Publications by authors named "Hua He"

674 Publications

Prospective study of clinical characteristics of melanoma patients with retinopathy caused by a high-dose interferon α-2b.

Melanoma Res 2021 Sep 13. Epub 2021 Sep 13.

Retinopathy is a rare side effect of interferon α-2b treatment. The goal of this study was to prospectively investigate the clinical characteristics of Chinese patients with melanomas who developed retinopathy following high doses of interferon α-2b (HD-IFN) therapy. The study included 56 melanoma stage I-III patients that were treated with HD-IFN. Fourty-three patients developed HD-IFN-induced retinopathies. Forty-three melanoma patients (76%) developed retinopathy after being treated with HD-IFN. Among these patients, 49% had cotton-wool spots, 19% had retinal hemorrhage, and 30% had retinal hemorrhage. The median time of occurrence of retinopathy was 4 weeks after treatment, and the median time of duration was 4 weeks. No patient showed other symptoms except one who had blurred vision. A comparison of clinical characteristics (age, gender, primary site, stage, and ulceration) and laboratory examinations (white blood cell and platelet counts, hemoglobin, serum lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, triiodothyronine, thyroxine, thyroid-stimulating hormone, and lipid) between the HD-IFN-induced retinopathy patients and nonretinopathy patients did not show any significant differences (P > 0.05). Although all patients that developed retinopathy had diabetes or hypertension, an equal percentage of patients were without retinopathy had diabetes or hypertension. HD-IFN therapy in patients with melanomas may induce mild retinopathy. Our results; however, do not necessarily suggest to discontinue the HD-IFN treatment because retinopathy is a reversible disorder.
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http://dx.doi.org/10.1097/CMR.0000000000000769DOI Listing
September 2021

Correction to: Surface-imprinted β-cyclodextrin-functionalized carbon nitride nanosheets for fluorometric determination of sterigmatocystin.

Mikrochim Acta 2021 Sep 8;188(10):332. Epub 2021 Sep 8.

Department of Analytical Chemistry, China Pharmaceutical University, Nanjing, 211198, China.

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http://dx.doi.org/10.1007/s00604-021-04961-4DOI Listing
September 2021

Large-for-gestational-age, leptin and adiponectin in infancy.

J Clin Endocrinol Metab 2021 Sep 3. Epub 2021 Sep 3.

Department of Obstetrics and Gynecology, Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada.

Context: Fetal overgrowth "programs" an elevated risk of obesity and type 2 diabetes in adulthood. Plausibly, adipokines may be involved in programming metabolic health.

Objective: To evaluate whether large-for-gestational-age (LGA), an indicator of fetal overgrowth, is associated with altered circulating leptin and adiponectin levels in infancy, and assess the determinants.

Study Design, Population, Outcomes: In the Canadian 3D birth cohort, we studied 70 LGA (birth weight >90 th percentile) and 140 optimal-for-gestational-age (OGA, 25 th-75 th percentiles) infants matched by maternal ethnicity, smoking and gestational age at delivery. The primary outcomes were fasting leptin, total and high molecular weight (HMW) adiponectin concentrations at age 2 years.

Results: LGA infants had higher body mass index (BMI) than OGA infants. However, there were no significant differences in leptin, total and HMW adiponectin concentrations. Leptin concentrations were positively associated with female sex, weight (z score) gain 0-24 months, current BMI and the sum of triceps and subscapular skinfold thickness, and negatively associated with maternal age and Caucasian ethnicity. Female sex was associated with lower total and HMW adiponectin concentrations. Weight (z score) gain 0-24 months and current BMI were positively correlated with total and HMW adiponectin concentrations in LGA infants only.

Conclusions: The study is the first to demonstrate that LGA does not matter for circulating leptin and adiponectin concentrations in infancy, and there may be LGA-specific positive associations between weigh gain or current BMI and adiponectin concentrations in infancy, suggesting dysfunction in establishing the adiposity-adiponectin negative feedback loop in LGA subjects.
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http://dx.doi.org/10.1210/clinem/dgab642DOI Listing
September 2021

[Effects of continuous oral health education on patients with fixation after traumatic dislocation of teeth].

Shanghai Kou Qiang Yi Xue 2021 Jun;30(3):288-291

Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology. Shanghai 200011, China. E-mail:

Purpose: To investigate the effect of continuous oral health education on patients with fixation after traumatic dislocation of teeth.

Methods: Sixty patients with fixation after traumatic dislocation of teeth from the Dental Emergency Department of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were randomly divided into control group and experimental group, thirty cases in each group. Patients in the control group were given clinical education at the time of treatments, while patients in the experimental group were given continuous oral health education after treatments. Pulp vitality, plaque index and oral hygiene behavior of the two groups were compared using SPSS 21.0 software package.

Results: The pulp activity of the experimental group was significantly higher than that of the control group 3 and 6 months after operation(P<0.05). The plaque index of the experimental group was significantly lower than that of the control group at 1st, 3rd, and 6th month after operation(P<0.05). The proportion of correct brushing, regular oral examination and good oral habits of the experimental group was significantly higher than those of the control group(P<0.05).

Conclusions: Application of continuous oral health education in patients with fixation after traumatic dislocation of teeth can raise the living ratio of dental pulp, reduce plaque index and improve oral hygiene, which is worthy of clinical promotion and application.
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June 2021

Molecular characterization, expression profile and transcriptional regulation of the CYP19 gene in goose ovarian follicles.

Gene 2022 Jan 26;806:145928. Epub 2021 Aug 26.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China. Electronic address:

Cytochrome P450 Family 19 (CYP19) is a crucial enzyme to catalyze the conversion of androgens to estrogens. However, the regulatory mechanism of goose CYP19 gene remains poorly understood. The present study attempted to obtain the full-length coding sequence (CDS) and 5'-flanking sequence of CYP19 gene, to investigate its expression and distribution profiles in different sized follicles, and to analyze the transcriptional regulatory mechanism of CYP19 gene in goose. Results showed that its CDS consisted of 1512 nucleotides and the encoded amino acid sequence contained a classical P450 structural domain. Homology analysis showed that there were high homologies of nucleotide and amino acid sequences between goose and other avian species. Its promoter sequence spanned from -1925 bp to the transcription start site (ATG) and several transcriptional factors were predicted in this region. Further analysis from luciferase assay showed that the luciferase activity was the highest spanning from -118 to -1 bp by constructing deletion promoter reporter vector. In addition, result from quantitative real-time polymerase chain reaction indicated that the mRNA level of CYP19 gene were highly expressed in theca layer of the fifth largest follicle, and the cellular location was in the theca externa cells by immunohistochemistry. Taken together, it could be concluded that the transcription activity of CYP19 gene was activated by transcriptional factors in its proximal region of promoter to promote the synthesis of estrogens, regulating the selection of pre-hierarchical into hierarchical follicle in goose.
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http://dx.doi.org/10.1016/j.gene.2021.145928DOI Listing
January 2022

Changes in gut-microbiota-related metabolites and long-term improvements in lipoprotein subspecies in overweight and obese adults: the POUNDS lost trial.

