Publications by authors named "Jianping Hu"

175 Publications

Progression of myopia in a natural cohort of Chinese children during COVID-19 pandemic.

Graefes Arch Clin Exp Ophthalmol 2021 Jul 21. Epub 2021 Jul 21.

Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, NO.1 Dongjiaominxiang Street, Dongcheng District, Beijing, 100730, China.

Purpose: To determine myopia progression in children during the COVID-19 and the related factors associated with myopia.

Methods: All subjects underwent three-timepoint ocular examinations that were measured in July 2019, January, and August 2020. We compared the changes in uncorrected visual acuity (UCVA), mydriatic spherical equivalent (SE), and axial length (AL) between two periods (before and during COVID-19). A questionnaire was performed to investigate risk factors for myopia.

Results: Compared with before the COVID-19, the mean (S.D.) myopia progression during the COVID-19 was significantly higher in right eyes (- 0.93 (0.65) vs. - 0.33 (0.47) D; p < 0.001). However, the differences in UCVA changes and the axial elongation between two periods were clinically insignificant. Through logistic regressive analysis, we found the difference of the SE changes was associated with the baseline AL (P = 0.028; 95% confidence interval [CI], 1.058, 2.632), online education (P = 0.02; 95% CI, 1.587, 8.665), and time of digital screen (p < 0.005; 95% CI, 1.587, 4.450).

Conclusions: Children were at higher risk of myopia progression during COVID-19, which was associated with the baseline AL, the longtime online learning, and digital screen reading.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00417-021-05305-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294263PMC
July 2021

Ptercresions A-C: a new terpene glycoside and two sesquiterpenes with hepatoprotective activity from L.

Nat Prod Res 2021 Jun 29:1-7. Epub 2021 Jun 29.

Hepatobiliary pancreatic splenic surgery, Ya'an people's Hospital, Ya'an, Sichuan, P. R. China.

Three new terpenes were isolated from L., namely Ptercresions A (), B () and C (), together with three known sesquiterpenes and one terpene glycoside, respectively, identified as (2 , 3 )-pterosin C (), (2 ,3 )-pterosin C (), pterosin D (), creosideI(). The structures of isolates were determined by HR-ESI-MS, ECD, NMR and acid hydrolysate analysis. The hepatoprotective activities of compounds - were studied against Paracetamol-induced L-02 hepatocyte injury. The results revealed that compounds showed certain anti-hepatocyte injury activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14786419.2021.1941949DOI Listing
June 2021

Systemic Bioinformatic Analyses of Nuclear-Encoded Mitochondrial Genes in Hypertrophic Cardiomyopathy.

Front Genet 2021 12;12:670787. Epub 2021 May 12.

Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease and mitochondria plays a key role in the progression in HCM. Here, we analyzed the expression pattern of nuclear-encoded mitochondrial genes (NMGenes) in HCM and found that the expression of NMGenes was significantly changed. A total of 316 differentially expressed NMGenes (DE-NMGenes) were identified. Pathway enrichment analyses showed that energy metabolism-related pathways such as "pyruvate metabolism" and "fatty acid degradation" were dysregulated, which highlighted the importance of energy metabolism in HCM. Next, we constructed a protein-protein interaction network based on 316 DE-NMGenes and identified thirteen hubs. Then, a total of 17 TFs (transcription factors) were predicted to potentially regulate the expression of 316 DE-NMGenes according to iRegulon, among which 8 TFs were already found involved in pathological hypertrophy. The remaining TFs (like GATA1, GATA5, and NFYA) were good candidates for further experimental verification. Finally, a mouse model of transverse aortic constriction (TAC) was established to validate the genes and results showed that DDIT4, TKT, CLIC1, DDOST, and SNCA were all upregulated in TAC mice. The present study represents the first effort to evaluate the global expression pattern of NMGenes in HCM and provides innovative insight into the molecular mechanism of HCM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2021.670787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150003PMC
May 2021

Specifically targeting Mtb cell-wall and TMM transporter: the development of MmpL3 inhibitors.

Curr Protein Pept Sci 2021 Apr 20. Epub 2021 Apr 20.

Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, School of Pharmacy, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610106, China.

Tuberculosis (TB) remains a serious threat to whole human health. In particular, the drug resistance of Mycobacterium tuberculosis (Mtb) has become a huge challenge in clinical medicine, and it is extremely urgent to develop effective inhibitors with novel structures and mechanisms. Belonging to the Resistance, Nodulation and Division (RND) superfamily, Mycobacterial membrane proteins Large 3 (MmpL3) is mainly responsible for transporting mycolic acid outside cell membrane to form cell wall, and plays critical roles in iron acquisition which is vital to the survival of Mtb. As a potential Mtb target in recent years, its inhibitor research has attracted wide attention. A series of inhibitors (such as SQ109, AU1235, BM212, etc.) through experimental screening have been reported in succession, especially SQ109 has entered the clinical stage. In this paper, the structural biology information of target MmpL3 was summarized, and the structure-activity relationship (SAR) of inhibitors reported in recent years and their inhibitory mechanism both were reviewed, aiming to provide help for the rational design of MmpL3 inhibitors in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389203722666210421105733DOI Listing
April 2021

Classification and Design of HIV-1 Integrase Inhibitors Based on Machine Learning.

Comput Math Methods Med 2021 1;2021:5559338. Epub 2021 Apr 1.

Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, School of Pharmacy, Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610106, China.

