Publications by authors named "Shan Wu"

346 Publications

Atrazine Promoted Epithelial Ovarian Cancer Cells Proliferation and Metastasis by Inducing Low Dose Reactive Oxygen Species (ROS).

Iran J Biotechnol 2021 Apr 1;19(2):e2623. Epub 2021 Apr 1.

Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun 130041, China.

Background: Atrazine (ATZ) is a triazine herbicide that is widely used in agriculture and has been detected in surface and underground water. Recently, laboratory and epidemiological research have found that the bioaccumulation of ATZ in the environment leads to biotoxicity in the human immune and endocrine systems and results in tumor development.

Objective: To investigate the effects of ATZ exposure on epithelial ovarian cancer (EOC) cells and elucidate the potential mechanisms governing these effects.

Materials And Methods: The human EOC cell lines Skov3 and A2780 were used in this study to explore the effects and mechanisms of ATZ exposure on EOC. The mouse embryonic osteoblastic precursor MC3T3-E1 cells served as the control cells to determine the effects of ATZ on cancer cell lines. After exposure to ATZ, the MTT assay, flow cytometry, the colony formation assay, immunohistochemical staining, the cell scratch assay, and the Transwell assay were used to evaluate the proliferative activity, invasion, and migration capabilities of EOC cell lines. Moreover, flow cytometry was also applied to detect the level of reactive oxygen species (ROS) in these two EOC cell lines, as well as the MC3T3-E1 cells. To further illustrate the underlying mechanisms governing the effect of ATZ on EOC, real-time PCR and Western blotting were employed to assess the transcription and the expression level of Stat3 signaling pathway-related genes in Skov3 and MC3T3-E1 cells.

Results: The results showed that following ATZ treatment, the cell proliferation, migration, and invasion potencies of Skov3 and A2780 cells were increased compared to those of the control group. Meanwhile, the ROS levels of EOC and MC3T3-E1 cells were notably elevated after ATZ treatment. In Skov3 cells, the expression levels of p53 and p21 were downregulated, while those of Cyclin E, vascular endothelial growth factor (VEGF), matrix metallopeptidase 2 (MMP2), MMP9, signal transducers and activators of transcription 3 (Stat3), and p-Stat3 were upregulated by ATZ treatment. In MC3T3-E1 cells, however, ATZ treatment did not affect the level of p53/p21 mRNA compared to the control groups. Moreover, there was no significant change in the expression levels of Stat3 and p-Stat3 in MC3T3-E1 cells exposed to ATZ. This phenomenon was observed while the proliferation rate was enhanced in MC3T3-E1 cells by ATZ.

Conclusions: The results of this study suggest that ATZ effectively promotes the proliferation and metastasis of EOC cells through the Stat3 signaling pathway by inducing low levels of ROS. Additionally, although ATZ might also induce proliferative potential in normal cells, the mechanisms governing its effects in these cells might be different from those in EOC cells.
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http://dx.doi.org/10.30498/IJB.2021.2623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358173PMC
April 2021

The Mutation of Arabidopsis Highlights How the Thiamin Economy Impacts the Methylerythritol 4-Phosphate Pathway.

Front Plant Sci 2021 6;12:721391. Epub 2021 Aug 6.

Department of Horticultural Sciences, University of Florida, Gainesville, FL, United States.

The thiamin-requiring mutants of Arabidopsis have a storied history as a foundational model for biochemical genetics in plants and have illuminated the central role of thiamin in metabolism. Recent integrative genetic and biochemical analyses of thiamin biosynthesis and utilization imply that leaf metabolism normally operates close to thiamin-limiting conditions. Thus, the mechanisms that allocate thiamin-diphosphate (ThDP) cofactor among the diverse thiamin-dependent enzymes localized in plastids, mitochondria, peroxisomes, and the cytosol comprise an intricate thiamin economy. Here, we show that the classical () mutant is a point mutation in plastid localized (), a key regulated enzyme in the methylerythritol 4-phosphate (MEP) isoprene biosynthesis pathway. Substitution of a lysine for a highly conserved glutamate residue (E323) located at the subunit interface of the homodimeric enzyme conditions a hypomorphic phenotype that can be rescued by supplying low concentrations of thiamin in the medium. Analysis of leaf thiamin vitamers showed that supplementing the medium with thiamin increased total ThDP content in both wild type and mutant plants, supporting a hypothesis that the mutant DXS1 enzyme has a reduced affinity for the ThDP cofactor. An unexpected upregulation of a suite of biotic-stress-response genes associated with accumulation of downstream MEP intermediate MEcPP suggests that causes mis-regulation of DXS1 activity in thiamin-supplemented plants. Overall, these results highlight that the central role of ThDP availability in regulation of DXS1 activity and flux through the MEP pathway.
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http://dx.doi.org/10.3389/fpls.2021.721391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377734PMC
August 2021

