College of Life Sciences, Shandong Agricultural University, Ta'an 271000, China.

Elucidation of the underlying mechanisms of plant growth promotion of rhizobacteria is very important. This study explored the mechanism by which LZP02 promotes growth in rice roots through proteomic, transcriptomic, and metabolomic techniques. The results showed that LZP02 promoted the absorption of phosphorous, calcium, and magnesium ions by colonization of rice roots and enhanced peroxidase, catalase, superoxide dismutase, and CaMg adenosine triphosphatase activities and chlorophyll contents in rice. The proteomic results showed that most of the differentially expressed proteins were involved in carbohydrate metabolism and that the biosynthesis of other secondary metabolites was also increased. According to RNA-seq and reverse transcription-quantitative PCR analyses, expression of some genes involved in carbohydrate metabolism and phenylpropanoid biosynthesis was upregulated in rice roots. Regarding metabolomics, phenylpropanoid biosynthesis, starch and sucrose metabolism, the pentose phosphate pathway, and glyoxylate and dicarboxylate metabolism were increased. The results indicated that LZP02 promoted the growth of rice roots by enhancing carbohydrate metabolism and phenylpropanoid biosynthesis.
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http://dx.doi.org/10.1094/MPMI-04-20-0106-RDOI Listing
October 2020

Triptolide inhibits pancreatic cancer cell proliferation and migration via down-regulating PLAU based on network pharmacology of Tripterygium wilfordii Hook F.

Eur J Pharmacol 2020 Aug 25;880:173225. Epub 2020 May 25.

Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China.

Tripterygium wilfordii Hook F (TwHF) exhibits anti-tumor efficacy in pancreatic ductal adenocarcinoma (PDAC), however the pharmacological mechanisms are unclear due to complicated formulae and target genes. Using Traditional Chinese Medicine Systems Pharmacology and GeneCards databases, we performed a network pharmacology (NP) of TwHF and screened out 22 ingredients and 25 target genes associated with PDAC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the 25 target genes were performed. Using STRING database, protein-protein interaction network of the 25 target genes was constructed, and indicated that triptolide (TL)-plasminogen activator urokinase (PLAU) as a potential target for PDAC treatment. Hence, in vitro experiments were performed and validated that TL inhibited PDAC cell proliferation and migration by suppressing PLAU expression. The results of Western blot suggested that PLAU activated endothelial-mesenchymal transition (EMT) progression. In two Gene Expression Omnibus datasets (GSE16515 and GSE28735), PLAU was up-regulated in tumor tissues, and PLAU overexpression was associated with poor overall survival of PDAC cohort of The Cancer Genome Atlas (P < 0.01). Immunohistochemistry illustrated that overexpression of PLAU protein was related to lymph node metastasis in 20 PDAC patients (P < 0.01). Based on NP of TwHF, we identified and validated that TL-PLAU could serve as a potential target for PDAC treatment.
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http://dx.doi.org/10.1016/j.ejphar.2020.173225DOI Listing
August 2020

Changes in the gut microbiota of honey bees associated with jujube flower disease.

Ecotoxicol Environ Saf 2020 Jul 22;198:110616. Epub 2020 Apr 22.

School of Physical Exercise and Education, Shanxi University, Taiyuan, Shanxi, China.

Honeybees are prone to poisoning after collecting jujube nectar during the jujube flowering period ('honeybee's jujube flower disease'). To explore the mechanism of honeybee poisoning, the gut microbiota of honeybees undergoing the disease were characterised based on amplicon sequencing of the 16 S rRNA gene. Our results showed that the composition and diversity of the gut microbiota were significantly altered in diseased honeybees. We observed a decrease in the relative abundance of Proteobacteria and increased abundances of Firmicutes and Actinobacteria in the midgut and hindgut of diseased honeybees. Moreover, linear discriminant analysis (LDA) effect size revealed significantly selected enrichment of Fructobacillus and Snodgrassella in the midguts from diseased honeybees and Lactobacillus, Bifidobacterium, and Snodgrassella in the hindguts from diseased honeybees. Tax4Fun anylasis indicated that the functional potential of the diseased honeybee gut bacterial community was significantly changed relative to the healthy honeybee. Carbohydrate metabolism, nucleotides metabolism, amino acid synthesis metabolism, coenzyme and vitamins metabolism were increased, while energy metabolism and xenobiotic biodegradation and metabolism were decreased in the diseased honeybees. These results provide a new perspective for evaluating the response of honeybees to jujube flower disease based on changes in the intestinal microflora.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110616DOI Listing
July 2020