Int J Obes (Lond) 2021 Aug 23. Epub 2021 Aug 23.

Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.

Background/objectives: Alterations in gut microbiota have been linked to obesity and impaired lipid metabolism. Lipoproteins are heterogeneous, and lipoprotein subspecies containing apolipoprotein C-III (apoCIII) have adverse associations with obesity and related cardiometabolic abnormalities. We investigated associations of weight-loss diet-induced decreases in atherogenic gut-microbial metabolites, trimethylamine N-oxide (TMAO) and L-carnitine, with improvements in atherogenic lipoproteins containing apoCIII among patients with obesity.

Subjects/methods: This study included overweight and obese adults who participated in a 2-year weight-loss dietary intervention, the POUNDS Lost trial. Blood levels of TMAO and L-carnitine were measured at baseline and 6 months after the intervention; 6-month changes in the metabolites were calculated. We evaluated 2-year changes in lipid profiles (n = 395) and cholesterol [Chol] in lipoprotein (very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)) subfractions defined by the presence or absence of apoCIII (n = 277).

Results: The initial (6-month) decrease in L-carnitine was significantly associated with long-term (2-year) reductions in non-HDL-Chol and LDL-Chol (p < 0.05). Also, the decrease in L-carnitine was significantly related to decreases in Chol in LDL with apoCIII (p = 0.034) and Chol in [LDL + VLDL] with apoCIII (p = 0.018). We found significant interactions between dietary fat and TMAO on changes in LDL-Chol (P= 0.013) and Chol in [LDL + VLDL] with apoCIII (P= 0.0048); a greater increase in TMAO was related to lesser improvements in the lipoprotein outcomes if participants consumed a high-fat compared to a low-fat diet.

Conclusions: Changes in TMAO and L-carnitine induced by weight-loss diets were associated with long-term improvements in atherogenic lipoproteins containing apoCIII, implicating that these metabolic changes might be predictive of an individual's response to the dietary treatment to modify the unfavorable lipid profiles in obese patients. Dietary fat intake might modify associations of TMAO changes with long-term improvements of atherogenic cholesterol metabolism in overweight and obese adults. CLINICALTRIALS.

Gov Identifier: NCT00072995.
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http://dx.doi.org/10.1038/s41366-021-00939-7DOI Listing
August 2021

Study on performance of mimic uricase and its application in enzyme-free analysis.

Anal Bioanal Chem 2021 Aug 20. Epub 2021 Aug 20.

Department of Analytical Chemistry, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, Jiangsu, China.

Nanozymes were the novel research field to replace natural enzymes because of stability and low cost. However, the research on nanozymes was mainly focused on peroxidase, and there was little research about nanozymes with oxidase-like activity, especially mimic oxidase of small molecules related to human physiology. High levels of uric acid (UA) in the body can cause hyperuricemia and gout. And natural uricase cured this disease because it could oxidize UA. The oxidase-like activity of mixed valence state metal organic frameworks with cerium (MVSM) had been studied, but MVSM was found to have uricase-like activity in this article. The catalytic process of UA with MVSM was studied by a variety of analytical methods, which was similar to the natural uricase except for further oxidation of HO. The catalytic activity constants of MVSM were acquired by the Michaelis-Menten equation. MVSM had a better ability to catalyze UA in in vivo and in vitro experiments. An enzyme-free analysis-based mimic uricase for UA was established. All the experimental results proved that MVSM had a good prospect to replace the natural uricase. A nanomaterial, mixed valence state Ce-MOF (MVSM), with uricase-like activity has been found in vivo and in vitro. This material has potential to be a fluorescent analysis for detecting uric acid without uricase.
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http://dx.doi.org/10.1007/s00216-021-03620-0DOI Listing
August 2021

Reference biometry of foetal brain by prenatal MRI and the distribution of measurements in foetuses with ventricular septal defect.

Ann Med 2021 12;53(1):1428-1437

Department of Imaging Center, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: To provide the reference biometric measurements of the normal foetal brain by prenatal MRI and describe the distribution of measurements in the foetuses with ventricular septal defect (VSD).

Methods: This retrospective study analysed the biometric measurements of 218 foetuses between 18 - 37 gestational weeks with normal MRI findings from July 2014 to August 2019, as well as 18 foetuses with VSD. The measurements included fronto-occipital diameter (FOD), biparietal diameter (BPD), and transverse cerebellar diameter (TCD). All the prenatal MRI examinations have been taken on the same 1.5 T MR unit with a standard protocol of the foetal brain. All the linear measurements of the foetal brain were obtained on the T2-weighted imaging. The distribution of measurements in 18 foetuses with VSD was plotted on centile curves.

Results: The reference data were presented in mean, standard deviation, 95% predicted confidence intervals, and the 3rd, 10th, 25th, 50th, 75th, 90th, 97th centiles at each gestational age. The value of TCD in 56% (10/18 cases) foetuses with VSD was lower than the 3rd centile, and the rate for FOD and BPD was 33% (6/18 cases) and 22% (4/18 cases) separately. On the curves, most VSD cases with measurements lower than the 3rd centile were in relatively early gestational stage (≤28 weeks).

Conclusions: We have presented reference linear biometry of the foetal brain by prenatal MRI from 18 to 37 gestational weeks, which could help us to interpret and monitor the brain development for foetuses with VSD and other congenital heart diseases.Key messages:We have presented reference linear biometry of the foetal brain by prenatal MRI from 18 to 37 gestational weeks in multiple statistical methods: mean and standard deviation; 95% predicted confidence intervals and the 3rd, 10th, 25th, 50th, 75th, 90th, 97th centiles.Our data showed that the involvement of the brain in VSD may be not globally, but regionally, and the cerebellum may be more possible to be involved.We speculated that the earlier the VSD diagnosed the worse the brain involved, which might suggest a poor outcome and necessary follow-up.
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http://dx.doi.org/10.1080/07853890.2021.1969590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381939PMC
December 2021

Oligomerization-Enhanced Receptor-Ligand Binding Revealed by Dual-Color Simultaneous Tracking on Living Cell Membranes.

