Publications by authors named "Lijun Zhao"

174 Publications

Enhenced cell adhesion on collagen I treated parylene-C microplates.

J Biomater Sci Polym Ed 2021 Aug 1:1-15. Epub 2021 Aug 1.

Department of Biomedical Engineering, Research Center for Nano-Biomaterials & Regenerative Medicine, College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan, PR China.

On account of unique mechanical property and inertia, parylene-C has become a promising material for microdevices especially in three-dimensional microstructures loaded with cells. However, parylene-C is not favorable for cell adhesion, and a routine procedure is to modify it with a new adhesive layer. Herein, the parylene-C substrates with or without collagen Ӏ (Col-I) coating were adopted to estimate the influence of micro-environment change on cell attachment and spreading. After modification with Col-I, cauliflower-like particles presented on the substrate surface. Contact angle was significantly decreased after Col-I modification, which suggested the surface hydrophilicity was enhanced. Furthermore, cells cultured on parylene-C surface with Col-I treatment showed increased proliferation rate and spreading areas. In order to test the adhesion strength, a series of fixed size parylene-C microplates was fabricated, and cell suspension concentration was adjusted to culture a single cell on one microplate. The microplate was folded by the autogenous shrinkage force of cell. The folding angles of parylene-C microplates with Col-I treatment exhibited higher folding angle (112.6 ± 15.6°) than untreated samples (46.7 ± 5.9°). The work proved the existence of Col-I layer was particularly important, especially in analysis of cells mechanics using parylene-C microplate as a substrate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09205063.2021.1958465DOI Listing
August 2021

Super-enhancer-driven Sorting Nexin 5 expression promotes dopaminergic neuronal ferroptosis in Parkinson's disease models.

Biochem Biophys Res Commun 2021 Aug 13;567:35-41. Epub 2021 Jun 13.

Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China. Electronic address:

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide. Recent studies revealed that the ferroptosis pathway is involved in the death process of dopaminergic neurons in PD. The aberrant endosomal sorting pathway, which results in aberrant iron level in eukaryotic cells, may serve a role in the ferroptosis pathway in PD condition. However, its specific molecular mechanisms remained unclear. In the present study, we performed chromatin immunoprecipitation (ChIP) assay, the rank ordering of super-enhancers (ROSE) algorithm, and RNA interference (RNAi) to explore the regulatory mechanism of PD-specific super-enhancer (SE) in the endosomal sorting pathway and ferroptosis pathway of 6-OHDA-lesioned rats and cells. The ChIP assay and ROSE algorithm results showed that there are specific SEs expression in 6-OHDA-lesioned SNc of PD rats, and the most significant expression gene is Sorting Nexin 5 (SNX5). SNX5 silencing by RNAi experiments significantly decreased the level of ferroptosis in 6-OHDA-lesioned PC12 cells, suggesting the correlation between the SNX5, ferroptosis, and PD. In conclusion, this study investigated the mechanism by which PD-specific SE driven SNX5 promoted the ferroptosis level in PD models. This study further improved the understanding of the mechanism of ferroptosis during PD injury and provided potential therapeutic targets and clinical diagnostic markers in PD condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2021.06.024DOI Listing
August 2021

Long non‑coding RNA SNHG3 promotes the development of non‑small cell lung cancer via the miR‑1343‑3p/NFIX pathway.

Int J Mol Med 2021 Aug 16;48(2). Epub 2021 Jun 16.

Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, P.R. China.

The aim of the present study was to identify the function of long non‑coding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) and examine its effects on non‑small cell lung cancer (NSCLC). A series of experiments were employed to evaluate the effects of SNHG3 on the progression of NSCLC, including Cell Counting Kit‑8, 5‑Ethynyl‑2'‑deoxyuridine, flow cytometry, wound healing, Transwell, western blotting and reverse transcription‑quantitative PCR assays. Bioinformatics analyses and a luciferase reporter assay were performed to identify the target gene of SNHG3 and microRNA (miR)‑1343‑3p. Finally, recuse experiments were conducted to verify the effect of SNHG3 and its target gene on proliferation, apoptosis, migration and invasion. The findings indicated that lncRNA SNHG3 was highly expressed in NSCLC tissues and cell lines. Knockdown of lncRNA SNHG3 inhibited cell proliferation, migration and invasion, and accelerated cell apoptosis in NSCLC cell lines. The results of the bioinformatics analysis and the luciferase reporter assay indicated that lncRNA SNHG3 directly bound to miR‑1343‑3p and that it could downregulate the expression levels of miR‑1343‑3p to promote the progression of NSCLC. Rescue experiments indicated that lncRNA SNHG3 increased nuclear factor IX (NFIX) expression by sequestering miR‑1343‑3p in NSCLC. These results suggested that the SNHG3/miR‑1343‑3p/NFIX axis may serve as a novel prognostic biomarker and therapeutic target for NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijmm.2021.4980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208627PMC
August 2021

Niujiaodihuang Detoxify Decoction inhibits ferroptosis by enhancing glutathione synthesis in acute liver failure models.

J Ethnopharmacol 2021 Jun 12;279:114305. Epub 2021 Jun 12.

School of Pharmacy, Guangdong Medical University, Dongguan, 524023, China. Electronic address:

Ethnopharmacological Relevance: Niujiaodihuang Detoxify Decoction (NDD) is an integrated traditional Chinese medicine prescription that has been used as a therapeutic agent for the treatment of acute liver failure (ALF). However, the mechanisms underlying its action remain unclear.

Aim Of The Study: To determine the protective effect of NDD on D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced ALF and explore the underlying mechanisms.

Materials And Methods: We characterized the NDD fingerprint by HPLC and established D-GalN/LPS-induced ALF models in Sprague-Dawley rats and LO2 cells. Next, we measured the protective and antiferroptotic effects of NDD in vivo and in vitro. To further investigate the molecular mechanisms underlying the effects of NDD, we performed metabolomic analysis of the liver tissue using LC-MS/MS.

Results: Results of serum biochemical analysis, liver histopathology, and cell viability showed that NDD effectively relieved the liver injury. It reduced the accumulation of labile iron and alleviated lipid peroxidation by enhancing GPX4 activity. The mitochondrial morphology indicated that NDD exerted its hepatoprotective effect through an antiferroptotic activity. Metabolomic analysis showed that NDD treatment increased the levels of cysteine, decreased those of glutamate, and ameliorated the D-GalN/LPS-induced reduction in the levels of glutathione (GSH). The results for intracellular levels of reduced (GSH) and oxidized (GSSG) glutathione were consistent with those of metabolomic analysis.

