Publications by authors named "Yun Sun"

597 Publications

A joint method for the screening of pharmacological chaperones for phenylalanine hydroxylase.

Org Biomol Chem 2021 Jun 11. Epub 2021 Jun 11.

The affiliated Obstetrics and Gynecology Hospital with Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Center of Genetic Medicine, Nanjing 210004, Jiangsu, P.R. China.

Phenylalanine hydroxylase (PAH) deficiency (PAHD) is an autosomal recessive disorder that causes severe injury to the nervous system, the treatment of which mainly depends on dietary therapy. The limited treatment options for PAHD are an incentive to develop new methods to identify more efficient therapeutic drugs, such as agonists which could improve PAH activity. In this study, we aimed to establish a rapid and convenient method for the screening and verification of PAH agonists. We compared fluorospectrophotometry and tandem mass spectrometry for detection of enzymatic formation of tyrosine, finding that the latter was a more sensitive method. We optimized immunoprecipitation purification conditions and measurement conditions of PAH activity. The optimal ratio between PAH protein and magnetic beads was 500 μg protein per 20 μL beads, and the optimized conditions for the detection of PAH enzymatic activity included the presence of 75 μM coenzyme ((6R)-l-erythro-5,6,7,8-tetrahydrobiopterin) and 30 min reaction time. Based on virtual screening, we screened ten candidate agonists from the FDA drug library. Three of these (nefopam, fluocinonide, and risperidone) were found to activate the enzyme in a dose-dependent manner (0.1-10 μM) by the joint method. We tested the efficacy of the three agonists on three PAH mutations (p.I65T, p.H107R, and p.D101N) that influence enzyme activity, and found that risperidone could specifically activate D101N-mutated enzyme. In conclusion, we established a joint method that is highly reliable, cost-effective, labor-saving, and time-saving. And we also found a specific agonist for D101N-mutated PAH by this joint method which may assist the development of clinical treatment for PAHD patients with different enzyme deficiencies.
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http://dx.doi.org/10.1039/d1ob00638jDOI Listing
June 2021

Bacterial community dynamics during different stages of processing of smoked bacon using the 16S rRNA gene amplicon analysis.

Int J Food Microbiol 2021 Aug 28;351:109076. Epub 2021 Jan 28.

College of Food Science and Light Industry, Nanjing Tech University, Nanjing 211816, China. Electronic address:

To identify the microbial community and origin of the spoilage flora of bacon, the changes in microbial population numbers and community structure were followed along the processing line, using culture-independent and culture-dependent methods. 16S rRNA gene amplicon sequencing (16S-seq) analysis showed that community complexity and structure significantly differed at different processing stages. Some 428 bacterial groups were ascertained at genus level, and Acinetobacter, Pseudomonas, Psychrobacter, and Brochothrix were the predominant bacteria on raw meats. After curing specimens dominated by Psychrobacter, Weissella, Vibrio, Leuconostoc, Myroides, Acinetobacter, and Lactobacillus, a total of 33 species were identified by traditional microbiological analyses and direct sequence determination methods. Our results indicated that curing should be considered one of the primary factors during various processing steps, presumably contaminating the products directly or indirectly.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2021.109076DOI Listing
August 2021

Functional characterization of cathepsin B and its role in the antimicrobial immune responses in golden pompano (Trachinotus ovatus).

Dev Comp Immunol 2021 May 31;123:104128. Epub 2021 May 31.

State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, PR China.

Cathepsin B (CTSB) is one of the typical representatives of cysteine protease family. It has the activity of both exopeptidase and endopeptidase. It plays an important role in antigen presentation, degradation, apoptosis, inflammatory response and physiological process of many diseases. In this study, CTSB of Trachinotus ovatus (TroCTSB) was cloned, and its structure and function were analyzed. The results showed that the coding region of TroCTSB was 993 bp, encoding 330 amino acid residues. The homology analysis showed that the amino acid sequence of TroCTSB was similar to that in other teleosts and mammals (68.69%-88.48%). Under normal physiological conditions, TroCTSB was widely distributed in various tissues with the highest expression level in stomach, followed by liver, and the lowest expression level in blood. The optimal pH and temperature of purified recombinant protein rTroCTSB were 5.5 and 40 °C, respectively. The toxicity test of metal ions showed that Fe, Cu, Ca and Zn could all inhibit the activity of TroCTSB, with Zn ranking the first. In addition, after Edwardsiella tarda infection, the expression of TroCTSB was significantly up-regulated in liver, spleen and head kidney. The overexpression of TroCTSB significantly inhibited the infection of E. tarda in golden pompano tissues, and the knockdown of TroCTSB remarkably promoted the reproduction of E. tarda in golden pompano tissues in vivo. This study suggests that TroCTSB was involved in the antibacterial immune response of T. ovatus, and provided a reference for further research in elucidating the resistance mechanism of TroCTSB.
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http://dx.doi.org/10.1016/j.dci.2021.104128DOI Listing
May 2021

Rapid screening of active components group with Topoisomerase I inhibitory activity in Sophora alopecuroides L. based on ultrafiltration coupled with UPLC-QTOF-MS.

Curr Pharm Biotechnol 2021 Jun 1. Epub 2021 Jun 1.

College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.

Background: Topoisomerase I (Topo I) is a key target of many antitumor drugs in vivo. Alkaloids in Sophora alopecuroides L. can reportedly inhibit Topo I activity, but the pharmacodynamic material basis has not yet been determined.

Objective: The objective of this study is to rapidly identify active components group which inhibit Topo I in S. alopecuroides L.

Methods: Affinity ultrafiltration-ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UF-UPLC-QTOF-MS) screening system based on Topo I protein was established to screen and isolate a total alkaloid fraction in S. alopecuroides L. Topo I inhibitory activity and anti-tuomor proliferation activity of the screened components were evaluated, and their molecular mechanisms were studied.