J Phys Chem Lett 2021 Sep 19;12(34):8164-8169. Epub 2021 Aug 19.

State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao 266580, P. R. China.

GPCR oligomerization plays a critical role in cellular signaling, yet the stoichiometry of the interactions between oligomers and binding ligands in living cells remains a longstanding challenge. Here, by developing a dual-color simultaneous tracking system based on a total internal reflection fluorescence microscope (TIRFM), the CCR5-CCL5 interactions are visualized and quantitatively assessed in real time. Results show that each oligomeric state of CCR5 could bind with CCL5 but with different binding affinities; CCR5 dimers have a 3.5-fold higher binding affinity than the monomers. The dimerization may cause an asymmetric conformational change which makes the first binding pocket have a 3.5-fold higher binding affinity and the second have only a half compared with the monomeric CCR5. This study is the first example to directly scrutinize the CCR5-CCL5 interactions at the single-molecule level on living cell membranes and will offer great potential for the interaction stoichiometry study of diverse surface proteins.
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http://dx.doi.org/10.1021/acs.jpclett.1c01844DOI Listing
September 2021

Adherence to Traditional Chinese Postpartum Practices and Postpartum Depression: A Cross-Sectional Study in Hunan, China.

Front Psychiatry 2021 27;12:649972. Epub 2021 Jul 27.

Xiangya School of Public Health, Central South University, Changsha, China.

The relationship between adherence to traditional Chinese postpartum practices (known as "doing-the-month") and postpartum depression (PPD) remains unknown. Practices including restrictions on diet, housework and social activity, personal hygiene, and cold contact, could introduce biological, psychological, and socio-environmental changes during postpartum. The cross-sectional study included 955 postpartum women in obstetric clinics in Hunan Province of China between September 2018 to June 2019. Thirty postpartum practices were collected by a self-report online structured questionnaire. Postpartum depression symptoms were assessed by the Chinese version of the Edinburgh Postnatal Depression Scale (EPDS). Multivariable linear regression was used to estimate the differences in EPDS scores according to adherence to postpartum practices. Firth's bias-reduced logistic regression was employed to analyze the binary classification of having PPD symptoms (EPDS ≥ 10). Overall, both moderate and low adherence to postpartum practices appeared to be associated with higher EPDS scores (adjusted difference 1.07, 95% CI 0.20, 1.94 for overall moderate adherence; and adjusted difference 1.72, 95% CI 0.84, 2.60 for overall low adherence). In analyses by practice domain, low adherence to housework-related and social activity restrictions was associated with having PPD symptoms compared with high adherence (OR 1.61, 95% CI 1.07, 2.43). Low adherence to traditional Chinese postpartum practices was associated with higher EPDS scores indicating PPD symptoms, especially in the domain of housework-related and social activity restrictions. Psychosocial stress and unsatisfactory practical support related to low adherence to postpartum practices might contribute to PPD. Longitudinal study and clinical assessment would be needed to confirm these findings.
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http://dx.doi.org/10.3389/fpsyt.2021.649972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353075PMC
July 2021

Blood Pressure Visit Intensification in Treatment (BP-Visit) Findings: a Pragmatic Stepped Wedge Cluster Randomized Trial.

J Gen Intern Med 2021 Aug 11. Epub 2021 Aug 11.

Tulane University, New Orleans, LA, USA.

Background: Shortening time between office visits for patients with uncontrolled hypertension represents a potential strategy for improving blood pressure (BP).

Objective: We evaluated the impact of multimodal strategies on time between visits and on improvement in systolic BP (SBP) among patients with uncontrolled hypertension.

Design: We used a stepped-wedge cluster randomized controlled trial with three wedges involving 12 federally qualified health centers with three study periods: pre-intervention, intervention, and post-intervention.

Participants: Adult patients with diagnosed hypertension and two BPs ≥ 140/90 pre-randomization and at least one visit during post-randomization control period (N = 4277).

Intervention: The core intervention included three, clinician hypertension group-based trainings, monthly clinician feedback reports, and monthly meetings with practice champions to facilitate implementation.

Main Measures: The main measures were change in time between visits when BP was not controlled and change in SBP. A secondary planned outcome was changed in BP control among all hypertension patients in the practices.

Key Results: Median follow-up times were 34, 32, and 32 days and the mean SBPs were 142.0, 139.5, and 139.8 mmHg, respectively. In adjusted analyses, the intervention did not improve time to the next visit compared with control periods, HR = 1.01 (95% CI: 0.98, 1.04). SBP was reduced by 1.13 mmHg (95% CI: -2.10, -0.16), but was not maintained during follow-up. Hypertension control (< 140/90) in the practices improved by 5% during intervention (95% CI: 2.6%, 7.3%) and was sustained post-intervention 5.4% (95% CI: 2.6%, 8.2%).

Conclusions: The intervention failed to shorten follow-up time for patients with uncontrolled BP and showed very small, statistically significant improvements in SBP that were not sustained. However, the intervention showed statistically and clinically relevant improvement in hypertension control suggesting that the intervention affected clinician decision-making regarding BP control apart from visit frequency. Future practice initiatives should consider hypertension control as a primary outcome.

Clinical Trial: www.ClinicalTrials.gov Identifier: NCT02164331.
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http://dx.doi.org/10.1007/s11606-021-07016-9DOI Listing
August 2021

CYB561D2 up-regulation activates STAT3 to induce immunosuppression and aggression in gliomas.

J Transl Med 2021 08 9;19(1):338. Epub 2021 Aug 9.

Department of Neurosurgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.

Background: Fine tuned balance of reactive oxygen species (ROS) is essential for tumor cells and tumor cells use immune checkpoints to evade attack form immunity system. However, it's unclear whether there is any crosstalk between these two pathways. CYB561D2, an antioxidant protein, is part of 5-gene prognosis signature in gliomas and its involvement in gliomas is unknown. Here, we aim to provide a detailed characterization of CYB561D2 in gliomas.

Methods: CYB561D2 expression was measured in clinical samples of gilomas and normal tissues. The effects of CYB561D2 on immunity related genes and tumor behaviors were investigated in glioma cell lines with various in vitro and in vivo assays.