Multiple low-frequency and rare HLA-B allelic variants are associated with reduced risk in 1,105 nasopharyngeal carcinoma patients in Hunan province, southern China.

Int J Cancer 2020 09 9;147(5):1397-1404. Epub 2020 Apr 9.

Immunogenetics Research Group, Department of Immunology, College of Basic Medical Sciences, Central South University, Changsha, Hunan, China.

In our study, 1,105 cases of nasopharyngeal carcinoma (NPC) and 1,430 normal controls recruited from Hunan province, southern China were typed for human leukocyte antigen (HLA)-B locus by Sanger sequencing exons 2-4. Besides confirming the NPC association with HLA-B*46:01 allele, HLA-A*02:07-B*46:01 and HLA-A*33:03-B*58:01 haplotypes (all positive), and HLA-B*13 lineage (negative), all of which were relatively common, strong negative associations were observed for five low-frequency and rare alleles or lineages, including HLA-B*07, -B*27:04, -B*39, -B*51:02 and -B*55:02, with odds ratio (OR) ranging from 0.16 to 0.3 (all p < 0.05). These strong protective associations were independent of linkage disequilibrium (LD) between HLA-A and HLA-B loci. Further analysis indicated a single amino acid change from histidine to tyrosine at residue 171 is probably crucial for the mutant allele, HLA-B*51:02, to mediate resistance to NPC. A subset of NPC cases (n = 821) and normal controls (n = 1,035) were tested for antivirus capsid antigen immunoglobulin A (anti-VCA IgA), which differed drastically between the two groups [67.7% vs. 5.5%, OR (95% confidence interval) = 36 (26.55-48.81), p < 0.0001]. HLA-B allelic variation did not associate with seropositivity for anti-VCA IgA in either group. Results from our study show, more clearly than previously, the existence of a cluster of low-frequency and rare HLA-B variants conferring low, or very low risk to NPC, a phenomenon not observed in other ethnic groups. Our data shed new insights into genetic susceptibility to NPC in southern Chinese populations. Future independent studies are warranted to replicate the findings reported in our study.
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http://dx.doi.org/10.1002/ijc.32992DOI Listing
September 2020

Efficacy evaluation of personalized coaptation in neurotization for motor deficit after peripheral nerve injury: A systematic review and meta-analysis.

Brain Behav 2020 04 3;10(4):e01582. Epub 2020 Mar 3.

Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Introduction: Peripheral neurotization, recently as a promising approach, has taken effect in recovering motor function after damage to a peripheral nerve root. Neural anastomosis comprised of nerve conduit and neurorrhaphy participates in the nerve reconstruction. Current literature lacks evidence supporting an individualized coaptation for rescue of locomotor loss in rat subjects with paraplegia secondary to peripheral nerve injury (PNI).

Methods: This meta-analysis intends to qualify the specificity of gap-specific coaptation in treating a paralyzed limb following PNI. We used a highly sensitive search strategy to identify all published studies in multiple databases up to 1 May 2019. All identified trials were systematically evaluated using specific inclusion and exclusion criteria. Cochrane methodology was also applied to the results of this study.