Results: Six compounds bound specifically to Topo I were obtained. Further screening showed that matrine, cytisine, and sophoridine presented higher inhibitory activity on Topo I and were able to inhibit the proliferation of breast cancer MDA-MB-468 cells with IC50 values of 9.40 ± 1.12 mM, 17.4 ± 2.20 mM and 10.4 ± 1.37 mM, respectively. To the best of our knowledge, their dual molecular mechanisms against Topo I have been discussed here for the first time: (1) stabilization of Topo I-DNA complex and (2) inhibition or blocking of Topo I binding to DNA.

Conclusion: Matrine, cytisine, and sophoridine from S. alopecuroides L. were defined as the active components group with Topo I inhibitory activity and their pharmacological mechanism was confirmed, which provided an important base for further research and development of antitumor components fromS. alopecuroides L.
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http://dx.doi.org/10.2174/1389201022666210602105609DOI Listing
June 2021

Therapeutic Opportunities of Interleukin-33 in the Central Nervous System.

Front Immunol 2021 17;12:654626. Epub 2021 May 17.

Department of Neurosurgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.

Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is involved in various diseases. IL-33 exerts its effects via its heterodimeric receptor complex, which comprises suppression of tumorigenicity 2 (ST2) and the IL-1 receptor accessory protein (IL-1RAP). Increasing evidence has demonstrated that IL-33/ST2 signaling plays diverse but crucial roles in the homeostasis of the central nervous system (CNS) and the pathogenesis of CNS diseases, including neurodegenerative diseases, cerebrovascular diseases, infection, trauma, and ischemic stroke. In the current review, we focus on the functional roles and cellular signaling mechanisms of IL-33 in the CNS and evaluate the potential for diagnostic and therapeutic applications.
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http://dx.doi.org/10.3389/fimmu.2021.654626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165230PMC
May 2021

Biodegradable BiOCl platform for oxidative stress injury-enhanced chemodynamic/radiation therapy of hypoxic tumors.

Acta Biomater 2021 May 24. Epub 2021 May 24.

Institute of Bismuth Science and College of Science, University of Shanghai for Science and Technology, Shanghai 200093, China. Electronic address:

Various physiological characteristics of the tumor microenvironment (TME), such as hypoxia, overexpression of glutathione (GSH) and hydrogen peroxide (HO), and mild acidity, can severely reduce the efficacy of many cancer therapies. Altering the redox balance of the TME and increasing oxidative stress can accordingly enhance the efficacy of tumor therapy. Herein, we developed a bismuth-based Cu-doped BiOCl nanotherapeutic platform, BCHN, able to self-supply HO for TME-regulated chemodynamic therapy (CDT) combined with sensitized radiotherapy (RT). BCHN released HO and consumed GSH to degrade the composite in the slightly acidic TME, and generated hydroxyl radicals (•OH) via a Fenton-like reaction catalyzed by copper ions, to achieve oxidative stress-enhanced CDT. The Fenton-like reaction also catalyzed HO to produce O to relieve tumor hypoxia, and combined with the X-ray-blocking property of bismuth to realize TME-enhanced radiotherapy. Synergistic CDT/RT has previously been shown to effectively inhibit tumor cell proliferation and achieve effective tumor control. The current results demonstrated a highly efficient multifunctional bio-degradable nanoplatform for oncotherapy. STATEMENT OF SIGNIFICANCE: Tumor microenvironment-modulated synergy of radiotherapy and chemodynamic therapy is conducive to rapid tumor ablation. Based on this principle, we fabricated a biodegradable BiOCl-based nanocomposite, BCHN. By supplying HO, a Fenton-like reaction generated •OH and O catalyzed by copper ions, and consumed glutathione to biodegrade the composite. Overall, these actions increased tumor oxidative stress and realized the synergistic anti-tumor actions of chemodynamic therapy combined with bismuth-based sensitization radiotherapy. This strategy thus provides a unique approach to oncology therapy.
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http://dx.doi.org/10.1016/j.actbio.2021.05.016DOI Listing
May 2021

Prevalence of granular corneal dystrophy type 2-related p.R124H variant in a South Korean population.

Mol Vis 2021 8;27:283-287. Epub 2021 May 8.

GC Genome, Yongin, Korea.

Purpose: Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant disorder and is associated with the arginine to histidine substitution at codon 124 (p.R124H) of the gene. Although p.R124H is known to be the most common corneal dystrophy-related pathogenic variant, there are few data on the frequency of this variant in the South Korean population.

Methods: In total, 2,060 anonymous DNA samples from a public umbilical cord blood bank were tested for the p.R124H variant using real-time PCR.

Results: Six of the 2,060 samples [0.29%; 95% confidence interval (CI), 0.12-0.67%] were heterozygous for the p.R124H variant. The prevalence of the GCD2-related p.R124H variant in this population was estimated to be 291.3 per 100,000 [95% confidence interval (CI), 118.5-667.0].

Conclusions: To our knowledge, this is the largest study that has estimated the prevalence of the GCD2-related p.R124H variant in South Korea.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116257PMC
May 2021

C4OH is a potential newborn screening marker-a multicenter retrospective study of patients with beta-ketothiolase deficiency in China.

Orphanet J Rare Dis 2021 May 17;16(1):224. Epub 2021 May 17.

Department of Genetics and Metabolism, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, 310052, China.

Background: Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disorder caused by biallelic mutation of ACAT1 that affects both isoleucine catabolism and ketolysis. There is little information available regarding the incidence, newborn screening (NBS), and mutational spectrum of BKTD in China.

Results: We collected NBS, biochemical, clinical, and ACAT1 mutation data from 18 provinces or municipalities in China between January 2009 and May 2020, and systematically assessed all available published data from Chinese BKTD patients. A total of 16,088,190 newborns were screened and 14 patients were identified through NBS, with an estimated incidence of 1 per 1 million newborns in China. In total, twenty-nine patients were genetically diagnosed with BKTD, 12 of which were newly identified. Most patients exhibited typical blood acylcarnitine and urinary organic acid profiles. Interestingly, almost all patients (15/16, 94%) showed elevated 3-hydroxybutyrylcarnitine (C4OH) levels. Eighteen patients presented with acute metabolic decompensations and displayed variable clinical symptoms. The acute episodes of nine patients were triggered by infections, diarrhea, or an inflammatory response to vaccination. Approximately two-thirds of patients had favorable outcomes, one showed a developmental delay and three died. Twenty-seven distinct variants were identified in ACAT1, among which five were found to be novel.