Conclusion: Our findings indicate that NDD exerts hepatoprotective activity by evoking the reprogramming of GSH metabolism, and thereby, inhibiting ferroptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2021.114305DOI Listing
June 2021

Essential hypertension in patients exposed to high-arsenic exposed areas in western China: Genetic susceptibility and urinary arsenic metabolism characteristics.

J Trace Elem Med Biol 2021 Sep 21;67:126778. Epub 2021 May 21.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Key Lab of Etiology and Epidemiology, Education Bureau of Hei Long Jiang Province & Ministry of Health, Harbin, 150081, China(1). Electronic address:

Objective: To clarify the urinary arsenic metabolism characteristics in individuals with essential hypertension and to analyze the relationship between lipid metabolism gene polymorphisms and susceptibility to essential hypertension in individuals in high-arsenic areas in western China.

Methods: A case-control study was conducted and involved individuals exposed to high arsenic levels (in this study, the arsenic content in the pressurized well water was 0-510.2 μg/L, and that in the mechanical well water was 167 μg/L) in two adjacent high-arsenic areas in Shanxi Province and the Inner Mongolia Autonomous Region, China. A total of 699 samples were collected, including 192 case samples (patients with hypertension) and 507 control samples (no hypertension). Blood pressure measurement data obtained from an epidemiological survey were used to determine whether the subjects had hypertension, and a logistic regression model was used to analyze the association between lipid metabolism gene polymorphisms and hypertension susceptibility. Blood and urine samples were collected based on epidemiological methods, single nucleotide polymorphisms (SNPs) were genotyped using a SNPscan™ multiple SNP typing kit, and urinary arsenic concentrations were determined using the hydride generation atomic fluorescence method (HG-AFS).

Results: ADIPOQ/rs266729 was the dominant genetic model [(GC + GG) vs CC = 0.686:1, 95 % CI = 0.478-0.983], and FABP2/rs1799883 was the recessive genetic model [TT vs (CC + TC) = 1.690:1, 95 % CI = 1.014-2.816]. The distribution of the urinary arsenic secondary methylation ratio (SMR) [dimethylated arsenic (DMA)/monomethylated arsenic (MMA)] was different between hypertensive patients and controls.

Conclusion: ADIPOQ/rs266729 and FABP2/rs1799883 polymorphisms affect susceptibility to essential hypertension in individuals exposed to high levels of arsenic; there was a clear difference in the urinary arsenic metabolism pattern between hypertensive patients and controls.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtemb.2021.126778DOI Listing
September 2021

Switchable Binding Energy of Ionic Compounds and Application in Customizable Ligand Exchange for Colloid Nanocrystals.

J Phys Chem Lett 2021 Jun 1;12(22):5271-5278. Epub 2021 Jun 1.

Key Laboratory for Physical Electronics and Devices of the Ministry of Education, School of Electronic Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shannxi 710049, P. R. China.

The ability to engineer the surface ligands or adsorbed molecules on colloid nanocrystals (NCs) is important for various applications, as the physical and chemical properties are strongly affected by the surface chemistry. Here, we develop a facile and generalized ionic compound-mediated ligand-exchange strategy based on density functional theory calculations, in which the ionic compounds possess switchable bonding energy when they transfer between the ionized state and the non-ionized state, hence catalyzing the ligand-exchange process. By using an organic acid as the intermediate ligand, ligands such as oleylamine, butylamine, polyvinylpyrrolidone, and poly(vinyl alcohol) can be freely exchanged on the surface of Au NCs. Benefiting from this unique ligand-exchange strategy, the ligands with strong bonding energy can be replaced by weak ones, which is hard to realize in traditional ligand-exchange processes. The ionic compound-mediated ligand exchange is further utilized to improve the catalytic properties of Au NCs, facilitate the loading of nanoparticles on substrates, and tailor the growth of colloid NCs. These results indicate that the mechanism of switchable bonding energy can be significantly expanded to manipulate the surface property and functionalization of NCs that have applications in a wide range of chemical and biomedical fields.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpclett.1c00669DOI Listing
June 2021

All five COVID-19 outbreaks during epidemic period of 2020/2021 in China were instigated by asymptomatic or pre-symptomatic individuals.

J Biosaf Biosecur 2021 Jun 21;3(1):35-40. Epub 2021 May 21.

Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi Province 030001, PR China.

Introduction: The significance of asymptomatic or pre-asymptomatic individuals in driving the COVID-19 epidemic in China or other countries remains uncertain.

Method: We collected and analyzed all the epidemiologic and virological diagnostic details of the infected individuals released by public health authorities and reiterated every episode of outbreak on a timeline. All individuals associated with the five outbreaks had tested positive for SARS-CoV-2 infection.

Results: In this study, all five COVID-19 outbreaks reported in China since October 2020 were analyzed. The Kashgar outbreak in Xinjiang province came into light for the first time on October 22, 2020. However, it was initiated before October 11, 2020, by a local asymptomatic import and export worker, who was infected at the working place. Subsequently, his wife caught the infection, which led to 430 more infections reported in the outbreak. The Beijing outbreak with 41 cases was noticed for the first time on December 22, 2020. However, our analysis revealed that it was initiated by an asymptomatic individual from Indonesia on December 10, 2020. The Shenyang outbreak, with 38 cases, noticed for the first time on December 23, 2020, was initiated by a pre-symptomatic individual from South Korea on December 13, 2020.

Conclusion: The asymptomatic or pre-symptomatic individuals during the asymptomatic period were unsuspectingly infected by SARS-CoV-2, and unintentionally transmitted the virus to a large number of people. These findings suggest that early detection of asymptomatic or pre-symptomatic individuals is of critical importance in preventing future outbreaks or epidemics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jobb.2021.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139231PMC
June 2021

Effects of withdrawing an atherogenic diet on the atherosclerotic plaque in rabbits.

Exp Ther Med 2021 Jul 12;22(1):751. Epub 2021 May 12.

Department of General Practice, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China.