Results: Twelve studies, including 349 rat subjects, met eligibility criteria. For a medium nerve defect (0.5-3.0 cm), nerve conduit was more likely than neurorrhaphy to precipitate axon regeneration and improve motor outcome of the hemiplegic limb (OR = 3.61, 95% CI = 1.80, 7.26, p < .0003) at 3-month follow-up, whereas neurorrhaphy might take its place in promoting limb motor function in a small nerve gap (<0.5 cm) (OR = 0.48, 95% CI = 0.22, 1.07, p < .007). For a small nerve defect, nerve conduit still demonstrated visible effectiveness in recovery of limb motion albeit poorer than neurorrhaphy (OR = 1.50, 95% CI = 0.92, 2.47, p < .05).

Conclusion: Selective neurotization facilitates motor regeneration after nerve transection, and advisable choice of neural coaptation can maximize functional outcome on an individual basis.
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http://dx.doi.org/10.1002/brb3.1582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177589PMC
April 2020

Continuous hydrogen and methane production from the treatment of herbal medicines wastewater in the two-phase 'UASB-IC' system.

Water Sci Technol 2019 Sep;80(6):1134-1144

College of Environmental and Chemical Engineering, Heilongjiang University of Science and Technology, Harbin 150022, China E-mail:

A two-phase anaerobic system comprised of upflow anaerobic sludge bed (UASB) reactor for hydrogen production and internal circulation reactor (IC) for methane production was proposed and investigated at laboratory scale and mesophilic temperature (35 °C). Hydrogen was efficiently produced from the UASB with the highest production rate of 3.00 ± 0.04 L · L · d at optimum hydraulic retention time (HRT) of 6 h and in the IC, methane was also produced from residual organic matter and soluble metabolite products (SMP) with a production rate of 2.54 ± 0.04 L · L · d at optimum HRT of 15 h. Finally, system HRT of 21 h was determined to be the optimum HRT at which energy conversion efficiency increased from 9.6 ± 0.1% (hydrogen only production) to 72.4 ± 2.5% (hydrogen and methane coproduction) and system chemical oxygen demand (COD) removal reached up to the high level of 90.1 ± 2.1%.
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http://dx.doi.org/10.2166/wst.2019.352DOI Listing
September 2019

A laboratory practice that uses the polymerase chain reaction-sequence specific priming technique to rapidly screen for HLA-DR2 allotype from germline DNA in immunology course for undergraduate medical students.

Biochem Mol Biol Educ 2020 03 3;48(2):175-180. Epub 2019 Dec 3.

Laboratory of Cellular and Molecular Biology, College of Basic Medical Sciences, Central South University, Changsha, Hunan, China.

In this article, we describe an in-house polymerase chain reaction-sequence specific priming (PCR-SSP) assay designed for undergraduate medical students as part of the experimental pathogen biology and immunology (EPBI) course. It screens human leukocyte antigen (HLA)-DR2 allotype from genomic DNA samples using a rapid and single-tube PCR technique, yielding definitive typing result without conventional post-amplification step like probing or Sanger sequencing. This laboratory exercise offers the undergraduate medical students an opportunity to learn about current molecular biology techniques in HLA genotyping with limited effort and cost, in addition to a better understanding of concepts presented in the classroom lectures. Upon completing this experiment module, the students show statistically significant improvement in several key indexes, such as the knowledge about the mainstream HLA DNA typing techniques, awareness of the relevance of this knowledge for their future scientific research, immunogenetics-related basic laboratory skills they acquire, and interest and desire for mastering this assay (all p < .05). This easy to implement set of experiments is composed of a two-session lab module occupying eight teaching hours, and has been run successfully in our laboratory.
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http://dx.doi.org/10.1002/bmb.21322DOI Listing
March 2020

The value of anti-rods and rings antibodies in Western China population: A retrospective study.

Scand J Immunol 2020 Mar 3;91(3):e12848. Epub 2019 Dec 3.

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.