Results: CYB561D2 expression was enhanced in gliomas compared to control tissues. CYB561D2 up-regulation was associated with high grading of gliomas and short survival in patients. CYB561D2 expression was induced by HO in glioma cell lines. CYB561D2 and its functional product ascorbate activated STAT3 dose-dependently. CYB561D2 over-expression increased PD-L1, CCL2 and TDO2 expression, and induced immunosuppression in co-cultured T cells. In in vitro assays, CYB561D2 knock-down suppressed cell growth, colony formation, migration and promoted apoptosis. In contrast, CYB561D2 over-expression reduced survival rate in intracranial glioma model and this effect could be blocked by dominant negative-STAT3. The CYB561D2 up-regulation and the positive association of CYB561D2 with PD-L1, CCL2 and TDO2 expression were cross-validated in open-access datasets.

Conclusions: CYB561D2 up-regulation induces immunosuppression and aggression via activating STAT3 in gliomas and CYB561D2 mediates ROS-tumor immunity crosstalk.
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http://dx.doi.org/10.1186/s12967-021-02987-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351164PMC
August 2021

Surface molecularly imprinted polymers fabricated by differential UV-vis spectra and reverse prediction method for the enrichment and determination of sterigmatocystin.

Food Chem 2022 Jan 28;367:130715. Epub 2021 Jul 28.

Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 211198, China; Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing 211198, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 211198, China. Electronic address:

A novel magnetic molecularly imprinted polymers (MMIPs) with a new functional monomer Triallyl isocyanurate was synthesized successfully to enrich and detect sterigmatocystin (STG) in wheat samples. The differential UV-vis spectra and the reverse prediction method were selected to achieve the optimal synthesis conditions of the MMIPs, which were characterized well. The adsorption experiment showed that MMIPs have high selectivity and sensitivity. A magnetic solid phase extraction combined with high performance liquid chromatography (MSPE-HPLC) method based on the MMIPs was successfully established with the optimal extraction condition. The linear range and RSD were 1.8-25 ng·g and 2.6-4.1%, respectively. The recovery of this method was 87.6-96.9% and the limit of detection (LOD) was 0.63 ng·g. The excellent sensitivity and selectivity of this method were confirmed by experiment of the extraction and detection of STG in wheat extracts. This work extends the use of molecular imprinting in mycotoxins applications.
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http://dx.doi.org/10.1016/j.foodchem.2021.130715DOI Listing
January 2022

Integrated mRNA and miRNA transcriptome analysis provides novel insights into the molecular mechanisms underlying goose pituitary development during the embryo-to-hatchling transition.

Poult Sci 2021 Sep 10;100(9):101380. Epub 2021 Jul 10.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China.

It is well established that the endocrine system plays a pivotal role in preparing the avian embryos for the abrupt switch from chorioallantoic to pulmonary respiration during the critical embryo-to-hatchling transition. However, as the master gland of the endocrine system, there has been little research focusing on the molecular mechanisms controlling the development and function of the pituitary gland during the peri-hatch period in birds. In the present study, we aimed to determine the genome-wide mRNA and miRNA transcriptome profiles of the pituitary during the embryo-to-hatchling transition period from embryonic day 22 (E22) to post-hatching day 6 (P6) in the goose (Anser cygnoides). Of note, expression of Anser_cygnoides_newGene_32456 and LOC106031011 were significantly different among these 4 stages (i.e., E22, E26, P2, and P6). Meanwhile, the neuroactive ligand-receptor interaction pathway was significantly enriched by the DEGs commonly identified among three pairwise comparisons. At the miRNA transcriptome level, there were not commonly identified DE miRNAs among these 4 stages, while the 418 of their predicted target genes were mutually shared. Both the target genes of DE miRNAs in each comparison and these 418 shared target genes were significantly enriched in the ECM-receptor interaction and focal adhesion pathways. In the predicted miRNA-mRNA interaction networks of these 2 pathways, novel_miRNA_467, novel_miRNA_154, and novel_miRNA_340 were the hub miRNAs. In addition, multiple DE miRNAs also showed predicted target relationships with the DEGs associated with extracellular matrix (ECM) components. Among them, expression of novel_miR_120, tgu-miR-92-3p, and novel_miR_398 was significantly negatively correlated with that of LAMC3 (laminin subunit gamma3), suggesting that these miRNAs may regulate pituitary tissue remodeling and functional changes through targeting LAMC3 during development. These identified DE mRNAs and miRNAs as well as their predicted interaction networks involved in regulation of tissue remodeling and cellular functions were most likely to play critical roles in facilitating the embryo-to-hatchling transition. These results provide novel insights into the early developmental process of avian pituitary gland and will help better understand the underlying molecular mechanisms.
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http://dx.doi.org/10.1016/j.psj.2021.101380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350522PMC
September 2021

A Fast and Efficient Approach to Obtaining High-Purity Glioma Stem Cell Culture.

Front Genet 2021 6;12:639858. Epub 2021 Jul 6.

Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Glioma is the most common and malignant primary brain tumor. Patients with malignant glioma usually have a poor prognosis due to drug resistance and disease relapse. Cancer stem cells contribute to glioma initiation, progression, resistance, and relapse. Hence, quick identification and efficient understanding of glioma stem cells (GSCs) are of profound importance for therapeutic strategies and outcomes. Ideally, therapeutic approaches will only kill cancer stem cells without harming normal neural stem cells (NSCs) that can inhibit GSCs and are often beneficial. It is key to identify the differences between cancer stem cells and normal NSCs. However, reports detailing an efficient and uniform protocol are scarce, as are comparisons between normal neural and cancer stem cells. Here, we compared different protocols and developed a fast and efficient approach to obtaining high-purity glioma stem cell by tracking observation and optimizing culture conditions. We examined the proliferative and differentiative properties confirming the identities of the GSCs with relevant markers such as Ki67, SRY-box containing gene 2, an intermediate filament protein member nestin, glial fibrillary acidic protein, and s100 calcium-binding protein (s100-beta). Finally, we identified distinct expression differences between GSCs and normal NSCs including cyclin-dependent kinase 4 and tumor protein p53. This study comprehensively describes the features of GSCs, their properties, and regulatory genes with expression differences between them and normal stem cells. Effective approaches to quickly obtaining high-quality GSCs from patients should have the potential to not only help understand the diseases and the resistances but also enable target drug screening and personalized medicine for brain tumor treatment.
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http://dx.doi.org/10.3389/fgene.2021.639858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291338PMC
July 2021

Novel role for caspase recruitment domain family member 14 and its genetic variant rs11652075 in skin filaggrin homeostasis.