Dietary multivalent anti-Helicobacter pylori immunoglobulin Y significantly increase the H. pylori eradication and improve the clinical symptoms in patients.

Helicobacter 2021 Oct 11;26(5):e12843. Epub 2021 Aug 11.

Department of Biological Engineering, Sichuan University of Science & Engineering, Zigong, China.

Background: The oral chicken immunoglobulin Y (IgY) as a novel model of immunotherapy to control Helicobacter pylori (H. pylori, Hp) infection has gained much interest in recent years. However, none of the current IgY therapies showed a total eradication of H. pylori on patients.

Methods: In this report, the recombinant antigens of H. pylori, including UreB (1710 bp), BabA2 (1269 bp), and FlaA (399 bp), were, respectively, expressed and purified, and then mixed and subjected to immunize laying hens for the preparation of multivalent anti-H. pylori immunoglobulin Y (anti-Hp mIgY). Next, the biological activities of anti-Hp mIgY, including the recognition to antigens and the inhibition on H. pylori growth, were tested. Moreover, to perform a clinical trial, 94 Hp-infected patients, according to the values of C urea breath test and the characteristics of gastroscopy of volunteers, were enrolled to evaluate the effects of dietary anti-Hp mIgY against H. pylori infection. After continuous dietary of anti-Hp mIgY for 2 weeks, the oral administration was terminated. The clinical symptoms of the patients were followed up at 2nd, 4th, and 6th week, respectively, and the C urea breath test were re-examined at 6th week.

Results: The anti-Hp mIgY could bind to recombinant antigens very well, and the titers of anti-Hp mIgY to UreB, Baba2, and FlaA, are 62.5, 125, and 250 μg/ml, respectively. The in vitro antibacterial test showed that the 2 mg/ml of anti-Hp mIgY could completely inhibit the H. pylori growth for 36 h. After a 2-week dietary of anti-Hp mIgY, the value of C urea breath test was significantly decreased by 56.0% (25.9 ± 14.1 vs 11.4 ± 9.78, p < 0.001), the total improvement rate of clinical symptoms in volunteers was 87.3%, and the H. pylori eradication rate was 30.6%.

Conclusion: Two-week dietary of anti-Hp mIgY greatly improved the clinical symptoms and the quality of life of Hp-infected patients, and the H. pylori eradication rate reached up to 30.6%.
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http://dx.doi.org/10.1111/hel.12843DOI Listing
October 2021

Anthocyanin extract from Lycium ruthenicum enhanced production of biomass and polysaccharides during submerged fermentation of Agaricus bitorquis (Quél.) Sacc. Chaidam.

Bioprocess Biosyst Eng 2021 Jul 23. Epub 2021 Jul 23.

College of Agriculture and Animal Husbandry, Qinghai University, No.251 Ningda Road, Xining, 810016, Qinghai, China.