A key enzyme in human immunodeficiency virus type 1 (HIV-1) life cycle, integrase (IN) aids the integration of viral DNA into the host DNA, which has become an ideal target for the development of anti-HIV drugs. A total of 1785 potential HIV-1 IN inhibitors were collected from the databases of ChEMBL, Binding Database, DrugBank, and PubMed, as well as from 40 references. The database was divided into the training set and test set by random sampling. By exploring the correlation between molecular descriptors and inhibitory activity, it is found that the classification and specific activity data of inhibitors can be more accurately predicted by the combination of molecular descriptors and molecular fingerprints. The calculation of molecular fingerprint descriptor provides the additional substructure information to improve the prediction ability. Based on the training set, two machine learning methods, the recursive partition (RP) and naive Bayes (NB) models, were used to build the classifiers of HIV-1 IN inhibitors. Through the test set verification, the RP technique accurately predicted 82.5% inhibitors and 86.3% noninhibitors. The NB model predicted 88.3% inhibitors and 87.2% noninhibitors with correlation coefficient of 85.2%. The results show that the prediction performance of NB model is slightly better than that of RP, and the key molecular segments are also obtained. Additionally, CoMFA and CoMSIA models with good activity prediction ability both were constructed by exploring the structure-activity relationship, which is helpful for the design and optimization of HIV-1 IN inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5559338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035010PMC
April 2021

Financial Self-Efficacy and General Life Satisfaction: The Sequential Mediating Role of High Standards Tendency and Investment Satisfaction.

Front Psychol 2021 17;12:545508. Epub 2021 Mar 17.

School of Psychology, South China Normal University, Guangzhou, China.

Important strides have been made toward understanding the relationship between self-efficacy and life satisfaction. However, existing studies have largely focused on work and academic domains, leaving self-efficacy in the finance domain less frequently investigated. The present study applied the self-efficacy construct to the finance domain, namely "financial self-efficacy" (FSE), and tested the sequential mediating roles of high standards tendency and investment satisfaction in the relationship between FSE and general life satisfaction. A total of 323 employees from finance-related businesses completed anonymous questionnaires regarding FSE, high standards tendency, investment satisfaction, and general life satisfaction. Results indicated that FSE influenced general life satisfaction through investment satisfaction, and sequentially through high standards tendency and investment satisfaction. These results provide contributions to the current literature on life satisfaction, and positive psychology literature by shedding light on the roles of high standards tendency and investment satisfaction in the relation between FSE and general life satisfaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyg.2021.545508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009975PMC
March 2021

Molecular basis for substrate recognition by the bacterial nucleoside transporter NupG.

J Biol Chem 2021 Jan-Jun;296:100479. Epub 2021 Feb 26.

Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, Department of Obstetrics, West China Second Hospital, Sichuan University, Chengdu, China. Electronic address:

Nucleoside homeostasis, which is mediated by transporters and channels, is essential for all life on Earth. In Escherichia coli, NupG mediates the transport of nucleosides and was deemed to be the prototype of the nucleoside proton symporter (NHS) family and the major facilitator superfamily. To date, the substrate recognition and transport mechanisms of NHS transporters are still elusive. Here, we report two crystal structures of NupG (WT and D323A NupG) resolved at 3.0 Å. Both structures reveal an identical inward-open conformation. Together with molecular docking and molecular dynamics simulations and in vitro uridine-binding assays, we found that the uridine binding site, which locates in the central cavity between N and C domains of NupG, is constituted by R136, T140, F143, Q225, N228, Q261, E264, Y318, and F322. Moreover, we found that D323 is very important for substrate binding via in vitro uridine-binding assays using D323 mutations, although it does not have a direct contact with uridine. Our structural and biochemical data therefore provide an important framework for the mechanistic understanding of nucleoside transporters of the NHS family.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbc.2021.100479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042404PMC
February 2021

Combination of MAPK inhibition with photothermal therapy synergistically augments the anti-tumor efficacy of immune checkpoint blockade.

J Control Release 2021 04 22;332:194-209. Epub 2021 Feb 22.

Laboratory of Tumor Targeted and Immune Therapy, Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041 Chengdu, Sichuan, China. Electronic address:

The combination of MAPK-targeted therapy and immune checkpoint blockade is one of the most promising regimens for patients with advanced melanoma. However, the synergistic efficacy of the combo regimen is still controversial in clinical trials. Here, we report that MAPK inhibition induced T-cell suppression within tumor microenvironment is mediated by attenuation of HSP27/HSP70 and deficiency of neoantigen presentation. To address this problem, we designed a photothermal-responsive on-demand controlled drug release gold nano-system to carry BRAF inhibitor. The nano-system can be specifically delivered into tumor cells rather than T-cells, and effectively transformed the optical energy into heat energy upon laser irradiation. Combination of photothermal and targeted therapy significantly promoted immunogenic cell death and T-cell infiltration. On top of this regimen, systematically administration of PD-1 antibody not only suppressed local-treated tumor but also inhibited abscopal tumor by enhancing generalized immune-related antitumor response. More importantly, the triple-combo regimen could efficiently convert immune "cold" tumors into "hot" ones. In conclusion, our research proves the advantage of photothermal-targeted-immune triple combinatorial regimen in treating tumors which are clinical unresectable multifocal and lack of T-cell infiltration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jconrel.2021.02.020DOI Listing
April 2021

A20 Inhibits Intraocular Inflammation in Mice by Regulating the Function of CD4+T Cells and RPE Cells.

Front Immunol 2020 4;11:603939. Epub 2021 Feb 4.

The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China.

A20 is a negative regulator of inflammation and immunity and plays a role in several autoimmune and inflammatory diseases. Here, we demonstrate that A20 overexpression significantly ameliorates severity of EAU by inhibiting the infiltration of Th1 and Th17 cells, and by protecting integrity of the blood retinal barrier. studies showed that A20 silencing could promote CD4+T cells toward a Th1 and Th17 phenotype. A decreased expression of A20 in CD4+T cells was noticed in active BD patients but not in VKH patients. Furthermore, silencing of A20 in hRPE cells induced the production of IL-6, IL-8, and MCP-1 and downregulated ZO-1 and occludin expression which is mediated by inhibition of MAPK and NF-κB pathways. This study reveals a mechanism by which A20 prevents autoimmune uveitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.603939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890008PMC
June 2021

Novel bivalent BET inhibitor N2817 exhibits potent anticancer activity and inhibits TAF1.