Conclusion: This study presented the largest series of BKTD cohorts in China. Our results indicated that C4OH is a useful marker for the detection of BKTD. The performance of BKTD NBS could be improved by the addition of C4OH to the current panel of 3-hydroxyisovalerylcarnitine and tiglylcarnitine markers in NBS. The mutational spectrum and molecular profiles of ACAT1 in the Chinese population were expanded with five newly identified variants.
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http://dx.doi.org/10.1186/s13023-021-01859-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130433PMC
May 2021

Effect of orlistat on live birth rate in overweight or obese women undergoing IVF-ET: A randomized clinical trial.

J Clin Endocrinol Metab 2021 May 15. Epub 2021 May 15.

Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University; The Key Laboratory of Reproductive Endocrinology of Ministry of Education; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China.

Context: Obesity management prior to infertility treatment remains a challenge. To date, results from randomized clinical trials involving weight loss by lifestyle interventions have shown no evidence of improved live birth rate.

Objective: To determine whether pharmacologic weight-loss intervention before in vitro fertilization and embryo transfer (IVF-ET) can improve live birth rate among overweight or obese women.

Design, Setting, And Participants: We conducted a randomized, double-blinded, placebo-controlled trial across 19 reproductive medical centers in China, from July 2017 to January 2019. A total of 877 infertile women scheduled for IVF who had a body mass index of 25kg/m 2 or greater were randomly assigned.

Interventions: The participants were randomized to receive orlistat (n=439) or placebo (n=438) treatment for 4-12 weeks.

Main Outcomes And Measures: Live birth rate after fresh embryo transfer.

Results: The live birth rate was not significantly different between the two groups (112 of 439 [25.5%] with orlistat and 112 of 438 [25.6%] with placebo; P=.984). No significant differences existed between the groups as to the rates of conception, clinical pregnancy, and pregnancy loss. A statistically significant increase in singleton birthweight was observed after orlistat treatment (3487.50g versus 3285.17g in the placebo group; P=.039). The mean change in body weight during the intervention was -2.49kg in the orlistat group, as compared to -1.22kg in the placebo group, with a significant difference (P=.005).

Conclusions: Orlistat treatment, prior to IVF-ET, did not improve live birth rate among overweight or obese women, although it was beneficial for weight reduction.
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http://dx.doi.org/10.1210/clinem/dgab340DOI Listing
May 2021

Neonatal screening and genotype-phenotype correlation of hyperphenylalaninemia in the Chinese population.

Orphanet J Rare Dis 2021 May 12;16(1):214. Epub 2021 May 12.

Genetic Medicine Center, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, 123 Tianfei St., Qinhuai District, Nanjing, 210004, People's Republic of China.

Background: Hyperphenylalaninemia (HPA) is the most common amino acid metabolic disease involving phenylalanine hydroxylase (PAH, OMIM*612,349) deficiency or coenzyme tetrahydrobiopterin (BH4) deficiency. Patients with severe HPA often have a difficult life. Early diagnosis of HPA before the development of symptoms is possible via neonatal screening, facilitating appropriate treatment and reducing mortality and disability rates. This study revealed the prevalence, mutational and phenotypic spectrum, and prognosis of HPA by neonatal screening from January 2001 to September 2020 in Nanjing, Jiangsu Province, China.

Methods: Through a retrospective analysis of the information available in the neonatal screening database, the clinical presentations, laboratory data, molecular characteristics and treatment follow-up data of HPA patients detected by neonatal screening were evaluated.

Results: We diagnosed 181 patients with HPA from 1 to 957 newborns, giving an incidence of 1:6873. Among these patients, 177 were identified as PAH deficient and four patients were BH4 deficient. The average current age of the patients was 6.38 years old. The most common mutations of PAH were c.728 C > A/ p.Arg243Gln (13.83 %), c.158G > A/ p.Arg53His (9.57 %), c.611 A > G/ p.Tyr204Cys (7.44 %), and c.721 C > T/ p.Arg241Cys (6.38 %).

Conclusions: This study revealed the prevalence, phenotype-genotype, and prognosis of HPA in China and contributes to the updating of PAHD data for China and worldwide. Our study not only expanded the spectrum of phenotypes and genotype but also provided a valuable tool for improved genetic counseling and management of future cases.
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http://dx.doi.org/10.1186/s13023-021-01846-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114530PMC
May 2021

[Consensus on screening, diagnosis and treatment of multiple acyl-CoA dehydrogenase deficiency].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 May;38(5):414-418

National Clinical Research Center for Child Health and Disease, Children's Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaricacidemia type II, is a relatively common disorder of fatty acid oxidation metabolism. The clinical manifestations are highly heterogeneous, symptoms can develop from newborn to adulthood. Neonatal onset type is more serious with high mortality. The symptoms of late onset patients include lipid deposition myopathy and vomiting, liver disease, and encephalopathy. Analysis of blood acyl carnitine spectrum by tandem mass spectrometry can be used for the screening. Late onset patients have relatively good prognosis with vitamin B treatment. The purpose of this consensus is to standardize the diagnosis, treatment and management of MADD, so as to improve the prognosis of patients and reduce death and disability.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200829-00630DOI Listing
May 2021

Genetic basis of high aroma and stress tolerance in the oolong tea cultivar genome.

Hortic Res 2021 May 1;8(1):107. Epub 2021 May 1.

College of Horticulture, Fujian Agriculture and Forestry University/Key Laboratory of Tea Science in Universities of Fujian Province, 350002, Fuzhou, China.