Lifestyle interventions and pharmacotherapy are the most common of non-invasive treatments for atherosclerosis, but the individual effect of diet on plaques remains unclear. The current study aimed to investigate the effect of withdrawing the atherogenic diet on plaque in the aortas of rabbits. Experimental atheroma was induced in 33 rabbits using a 1% high cholesterol diet for 30 days (H-30 d) or 90 days (H-90 d, baseline group). After 90 days of the atherogenic diet, the remaining animals were divided into four groups: A total of 10 rabbits continued to consume the atherogenic diet for 50 days (H-90 d & H-50 d; n=5) or 140 days (H-90 d & H-140 d; n=5). Another 13 rabbits were switched to a chow diet for 50 days (H-90 d & C-50 d; n=7) or 140 days (H-90 d & C-140 d; n=6). A total of 10 age-matched rabbits in the control groups were fed a chow diet for 90 and 230 days, respectively. The or cross-sectional plaque areas were determined using oil red O staining and elastic van Gieson staining. Immunohistochemistry analyses were used to assess the macrophages or smooth muscle cell contents. When fed an atherogenic diet for 90 days, the rabbits' abdominal aortas exhibited severe atherosclerotic lesions (the median plaque area was 63.6%). After withdrawing the atherogenic diet, the plaque area did not shrink with feeding the chow diet compared with the baseline, but increased to 71.8 or 80.5% after 50 or 140 days, respectively. After removing cholesterol from the diet, the lipids content in the plaques increased during the first 50 days, and then decreased compared with the baseline group. Furthermore, withdrawing the atherogenic diet increased the total collagen content and the percentage of the smooth muscle cells, alleviated macrophage infiltration, decreased the vulnerable index and promoted the cross-linking of collagen. Feeding the rabbits an atherogenic diet followed by removal of cholesterol from the diet did not lead to the regression of established lesions but instead delayed the progression of the lesions and promoted the stabilization of the plaque.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2021.10183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135140PMC
July 2021

Quercetin Ameliorates Gut Microbiota Dysbiosis That Drives Hypothalamic Damage and Hepatic Lipogenesis in Monosodium Glutamate-Induced Abdominal Obesity.

Front Nutr 2021 29;8:671353. Epub 2021 Apr 29.

National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

Monosodium glutamate (MSG)-induced abdominal obesity, conventionally caused by hypothalamic damage, is a critical risk factor for health problem. Microbiota-gut-brain axis plays important roles in a variety of metabolic diseases. However, whether gut microbiota is involved in the pathogenesis for MSG-induced abdominal obesity and the effect of quercetin on it remains unclear. Herein, we find that MSG-induced gut microbiota dysbiosis contributes to neuronal damage in the hypothalamus, as indicated by antibiotics-induced microbiota depletion and co-house treatment. Inspired by this finding, we investigate the mechanism in-depth for MSG-induced abdominal obesity. Liver transcriptome profiling shows retinol metabolism disorder in MSG-induced abdominal obese mice. In which, retinol saturase (RetSat) in the liver is notably up-regulated, and the downstream lipogenesis is correspondingly elevated. Importantly, microbiota depletion or co-house treatment eliminates the difference of RetSat expression in the liver, indicating gut microbiota changes are responsible for liver retinol metabolism disorder. Moreover, this study finds dietary quercetin could modulate MSG-induced gut microbiota dysbiosis, alleviate hypothalamic damage and down-regulate liver RetSat expression, thus ameliorating abdominal obesity. Our study enriches the pathogenesis of MSG-induced abdominal obesity and provides a prebiotic agent to ameliorate abdominal obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnut.2021.671353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116593PMC
April 2021

Carbohydrate intake and circadian synchronicity in the regulation of glucose homeostasis.

Curr Opin Clin Nutr Metab Care 2021 Jul;24(4):342-348

Adelaide Medical School, University of Adelaide.

Purpose Of Review: Glucose metabolism is under circadian regulation, with insulin secretion and sensitivity being highest in the morning as compared to the evening. The present review will discuss the existing evidence for the role of meal and macronutrient timing to improve glucose metabolism and reset circadian clocks, with a focus on the evidence in humans.

Recent Findings: Shortening the daily eating window (also known as time-restricted eating), or skewing food intake towards breakfast and away from the evening meal both improve glucose control in people with impaired glucose metabolism. Insulin is recently purported to be a zeitgeber and thus an important reset signal for peripheral circadian clocks in vitro and in mice. Although few studies have tested the impact of macronutrient timing in humans, eating a greater proportion of carbohydrates earlier, rather than later, in the day is associated with better glucose control.

Summary: The impact of carbohydrate intake timing on endogenous central and peripheral clocks, and its potential to optimize circadian regulation and improve glycaemic control, are not well understood but are currently under intense exploration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCO.0000000000000756DOI Listing
July 2021

A Novel Transcription Factor-Based Prognostic Signature in Endometrial Cancer: Establishment and Validation.

Onco Targets Ther 2021 13;14:2579-2598. Epub 2021 Apr 13.

Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, People's Republic of China.

Background: Endometrial cancer (EC) is a common malignancy of the female reproductive system worldwide. Increasing evidence has suggested that many transcription factors are aberrantly expressed in various cancers. This study aimed to develop a transcription factor-based prognostic signature for EC.

Methods: Gene expression data and clinical data of EC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression and Multivariate Cox regression analysis was used to construct a prognostic signature. Then, the efficacy of the prognostic signature was validated in a training cohort, testing cohort and then the entire cohort. Correlations between clinical features and the model were also analyzed, and a nomogram based on the multivariate Cox analysis was developed. Furthermore, we verified the effect of a key transcription factor, E2F1, on biological functions of EC in vitro.

Results: We developed a nine-transcription factor (MSX1, HOXB9, E2F1, DLX4, BNC2, DLX2, PDX1, POU3F2, and FOXP3) prognostic signature. Compared with those in the low-risk group, patients in the high-risk group had worse clinical outcomes. The area under the curve (AUC) of this prognostic signature for 5-year survival was 0.806 in the training cohort, 0.710 in the testing cohort and 0.761 in the entire cohort. Gene set enrichment analysis (GSEA) revealed a correlation between the prognostic signature and various cancer signaling pathways, and a hub transcription factor regulatory network was constructed. The prognostic signature was confirmed to have independent predictive value. Finally, a nomogram based on the prognostic signature and clinical independent prognostic factors was also established and performed well according to the calibration curves. Further, knockdown of E2F1 inhibited invasion and metastasis of EC cells.