Biochem Pharmacol 2021 03 1;185:114435. Epub 2021 Feb 1.

Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China; University of Chinese Academy of Sciences, NO.19A Yuquan Road, Beijing 100049, China. Electronic address:

Bromodomain and extra-terminal domain (BET) family proteins are promising anticancer targets. Most BET inhibitors in clinical trials are monovalent. They competitively bind to one of the bromodomains (BD1 and BD2) in BET proteins and exhibit relatively weak anticancer activity, poor pharmacokinetics, and low metabolic stability. Here, we evaluated the anticancer activity of a novel bivalent BET inhibitor, N2817, which consists of two molecules of the monovalent BET inhibitor 8124-053 connected by a common piperazine ring, rendering a long linker unnecessary. Compared with ABBV-075, one of the potent monovalent BET inhibitors reported to date, N2817 showed greater potency in inhibiting proliferation, arresting cell-cycle, inducing apoptosis, and suppressing the growth of tumor xenografts. Moreover, N2817 showed high metabolic stability, a relatively long half-life, and no brain penetration after oral administration. Additionally, N2817 directly bound and inhibited another BD-containing protein, TAF1 (BD2), as evidenced by a reduction in mRNA and protein levels. TAF1 inhibition contributed to the anticancer effect of N2817. Therefore, this study offers a new paradigm for designing bivalent BET inhibitors and introduces a novel potent bivalent BET inhibitor and a new anticancer mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bcp.2021.114435DOI Listing
March 2021

Clinical characteristics, rates of blindness, and geographic features of PACD in China.

Can J Ophthalmol 2021 Jan 21. Epub 2021 Jan 21.

The Eye Hospital of Wenzhou Medical University, Wenzhou, China.

Objective: To analyze the rates of blindness with the demographics and clinical characteristics of patients with primary angle-closure disease (PACD) to provide a comprehensive epidemiologic reference in China.

Methods: A retrospective analysis was conducted in the Chinese Glaucoma Study Consortium database, which is a national multicenter glaucoma research alliance of 111 hospitals participating between December 21, 2015 and September 9, 2018. The diagnosis of PACD was made by qualified physicians through examination. Comparison of sex, age, family history, subtypes of PACD, and blindness were analyzed.

Results: A total of 5762 glaucoma patients were included, of which 4588 (79.6%) had PACD. Of PACD patients, 72.1% were female with the sex ratio (F/M) of 2.6, and the average age of patients was 63.8±9.3 years with the majority between 60 and 70 years. Additionally, 30% of these patients had low vision in one eye, 8.8% had low vision in both eyes, 1.7% had blindness in one eye, and 0.3% had blindness in both eyes. There were statistical differences with regards to age between male and female patients with PACD, with male patients being older on average. Primary angle-closure glaucoma was more commonly diagnosed in males (60%) compared to females (35.9%), whereas acute primary angle closure (APAC) was more commonly diagnosed in females (54.3%) compared to males (37.7%). The visual acuity in APAC patients was lower and the rate of low vision and blindness was higher than other subtypes.

Conclusion: PACD was the major type of glaucoma in Chinese hospitals. There were more female patients with PACD, mostly between 60 and 70 years old, with higher rates of APAC in women. APAC resulted in the worst visual outcomes of all PACD subtypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcjo.2020.12.010DOI Listing
January 2021

An Adaptive Roller Speed Control Method Based on Monitoring Value of Real-Time Seed Flow Rate for Flute-Roller Type Seed-Metering Device.

Sensors (Basel) 2020 Dec 25;21(1). Epub 2020 Dec 25.

School of Agricultural Engineering, Jiangsu University, Zhenjiang 212013, China.

In order to obtain desirable crop yields, grain seeds need to be sown at the optimal seed amount per hectare with uniform distribution in the field. In previous grain sowing processes, the seeding rates are controlled by the rotational speed of the flute roller which significantly effects the uniform distribution of the seeds due to disturbances, such as the reduction of the seeds' mass in the hopper and the change of working length of the flute roller. In order to overcome the above problem, we developed an adaptive roller speed control system based on the seed flow rate sensor. The developed system can monitor and feedback actual seeding rates. In addition, based on the monitoring value of the real-time seeding rates, an adaptive roller speed control method (ARSCM), which contains an algorithm for calculating the seeding rate with a compensation, was proposed. Besides, the seeding performance of the ARSCM and that of the conventional roller speed control method (CRSCM) were compared. The results of constant-velocity experiments demonstrated that the accuracy (SA) and the coefficient of variation (SCV) of the seeding rates controlled by the ARSCM were 94.12% and 6.77%, respectively. As for the CRSCM, the SA and SCV were 89.00% and 8.95%, respectively. Under variable-velocity conditions, the SA and SCV of the proposed system were 91.58% and 11.08%, respectively, while those of the CRSCM were 88.48% and 13.08%, respectively. Based on the above results, this study concluded that the ARSCM is able to replace the CRSCM in practical sowing processes for the optimal and uniform seed distribution in the field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s21010080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796428PMC
December 2020

Distribution of ocular biometry in young Chinese eyes: The Anyang University Students Eye Study.

Acta Ophthalmol 2020 Dec 16. Epub 2020 Dec 16.

Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Purpose: To investigate the distribution of ocular biometric parameters and its association to refraction in university students in central China.