Tea plants (Camellia sinensis) are commercially cultivated in >60 countries, and their fresh leaves are processed into tea, which is the most widely consumed beverage in the world. Although several chromosome-level tea plant genomes have been published, they collapsed the two haplotypes and ignored a large number of allelic variations that may underlie important biological functions in this species. Here, we present a phased chromosome-scale assembly for an elite oolong tea cultivar, "Huangdan", that is well known for its high levels of aroma. Based on the two sets of haplotype genome data, we identified numerous genetic variations and a substantial proportion of allelic imbalance related to important traits, including aroma- and stress-related alleles. Comparative genomics revealed extensive structural variations as well as expansion of some gene families, such as terpene synthases (TPSs), that likely contribute to the high-aroma characteristics of the backbone parent, underlying the molecular basis for the biosynthesis of aroma-related chemicals in oolong tea. Our results uncovered the genetic basis of special features of this oolong tea cultivar, providing fundamental genomic resources to study evolution and domestication for the economically important tea crop.
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http://dx.doi.org/10.1038/s41438-021-00542-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087695PMC
May 2021

Ly-6D of Japanese flounder (Paralichthys olivaceus) functions as a complement regulator and promotes host clearance of pathogen.

Dev Comp Immunol 2021 Sep 20;122:104104. Epub 2021 Apr 20.

Institute of Tropical Bioscience and Biotechnology, Hainan Academy of Tropical Agricultural Resource, CATAS, Haikou, 571101, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071, China; Hainan Provincial Key Laboratory for Functional Components Research and Utilization of Marine Bio-resources, Haikou, 571101, China. Electronic address:

The Lymphocyte antigen-6 (Ly-6) superfamily has been considered to play an important role in the innate immunity of mammals. The functions of Ly-6 proteins are diverse since their low sequence homology. Currently, the function of Ly-6D, a member of Ly-6 family proteins, is completely unknown in teleost. In the present study, we identified and characterized a Ly-6D homologue (named PoLy-6D) from the teleost fish Paralichthys olivaceus and examined its immune function. PoLy-6D possesses a hydrophobic signal peptide, a LU domain including a conserved "LXCXXC" motif in N-terminus and a "CCXXXXCN" motif in C-terminus. Under normal physiological condition, PoLy-6D expression distributes in all the examined tissues, the highest three tissues are successively spleen, head kidney, and blood. When infected by extracellular and intracellular bacterial pathogens and viral pathogen, PoLy-6D expression was induced and the patterns vary with different types of microbial pathogens infection and different immune tissues. In vitro experiment showed recombinant PoLy-6D (rPoLy-6D) inhibited the lysis of rabbit red blood cells by serum and selectively improved bacterial survival in serum. After serum were treated by antibody of rPoLy-6D, bacteriostatic effect of serum was obviously enhanced. These results indicate the importance of PoLy-6D as a complement regulator. rPoLy-6D possessed the binding activity to multiple bacteria but did not exhibit antimicrobial activities. The interaction between rPoLy-6D and bacteria suggests that PoLy-6D is involved in host clearance of pathogens probably by serving as a receptor for pathogens. Overexpression of PoLy-6D in vivo promoted the host defense against invading E. piscicida. These findings add new insights into the regulation mechanism of the complement system in teleost and emphasize the importance of Ly-6D products for the control of pathogen infection.
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http://dx.doi.org/10.1016/j.dci.2021.104104DOI Listing
September 2021

SARS-CoV-2-induced Overexpression of miR-4485 Suppresses Osteogenic Differentiation and Impairs Fracture Healing.

Int J Biol Sci 2021 25;17(5):1277-1288. Epub 2021 Mar 25.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan, Hubei 430022, China.

The angiotensin-converting enzyme 2 (ACE2) receptor has been identified as the cell entry point for SARS-CoV-2. Although ACE2 receptors are present in the bone marrow, the effects of SARS-CoV-2 on the biological activity of bone tissue have not yet been elucidated. In the present study we sought to investigate the impact of SARS-CoV-2 on osteoblastic activity in the context of fracture healing. MicroRNA-4485 (miR-4485), which we found to be upregulated in COVID-19 patients, negatively regulates osteogenic differentiation. We demonstrate this effect both and . Moreover, we identified the toll-like receptor 4 (TLR-4) as the potential target gene of miR-4485, and showed that reduction of TLR-4 induced by miR-4485 suppresses osteoblastic differentiation . Taken together, our findings highlight that up-regulation of miR-4485 is responsible for the suppression of osteogenic differentiation in COVID-19 patients, and TLR-4 is the potential target through which miR-4485 acts, providing a promising target for pro-fracture-healing and anti-osteoporosis therapy in COVID-19 patients.
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http://dx.doi.org/10.7150/ijbs.56657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040480PMC
May 2021

The effectiveness and safety of LMWH for preventing thrombosis in patients with spinal cord injury: a meta-analysis.

J Orthop Surg Res 2021 Apr 14;16(1):262. Epub 2021 Apr 14.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road. 1277#, Wuhan, 430022, Hubei, P. R. China.

Background: Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are commonly used for preventing venous thrombosis of the lower extremity in patients with traumatic spinal cord injury. Although, LMWH is the most commonly used drug, it has yet to be established whether it is more effective and safer than UFH. Further, a comparison of the effectiveness of LMWH in preventing thrombosis at different locations and different degrees of spinal cord injury has also not been clearly defined.

Materials And Methods: Cohort studies comparing the use of LMWH and UFH in the prevention of lower limb venous thrombosis in patients with spinal cord injury were identified using PubMed. The risk of bias and clinical relevance of the included studies were assessed using forest plots. The Newcastle-Ottawa quality assessment scale was used to evaluate the quality of the included studies. The main results of the study were analyzed using Review Manager 5.3.

Results: A total of five studies were included in this meta-analysis. Four studies compared the effectiveness and safety of LMWH and UFH in preventing thrombosis in patients with spinal cord injury. No significant differences were found between the therapeutic effects of the two drugs, and the summary RR was 1.33 (95% CI 0.42-4.16; P = 0.63). There was also no significant difference in the risk of bleeding between the two medications, and the aggregate RR was 0.78 (95% CI 0.55-1.12; P = 0.18). When comparing the efficacy of LMWH in preventing thrombosis in different segments and different degrees of spinal cord injury, no significant differences were found.

Conclusions: The results of this analysis show that compared with UFH, LMWH has no obvious advantages in efficacy nor risk prevention, and there is no evident difference in the prevention of thrombosis for patients with injuries at different spinal cord segments.
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http://dx.doi.org/10.1186/s13018-021-02412-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048068PMC
April 2021

Early rehabilitation after lung transplantation with extracorporeal membrane oxygenation (ECMO) of COVID-19 patient: a case report.