J Allergy Clin Immunol 2021 Jul 13. Epub 2021 Jul 13.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address:

Background: Low epidermal filaggrin (FLG) is a risk factor for atopic dermatitis (AD) and allergic comorbidity. FLG mutations do not fully explain the variation in epidermal FLG levels, highlighting that other genetic loci may also regulate FLG expression.

Objective: We sought to identify genetic loci that regulate FLG expression and elucidate their functional and mechanistic consequences.

Methods: A genome-wide association study of quantified skin FLG expression in lesional and baseline non(never)-lesional skin of children with AD in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort was conducted. Clustered regularly interspaced short palindromic repeat approaches were used to create isogenic human keratinocytes differing only at the identified variant rs11652075, and caspase recruitment domain family member 14 (CARD14)-deficient keratinocytes for subsequent mechanistic studies.

Results: The genome-wide association study identified the CARD14 rs11652075 variant to be associated with FLG expression in non(never)-lesional skin of children with AD. Rs11652075 is a CARD14 expression quantitative trait locus in human skin and primary human keratinocytes. The T variant destroys a functional cytosine-phosphate-guanine site, resulting in reduced cytosine-phosphate-guanine methylation at this site (but not neighboring sites) in TT and CT compared with CC primary human keratinocytes and Mechanisms of Progression of Atopic Dermatitis to Asthma in Children children's skin samples, and rs11652075 increases CARD14 expression in an allele-specific fashion. Furthermore, studies in clustered regularly interspaced short palindromic repeat-generated CC and TT isogenic keratinocytes, as well as CARD14-haplosufficient and deficient keratinocytes, reveal that IL-17A regulates FLG expression via CARD14, and that the underlying mechanisms are dependent on the rs11652075 genotype.

Conclusions: Our study identifies CARD14 as a novel regulator of FLG expression in the skin of children with AD. Furthermore, CARD14 regulates skin FLG homeostasis in an rs11652075-dependent fashion.
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http://dx.doi.org/10.1016/j.jaci.2021.07.003DOI Listing
July 2021

Integrative analysis of histomorphology, transcriptome and whole genome resequencing identified DIO2 gene as a crucial gene for the protuberant knob located on forehead in geese.

BMC Genomics 2021 Jun 30;22(1):487. Epub 2021 Jun 30.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, 611130, Chengdu, China.

Background: During domestication, remarkable changes in behavior, morphology, physiology and production performance have taken place in farm animals. As one of the most economically important poultry, goose owns a unique appearance characteristic called knob, which is located at the base of the upper bill. However, neither the histomorphology nor the genetic mechanism of the knob phenotype has been revealed in geese.

Results: In the present study, integrated radiographic, histological, transcriptomic and genomic analyses revealed the histomorphological characteristics and genetic mechanism of goose knob. The knob skin was developed, and radiographic results demonstrated that the knob bone was obviously protuberant and pneumatized. Histologically, there were major differences in structures in both the knob skin and bone between geese owing knob (namely knob-geese) and those devoid of knob (namely non-knob geese). Through transcriptome analysis, 592 and 952 genes differentially expressed in knob skin and bone, and significantly enriched in PPAR and Calcium pathways in knob skin and bone, respectively, which revealed the molecular mechanisms of histomorphological differences of the knob between knob- and non-knob geese. Furthermore, integrated transcriptomic and genomic analysis contributed to the identification of 17 and 21 candidate genes associated with the knob formation in the skin and bone, respectively. Of them, DIO2 gene could play a pivotal role in determining the knob phenotype in geese. Because a non-synonymous mutation (c.642,923 G > A, P265L) changed DIO2 protein secondary structure in knob geese, and Sanger sequencing further showed that the AA genotype was identified in the population of knob geese, and was prevalent in a crossing population which was artificially selected for 10 generations.

Conclusions: This study was the first to uncover the knob histomorphological characteristics and genetic mechanism in geese, and DIO2 was identified as the crucial gene associated with the knob phenotype. These data not only expand and enrich our knowledge on the molecular mechanisms underlying the formation of head appendages in both mammalian and avian species, but also have important theoretical and practical significance for goose breeding.
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http://dx.doi.org/10.1186/s12864-021-07822-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244220PMC
June 2021

Nanoscopic Imaging of Nucleolar Stress Enabled by Protein-Mimicking Carbon Dots.

Nano Lett 2021 07 28;21(13):5689-5696. Epub 2021 Jun 28.

State Key Laboratory of Heavy Oil Processing and College of Chemical Engineering, China University of Petroleum (East China), Qingdao 266580, China.

The nucleolus is a central hub for coordinating cellular stress responses during cancer development and treatment. Accurate identification of nucleolar stress response is crucially desired for nucleolus-based diagnostics and therapeutics but technically challenging due to the need to address the ultrastructural analysis. Here, we report a protein-like CD with the integration of fluorescent blinking domains and RNA-binding motifs, which offers the ability to perform enhanced super-resolution imaging of the nucleolar ultrastructure. This image allows extraction of multidimensional information from the nucleolus for accurate distinguishment of different cells from the same cell types. Furthermore, we demonstrate for the first time this CD-depicted nucleolar ultrastructure as a sensitive hallmark to identify and discriminate subtle responses to various stressors as well as to afford RNA-related information that has been inaccessible by conventional immunofluorescence methods. This protein-mimicking CD could become a broadly useful probe for nucleolar stress studies in cell diagnostics and therapeutics.
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http://dx.doi.org/10.1021/acs.nanolett.1c01420DOI Listing
July 2021

The lncRNA HOTAIR regulates autophagy and affects lipopolysaccharide-induced acute lung injury through the miR-17-5p/ATG2/ATG7/ATG16 axis.

J Cell Mol Med 2021 Aug 27;25(16):8062-8073. Epub 2021 Jun 27.

Department of Pulmonary and Critical Care Medicine, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.