Methods: Ocular biometric parameters including axial length (AL), central corneal thickness (CCT), keratometry power (K), anterior chamber depth (AQD) and lens thickness (LT) were measured by an optical biometry in a cohort of university students. Corneal radius of curvature (CR), lens position (LP), lens power (P ), vitreous chamber depth (VCD) and AL to corneal radius ratio (AL/CR) were calculated. Cycloplegic refraction was measured using an autorefractor.

Results: A total of 7650 undergraduate students participated in this study, with a mean age of 20.0 ± 1.4 years. The following ocular biometric parameters were measured: AL (24.78 ± 1.21 mm), CCT (539.83 ± 33.03 μm), AQD (3.23 ± 0.25 mm), LT (3.47 ± 0.18 mm), CR (7.79 ± 0.27 mm), LP (4.97 ± 0.23 mm), VCD (17.55 ± 1.15 mm), P (25.00 ± 1.07 dioptres) and AL/CR (3.18 ± 0.15). Male subjects were found to have longer AL, thicker CCT, flatter CR, thinner lens, deeper AQD and VCD than female ones. Myopic subjects were found to have longer AL, thinner CCT, steeper CR, thinner and posterior lens, deeper AQD and VCD, lower P and larger AL/CR than emmetropes and hyperopes. Spherical equivalent (SE) showed a negative correlation with AL/CR (r = -0.914), AL (r = -0.755) and VCD (r = -0.751).

Conclusions: This study provided a range of reference values for the main ocular biometric parameters in young adults and reported their distributions based on gender and refractive status. Our study indicates that SE has a strong correlation with AL/CR ratio, AL and VCD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.14710DOI Listing
December 2020

Retrospective Clinical Evaluation of Negative-Pressure Wound Therapy for Infection Prevention Following Malignant Pelvic Bone Tumor Resection Reconstruction.

Adv Skin Wound Care 2021 Jan;34(1):1-6

At the Tenth People's Hospital affiliated with Tongji University, Tongji University School of Medicine, in Shanghai, China, Tao Cai, MD, is a resident physician; Lei Zhang, MD, is an attending physician; Kunpeng Zhu, MD, is a physician; Jianping Hu, MD, is a physician; Taichen Zhan, MD, is a physician; Liwei Liu, MD, is an anesthetist; Cheng Li, MD, is an anesthetist; and Chunlin Zhang, MD, is a professor. Acknowledgments: The results of this project were previously reported at the 19th conference of the International Society of Limb Salvage, Osaka, Japan.

Objective: To evaluate the clinical outcomes of negative-pressure wound therapy (NPWT) for infection prevention following pelvic reconstruction after malignant bone tumor resection.

Methods: The study involved 82 patients who underwent pelvic reconstruction following en-bloc resection of malignant bone tumors between January 2003 and January 2016. Forty patients were treated with NPWT via implantation of vacuum-sealing drainage (VSD) materials into the pelvic cavity to prevent infection and wound problems (VSD group), and the remaining 42 patients underwent conventional treatment (control group). Study authors compared the inpatient length of stay, antibiotic use, drainage volume, time to wound closure, and infection rates between groups. Investigators also conducted cell cultures of the wound cavity washing fluid and hematoxylin-eosin staining for VSD materials to find recurrent tumor cells.

Results: In the VSD group, one patient (2.5%) had a superficial wound problem. In the control group, 18 patients (42.9%) had deep infection or wound problems. The VSD group had a significantly decreased infection rate, duration of antibiotic administration and inpatient stay, as well as increased wound healing compared with the control group (P < .05). Further, no tumor cells were observed in the VSD material or the wound cavity washing fluid.

Conclusions: The application of NPWT with VSD material may be an effective and reliable method for preventing infection in patients who undergo pelvic reconstruction following malignant tumor resection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.ASW.0000723280.71047.73DOI Listing
January 2021

Ubiquitin-like protein FAT10 suppresses SIRT1-mediated autophagy to protect against ischemic myocardial injury.

J Mol Cell Cardiol 2021 04 9;153:1-13. Epub 2020 Dec 9.

Jiangxi Key Laboratory of Molecular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China. Electronic address:

Autophagy plays a deleterious role in ischemic myocardial injury. The deacetylase SIRT1 is a well-established regulator of autophagy that can be modified by the ubiquitin-like protein SUMO1. Our previous work demonstrated that another ubiquitin-like protein, FAT10, exerts cardioprotective effects against myocardial ischemia by stabilizing the caveolin-3 protein; however, the effects of FAT10 on autophagy through SIRT1 are unclear. Here, we constructed a Fat10-knockout rat model to evaluate the role of FAT10 in autophagy. In vivo and in vitro assays confirmed that FAT10 suppressed autophagy to protect the heart from ischemic myocardial injury. Mechanistically, FAT10 was mainly involved in the regulation of the autophagosome formation process. FAT10 affected autophagy through modulating SIRT1 degradation, which resulted in reduced SIRT1 nuclear translocation and inhibited SIRT1 activity via its C-terminal glycine residues. Notably, FAT10 competed with SUMO1 at the K734 modification site of SIRT1, which further reduced LC3 deacetylation and suppressed autophagy. Our findings suggest that FAT10 inhibits autophagy by antagonizing SIRT1 SUMOylation to protect the heart from ischemic myocardial injury. This is a novel mechanism through which FAT10 regulates autophagy as a cardiac protector.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yjmcc.2020.11.007DOI Listing
April 2021

Potent and Selective Mitogen-Activated Protein Kinase Kinase 1/2 (MEK1/2) Heterobifunctional Small-molecule Degraders.

J Med Chem 2020 12 7;63(24):15883-15905. Epub 2020 Dec 7.

Mount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.