Conclusion: Our study developed and validated a transcription factor-based prognostic signature that accurately predicts prognosis of EC patients. Moreover, E2F1 may represent a potential target for the treatment of EC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S293085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053499PMC
April 2021

High prevalence of vitamin D deficiency in Shenzhen pregnant women.

J Matern Fetal Neonatal Med 2021 Apr 19:1-8. Epub 2021 Apr 19.

Central Research Laboratory, Department of Clinical Laboratory, Innovative Research Center of Traditional Chinese Medicine, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, The Second People's Hospital of Bao'an Shenzhen (Group), Shajing People's Hospital of Bao'an Shenzhen, Shenzhen, China.

Background: Vitamin D deficiency is a public health problem worldwide. Vitamin D deficiency in pregnant women often leads to negative clinical consequence and has been distributed differently in certain latitudes. Here, we aimed to determine the prevalence of vitamin D deficiency in pregnant women in Shenzhen City and investigate the influencing factors.

Methods: A total of 27,166 healthy pregnant women, undergoing prenatal examinations in our hospital between July 2014 and December 2018, were enrolled in our study. Maternal characteristics, including the duration of pregnancy, age and enrollment time, were recorded. The concentrations of serum 25(OH)D in the blood samples were detected by immunochemistry assays.

Results: For the total study population, the median serum 25(OH)D concentration was 23.36 [17.98-29.51] ng/mL, and 34.3% and 42.4% of the participants exhibited vitamin D deficiency (serum 25(OH)  < 20 ng/mL) and insufficiency (serum 25(OH)D 21-29 ng/mL), respectively. Vitamin D deficiency decreased with gestation (37.83%, 33.8%, and 29.3% for the first trimester, second trimester and third trimester, respectively,  < .001) and decreased by age (36.03%, 35.20%, 31.86% and 29.83%, for the age groups 18-24, 25-29, 30-34 and 35-46 years, respectively,  < .001). This prevalence had conspicuous seasonality (winter vs. autumn, OR 3.69, 95% CI: 3.42-3.99,  < .001). Temperature was positively associated with women's serum 25(OH)D level ( = 0.48,  < .001).

Conclusions: Overall, we demonstrated that vitamin D deficiency in pregnant women in Shenzhen was common and was affected by gestation, age and season/temperature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14767058.2021.1910667DOI Listing
April 2021

Switchable CAR-T Cells Outperformed Traditional Antibody-Redirected Therapeutics Targeting Breast Cancers.

ACS Synth Biol 2021 05 15;10(5):1176-1183. Epub 2021 Apr 15.

California Institute for Biomedical Research, 11119 North Torrey Pines Road, La Jolla, California 92037, United States.

Various antibody-redirected immunotherapeutic approaches, including antibody-drug conjugates (ADCs), bispecific antibodies (bsAbs), and chimeric antigen receptor-T (CAR-T) cells, have been devised to produce specific activity against various cancer types. Using genetically encoded unnatural amino acids, we generated a homogeneous Her2-targeted ADC, a T cell-redirected bsAb, and a FITC-modified antibody capable of redirecting anti-FITC CAR-T (switchable CAR-T; sCAR-T) cells to target different Her2-expressing breast cancers. sCAR-T cells showed activity against Her2-expressing tumor cells comparable to that of conventional anti-Her2 CAR-T cells and superior to that of ADC- and bsAb-based approaches. To prevent antigen escape, we designed bispecific sCAR-T cells targeting both the Her2 receptor and IGF1R, which showed an overall improved activity against cancer cells with low Her2 expression. This study increases our understanding of various explored cancer therapeutics and underscores the efficient application of sCAR-T cells as a promising therapeutic option for breast cancer patients with low or heterogeneous antigen expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acssynbio.1c00007DOI Listing
May 2021

Identification of GSPT1 as prognostic biomarker and promoter of malignant colon cancer cell phenotypes via the GSK-3β/CyclinD1 pathway.

Aging (Albany NY) 2021 04 4;13(7):10354-10368. Epub 2021 Apr 4.

Department of General Surgery, Mianyang Central Hospital, Mianyang Central Hospital of Chongqing Medical University, Mianyang 621000, Sichuan Province, P.R. China.

Colon cancer is the third most common malignant tumor and its mortality rate ranks fourth among all malignant tumor types. Bioinformatics analysis has shown that is dysregulated in colon cancer and is associated with tumor progression. However, the underlying mechanism remains unclear. To address this research gap, we examined the impact of on cell proliferation, apoptosis, migration, and invasion as well as tumor growth in colon cancer by using a Cell Counting Kit-8 assay, flow cytometry, transwell migration assay, transwell invasion assay, and tumor xenograft model-based analysis, respectively. was significantly up-regulated in colon cancer tissues and cell lines. High GSPT1 expression was correlated with a larger tumor size. Depletion of GSPT1 suppressed cell proliferation, migration, and invasion-induced colon cancer cell apoptosis and restrained tumorigenicity in HCT116 colon cancer cells. Taken together, our findings suggest that the GSPT1/GSK pathway exerts tumor-promoting actions in colon cancer oncogenesis and progression. The GSPT1/GSK pathway may thus be an effective target for controlling colon cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064227PMC
April 2021

(+)-Terpinen-4-ol Inhibits Biofilm Formation by Upregulating the Interspecies Quorum Sensing Signals Diketopiperazines and Diffusing Signaling Factors.

J Agric Food Chem 2021 Mar 16;69(11):3496-3510. Epub 2021 Mar 16.