Long non-coding ribonucleic acids (lncRNAs) play critical roles in acute lung injury (ALI). We aimed to explore the involvement of lncRNA HOX transcript antisense intergenic ribonucleic acid (HOTAIR) in regulating autophagy in lipopolysaccharide (LPS)-induced ALI. We obtained 1289 differentially expressed lncRNAs or messenger RNAs (mRNAs) via microarray analysis. HOTAIR was significantly upregulated in the LPS stimulation experimental group. HOTAIR knockdown (si-HOTAIR) promoted cell proliferation in LPS-stimulated A549 and BEAS-2B cells, suppressing the protein expression of autophagy marker light chain 3B and Beclin-1. Inhibition of HOTAIR suppressed LPS-induced cell autophagy, apoptosis and arrested cells in the G0/G1 phase prior to S phase entry. Further, si-HOTAIR alleviated LPS-induced lung injury in vivo. We predicted the micro-ribonucleic acid miR-17-5p to target HOTAIR and confirmed this via RNA pull-down and dual luciferase reporter assays. miR-17-5p inhibitor treatment reversed the HOTAIR-mediated effects on autophagy, apoptosis, cell proliferation and cell cycle. Finally, we predicted autophagy-related genes (ATGs) ATG2, ATG7 and ATG16 as targets of miR-17-5p, which reversed their HOTAIR-mediated protein upregulation in LPS-stimulated A549 and BEAS-2B cells. Taken together, our results indicate that HOTAIR regulated apoptosis, the cell cycle, proliferation and autophagy through the miR-17-5p/ATG2/ATG7/ATG16 axis, thus driving LPS-induced ALI.
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http://dx.doi.org/10.1111/jcmm.16737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358883PMC
August 2021

Ultrasensitive Detection of Exosome Using Biofunctionalized Gold Nanorods on a Silver-Island Film.

Nano Lett 2021 07 17;21(13):5532-5539. Epub 2021 Jun 17.

College of Life Science and Oceanography, Shenzhen University, Shenzhen 518060, Guangdong, China.

Exosomes are often a promising source of biomarkers for cancer diagnosis in the early stages. Therefore, it is important to develop a sensitive and low-cost detection method. Here, we introduce a new substrate using gold nanorods (GNRs) on a silver-island film that produces a 360-fold AF647 molecule fluorescence enhancement compared to glass. The amplified fluorescence was proven theoretically by using finite difference time-domain simulation (FDTD). Utilizing the enhanced fluorescence from the substrate, GNRs attached with the biomolecules and created a sandwich immunoassay that can significantly detect human CD63 antigen on the exosome. By applying the method, the detection limit of mouse IgG goes down to 0.3 ng/mL, which is considerably better than the existing methods. Moreover, the sensitivity and accuracy for clinical plasma from six patients confirm its diagnostic feasibility. The proposed substrate can be uniformly extended to the identification of other biomarkers by modifying the antibodies on the surfaces of the GNRs.
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http://dx.doi.org/10.1021/acs.nanolett.1c00830DOI Listing
July 2021

Deep-Learning-Assisted Single-Molecule Tracking on a Live Cell Membrane.

Anal Chem 2021 Jun 16. Epub 2021 Jun 16.

State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao 266580, China.

Single-molecule fluorescence imaging is a powerful tool to study protein function by tracking molecular position and distribution, but the precise and rapid identification of dynamic molecules remains challenging due to the heterogeneous distribution and interaction of proteins on the live cell membrane. We now develop a deep-learning (DL)-assisted single-molecule imaging method that can precisely distinguish the monomer and complex for rapid and real-time tracking of protein interaction. This DL-based model, which comprises convolutional layers, max pooling layers, and fully connected layers, is trained to reach an accuracy of >98% for identifying monomer and complex. We use this method to investigate the dynamic process of chemokine receptor CXCR4 on the live cell membrane during the early signaling stage. The results show that, upon ligand activation, the CXCR4 undergoes a dynamic process of forming a receptor complex. We further demonstrate that the CXCR4 complex tends to be internalized at 2.5-fold higher rate into the cell interior than the monomer via the clathrin-dependent pathway. This study is the first example to scrutinize the early signaling process of CXCR4 at the single-molecule level on the live cell membrane. We envision that this DL-assisted imaging method would be a broadly useful technique to study more protein families for elucidating their physiological and pathological functions.
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http://dx.doi.org/10.1021/acs.analchem.1c00547DOI Listing
June 2021

Visual Recognition and Detection of Clindamycin by [email protected] Core-Shell Nanoparticles.

ACS Omega 2021 Jun 26;6(22):14260-14267. Epub 2021 May 26.

Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

The work described a new colorimetric sensor for the quantitative detection of clindamycin based on [email protected] core-shell nanoparticles ([email protected] NPs). The obtained [email protected] NPs were characterized by transmission electron microscopy (TEM) and ultraviolet and visible spectrophotometry (UV-vis). When [email protected] NPs were added to a clindamycin solution, it can be observed that the color immediately changed from bright yellow to gray-blue and the absorption spectrum also changed, realizing the visual detection of clindamycin. Under optimal conditions, the absorption ratio ( / ) of the UV-vis spectra increased linearly with the concentration of clindamycin ranging from 6.25 × 10 to 7.50 × 10 mol/L ( = 0.9945), with a limit of detection (LOD) of 2.00 × 10 mol/L and good recovery of 100.0-102.0% (relative standard deviation (RSD) < 2%). The detection process was convenient without complicated instruments. Compared with other analytes, the [email protected] NPs detection system has good selectivity for clindamycin. In addition, the [email protected] NPs colorimetric sensor was successfully used to determine clindamycin in human urine samples. This study provides a simple, rapid, intuitive, and low-cost visualization analysis method of clindamycin, which was helpful for the visualization detection of other targets.
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http://dx.doi.org/10.1021/acsomega.1c01028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190807PMC
June 2021

Decreased Low-Density Lipoprotein Cholesterol Level Indicates Poor Prognosis of Severe and Critical COVID-19 Patients: A Retrospective, Single-Center Study.

Front Med (Lausanne) 2021 26;8:585851. Epub 2021 May 26.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Coronavirus disease 2019 (COVID-19) has become a global public health crisis. Reduced low-density lipoprotein cholesterol (LDL-C) levels were observed in COVID-19 patients. The present study aimed to explore the relationship between LDL-C levels and the prognosis of severe and critical COVID-19 patients. A total of 211 severe and critical COVID-19 patients were enrolled and divided into four groups according to the LDL-C levels, including 53 patients in Group A (LDL-C ≥ 2.71 mmol/L), 53 patients in Group B (2.28 ≤ LDL-C < 2.71 mmol/L), 53 patients in Group C (1.83 ≤ LDL-C < 2.28 mmol/L) and 52 patients in Group D (LDL-C < 1.83 mmol/L). LDL-C levels were lower in critically ill patients than in severe patients. The main symptoms before admission, characteristics on admission and comorbidities of enrolled patients did not differ among the four groups. Compared with patients with high LDL-C levels, patients with low LDL-C levels were more likely to have immune and inflammation dysfunction, renal dysfunction, liver dysfunction and cardiac dysfunction on admission. The proportions of patients with shock and acute cardiac injury, of those admitted to intensive care unit (ICU) and of those treated with mechanical ventilation were inversely related to LDL-C level. The mortality of COVID-19 patients increased with LDL-C reduction. Serum LDL-C levels of COVID-19 patients was negatively correlated with CRP level, but positively correlated with lymphocyte count, as shown by Pearson correlation analysis. Proportional hazard models showed that low LDL-C levels were associated with increased risk of hospitalization death, cardiac injury and admission to the ICU. Taken together, these results suggest that decreased LDL-C levels indicate poor prognosis of severe and critical COVID-19 patients.
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http://dx.doi.org/10.3389/fmed.2021.585851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187559PMC
May 2021