Previously, we reported a first-in-class von Hippel-Lindau (VHL)-recruiting mitogen-activated protein kinase kinases 1 and 2 (MEK1/2) degrader, MS432. To date, only two MEK1/2 degrader papers have been published and very limited structure-activity relationships (SAR) have been reported. Here, we describe our extensive SAR studies exploring both von Hippel-Lindau (VHL) and cereblon (CRBN) E3 ligase ligands and a variety of linkers, which resulted in two novel, improved VHL-recruiting MEK1/2 degraders, (MS928) and (MS934), and the first CRBN-recruiting MEK1/2 degrader (MS910). These compounds potently and selectively degraded MEK1/2 by hijacking the ubiquitin-proteasome system, inhibited downstream signaling, and suppressed cancer cell proliferation. Furthermore, concurrent inhibition of BRAF or PI3K significantly potentiated the antitumor activity of degrader , suggesting that the combination of MEK1/2 degradation with BRAF or PI3K inhibition may provide potential therapeutic benefits. Finally, besides being more potent, degrader displayed improved plasma exposure levels in mice, representing the best MEK1/2 degrader to date for in vivo studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jmedchem.0c01609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770057PMC
December 2020

Selenium-doped calcium phosphate biomineral reverses multidrug resistance to enhance bone tumor chemotherapy.

Nanomedicine 2021 02 10;32:102322. Epub 2020 Nov 10.

Department of Orthopaedic Surgery, Institute of Bone Tumor, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, PR China. Electronic address:

The construction of a functional drug delivery system to reverse the multidrug resistance (MDR) of bone tumors in cases of failed chemotherapy remains a challenge. Herein, we demonstrate a selenium-doped calcium phosphate (Se-CaP) biomineral with high biocompatibility, biodegradability and pH-sensitive drug release properties. Se-CaP may not only serve as an effective drug-carrier to enhance the uptake of doxorubicin (DOX), but may also synchronously induce caspases-mediated apoptosis of osteosarcoma by generating intracellular reactive oxygen species (ROS). Furthermore, in vitro and in vivo studies obviously demonstrate that Se-CaP can reverse the MDR of osteosarcoma by down-regulating the expression of MDR-related ABC (ATP binding cassette) transporters proteins (ABCB1 and ABCC1). Finally, DOX-loaded Se-CaP can significantly inhibit DOX-resistant MG63 (MG63/DXR) tumor growth in nude mice. Considering its biomimetic chemical properties, the Se-CaP biomineral, with the multiple functions mentioned above, could be a promising candidate for treating bone tumors with MDR characteristics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nano.2020.102322DOI Listing
February 2021

MicroRNA-20a-5p suppresses tumor angiogenesis of non-small cell lung cancer through RRM2-mediated PI3K/Akt signaling pathway.

Mol Cell Biochem 2021 Feb 30;476(2):689-698. Epub 2020 Oct 30.

Respiratory and Critical Illness Ward 1, Henan Chest Hospital, No. 1, Weiwu Road, Zhengzhou, 450000, Henan, China.

The current therapeutic strategies for non-small cell lung cancer (NSCLC) are limited and unsatisfactory. MicroRNAs (miRNAs) participate in tumor angiogenesis in NSCLC. The aim of this study was to investigate the role of miR-20a-5p (miR-20a) in human NSCLC metastasis. In the current study, bioinformatics analysis and RT-PCR were performed to examine the expression level of miR-20a in tissues of NSCLC patients and NSCLC cell lines, respectively. Western blot was performed to test the protein levels. Cell proliferation, migration and angiogenesis capacity were tested by 5-ethynyl-29-deoxyuridine (EdU) assay, transwell assay and tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the interaction between miR-20a and paired ribonucleotide reductase regulatory subunit M2 (RRM2). We found that the expression of RRM2 was upregulated, while the expression of miR-20a was downregulated in cancer tissues compared with adjacent tissues in NSCLC patients. We also detected the expression level of RRM2 and miR-20a in NSCLC cell lines, showing A549 cell line exhibited the lowest expression level of miR-20a and highest expression level of RRM2. Overexpressed miR-20a not only dramatically suppressed NSCLC cells proliferation, endothelial cells migration and tube formation in vitro, but also inhibited tumor growth and angiogenesis in vivo. It was demonstrated that miR-20a suppressed NSCLC growth by inhibiting RRM2-mediated PI3K/Akt signaling pathway. These findings indicate that the novel identified miR-20a could function as a tumor suppressor in NSCLC through modulating the RRM2-mediated PI3K/Akt axis, and it could be a valid molecular target for NSCLC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11010-020-03936-yDOI Listing
February 2021

Linoleic acid inhibits in vitro function of human and murine dendritic cells, CD4T cells and retinal pigment epithelial cells.

Graefes Arch Clin Exp Ophthalmol 2021 Apr 20;259(4):987-998. Epub 2020 Oct 20.

The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, and Chongqing Eye Institute, Chongqing, People's Republic of China.

Purpose: Increased linoleic acid (LA) was observed in acute anterior uveitis (AAU) patient feces in our previous study. To investigate the immunoregulatory effect of LA, we studied the effect of LA on human and murine dendritic cells (DCs), CD4T cells, and retinal pigment epithelial (RPE) cells in vitro.

Methods: The level of LA in feces from AAU patients and healthy individuals was measured by gas chromatography coupled with a mass spectrometer (GC-MS). The immunoregulatory effect of LA on human and murine DCs, CD4 T cells, and RPE cells was evaluated by enzyme linked immunosorbent assay (ELISA) and flow cytometry (FCM). The effect of LA on DCs was evaluated by Tandem mass tag (TMT)-based proteomics analysis.