Department of Food Engineering, College of Biomass Science and Engineering, Sichuan University, Chengdu 610065, P. R. China.

is a Gram-positive endospore-forming foodborne pathogen that causes lethal food poisoning and significant economic losses, usually through biofilm- and endospore-induced recurrent cross- and postprocessing contamination. Due to the lack of critical inhibitory targets and control strategies, biofilm contamination is a problem that urgently needs a solution. In this study, the antibacterial and antibiofilm activities of several natural potential bacterial quorum sensing (QS) interferers, a group of spice-originated monoterpenoids, were screened, and terpinen-4-ol effectively inhibited growth and biofilm and spore germination with minimum growth inhibition and 50% biofilm inhibitory concentrations of 8 and 2 μmol/mL, respectively. FESEM/CLSM and phenotypic research illustrated that in addition to a decrease in the number of attached cells, (+)-terpinen-4-ol also obviously reduced extracellular matrix synthesis, especially exopolysaccharides, and inhibited the swarming motility and protease activity of . (+)-Terpinen-4-ol did not exert a significant effect on AI-2 signals in . Accordingly, the -produced interspecies QS signals diffusing signal factors (DSFs, C8-C15) and diketopiperazines (DKPs) were detected and identified here, which suppressed biofilm formation in a concentration-dependent manner. (+)-Terpinen-4-ol significantly increased the levels of specific DSF and DKP signals in and down-regulated the gene expression of some homologues in transcription level. Moreover, both DKPs and DSFs inhibited swarming motility and protease activity in , while just the DSF signals 2-dodecenoic acid and 11-methyl-2-dodecenoic acid inhibited exopolysaccharide synthesis like (+)-terpinen-4-ol. In summary, strains were found to produce nine DSF- and six DKP-type QS signaling molecules, which repressed biofilm formation. (+)-Terpinen-4-ol was confirmed to be a promising antibacterial and antibiofilm agent against upregulating DSFs and DKPs levels, and it could target the critical genes for DSFs turnover.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.0c07826DOI Listing
March 2021

Early-onset of type 2 diabetes mellitus is a risk factor for diabetic nephropathy progression: a biopsy-based study.

Aging (Albany NY) 2021 03 3;13(6):8146-8154. Epub 2021 Mar 3.

Division of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.

Several studies show that patients with early-onset diabetes have higher risk of diabetic complications than those diagnosed in middle age. However, whether early-onset of type 2 diabetes mellitus (T2DM) is a risk factor for diabetic nephropathy (DN) progression remains unclear, especially a lack of data in biopsy-confirmed cohort. In This study, we enrolled 257 patients with T2DM and biopsy-confirmed DN to investigate the role of early-onset T2DM in DN progression. Participants were divided into two groups according to the age of T2DM diagnosis: early-onset group (less than 40 years) and later-onset group (40 years or older). We found that patients with early-onset T2DM had higher glomerular grades and arteriolar hyalinosis scores than those in later-onset group. After adjusted for confounding factors, early-onset of T2DM remained an independent predictor of end-stage renal disease (ESRD) for patients with DN. In conclusion, although with the comparable renal function and proteinuria, patients with early-onset T2DM and DN had worse renal pathological changes than those with later-onset. Early-onset of T2DM might be an important predictor of ESRD for patients with DN, which called more attention to early supervision and prevention for patients with early-onset T2DM and DN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034912PMC
March 2021

Association between atherosclerotic cardiovascular diseases risk and renal outcome in patients with type 2 diabetes mellitus.

Ren Fail 2021 Dec;43(1):477-487

Division of Nephrology, West China Hospital of Sichuan University, Chengdu, China.

Aims: Chronic kidney disease (CKD) and diabetes mellitus increase atherosclerotic cardiovascular diseases (ASCVD) risk. However, the association between renal outcome of diabetic kidney disease (DKD) and ASCVD risk is unclear.

Methods: This retrospective study enrolled 218 type 2 diabetic patients with biopsy-proven DKD, and without known cardiovascular diseases. Baseline characteristics were obtained and the 10-year ASCVD risk score was calculated using the Pooled Cohort Equation (PCE). Renal outcome was defined as progression to end-stage renal disease (ESRD). The association between ASCVD risk and renal function and outcome was analyzed with logistic regression and Cox analysis.

Results: Among all patients, the median 10-year ASCVD risk score was 14.1%. The median of ASCVD risk score in CKD stage 1, 2, 3, and 4 was 10.9%, 12.3%, 16.5%, and 14.8%, respectively ( = 0.268). Compared with patients with lower ASCVD risk (<14.1%), those with higher ASCVD risk had lower eGFR, higher systolic blood pressure, and more severe renal interstitial inflammation. High ASCVD risk (>14.1%) was an independent indicator of renal dysfunction in multivariable-adjusted logistic analysis (OR, 3.997; 95%CI, 1.385-11.530;  = 0.010), though failed to be an independent risk factor for ESRD in patients with DKD in univariate and multivariate Cox analysis.

Conclusions: DKD patients even in CKD stage 1 had comparable ASCVD risk score to patients in CKD stage 2, 3, and 4. Higher ASCVD risk indicated severe renal insufficiency, while no prognostic value of ASVCD risk for renal outcome was observed, which implied macroangiopathy and microangiopathy in patients with DKD were related, but relatively independent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0886022X.2021.1893186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946063PMC
December 2021

Dietary Cholesterol Supplements Disturb Copper Homeostasis in Multiple Organs in Rabbits: Aorta Copper Concentrations Negatively Correlate with the Severity of Atherosclerotic Lesions.

Biol Trace Elem Res 2021 Mar 4. Epub 2021 Mar 4.

Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

Dietary cholesterol causes atherosclerosis along with a reduction of copper concentrations in the atherosclerosis wall. This study was to determine the relationship between aorta copper concentrations and the severity of atherosclerotic lesions as well as copper homeostasis in multiple organs in cholesterol-fed rabbits. Male New Zealand white rabbits, 10-week-old and averaged 2.0 kg, were fed a diet containing 1% (w/w) cholesterol or the same diet without cholesterol as controls. Twelve weeks after the feeding, aortic atherosclerotic lesions, serum cholesterol, and multiple organ copper concentrations were measured. Compared to controls, rabbits fed cholesterol-supplemented diet displayed higher serum cholesterol levels and developed atherosclerosis. Copper concentrations in the cholesterol-fed rabbits were increased in the serum and kidney but decreased in the atherosclerosis wall and multiple organs, including heart, liver, spleen, and lung. Furthermore, aorta copper concentrations negatively correlated, respectively, with the severity of the atherosclerotic lesion (r = - 0.64, p = 0.01), the microscope atherosclerotic lesion area (r = - 0.60, p = 0.02), and the stenosis of the lumen (r = - 0.54, p = 0.04). Dietary cholesterol not only causes atherosclerosis but also disturbs copper homeostasis in multiple organ systems. The negative correlation between aorta copper concentrations and the severity of atherosclerotic lesions suggests a vicious cycle between copper reduction and the pathogenesis of atherosclerosis. These changes in copper homeostasis would be additive to atherosclerosis as a risk factor for cardiovascular disease in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-021-02618-0DOI Listing
March 2021

Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes.

Sci Rep 2021 Feb 25;11(1):4658. Epub 2021 Feb 25.

Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia.

Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics and immunohistochemistry were used to identify differentially expressed proteins and enriched pathways in glomeruli. During the median follow-up period of 24 months, 144 (45%) patients progressed to ESRD. In multivariable models, the Renal Pathology Society classification failed to predict ESRD, although the solidified glomerulosclerosis (score 1: HR 1.65, 95% confidence interval [CI] 1.04-2.60; score 2: HR 2.48, 95% CI 1.40-4.37) and extracapillary hypercellularity (HR 2.68, 95% CI 1.55-4.62) were identified as independent risk factors. Additionally, single glomerular proteomics, combined with immunohistochemistry, revealed that complement C9 and apolipoprotein E were highly expressed in solidified glomerulosclerosis. Therefore, solidified glomerulosclerosis and extracapillary hypercellularity predict diabetic ESRD in Chinese patients. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change that may be associated with complement overactivation and abnormal lipid metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-83856-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907371PMC
February 2021

The Associations of Genital Mycoplasmas with Female Infertility and Adverse Pregnancy Outcomes: a Systematic Review and Meta-analysis.

Reprod Sci 2021 Jan 4. Epub 2021 Jan 4.

Clinical Medicine Research Center, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

The roles of genital mycoplasmas including Mycoplasma genitalium (M. genitalium), Mycoplasma hominis (M. hominis), Ureaplasma urealyticum (U. urealyticum), and Ureaplasma parvum (U. parvum) in reproductive diseases are equivocal. To investigate whether genital mycoplasmas are risk factors of female infertility and adverse pregnancy outcomes, we performed a systematic review and meta-analysis. Electronic databases were searched for related studies. A random-effects model or fixed-effects model was employed to generate forest plots. Pooled odd ratios (ORs) with 95% confidence intervals (CIs) were applied to measure the strength of associations. Meanwhile, heterogeneity was evaluated by H statistic and I statistic, and publication bias was explored by funnel plots based on Egger's test and Begg's test. The search yielded 2054 relevant records, and 35 articles were ultimately included for meta-analysis. M. genitalium was a significant risk factor for female infertility (OR, 13.03 [95% CI, 3.46-48.98]) and preterm birth (PTB) (OR, 1.81 [95% CI, 1.17-2.80]), but not for spontaneous abortion (SA) (OR, 0.58 [95% CI, 0.25-1.35]). M. hominis can significantly increase the potential risk of female infertility (OR, 1.56 [95% CI, 1.02-2.38]), SA (OR, 9.14 [95% CI, 4.14-20.18]), stillbirth (OR, 3.98 [95% CI, 1.39-11.36]), and premature rupture of membranes (PROM) (OR, 1.79 [95% CI, 1.26-2.55]), but was not associated with PTB (OR, 1.29 [95% CI, 0.78-2.15]). U. urealyticum had no significant risk effect on female infertility (OR, 0.68 [95% CI, 0.42-1.11]). Coinfections of M. hominis and Ureaplasma were significantly associated with female infertility, SA, and stillbirth, but not with PROM. On the basis of current evidences, this meta-analysis supports that M. genitalium is a risk factor for female infertility and PTB; M. hominis is a potential risk factor for female infertility, SA, stillbirth, and PROM; U. urealyticum has no significant association with female infertility; and the relationship of U. parvum with female infertility and adverse pregnancy outcomes needs to be paid more attention to and remains to be further revealed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43032-020-00399-wDOI Listing
January 2021

Clinicopathologic features and prognostic factors in older patients with biopsy-proven diabetic nephropathy.

Int Urol Nephrol 2021 Jun 3;53(6):1161-1170. Epub 2021 Jan 3.

Division of Nephrology, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan, China.

Purpose: The older population has increased sharply in China. However, renal clinical and histopathological data in this population are lacking. This study investigated the clinicopathologic features and the related risk factors for long-term renal survival in older patients with diabetic nephropathy (DN).

Methods: In this retrospective observational study, 74 older patients (≥ 60 years old) with type 2 diabetes mellitus and biopsy-proven DN from 2007 to 2019 were included. Clinical data were extracted from electronic records. Renal biopsy specimens were semiquantitatively evaluated using the Renal Pathology Society (RPS) classification system. Cox proportional hazard analysis was used to estimate hazard ratios (HRs) for progression to end-stage renal disease (ESRD).

Results: During the median follow-up period of 22 months, 24 (32%) older patients progressed to ESRD. Older patients who progressed to ESRD had poorer renal function, lower hemoglobin and albumin concentrations, more severe glomerular lesions, and higher percentages of Kimmelstiel-Wilson lesions than those who did not progress to ESRD. After adjusting for age, sex, baseline renal function, and pathological parameters, multivariate Cox proportional hazard analysis showed that RPS glomerular classification (HR 2.49, 95% confidence interval [CI] 1.03-6.04), estimated glomerular filtration rate (eGFR) (HR 0.76, 95% CI 0.58-0.99), and proteinuria (HR 3.85, 95% CI 1.44-10.27) were independent risk factors for progression to ESRD.

Conclusion: Lower eGFR, heavier proteinuria, and more severe RPS glomerular lesions were associated with ESRD in older patients with type 2 diabetes mellitus and DN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11255-020-02710-9DOI Listing
June 2021

A Navigation Probability Map in Pedestrian Dynamic Environment Based on Influencer Recognition Model.

Sensors (Basel) 2020 Dec 22;21(1). Epub 2020 Dec 22.

School of Mechatronics Engineering, Harbin Institute of Technology, Harbin 150001, China.

One of the challenging problems in robot navigation is efficient and safe planning in a highly dynamic environment, where the robot is required to understand pedestrian patterns in the environment, such as train station. The rapid movement of pedestrians makes the robot more difficult to solve the collision problem. In this paper, we propose a navigation probability map to solve the pedestrians' rapid movement problem based on the influencer recognition model (IRM). The influencer recognition model (IRM) is a data-driven model to infer a distribution over possible causes of pedestrian's turning. With this model, we can obtain a navigation probability map by analyzing the changes in the effective pedestrian trajectory. Finally, we combined navigation probability map and artificial potential field (APF) method to propose a robot navigation method and verified it on our data-set, which is an unobstructed, overlooked pedestrians' data-set collected by us.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s21010019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792780PMC
December 2020

Combining glomerular basement membrane and tubular basement membrane assessment improves the prediction of diabetic end-stage renal disease.