The study aimed to retrospectively investigate the clinical significance of anti-rods and rings (anti-RR) antibodies in antinuclear antibodies (ANAs) test samples of western China. Between January 2016 and November 2018, the laboratory data and clinical details of patients with positive anti-RR antibodies were collected and analysed. The results showed that total of 197 227 patients tested, 109 453 patients presented with positive ANAs (55.50%), but only 107 patients with positive anti-RR antibodies (0.10%), including 51 females and 56 males. Diagnose were established in 51 of 107 patients: 25 were hepatopathy (HCV 8/25, HBV 12/25); 13 were autoimmune diseases (AID); and 7 were renal insufficiency; 6 were chronic obstructive pulmonary disease (COPD). We make the conclusions that anti-RR antibodies have a low prevalence, and there is no gender difference. Anti-RR antibodies exist other diseases besides hepatitis C, such as HBV, some autoimmune diseases, renal insufficiency and COPD, which we need further investigation.
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http://dx.doi.org/10.1111/sji.12848DOI Listing
March 2020

Photoredox-Catalyzed Remote Difunctionalizations of Alkenes To Synthesize Fluoroalkyl Ketones with Dimethyl Sulfoxide as the Oxidant.

Org Lett 2019 Nov 4;21(22):9228-9231. Epub 2019 Nov 4.

College of Chemistry and Molecular Engineering , Zhengzhou University , Zhengzhou , Henan 453000 , China.

Visible light-mediated cascade remote oxyfluoroalkylation of alkenes under mild conditions is developed for the first time. The key point of this transformation is the incorporation of alkene fluoroalkylation-initiated remote benzyl C-H bond activation via a 1,5-H shift in a highly controlled site-selective manner and Kornblum reaction with dimethyl sulfoxide as the oxidant. With this method, a broad array of fluoroalkyl groups were introduced into a double bond to produce 1,6-fluoroalkylated ketones at room temperature.
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http://dx.doi.org/10.1021/acs.orglett.9b03594DOI Listing
November 2019

Antifibrotic Mechanism of Cinobufagin in Bleomycin-Induced Pulmonary Fibrosis in Mice.

Front Pharmacol 2019 13;10:1021. Epub 2019 Sep 13.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, Tianjin, China.

Idiopathic pulmonary fibrosis (IPF) is a progressive and usually fatal lung disease that is characterized by fibroblast proliferation and extracellular matrix remodeling, which result in irreversible distortion of the lung's architecture and the formation of focal fibrous hyperplasia. The molecular mechanism by which pulmonary fibrosis develops is not fully understood, and no satisfactory treatment currently exists. However, many studies consider that aberrant activation of TGF-β1 frequently promotes epithelial-mesenchymal transition (EMT) and fibroblast activation in pulmonary fibrosis. Cinobufagin (CBG), a traditional Chinese medicine, has been widely used for long-term pain relief, cardiac stimulation, and anti-inflammatory and local anesthetic treatments. However, its role in pulmonary fibrosis has not yet been established. We investigated the hypothesis that cinobufagin plays an inhibitory role on TGF-β1 signaling using a luciferase-reporter assay. We further explored the effect of cinobufagin on pulmonary fibrosis both and . The experiments showed that cinobufagin suppresses TGF-β1/Smad3 signaling in a dose-dependent manner, attenuates the activation and differentiation of lung fibroblasts and inhibits EMT induced by TGF-β1 in alveolar epithelial cells. The experiments indicated that cinobufagin significantly alleviates bleomycin-induced collagen deposition and improves pulmonary function. Further study showed that cinobufagin could attenuate bleomycin-induced inflammation and inhibit fibroblast activation and the EMT process . In summary, cinobufagin attenuates bleomycin-induced pulmonary fibrosis in mice suppressing inflammation, fibroblast activation and epithelial-mesenchymal transition.
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http://dx.doi.org/10.3389/fphar.2019.01021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753632PMC
September 2019

Transarterial Chemoembolization (TACE) Combined with Sorafenib in Treatment of HBV Background Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Propensity Score Matching Study.

Biomed Res Int 2019 28;2019:2141859. Epub 2019 Jul 28.