Results: Increased LA was observed in feces from AAU patients (1018.35 ± 900.01 mg/kg) as compared with healthy individuals (472.55 ± 365.49 mg/kg, p = 0.0136). LA attenuated the antigen-presenting function of human and murine DCs by decreasing the expression of CD40, the secretion of IL-6 and IL-12p70, and the ability to shift naïve T cells towards T helper type 1 (Th1) and Th17 cells. LA also inhibited the secretion of MCP-1 and IL-8 from RPE cells. Proteomics analysis showed differential expression of 28 proteins, including squalene epoxidase (SQLE), farnesyl-diphosphate farnesyltransferase 1 (FDFT1), and cytochrome P450 family 51 subfamily A member 1 (CYP51A1), in LA-treated DCs compared with controls. LA also accelerated the apoptosis of DCs from healthy individuals.

Conclusion: LA inhibited the function of human and murine DCs, CD4T cells, and RPE cells, regulated the expression of proteins, and promoted the apoptosis of human DCs. These results collectively suggest that LA might decrease the function of immune cells in vitro, and further studies are needed to investigate its role in the pathogenesis of AAU.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00417-020-04972-6DOI Listing
April 2021

Prevalence and changes of BMI categories in China and related chronic diseases: Cross-sectional National Health Service Surveys (NHSSs) from 2013 to 2018.

EClinicalMedicine 2020 Sep 11;26:100521. Epub 2020 Sep 11.

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: China has experienced rapid economic growth and reduced poverty, but the associated changes of BMI categories of the Chinese population in recent years are unclear.

Methods: We collected data from two-round cross-sectional National Health Service Surveys (NHSSs) conducted in China in 2013 and 2018. All family members with BMI available from the households sampled in NHSSs were included. We analyzed the standardized prevalence and changes of obesity and overweight by year, age, sex, and urban-rural area, and further identified risk factors for obesity and overweight.

Findings: 273,688 individuals were included in 2013 and 25,6304 included in 2018. The standardized prevalence of obesity and overweight in adults were 19.3% (95%CI 19.1-19.4%) in 2013 and 25.6% (95%CI 25.3-25.8%) in 2018, versus 19.4% (95%CI 19·1-19.8%) in children and adolescents in 2013 and 15.8% (95%CI 15.5-16.1%) in 2018. The standardized prevalence of obesity and overweight was 16.9% (95%CI 16.0-17.3%) in young adults aged 19-29 in 2018, 48.2% higher than that in 2013 (11.4% [95%CI 11.0-11.6%]). Although the obesity and overweight prevalence was higher in urban areas, the growth rate in rural areas was 1.8 times higher than that in urban areas. Low education levels, low-income quintiles, marital status, alcohol consumption and former-smoking status were associated with higher obesity and overweight prevalence in adults.

Interpretation: The rapidly increasing prevalence in young adults may lead to the growing chronic disease burden in the future, to the detriment of recent economic gains of rural families.

Funding: National Health Commission of the People's Republic of China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2020.100521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492818PMC
September 2020

Machine learning-based radiomics analysis in predicting the meningioma grade using multiparametric MRI.

Eur J Radiol 2020 Oct 28;131:109251. Epub 2020 Aug 28.

Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China. Electronic address:

Purpose: To investigate the prediction performance of radiomic models based on multiparametric MRI in predicting the meningioma grade.

Method: In all, 229 low-grade [Grade I] and 87 high-grade [Grade II/III] patients with pathologically diagnosed meningiomas were enrolled. Radiomic features from conventional MRI (cMRI), ADC maps and SWI were extracted based on the volume of entire tumor. Classification performance of different radiomic models (cMRI, ADC, SWI, cMRI + ADC, cMRI + SWI, ADC + SWI, and cMRI + ADC + SWI models) was evaluated by a nested LOOCV approach, combining the LASSO feature selection and RF classifier that was trained (1) without subsampling, and (2) with the synthetic minority over-sampling technique (SMOTE). The prediction performance of radiomic models was assessed using ROC curve and AUC of them was compared using Delong's test.

Results: The cMRI + ADC + SWI model demonstrated the best performance without or with subsampling, which AUCs were 0.84 and 0.81, respectively. Following the cMRI + ADC + SWI model, the AUC range of the other models was 0.75-0.80 without subsampling, and was 0.71-0.79 with subsampling. Although the cMRI + ADC model and cMRI + SWI model showed higher AUCs than the cMRI model without subsampling (0.77 vs 0.80, P = 0.037 and 0.77 vs 0.80, P = 0.009, respectively), there was no significant difference among these models with subsampling (0.78 vs 0.77, P = 0.552 and 0.78 vs 0.79, P = 0.246, respectively).

Conclusions: Multiparametric radiomic model based on cMRI, ADC map and SWI yielded the best prediction performance in predicting the meningioma grade, which might offer potential guidance in clinical decision-making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejrad.2020.109251DOI Listing
October 2020

A technique for quantifying the sensitivity of dosimetric tool gamma with 2D detector array in pretreatment IMRT plans by segment deletion method.

Radiol Med 2021 Mar 17;126(3):453-459. Epub 2020 Aug 17.

School of Advanced Sciences, Vellore Institute of Technology, Vellore, 632014, India.

Objectives: Motivation of this study is to check the sensitivity of dosimetric tool gamma with 2D detector array combination when unexpected errors occur while transferring intensity-modulated radiation therapy treatment plans from planning system to treatment unit.

Methods: This study consists of 17 head and neck cancer patient's treatment plans. Nine types of verification plans are created for all 17 clinically approved treatment plans by consecutively deleting different segments (up to eight) one by one from each field of the plan. Decrement factor (χ) is introduced in our study which illustrated the degree of decay of gamma passing rate when intentional errors are introduced. We analyzed the data by two different methods-one without selecting the region of interest (ROI) in dose distributions and the other by selecting the region of interest.