J Diabetes 2021 Jul 5;13(7):572-584. Epub 2021 Jan 5.

Division of Nephrology, West China Hospital of Sichuan University, Chengdu, China.

Background: To address the prognostic value of combining tubular basement membrane (TBM) and glomerular basement membrane (GBM) thickness in diabetic nephropathy (DN).

Methods: This retrospective study enrolled 110 patients with type 2 diabetes and biopsy-proven DN from 2011 to 2018. The pathological findings were confirmed according to the Renal Pathology Society classifications. GBM and TBM thicknesses were determined using the Haas' direct measurement/arithmetic mean method and orthogonal intercept method, respectively. Cox proportional hazard models were used to investigate the hazard ratios (HRs) for the influence of combined GBM and TBM thickness for predicting end-stage renal disease (ESRD).

Results: Patients were assigned to three groups according to the median GBM and TBM thickness: GBM TBM (GBM < 681 nm and TBM < 1200 nm), GBM TBM /GBM TBM (GBM ≥ 681 nm and TBM < 1200 nm, or GBM < 681 nm and TBM ≥ 1200 nm), and GBM TBM (GBM ≥ 681 nm and TBM ≥ 1200 nm). The GBM TBM /GBM TBM and GBM TBM groups displayed poorer renal function, a more severe glomerular classification and interstitial inflammation, and poorer renal survival rates than the GBM TBM group The GBM TBM /GBM TBM and GBM TBM groups had adjusted HRs of 1.49 (95% confidence interval [CI], 1.21-9.75) and 3.07 (95% CI, 2.87-12.78), respectively, compared with the GBM TBM group.

Conclusions: TBM thickness enhanced GBM thickness for renal prognosis in patients with type 2 diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1753-0407.13150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246816PMC
July 2021

hnRNPLL controls pluripotency exit of embryonic stem cells by modulating alternative splicing of Tbx3 and Bptf.

EMBO J 2021 Feb 22;40(4):e104729. Epub 2020 Dec 22.

State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.

The regulatory circuitry underlying embryonic stem (ES) cell self-renewal is well defined, but how this circuitry is disintegrated to enable lineage specification is unclear. RNA-binding proteins (RBPs) have essential roles in RNA-mediated gene regulation, and preliminary data suggest that they might regulate ES cell fate. By combining bioinformatic analyses with functional screening, we identified seven RBPs played important roles for the exit from pluripotency of ES cells. We characterized hnRNPLL, which mainly functions as a global regulator of alternative splicing in ES cells. Specifically, hnRNPLL promotes multiple ES cell-preferred exon skipping events during the onset of ES cell differentiation. hnRNPLL depletion thus leads to sustained expression of ES cell-preferred isoforms, resulting in a differentiation deficiency that causes developmental defects and growth impairment in hnRNPLL-KO mice. In particular, hnRNPLL-mediated alternative splicing of two transcription factors, Bptf and Tbx3, is important for pluripotency exit. These data uncover the critical role of RBPs in pluripotency exit and suggest the application of targeting RBPs in controlling ES cell fate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15252/embj.2020104729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883296PMC
February 2021

Self-replicating catalyzed hairpin assembly for rapid aflatoxin B1 detection.

Anal Methods 2021 01;13(2):222-226

Analysis and Testing Center of Sichuan Academy of Agricultural Science, Chengdu 610066, China.

Herein, a rapid signal amplified aflatoxin B1 (AFB1) detection system based on self-replicating catalyzed hairpin assembly (SRCHA) has been constructed. In this SRCHA system, trigger DNA was initially blocked and two split trigger DNA sequences were integrated into two hairpin auxiliary probes, H1 and H2, respectively. In the presence of AFB1, the aptamer sequence was recognized by AFB1 and trigger DNA was released, which can initiate a CHA reaction and lead to the formation of a helix DNA H1-H2 complex. Then this complex can dissociate double-stranded probe DNA (F-Q) and the fluorescence signal was recovered. Meanwhile, the two split trigger DNA sequences came into close-enough proximity and a trigger DNA replica was formed. Then the obtained replicas can trigger an additional CHA reaction, leading to the rapid and significant enhancement of the fluorescence signal, and AFB1 can be detected within 15 min with a detection limit of 0.13 ng mL-1. This AFB1 detection system exhibits potential application in the on-site rapid detection of AFB1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0ay01827aDOI Listing
January 2021

Calcium and TRPV4 promote metastasis by regulating cytoskeleton through the RhoA/ROCK1 pathway in endometrial cancer.

Cell Death Dis 2020 11 23;11(11):1009. Epub 2020 Nov 23.

Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, 100044, China.

Transient receptor potential vanilloid 4 (TRPV4) is a calcium-permeable cation channel that has been associated with several types of cancer. However, its biological significance, as well as its related mechanism in endometrial cancer (EC) still remains elusive. In this study, we examined the function of calcium in EC, with a specific focus on TRPV4 and its downstream pathway. We reported here on the findings that a high level of serum ionized calcium was significantly correlated with advanced EC progression, and among all the calcium channels, TRPV4 played an essential role, with high levels of TRPV4 expression associated with cancer progression both in vitro and in vivo. Proteomic and bioinformatics analysis revealed that TRPV4 was involved in cytoskeleton regulation and Rho protein pathway, which regulated EC cell migration. Mechanistic investigation demonstrated that TRPV4 and calcium influx acted on the cytoskeleton via the RhoA/ROCK1 pathway, ending with LIMK/cofilin activation, which had an impact on F-actin and paxillin (PXN) levels. Overall, our findings indicated that ionized serum calcium level was significantly associated with poor outcomes and calcium channel TRPV4 should be targeted to improve therapeutic and preventive strategies in EC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-020-03181-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683721PMC
November 2020

Associations Between High-Altitude Residence and End-Stage Kidney Disease in Chinese Patients with Type 2 Diabetes.

High Alt Med Biol 2020 Dec 12;21(4):396-405. Epub 2020 Nov 12.

Division of Nephrology, West China Hospital of Sichuan University, Chengdu, China.