Ann Transl Med 2021 Mar;9(6):512

Department of Rehabilitation Medicine, The First Affiliated Hospital of Zhejiang University, Hangzhou, China.

Even when severe acute respiratory syndrome coronavirus 2-related coronavirus disease 2019 (COVID-19) is treated with first-line drugs, it progresses and leads to irreversible loss of lung function in some critically ill patients, and lung transplantation is an effective treatment for end-stage chronic pulmonary disease. This case report mainly describes the rehabilitation of a 66-year-old female patient with severe COVID-19 after bilateral lung transplantation. The old patient had a body mass index of 31.2 kg/m. She underwent bilateral lung transplantation due to severe and irreversible injury of both lungs. Long-term mechanical ventilation and extracorporeal membrane oxygenation (ECMO) treatment and preoperative and postoperative high-dose corticosteroid therapy and due to the size of the donor lung does not match the size of the recipient's diseased lung, and the right middle lobe of the graft is removed before transplantation. Weaning from the ventilator failed due to weak neuromuscular drive, and muscle strength. A full, personalized pulmonary rehabilitation program was initiated with the help of the physical therapists, the respiratory therapy, the doctors, the nurses and psychotherapist team based on the functional levels. The rehabilitation intervention was conducted on postoperative day 4, This included posture management, airway clearance techniques, respiratory training, muscle strength training, transfer training, daily therapeutic bronchoscopy and psychological support. The ECMO was removed successfully on the fifth day. the patient's physical function, muscle strength and the quality of life has been improved. The good prognosis after rehabilitation indicates that early rehabilitation intervention is effective and feasible and safety for patients after lung transplantation.
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http://dx.doi.org/10.21037/atm-21-456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039682PMC
March 2021

Comparison of the AdvanSure RV Plus Real-Time RT-PCR and Real-Q RV II Detection Assays for Respiratory Viruses.

Ann Lab Med 2021 Sep;41(5):506-509

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3343/alm.2021.41.5.506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041588PMC
September 2021

Comparison of preimplantation genetic testing for aneuploidy versus intracytoplasmic sperm injection in severe male infertility.

Andrologia 2021 Jul 6;53(6):e14065. Epub 2021 Apr 6.

Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

The retrospective cohort study was conducted to evaluate the effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) for severe male factor (SMF) infertility on pregnancy outcomes in comparison with intracytoplasmic sperm injection (ICSI). A total of 206 couples with SMF were included in the study, among which, 102 couples underwent ICSI with next-generation sequencing (NGS)-based PGT-A (the PGT-A group), while 104 underwent ICSI only (the control group). Results showed while no differences were noted in clinical pregnancy rate (CPR) (66.7% versus. 69.9%, p = .64) and ongoing pregnancy rate (OPR) (62.2% versus. 54.7%, p = .29) per transfer between groups, early miscarriage rate (EMR) per transfer was significantly lower (6.7% versus. 21.6%, p = .02) in the PGT-A group. Cumulative OPR per patient remained similar between groups (54.9% versus. 55.8%, p = .90). Results of multivariable logistic regression also demonstrated the use of PGT-A was significantly associated with lower EMR (adjusted OR 0.17, 95%CI 0.05-0.55) in SMF, while it was not related to cumulative OPR. In conclusion, our results showed that NGS-based PGT-A can improve pregnancy outcomes for couples with SMF by significantly decreasing EMR without compromising cumulative OPR, indicating that NGS-based PGT-A could be offered as an appropriate approach for couples with SMF.
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http://dx.doi.org/10.1111/and.14065DOI Listing
July 2021

R2R3-MYB transcription factor family in tea plant (Camellia sinensis): Genome-wide characterization, phylogeny, chromosome location, structure and expression patterns.

Genomics 2021 May 2;113(3):1565-1578. Epub 2021 Apr 2.

College of Horticulture, Fujian Agriculture and Forestry University/Key Laboratory of Tea Science in University of Fujian Province, Fuzhou 350002, China. Electronic address:

MYB transcription factors play essential roles in many biological processes and environmental stimuli. However, the functions of the MYB transcription factor family in tea plants have not been elucidated. Here, a total of 122 CsR2R3-MYB genes were identified from the chromosome level genome of tea plant (Camellia sinensis). The CsR2R3-MYB genes were phylogenetically classified into 25 groups. Results from the structure analysis of the gene, conserved motifs, and chromosomal distribution supported the relative conservation of the R2R3-MYB genes family in the tea plant. Synteny analysis indicated that 122, 34, and 112 CsR2R3-MYB genes were orthologous to Arabidopsis thaliana, Oryza sativa and C. sinensis var. 'huangdan' (HD), respectively. Tissue-specific expression showed that all CsR2R3-MYB genes had different expression patterns in the tea plant tissues, indicating that these genes may perform diverse functions. The expression patterns of representative R2R3-MYB genes and the regulatory network of the main anthocyanin components were analyzed, which suggested that CsMYB17 may played a key role in the regulation of cya-3-O-gal, del-3-O-gal, cya-3-O-glu and pel-3-O-glu. Results from the qRT-PCR validation of selected genes suggested that CsR2R3-MYB genes were induced in response to drought, cold, GA, and ABA treatments. Overall, this study provides comprehensive and systematic information for research on the function of R2R3-MYB genes in tea plants.
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http://dx.doi.org/10.1016/j.ygeno.2021.03.033DOI Listing
May 2021

Iron Accumulation and Lipid Peroxidation in the Aging Retina: Implication of Ferroptosis in Age-Related Macular Degeneration.

Aging Dis 2021 Apr 1;12(2):529-551. Epub 2021 Apr 1.

1Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Iron is an essential component in many biological processes in the human body. It is critical for the visual phototransduction cascade in the retina. However, excess iron can be toxic. Iron accumulation and reduced efficiency of intracellular antioxidative defense systems predispose the aging retina to oxidative stress-induced cell death. Age-related macular degeneration (AMD) is characterized by retinal iron accumulation and lipid peroxidation. The mechanisms underlying AMD include oxidative stress-mediated death of retinal pigment epithelium (RPE) cells and subsequent death of retinal photoreceptors. Understanding the mechanism of the disruption of iron and redox homeostasis in the aging retina and AMD is crucial to decipher these mechanisms of cell death and AMD pathogenesis. The mechanisms of retinal cell death in AMD are an area of active investigation; previous studies have proposed several types of cell death as major mechanisms. Ferroptosis, a newly discovered programmed cell death pathway, has been associated with the pathogenesis of several neurodegenerative diseases. Ferroptosis is initiated by lipid peroxidation and is characterized by iron-dependent accumulation. In this review, we provide an overview of the mechanisms of iron accumulation and lipid peroxidation in the aging retina and AMD, with an emphasis on ferroptosis.
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http://dx.doi.org/10.14336/AD.2020.0912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990372PMC
April 2021

Non-Coding RNAs as Circulating Biomarkers for the Diagnosis of Intracranial Aneurysm: A Systematic Review and Meta-Analysis.

J Stroke Cerebrovasc Dis 2021 Jun 1;30(6):105762. Epub 2021 Apr 1.

Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, China. Electronic address:

Background: Early diagnosis of intracranial aneurysm (IA) is arduous in the current situation, and no biomarker is available for the screening of IA. We here systematically evaluate the diagnostic value of circulating non-coding RNA (ncRNA) for the diagnosis of IA.

Methods: We searched PubMed, Web of Science, Embase, Scopus and Cochrane Library databases from inception to June 2020. We included studies that investigated the diagnostic performance of circulating ncRNAs for the diagnosis of IA. We performed Random-effect meta-analyses for the diagnostic test accuracy to calculate pooled estimates. Subgroup analyses and sensitivity analyses were conducted to explore the source of heterogeneity.

Results: Thirteen studies, including 1,105 patients and 28 ncRNAs, were included. The pooled sensitivity and specificity were 0.80 (95% confidence interval [CI], 0.76-0.83) and 0.80 (95% CI, 0.76-0.84), respectively, and the area under the hierarchical summary receiver operating characteristic curve was 0.87 (95% CI, 0.84-0.89). The pooled positive and negative likelihood ratios were 3.97 (95% CI, 3.17-4.98) and 0.25 (95% CI, 0.21-0.31), corresponding with a diagnostic odds ratio of 15.63 (95% CI, 10.41-23.47). Subgroup analyses revealed that the diagnostic accuracy of miRNA, lncRNA and circRNA were not significantly different (p > 0.05). Circulating ncRNAs showed higher diagnostic accuracy for patients with unruptured IA than those with ruptured IA (p = 0.0122).

Conclusion: Current evidence suggests that the circulating ncRNA test could be an effective method for universal IA screening. Future clinical studies need to confirm the diagnostic role of specific ncRNAs.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105762DOI Listing
June 2021

Activation of AMPK restored impaired autophagy and inhibited inflammation reaction by up-regulating SIRT1 in acute pancreatitis.

Life Sci 2021 Jul 26;277:119435. Epub 2021 Mar 26.

Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, China. Electronic address:

Aims: Acute pancreatitis (AP) is a common inflammatory disorder with high incidence and mortality. AMPK-SIRT1 pathway is involved in a variety of diseases, but its role in AP remains elusive. This study was aimed to explore the role of AMPK-SIRT1 pathway in AP.

Main Methods: AP models in vivo and vitro were constructed by intraperitoneal administration of L-arginine and caerulein-stimulated respectively. Rat serum amylase, IL-6 and TNF-α were determined by ELISA. The expression levels of AMPK, SIRT1, Beclin-1, LC3 and p62 were determined by qRT-PCR and western blot. The number of autophagosome was checked by transmission electron microscope.

Key Findings: Compared with NC rats, serum amylase, IL-6 and TNF-α were increased in AP rats. The expressions of AMPK and SIRT1 were decreased, while Beclin-1, LC3II/Iratio and p62 were markedly increased in AP rats. After activation of AMPK by metformin, expressions of p-AMPKα, SIRT1 were significantly raised, while expressions of Beclin-1, LC3 II/I, p62, TNF-α, IL-6 were reduced, and the number of autophagosome was decreased significantly in caerulein-stimulated AR42J cells. The inhibition of AMPK by compound C obtained opposite results.

Significance: During AP occurrence, p-AMPK and SIRT1 were down-regulated, leading to the accumulation of p62, increase of autophagic vacuoles, damage of autophagy, and the occurrence of inflammation. It hinted that activation of AMPK restored impaired autophagy and inhibited inflammation reaction by up-regulating SIRT1. Our findings might provide important theoretical basis for explaining the pathogenesis of AP and investigating therapeutic target to treat and prevent AP.
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http://dx.doi.org/10.1016/j.lfs.2021.119435DOI Listing
July 2021

Optimal Candidates to Do Fresh Embryo Transfer in Those Using Oral Contraceptive Pretreatment in IVF Cycles.

Front Physiol 2021 11;12:576917. Epub 2021 Mar 11.

Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objective: Concern regarding the adverse impact of pretreatment of oral contraceptives (OC) prior to ovarian stimulation for fertilization (IVF) on pregnancy outcome has been debated. We investigated factors that may be associated with live birth rate (LBR) in fresh embryo transfer cycles after OC pretreatment.

Methods: A retrospective study was conducted at the Reproductive Center of Ren Ji Hospital, Shanghai, China. 814 women aged 20-35 years undergoing their first autologous IVF cycle and fresh embryo transfer after OC pretreatment were included. Long gonadotropin releasing hormone (GnRH) agonist (a) or GnRH antagonist (ant) protocol was used for ovarian stimulation. Predictive factors for LBR were identified using multivariate logistic regression analysis.