Results: By linear regression, the absolute value of slopes is 0.025, 0.024 and 0.015 without ROI and 0.030, 0.027 and 0.015 with ROI for 2%/2 mm, 3%/3 mm and 5%/5 mm criteria, respectively. The higher absolute value of the fitted slope indicates the higher sensitivity of this method to identify erroneous plan in treatment unit. The threshold value for 2%/2 mm equivalent to 95% passing criteria in 3%/3 mm used in clinical practice is obtained as 83.44%.

Conclusions: The 2D detector array with dosimetric tool gamma is less sensitive in detecting errors when unprecedented errors of segment deletion occur within the treatment plans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11547-020-01259-yDOI Listing
March 2021

Short-Term Prosocial Video Game Exposure Influences Attentional Bias Toward Prosocial Stimuli.

Cyberpsychol Behav Soc Netw 2020 Oct 22;23(10):702-707. Epub 2020 Jul 22.

Key Laboratory of Brain, Cognition and Education Sciences, South China Normal University, Ministry of Education, Guangzhou, P.R. China.

Research has shown that violent video games induce attentional bias toward aggressive information. However, the effects of prosocial video games on selective attention are poorly understood. This study investigated attentional bias toward prosocial stimuli at different presentation durations (i.e., 100, 500, and 1,250 milliseconds [ms]) after short-term prosocial video game exposure. Sixty males (mean age: 20.26 years; range: 19-23 years) participated in this study. Half of them played a prosocial video game for 30 minutes, whereas others played a neutral one. A spatial cueing paradigm was then used to investigate attentional bias. Results showed that there was both attention orientation and difficulty in attention disengagement toward prosocial stimuli when the presentation lasted 100 ms in the prosocial game group, but not in the neutral group. There was no group difference at 500 or 1,250 ms, suggesting that the attentional bias toward prosocial information might occur at the early stages of cognitive processing. These results provided initial evidence of the influence of prosocial video games on cognitive processing and advanced our understanding of related theories.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/cyber.2019.0745DOI Listing
October 2020

COVID-19 Docking Server: a meta server for docking small molecules, peptides and antibodies against potential targets of COVID-19.

Bioinformatics 2020 12;36(20):5109-5111

Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou 213001, China.

Motivation: The coronavirus disease 2019 (COVID-19) caused by a new type of coronavirus has been emerging from China and led to thousands of death globally since December 2019. Despite many groups have engaged in studying the newly emerged virus and searching for the treatment of COVID-19, the understanding of the COVID-19 target-ligand interactions represents a key challenge. Herein, we introduce COVID-19 Docking Server, a web server that predicts the binding modes between COVID-19 targets and the ligands including small molecules, peptides and antibodies.

Results: Structures of proteins involved in the virus life cycle were collected or constructed based on the homologs of coronavirus, and prepared ready for docking. The meta-platform provides a free and interactive tool for the prediction of COVID-19 target-ligand interactions and following drug discovery for COVID-19.

Availability And Implementation: http://ncov.schanglab.org.cn.

Supplementary Information: Supplementary data are available at Bioinformatics online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/btaa645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558834PMC
December 2020

Phosphine ligand-coated Cu nanoparticle-catalyzed selective semihydrogenation of alkynes: electronic or hindrance effects of the ligand?

Phys Chem Chem Phys 2020 Jul;22(29):16905-16913

National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, Chongqing Collaborative Innovation Center of Targeted and Innovative Therapeutics, College of Pharmacy & International Academy of Targeted Therapeutics and Innovation, Chongqing University of Arts and Sciences, Chongqing 402160, P. R. China.

Understanding the mechanism of a catalytic reaction is of fundamental importance not only scientifically but also technologically to the design of high-performance catalysts. In this work, the mechanisms of 1-phenyl-1-propyne and cis-β-methylstyrene hydrogenations catalyzed by Cu55 and ligand-coated Cu55 are explored in detail by means of density functional theory (DFT). The calculated results indicate that the semihydrogenation selectivity of the catalyst can be effectively controlled by employing a suitable ligand. That is, the PCy3 and PPh3 ligands used to coat Cu55 can largely raise the energy barrier of the rate-determining step for cis-β-methylstyrene hydrogenation. By the study of energy decomposition analysis (EDA) and charge density difference, it can be found that the deformation energies of the substrate fragments play a crucial role in the energy barriers of the rate-determining steps. The large hindrance effect of the ligands is beneficial for improving the semihydrogenation selectivity of the catalysts. This study provides significant information for future catalyst design and on the physical origin of the phosphine ligand-coated nanoparticle catalysis for semihydrogenation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cp02303eDOI Listing
July 2020

Is increased symptom interval associated with advanced stage and poorer outcome? A prospective multicenter study of 220 patients with osteosarcoma around the knee.

Cancer Epidemiol 2020 08 6;67:101776. Epub 2020 Jul 6.

Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Objective: Osteosarcoma is rare disease and there is a strong controversy about the potential impact of symptom interval on the stage of disease and patients' outcomes. We want to assess whether increased symptom interval (SI) is associated with advanced tumor stage and poor prognosis for patients with osteosarcoma.

Methods: We analyzed prospectively collected data of 220 patients younger than 40 years who had osteosarcoma around the knee. Symptom interval was analyzed to evaluate its impact on metastases at diagnosis, tumor volume, chemotherapy response and overall survival.

Results: The median of SI was 64.5 (Q1-Q3: 42-88) days. The 5-year overall survival rate for patients with different length of symptom interval (<42 days, 42-64 days, 65-87 days, > = 88 days) were 0.78 (95 %CI: 0.67-0.89), 0.49 (95 %CI: 0.35-0.63), 0.52 (95 %CI:0.39-0.65), and 0.65 (95 %CI:0.53-0.77) respectively(p = 0.013). Nonparametric test showed increased SI was associated with metastases at diagnosis (p = 0.008), but not associated with large tumor volume or poor chemotherapy response. Cox regression mode test showed that patient with increased SI had higher hazard ratio (42-64 days HR: 2.586 (95 %CI:1.360-4.915); 65-87 days, HR: 2.225 (95 %CI:1.170-4.233)) for poor outcomes compared to short SI (<42 days), though it was not significant in multivariate analysis (p = 0.182).