Zhao, Lijun, Xi Wang, Tingli Wang, Wenxin Fan, Honghong Ren, Rui Zhang, Yutong Zou, Huan Xu, Jie Zhang, Yunhong Wu, and Fang Liu. Associations between high-altitude residence and end-stage kidney disease in Chinese patients with type 2 diabetes. . 21:396-405, 2020. This study investigated whether living at high altitude was associated with progression to end-stage kidney disease (ESKD) in Chinese patients with diabetic nephropathy (DN). This retrospective study included 369 patients with type 2 diabetes mellitus (T2DM) and biopsy-confirmed DN. Cox proportional hazards models were used to estimate hazard ratios (HRs) for the influence of living at high altitude on ESKD. Patients living at ≥2,000 m above sea level were more likely to be Tibetan, and they had higher mean body mass indexes, glycosylated hemoglobin, hemoglobin concentrations, and baseline estimated glomerular filtration rates than those living at lower altitudes. During a median follow-up period of 20 months, 141 (38%) patients progressed to ESKD. In multivariable Cox analysis adjusted for age, sex, ethnicity, and clinical and pathological parameters, living at high altitude was independently associated with progression to ESKD in Chinese DN patients [HR 2.83, 95% confidence interval (CI) 1.05-7.58]. Compared with Han Chinese, Tibetans were at a lower risk of progression to ESKD (HR 0.15, 95% CI 0.04-0.59). Living at high altitude was independently associated with renal outcome in Han Chinese patients with T2DM and DN, but not native Tibetans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/ham.2020.0076DOI Listing
December 2020

The MIXTA-LIKE transcription factor CsMYB6 regulates fruit spine and tubercule formation in cucumber.

Plant Sci 2020 Nov 15;300:110636. Epub 2020 Aug 15.

College of Horticulture, Henan Agricultural University, 63 Nongye Road, Zhengzhou, 450002, China. Electronic address:

Cucumber fruit wart composed of tubercule and spine (trichome on fruit) is not only an important fruit quality trait in cucumber production, but also a well-studied model for plant cell-fate determination. The development of spine is closely related to the initiation and formation of tubercule. The spine differentiation regulator CsGL1 has been proved to be epistatic to the tubercule initiation factor CsTu, which is the only connection to be identified between spine and tubercule formations. Our previous studies found that the MIXTA-LIKE transcription factor CsMYB6 can suppress fruit spine initiation, which is independent of CsGL1. How the formation of spine and tubercule is regulated at the molecular level by CsMYB6 remains poorly understood. In this study, we characterized cucumber 35S:CsMYB6 transgenic plants, which displayed an obvious reduction in the number and size of fruit spines and tubecules. Molecular analyses showed that CsMYB6 directly interacted with the key spine formation factor CsTTG1 in regulating the formation of fruit spine, and CsTu in regulating the initiation of fruit tubercule, respectively. Based on these evidences, a novel regulatory network is proposed by which CsMYB6/CsTTG1 and CsMYB6/CsTu complexes play an important role in regulating epidermal development, including spine formation and tubercule initiation in cucumber.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.plantsci.2020.110636DOI Listing
November 2020

A G-quadruplex nanoswitch in the SGK1 promoter regulates isoform expression by K/Na balance and resveratrol binding.

Biochim Biophys Acta Gen Subj 2021 02 2;1865(2):129778. Epub 2020 Nov 2.

Key Laboratory of Ministry of Education for Medicinal Plant Resource and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China. Electronic address:

Background: High sodium intake can up-regulate the level of renal serum- and glucocorticoid-inducible kinase-1 (SGK1), which plays a pivotal role in controlling blood pressure via activation of the epithelial sodium channel (ENaC), which can lead to salt-sensitive hypertension. Increased potassium intake, or a vegetarian diet, counteracts salt-sensitive hypertension, but the underlying mechanisms are not fully understood.

Methods: Bioinformatics and molecular modeling were used to identify G-quadruplex (G4) and their conformations in the SGK1 promoter. CD spectra and UV melting dynamics were measured to study the stability of G4 as influenced by potassium/sodium balance and resveratrol. RT-PCR and Western blot were employed to study the effects of potassium and resveratrol on the SGK1 isoform expression.

Results: The SGK1 gene encodes a G4 structure in the proximal upstream of promoter-2; the G4 structure is stabilized by potassium or resveratrol, but destabilized by sodium. Super-physiological levels of sodium stimulate the transcription of all SGK1 isoforms, whereas resveratrol or potassium supplementation inhibits the transcription of iso-2 and iso-3, but not iso-1.

Conclusions: Stabilizing the G4 by potassium or resveratrol induces alternative promoter usage and/or pre-mRNA splicing in the transcription of SGK1.

General Significance: Potassium/sodium ion balance or resveratrol binding can act to regulate G4 molecular switches for controlling SGK1 gene expression, thereby presenting a new avenue for drug development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbagen.2020.129778DOI Listing
February 2021

Fibroblast growth factor 1 ameliorates adipose tissue inflammation and systemic insulin resistance via enhancing adipocyte mTORC2/Rictor signal.

J Cell Mol Med 2020 11 26;24(21):12813-12825. Epub 2020 Sep 26.

School of Sports and Health, Nanjing Sport Institute, Nanjing, China.

Obesity-induced activation and proliferation of resident macrophages and infiltration of circulating monocytes in adipose tissues contribute to adipose tissue inflammation and insulin resistance. These effects further promote the development of metabolic syndromes, such as type 2 diabetes, which is one of the most prevalent health conditions severely threatening human health worldwide. Our study examined the potential molecular mechanism employed by fibroblast growth factor 1 (FGF1) to improve insulin sensitivity. The leptin receptor-deficient obese mice (db/db) served as an insulin-resistant model. Our results demonstrated that FGF1-induced amelioration of insulin resistance in obese mice was related to the decreased levels of pro-inflammatory adipose tissue macrophages (ATMs) and plasma inflammatory factors. We found that FGF1 enhanced the adipocyte mTORC2/Rictor signalling pathway to inhibit C-C chemokine ligand 2 (CCL2) production, the major cause of circulating monocytes infiltration, activation and proliferation of resident macrophages in adipose tissues. Conversely, these alleviating effects of FGF1 were substantially abrogated in adipocytes with reduced expression of mTORC2/rictor. Furthermore, a model of adipocyte-specific mTORC2/Rictor-knockout (AdRiKO) obese mice was developed to further understand the in vitro result. Altogether, these results demonstrated adipocyte mTORC2/Rictor was a crucial target for FGF1 function on adipose tissue inflammation and insulin sensitivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.15872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687011PMC
November 2020
-->