Results: Multivariate logistic regression analysis demonstrated that using GnRH-ant protocol for ovarian stimulation was associated with significantly lower LBR (OR 0.70, 95% CI 0.52-0.93), while endometrial thickness on day of hCG trigger was associated with increased LBR (OR 1.16, 95% CI 1.06-1.27). Despite comparable patients' age, duration of infertility, BMI and basal FSH between GnRH-a and GnRH-ant groups, those using GnRH-ant resulted in significantly lower LBR compared to the GnRH-a group (37.4 vs. 48.5%, = 0.002). Using ROC analysis and a cut-off endometrial thickness of < and ≥ 9.5 mm, those < 9.5 mm using GnRH-ant resulted in significantly lower LBR (28.5 vs. 43.4%, = 0.004), while no differences were noted with an endometrial thickness ≥9.5 mm (49.6 vs. 51.1%, = 0.78).

Conclusions: Live birth was significantly impacted in OC pre-treated GnRH-ant cycles with an endometrial thickness of <9.5 mm on day of hCG trigger. Cryopreservation of all embryos in these cycles should be considered.
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http://dx.doi.org/10.3389/fphys.2021.576917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991902PMC
March 2021

Correction to: M2 Macrophagy-derived exosomal miRNA-5106 induces bone mesenchymal stem cells towards osteoblastic fate by targeting salt-inducible kinase 2 and 3.

J Nanobiotechnology 2021 Mar 27;19(1):88. Epub 2021 Mar 27.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

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http://dx.doi.org/10.1186/s12951-021-00828-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004442PMC
March 2021

Risk stratification by long non-coding RNAs profiling in COVID-19 patients.

J Cell Mol Med 2021 05 23;25(10):4753-4764. Epub 2021 Mar 23.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic worldwide. Long non-coding RNAs (lncRNAs) are a subclass of endogenous, non-protein-coding RNA, which lacks an open reading frame and is more than 200 nucleotides in length. However, the functions for lncRNAs in COVID-19 have not been unravelled. The present study aimed at identifying the related lncRNAs based on RNA sequencing of peripheral blood mononuclear cells from patients with SARS-CoV-2 infection as well as health individuals. Overall, 17 severe, 12 non-severe patients and 10 healthy controls were enrolled in this study. Firstly, we reported some altered lncRNAs between severe, non-severe COVID-19 patients and healthy controls. Next, we developed a 7-lncRNA panel with a good differential ability between severe and non-severe COVID-19 patients using least absolute shrinkage and selection operator regression. Finally, we observed that COVID-19 is a heterogeneous disease among which severe COVID-19 patients have two subtypes with similar risk score and immune score based on lncRNA panel using iCluster algorithm. As the roles of lncRNAs in COVID-19 have not yet been fully identified and understood, our analysis should provide valuable resource and information for the future studies.
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http://dx.doi.org/10.1111/jcmm.16444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107096PMC
May 2021

A flexible ultrasensitive optoelectronic sensor array for neuromorphic vision systems.

Nat Commun 2021 03 19;12(1):1798. Epub 2021 Mar 19.

Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang, China.

The challenges of developing neuromorphic vision systems inspired by the human eye come not only from how to recreate the flexibility, sophistication, and adaptability of animal systems, but also how to do so with computational efficiency and elegance. Similar to biological systems, these neuromorphic circuits integrate functions of image sensing, memory and processing into the device, and process continuous analog brightness signal in real-time. High-integration, flexibility and ultra-sensitivity are essential for practical artificial vision systems that attempt to emulate biological processing. Here, we present a flexible optoelectronic sensor array of 1024 pixels using a combination of carbon nanotubes and perovskite quantum dots as active materials for an efficient neuromorphic vision system. The device has an extraordinary sensitivity to light with a responsivity of 5.1 × 10 A/W and a specific detectivity of 2 × 10 Jones, and demonstrates neuromorphic reinforcement learning by training the sensor array with a weak light pulse of 1 μW/cm.
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http://dx.doi.org/10.1038/s41467-021-22047-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979753PMC
March 2021

Exploration of the cortical pathophysiology underlying visual disturbances in schizophrenia comorbid with depressive disorder-An evidence from mouse model.

Brain Behav 2021 May 17;11(5):e02113. Epub 2021 Mar 17.

Laboratory of Psychiatric-Neuroimaging-Genetic and Cor-morbidity (PNGC_Lab), Tianjin Anding Hospital, Mental Health Centre of Tianjin, Affiliated Teaching Hospital of Tianjin Medical University, Tianjin, China.

Introduction: Patients with schizophrenia frequently present with visual disturbances including hallucination, and this symptom is particularly prevalent in individuals with comorbid depressive disorders. Currently, little is known about the neurobiological mechanisms of such psychiatric symptoms, and few explanations for the co-occurrence of schizophrenia, depression, and visual disturbances are available.

Methods: In this study, we generated a mouse schizophrenia model in which depressive symptoms were also induced. We adopted in vivo two-photon calcium imaging and ex vivo electrophysiological recording of the primary visual cortex to reveal the synaptic transmission and neural activity in the mouse schizophrenia model.

Results: In vivo two-photon calcium imaging and ex vivo electrophysiological recording of the primary visual cortex revealed impaired synaptic transmission and abnormal neural activity in the schizophrenia model, but not in the depression model. These functional deficits were most prominent in the combined schizophrenia and depression model.

Conclusion: Overall, our data support a mechanism by which the visual cortex plays a role in visual disturbances in schizophrenia.
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http://dx.doi.org/10.1002/brb3.2113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119859PMC
May 2021

Addressing the role of 11β-hydroxysteroid dehydrogenase type 1 in the development of polycystic ovary syndrome and the putative therapeutic effects of its selective inhibition in a preclinical model.

Metabolism 2021 06 12;119:154749. Epub 2021 Mar 12.

Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China. Electronic address:

Background: Polycystic ovary syndrome (PCOS) is the most common metabolic and endocrine disorder among reproductive-age women, and the leading cause of anovulatory infertility. 11β-hydroxysteroid dehydrogenases-1 (11β-HSD1) catalysing the conversion of inactive cortisone to active cortisol plays a crucial role in various metabolic diseases. However, whether 11β-HSD1 is associated with the pathogenesis of PCOS and whether 11β-HSD1 can be a treating target of PCOS remain unknown.