Nanoparticle Delivery of STAT3 Alleviates Pulmonary Hypertension in a Mouse Model of Alveolar Capillary Dysplasia.

Circulation 2021 Aug 11;144(7):539-555. Epub 2021 Jun 11.

Center for Lung Regenerative Medicine, Perinatal Institute (F.S., G.W., A.P., K.X., J.G.-A., Y.Z., G.T.K., Z.D., A.W.D., V.V.K.), Cincinnati Children's Hospital Medical Center, OH.

Background: Pulmonary hypertension (PH) is a common complication in patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a severe congenital disorder associated with mutations in the gene. Although the loss of alveolar microvasculature causes PH in patients with ACDMPV, it is unknown whether increasing neonatal lung angiogenesis could prevent PH and right ventricular (RV) hypertrophy.

Methods: We used echocardiography, RV catheterization, immunostaining, and biochemical methods to examine lung and heart remodeling and RV output in mice carrying the mutation (identified in patients with ACDMPV). The ability of mutant embryonic stem cells to differentiate into respiratory cell lineages in vivo was examined using blastocyst complementation. Intravascular delivery of nanoparticles with a nonintegrating expression vector was used to improve neonatal pulmonary angiogenesis in mice and determine its effects on PH and RV hypertrophy.

Results: mice developed PH and RV hypertrophy after birth. The severity of PH in mice directly correlated with mortality, low body weight, pulmonary artery muscularization, and increased collagen deposition in the lung tissue. Increased fibrotic remodeling was found in human ACDMPV lungs. Mouse embryonic stem cells carrying the mutation were used to produce chimeras through blastocyst complementation and to demonstrate that embryonic stem cells have a propensity to differentiate into pulmonary myofibroblasts. Intravascular delivery of nanoparticles carrying cDNA protected mice from RV hypertrophy and PH, improved survival, and decreased fibrotic lung remodeling.

Conclusions: Nanoparticle therapies increasing neonatal pulmonary angiogenesis may be considered to prevent PH in ACDMPV.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.053980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373823PMC
August 2021

TSLP disease-associated genetic variants combined with airway TSLP expression influence asthma risk.

J Allergy Clin Immunol 2021 Jun 7. Epub 2021 Jun 7.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address:

Background: Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine important in initiation of allergic inflammation. Single nucleotide polymorphisms (SNPs) in TSLP are associated with asthma, yet studies have shown inconsistent associations between circulating TSLP and asthma. Studies that integrate the combined effects of TSLP genotype, TSLP mRNA, circulating TSLP levels, and asthma outcome are lacking.

Objectives: This study sought to recruit a novel cohort based on asthma-relevant TSLP SNPs and determine their impact on TSLP mRNA expression and TSLP circulating protein levels, and their individual and combined effects on asthma.

Methods: This study developed an algorithm to prioritize TSLP SNPs and recruited 51 carriers and noncarriers based on TSLP genotypes. TSLP mRNA was quantified in nasal epithelial cells and circulating TSLP levels in plasma. This study determined the associations of defined TSLP risk genotypes and/or TSLP mRNA and protein levels with asthma.

Results: TSLP mRNA expression, but not circulating TSLP, was significantly increased in people who are asthmatic compared with in people who are nonasthmatic (P = .007; odds ratio, 1.44). Notably, 90% of children with the defined TSLP risk genotypes and high nasal TSLP mRNA expression (top tertile) had asthma compared with 40% of subjects without risk genotypes and with low TSLP expression (bottom tertile) (P = .024). No association between circulating TSLP and asthma was observed.

Conclusions: Collectively, these data suggest childhood asthma is modified by the combined effects of TSLP genotype and TSLP expression in the nasal epithelium. The increased asthma risk likely manifests when genetic variation enables expression quantitative trait loci in the TSLP locus to elevate TSLP. It is important to consider both biomarkers when factoring asthma risk.
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http://dx.doi.org/10.1016/j.jaci.2021.05.033DOI Listing
June 2021

Oestrogen promotes lipids transportation through oestrogen receptor α in hepatic steatosis of geese in vitro.

J Anim Physiol Anim Nutr (Berl) 2021 Jun 10. Epub 2021 Jun 10.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, China.

Evidence has shown that oestrogen suppresses lipids deposition in the liver of mammals. However, the molecular mechanism of oestrogen action in hepatic steatosis of geese liver has yet to be determined. This study aimed to investigate the effect of oestrogen on lipid homeostasis at different states of geese hepatocytes in vitro. The results showed that an in vitro model of hepatic steatosis was induced by 1.5 mM sodium oleate via detecting the viability of hepatocytes and content of lipids. When the normal hepatocytes were administrated with different concentrations of oestrogen (E ), the expression levels of diacylglycerol acyltransferase 2 (DGAT2), microsomal triglyceride transfer protein (MTTP) and oestrogen receptors (ERs, alpha and beta) were up-regulated only at high concentrations of E , whereas the lipid content was not a significant difference. In goose hepatocytes of hepatic steatosis, however, the expression levels of MTTP, apolipoprotein B (apoB) and ERα/β significantly increased at 10 or 10  M E . Meanwhile, the lipids content significantly increased at 10 and 10  M E and decreased at 80 µM E . Further heatmap analysis showed that ERα was clustered with apoB and MTTP in either normal hepatocytes or that of hepatic steatosis. Taken together, E  might bind to ERα to up-regulate the expression levels of apoB and MTTP, promoting the transportation of lipids and alleviating lipids overload in hepatic steatosis of geese in vitro.
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http://dx.doi.org/10.1111/jpn.13590DOI Listing
June 2021

A new approach for investigating the relative contribution of basal glucose and postprandial glucose to HbA1.