Liver Cancer Institute, Department of Hepatic Oncology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China.

Objectives: Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) remains a challenge in management. Transarterial chemoembolization (TACE) has been used for patients with PVTT but efficiency was limited with a median overall survival of 4 to 6.1 months. The aim of this study is to evaluate the efficiency of TACE combined with sorafenib in HBV background HCC with PVTT.

Methods: A total of 498 patients were enrolled in the study including 69 patients who received TACE combined with sorafenib and 429 patients treated with TACE alone between January 1st, 2008, and April 30st, 2014. Using the 1:2 propensity score matching, 138 well-balanced patients were enrolled. Overall survival (OS) was compared between the two groups. The Kaplan-Meier method was used to evaluate the OS, and the differences between groups were analyzed with a log-rank test.

Results: TACE combined with sorafenib improved the OS of the patients compared with TACE alone (13.0 vs 6.0 months, p<0.001). After propensity score matching, the median OS of combination therapy and TACE were 13.0 and 7.0 months, respectively (p=0.001). Subgroup analysis revealed that the patients younger than 60 years old, male patients, AFP more than 400ng/ml, tumor size more than 5cm, or type III/IV PVTT had OS benefits from TACE combined with sorafenib.

Conclusions: Compared with TACE therapy alone, TACE combined with sorafenib could improve OS in HBV background HCC patients with PVTT. The patients who are younger, male, or with more tumor burden may benefit more from combination therapy.
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http://dx.doi.org/10.1155/2019/2141859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699376PMC
January 2020

Liraglutide improves insulin sensitivity in high fat diet induced diabetic mice through multiple pathways.

Eur J Pharmacol 2019 Oct 11;861:172594. Epub 2019 Aug 11.

Department of Physician Assistant, College of Health Professions, Central Michigan University MI, 48859, USA. Electronic address:

Glucagon like peptide-1 (GLP-1) promotes postprandial insulin secretion. Liraglutide, a full agonist of the GLP-1 receptor, reduces body weight, improve insulin sensitivity, and alleviate Non Alcoholic Fatty Liver Disease (NAFLD). However, the underlying mechanisms remain unclear. This study aims to explore the underlying mechanisms and cell signaling pathways involved in the anti-obesity and anti-inflammatory effects of liraglutide. Mice were fed a high fat high sucrose diet to induce diabetes, diabetic mice were divided into two groups and injected with liraglutide or vehicle for 14 days. Liraglutide treatment improved insulin sensitivity, accompanied with reduced expression of the phosphorylated Acetyl-CoA carboxylase-2 (ACC2) and upregulation of long chain acyl CoA dehydrogenase (LCAD) in insulin sensitive tissues. Furthermore, liraglutide induced adenosine monophosphate-activated protein kinase-α (AMPK-α) and Sirtuin-1(Sirt-1) protein expression in liver and perigonadal fat. Liraglutide induced elevation of fatty acid oxidation in these tissues may be mediated through the AMPK-Sirt-1 cell signaling pathway. In addition, liraglutide induced brown adipocyte differentiation in skeletal muscle, including induction of uncoupling protein-1 (UCP-1) and PR-domain-containing-16 (PRDM-16) protein in association with induction of SIRT-1. Importantly, liraglutide displayed anti-inflammation effect. Specifically, liraglutide led to a significant reduction in circulating interleukin-1 β (IL-1 β) and interleukin-6 (IL-6) as well as hepatic IL-1 β and IL-6 content. The expression of inducible nitric oxide synthase (iNOS-1) and cyclooxygenase-2 (COX-2) in insulin sensitive tissues was also reduced following liraglutide treatment. In conclusion, liraglutide improves insulin sensitivity through multiple pathways resulting in reduction of inflammation, elevation of fatty acid oxidation, and induction of adaptive thermogenesis.
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http://dx.doi.org/10.1016/j.ejphar.2019.172594DOI Listing
October 2019
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