Methods: This study was first designed to explore the role of 11β-HSD1 in PCOS development and the effect of selective 11β-HSD1 inhibitor administration on PCOS treatment. Follicular fluid and granulosa cells (GCs) were collected from 32 non-PCOS patients and 37 patients with PCOS to measure cortisol and 11β-HSDs levels. Female Sprague-Dawley rats (3-week-old) were injected with dehydroepiandrosterone (DHEA) to induce PCOS and their ovaries were collected to measure the abundance of corticosterone (CORT) and 11β-HSDs. To determine the role of 11β-HSD1 in PCOS development, we overexpressed 11β-HSD1 in the ovaries of female rats (5-week-old) or knocked down the expression of 11β-HSD1 in the ovaries from PCOS rats via lentivirus injection. After lentivirus infection, the body weights, ovarian weights, estrous cycles, reproductive hormones and morphology of the ovary were analysed in rats from different experimental groups. Then to figure out the translational potential of the selective 11β-HSD1 inhibitor in treating PCOS, PCOS rats were treated with BVT.2733, a selective 11β-HSD1 inhibitor and a cluster of PCOS-like traits were analysed, including insulin sensitivity, ovulatory function and fertility of rats from the Control, PCOS and PCOS+BVT groups. Rat ovarian explants and human GCs were used to explore the effect of CORT or cortisol on ovarian extracellular matrix remodelling.

Results: The elevated expression of 11β-HSD1 contributed to the increased cortisol and corticosterone (CORT) concentrations observed in the ovaries of PCOS patients and PCOS rats respectively. Our results showed that ovarian overexpression of 11β-HSD1 induced a cluster of PCOS phenotypes in rats including irregular estrous cycles, reproductive hormone dysfunction and polycystic ovaries. While knockdown of ovarian 11β-HSD1 of PCOS rats reversed these PCOS-like changes. Additionally, the selective 11β-HSD1 inhibitor BVT.2733 alleviated PCOS symptoms such as insulin resistance (IR), irregular estrous cycles, reproductive hormone dysfunction, polycystic ovaries, ovulatory dysfunction and subfertility. Moreover, we showed that cortisol target ovarian insulin signalling pathway and ovarian extracellular matrix (ECM) remodelling in vivo, in ovarian explants and in GCs.

Conclusion: Elevated 11β-HSD1 abundance in ovarian is involved in the pathogenesis of PCOS by impairing insulin signalling pathway and ECM remodelling. Selective inhibition of 11β-HSD1 ameliorates a cluster of PCOS phenotypes. Our study demonstrates the selective 11β-HSD1 inhibitor as a novel and promising strategy for the treatment of PCOS.
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http://dx.doi.org/10.1016/j.metabol.2021.154749DOI Listing
June 2021

Tumor Suppressor Gene XEDAR Promotes Differentiation and Suppresses Proliferation and Migration of Gastric Cancer Cells Through Upregulating the RELA/LXRα Axis and Deactivating the Wnt/β-Catenin Pathway.

Cell Transplant 2021 Jan-Dec;30:963689721996346

Department of General Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

X-linked ectodermal dysplasia receptor (XEDAR) is a new member of the tumor necrosis factor receptor (TNFR) family that induces cell death. The purpose of this study is to determine the tumor-suppressive potential of XEDAR in the development and differentiation of gastric cancer (GC). XEDAR levels were analyzed in human GC tissues and adjacent normal tissues by immunohistochemistry (IHC), quantitative real-time reverse transcription PCR (RT-qPCR), and Western blot analysis. We found that XEDAR expression was significantly downregulated in GC tissues and further decreased in low differentiated GC tissues. Overexpression of XEDAR in MKN45 and MGC803 cells suppressed the ability of cell proliferation and migration, whereas silencing XEDAR showed the opposite effect. Additionally, XEDAR silencing resulted in the upregulation of the differentiation molecular markers β-catenin, CD44 and Cyclin D1 at the protein levels, whereas XEDAR overexpression showed the opposite effect. Notably, XEDAR positively regulated the expression of liver X receptor alpha (LXRα) through upregulating the RELA gene that was characterized as a transcription factor of LXRα in this study. Inhibition of LXRα by GSK2033 or activation of the Wnt/β-catenin pathway by Wnt agonist 1 impaired the effect of XEDAR overexpression on differentiation of MKN45 cells. Moreover, inhibition of RELA mediated by siRNA could promote cell proliferation/migration and rescue the effect of XEDAR overexpression on cell behaviors and expression of genes. Subsequently, overexpression of XEDAR suppressed the growth of GC cells in . Taken together, our findings showed that XEDAR could promote differentiation and suppress proliferation and invasion of GC cells.
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http://dx.doi.org/10.1177/0963689721996346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923976PMC
February 2021

Genetic Analysis of Korean Adult Patients with Nontuberculous Mycobacteria Suspected of Primary Ciliary Dyskinesia Using Whole Exome Sequencing.

Yonsei Med J 2021 Mar;62(3):224-230

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: Nontuberculous mycobacteria (NTM) is ubiquitous in the environment, but NTM lung disease (NTM-LD) is uncommon. Since exposure to NTM is inevitable, patients who develop NTM-LD are likely to have specific susceptibility factors, such as primary ciliary dyskinesia (PCD). PCD is a genetically heterogeneous disorder of motile cilia and is characterized by chronic respiratory tract infection, organ laterality defect, and infertility. In this study, we performed whole exome sequencing (WES) and investigated the genetic characteristics of adult NTM patients with suspected PCD.

Materials And Methods: WES was performed in 13 NTM-LD patients who were suspected of having PCD by clinical symptoms and/or ultrastructural ciliary defect observed by transmission electron microscopy. A total of 45 PCD-causing genes, 23 PCD-candidate genes, and 990 ciliome genes were analyzed.

Results: Four patients were found to have biallelic loss-of-function (LoF) variants in the following PCD-causing genes: , , , and . In four other patients, only one LoF variant was identified, while the remaining five patients did not have any LoF variants.

Conclusion: At least 30.8% of NTM-LD patients who were suspected of having PCD had biallelic LoF variants, and an additional 30.8% of patients had one LoF variant. Therefore, PCD should be considered in patients with NTM-LD with symptoms or signs suspicious of PCD.
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http://dx.doi.org/10.3349/ymj.2021.62.3.224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934102PMC
March 2021