Conclusion: Increased SI but not the longest SI is associated with higher incidence of metastases at diagnosis; patients can benefit from an earlier diagnosis in terms of survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canep.2020.101776DOI Listing
August 2020

Stress-induced changes in modular organizations of human brain functional networks.

Neurobiol Stress 2020 Nov 25;13:100231. Epub 2020 May 25.

Key Laboratory for Biomedical Engineering of the Ministry of Education, Department of Biomedical Engineering, Zhejiang University, Zhejiang, 310000, China.

Humans inevitably go through various stressful events, which initiates a chain of neuroendocrine reactions that may affect brain functions and lead to psychopathological symptoms. Previous studies have shown stress-induced changes in activation of individual brain regions or pairwise inter-regional connectivity. However, it remains unclear how large-scale brain network is reconfigured in response to stress. Using a within-subjects design, we combined the Trier Social Stress Test and graph theoretical method to characterize stress-induced topological alterations of brain functional network. Modularity analysis revealed that the brain network can be divided into frontoparietal, default mode, occipital, subcortical, and central-opercular modules under control and stress conditions, corresponding to several well-known functional systems underpinning cognitive control, self-referential mental processing, visual, salience processing, sensory and motor functions. While the frontoparietal module functioned as a connector module under stress, its within-module connectivity was weakened. The default mode module lost its connector function and its within-module connectivity was enhanced under stress. Moreover, stress altered the capacity to control over information flow in a few regions important for salience processing and self-referential metal processing. Furthermore, there was a trend of negative correlation between modularity and stress response magnitude. These findings demonstrate that acute stress prompts large-scale brain-wide reconfiguration involving multiple functional modules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ynstr.2020.100231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262562PMC
November 2020

Analysis of the role of palmitoleic acid in acute anterior uveitis.

Int Immunopharmacol 2020 Jul 16;84:106552. Epub 2020 May 16.

The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, and Chongqing Eye Institute, Chongqing, PR China. Electronic address:

Purpose: To study the role of palmitoleic acid (PA) in the pathogenesis of acute anterior uveitis (AAU).

Methods: PA levels in feces from AAU patients were measured by gas chromatography coupled with a mass spectrometer (GC-MS) and compared with samples obtained from healthy individuals. Enzyme linked immunosorbent assay (ELISA) and flow cytometry (FCM) were used to assess the effect of PA on dendritic cells (DCs) and CD4T cells obtained from mice, AAU patients and healthy individuals. C57BL/6 mice were fed with PA or vehicle and experimental autoimmune uveitis (EAU) was induced with a human retinal IRBP651-670 peptide. Disease severity of EAU was evaluated by clinical manifestation and histology. Differentiation of splenic Type 1 helper T cells (Th1) and Th17 cells was evaluated by FCM. Tandem mass tag (TMT)-based proteomics analysis was used to identify differentially expressed proteins following incubation of DCs with PA.

Results: The fecal concentration of PA was increased in AAU patients as compared with healthy individuals. In vitro, PA promoted apoptosis of DCs and inhibited the secretion of TNF-α from mouse bone-marrow-derived dendritic cells (BMDCs) as well as in DCs from AAU patients and healthy individuals. It only decreased DCs surface marker expression and IL-12p70 secretion in BMDCs and healthy individuals DCs but not in AAU patient DCs. PA-treated BMDCs inhibited Th cell differentiation from mouse naïve CD4T cells and IL-17 and IFN-γ secretion in co-culture supernatants. PA also inhibited the differentiation of Th cells and secretion of IFN-γ and IL-17 in CD4T cells from mice, AAU patients and healthy individuals. In vivo, PA-treated EAU mice showed milder clinical and histopathological intraocular manifestations as compared with the control group. PA feeding inhibited differentiation of splenic Th17 cells, whereas Th1 cells were not affected. Up to 30 upregulated and 77 downregulated proteins were identified when comparing PA-treated DCs with controls.

Conclusion: An increased expression of fecal PA was observed in AAU patients. PA was shown to have immunoregulatory effects on DCs and CD4T cells and attenuated disease severity in EAU mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2020.106552DOI Listing
July 2020

Coding Variants in and May Contribute to Risk of Primary Angle Closure Glaucoma.

DNA Cell Biol 2020 Jun 12;39(6):949-957. Epub 2020 May 12.

Beijing Ophthalmology and Visual Science Key Lab, Beijing, P.R. China.

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. This study proposed to screen candidate PACG-associated variants in Chinese Han people. Whole exome sequencing was applied to five confirmed PACG patients and two primary angle closure suspect individuals within a PACG-enriched Chinese Han family. A series of bioinformatics analyses were implemented to obtain high-risk single nucleotide variant (SNV) loci for PACG, which were subsequently used for linkage analysis for identifying linkage genome regions. In addition, MassARRAY SNV genotyping was applied to high-risk PACG loci as well as those within linkage regions in another independent cohort including 251 PACG and 251 normal samples to further screen high-confidence SNVs. A total of 27 loci in 19 genes remained after linkage analysis. The 19 genes were significantly enriched in biological processes tightly related to PACG, including retinol metabolism and salmonella infection. Two nonsynonymous SNV loci, rs897804 in exon15 of and rs3745193 in exon7 of were recognized with higher variant frequency in PACG samples than that in control samples after association analysis of MassARRAY SNV genotyping data. This study sheds new light on the understanding of PACG incidence among Chinese Han people.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/dna.2019.5079DOI Listing
June 2020