Nutr Diabetes 2021 06 4;11(1):14. Epub 2021 Jun 4.

Innovation Center for Wound Repair, Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China.

To develop an accurate method for evaluating the relative contributions of basal glucose (BG) and postprandial glucose (PPG) to glycated haemoglobin (HbA1c) in subjects with hyperglycaemia using a Continuous Glucose Monitoring System (CGMS®). The subjects were divided into the normal glucose tolerance (NGT), impaired glucose tolerance (IGT), newly-diagnosed type 2 diabetes (NDDM), and drug-treated type 2 diabetes (T2DM) groups. We evaluated the relative contributions of BG and PPG to HbA1c in patients with hyperglycaemia according to three different baseline values. Subjects (n = 490) were grouped as follows: 92 NGT, 36 IGT, 131 NDDM, and 231 T2DM. The relative contributions of PPG to HbA1c were calculated using baseline values of 6.1 mmol/L, 5.6 mmol/L, and the 24-h glucose curve of the NGT group. The relative contribution of PPG to HbA1c decreased progressively from the IGT group to the T2DM group. Compared with the 24-h glucose curve as the baseline, the relative contribution of PPG was overestimated in 9.04% and 1.76% of the subjects when 6.1 mmol/L and 5.6 mmol/L were used as baselines, respectively (P < 0.01), in T2DM patients. The 24-h glucose curve of NGT is more suitable for studying the relative contributions of BG and PPG to HbA1c and it is more precise, as it considers physiological fluctuations in NGT after meals. However, 5.6 mmol/L can be used when the 24-h glucose curve for NGT is unavailable; using 6.1 mmol/L as a baseline value may overestimate the contribution to the HbA1c. There is no unified standard for assessing the contributions of basal glucose (BG) and postprandial glucose (PPG) to HbA1c. The 24-h glucose curve of NGT is more suitable for studying the relative contributions of BG and PPG to HbA1c, as it considers physiological fluctuations in NGT after meals. However, 5.6 mmol/L can be used when the 24-h glucose curve for NGT is unavailable; using 6.1 mmol/L as a baseline value may overestimate the contribution to the HbA1c.
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http://dx.doi.org/10.1038/s41387-021-00156-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178390PMC
June 2021

The Combination of Cell Cultured Technology and In Silico Model to Inform the Drug Development.

Pharmaceutics 2021 May 12;13(5). Epub 2021 May 12.

Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.

Human-derived in vitro models can provide high-throughput efficacy and toxicity data without a species gap in drug development. Challenges are still encountered regarding the full utilisation of massive data in clinical settings. The lack of translated methods hinders the reliable prediction of clinical outcomes. Therefore, in this study, in silico models were proposed to tackle these obstacles from in vitro to in vivo translation, and the current major cell culture methods were introduced, such as human-induced pluripotent stem cells (hiPSCs), 3D cells, organoids, and microphysiological systems (MPS). Furthermore, the role and applications of several in silico models were summarised, including the physiologically based pharmacokinetic model (PBPK), pharmacokinetic/pharmacodynamic model (PK/PD), quantitative systems pharmacology model (QSP), and virtual clinical trials. These credible translation cases will provide templates for subsequent in vitro to in vivo translation. We believe that synergising high-quality in vitro data with existing models can better guide drug development and clinical use.
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http://dx.doi.org/10.3390/pharmaceutics13050704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151315PMC
May 2021

Nanozyme based on graphene oxide modified with FeO, CuO, and cucurbit[6]uril for colorimetric determination of homocysteine.

Mikrochim Acta 2021 05 28;188(6):207. Epub 2021 May 28.

Department of Analytical Chemistry, China Pharmaceutical University, Nanjing, 211100, China.

A nanozyme based on graphene oxide modified with FeO NPs, CuO NPs, and cucurbit[6]uril has been successfully fabricated by a simple sonochemical technique. By employing CB[6] as a specific binding pocket and [email protected] as a peroxidase mimic, this novel nanozyme (BN I) is equipped with molecular recognition ability and enhanced peroxidase-like activity. On the basis of the inhibition effect of homocysteine (Hcy) towards the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) catalyzed by BN I, a simple colorimetric method is established for the sensitive and selective determination of Hcy. This proposed method displays a good linear response in the range 5-200 μM with a detection limit of 1.8 μM. In the practical assay of human plasma samples, the relative standard deviations (RSD) are lower than 11% and the recoveries are between 98.0 and 104.9%. In the assay of human urine samples, the RSD are below 9.0% and the recoveries range from 94.0 to 103.5%. The colorimetric method presented offers a convenient and accurate way for the determination of biomarkers in point-of-care testing (POCT).
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http://dx.doi.org/10.1007/s00604-021-04868-0DOI Listing
May 2021

Lipidomics profiling of goose granulosa cell model of stearoyl-CoA desaturase function identifies a pattern of lipid droplets associated with follicle development.

Cell Biosci 2021 May 22;11(1):95. Epub 2021 May 22.

Country Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, People's Republic of China.

Background: Despite their important functions and nearly ubiquitous presence in cells, an understanding of the biology of intracellular lipid droplets (LDs) in goose follicle development remains limited. An integrated study of lipidomic and transcriptomic analyses was performed in a cellular model of stearoyl-CoA desaturase (SCD) function, to determine the effects of intracellular LDs on follicle development in geese.

Results: Numerous internalized LDs, which were generally spherical in shape, were dispersed throughout the cytoplasm of granulosa cells (GCs), as determined using confocal microscopy analysis, with altered SCD expression affecting LD content. GC lipidomic profiling showed that the majority of the differentially abundant lipid classes were glycerophospholipids, including PA, PC, PE, PG, PI, and PS, and glycerolipids, including DG and TG, which enriched glycerophospholipid, sphingolipid, and glycerolipid metabolisms. Furthermore, transcriptomics identified differentially expressed genes (DEGs), some of which were assigned to lipid-related Gene Ontology slim terms. More DEGs were assigned in the SCD-knockdown group than in the SCD-overexpression group. Integration of the significant differentially expressed genes and lipids based on pathway enrichment analysis identified potentially targetable pathways related to glycerolipid/glycerophospholipid metabolism.

Conclusions: This study demonstrated the importance of lipids in understanding follicle development, thus providing a potential foundation to decipher the underlying mechanisms of lipid-mediated follicle development.
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http://dx.doi.org/10.1186/s13578-021-00604-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141238PMC
May 2021
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