Agaricus bitorquis (Quél.) Sacc. Chaidam (ABSC) is a wild edible fungus uniquely found in the Tibet Plateau. ABSC is rich in polysaccharides that are considered biologically active. This study aimed to determine the feasibility of enhancing exopolysaccharide (EPS) production by ABSC in shake flask culture by supplementing the fermentation medium with anthocyanin extract. Different concentrations of Lycium ruthenicum Murr. (LRM) anthocyanin crude extract were tested on ABSC fermentation. The activity of phosphoglucose isomerase (PGI), phosphoglucose mutase (PGM), and phosphomannose isomerase (PMI), enzymes presumably involved in EPS synthesis by ABSC, was determined. ABSC transcriptomic profile in response to the presence of anthocyanins during fermentation was also investigated. LRM anthocyanin crude extract (0.06 mg/mL) was most effective in increasing EPS content and mycelial biomass (by 208.10% and 105.30%, respectively, P < 0.01). The activity of PGI, PGM, and PMI was increased in a medium where LRM anthocyanin extract and its main components (proanthocyanidins and petunia anthocyanin) were added. RNA-Seq analysis showed that 349 genes of ABSC were differentially expressed during fermentation in the medium containing anthocyanin extract of LRM; 93 genes were up-regulated and 256 genes down-regulated. From gene ontology enrichment analysis, differentially expressed genes were mostly assigned to carbohydrate metabolism and signal transduction categories. Collectively, LRM anthocyanins extract positively affected EPS production and mycelial biomass during ABSC fermentation. Our study provides a novel strategy for improving EPS production and mycelial growth during ABSC liquid submerged fermentation.
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http://dx.doi.org/10.1007/s00449-021-02605-8DOI Listing
July 2021

Polysaccharides Ameliorate Diet-Induced Gallstone Formation by Modulating Synthesis of Bile Acids and the Gut Microbiota.

Front Pharmacol 2021 1;12:701003. Epub 2021 Jul 1.

Digestive Endoscopic Center, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Cholesterol gallstone (CG) disease has relationships with several metabolic abnormalities. polysaccharides (APS) have been shown to have multiple benefits against metabolic disorders. We attempted to uncover the effect and mechanism of action of APS on diet-induced CG formation in mice. Animals were fed a chow diet or lithogenic diet (LD) with or without APS supplementation. The effect of APS on CG formation was evaluated. The level of individual bile acids (BAs) in gallbladder bile and ileum were measured by liquid chromatography-tandem mass spectrometry. Real-time reverse transcription-quantitative polymerase chain reaction and western blotting were used to assess expression of the genes involved in BA metabolism and the enterohepatic circulation. Cecal contents were collected to characterize microbiota profiles. APS ameliorated LD-induced CG formation in mice. APS reduced the level of total cholesterol, bile acid hydrophobicity index and cholesterol saturation index in gallbladder bile. The protective effect of APS might result from reduced absorption of cholic acid in the intestine and increased hepatic BA synthesis. APS relieved the LD-induced activation of the intestinal farnesoid X receptor and decreased ileal expression of fibroblast growth factor 15. In the liver, expression of cytochrome P450 () enzyme and was increased, whereas expression of adenosine triphosphate-binding cassette () transporters and was decreased by APS. APS improved the diversity of the gut microbiota and increased the relative abundance of the Bacteroidetes phylum. APS had demonstratable benefits against CG disease, which might be associated with enhanced BA synthesis and improved gut microbiota. Our results suggest that APS may be a potential strategy for the prevention of CG disease.
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http://dx.doi.org/10.3389/fphar.2021.701003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281024PMC
July 2021

Methylenetetrahydrofolate Reductase Gene Polymorphism-Dietary Pattern Interaction on Hyperhomocysteinemia in a Chinese Population: A Cross-Sectional Study.

Front Cardiovasc Med 2021 24;8:638322. Epub 2021 Jun 24.

Health Management Institute, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People's Liberation Army General Hospital, Beijing, China.

Hyperhomocysteinemia (Hhcy) has been recognized as a risk factor of several chronic diseases. There is accumulating evidence that both genetic and dietary factors had a notable impact on the risk of Hhcy. The present study aims to investigate the interaction effect on Hhcy between methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and dietary intake. Data were collected in a cross-sectional survey conducted in China; 3,966 participants with complete information on sociodemographic characteristics, anthropometric measurements, and dietary intake were included in the analyses. Dietary patterns were identified by factor analysis combined with cluster analysis. Blood samples were collected and genotypes were tested. Both the multiplicative statistical model and the additive model were conducted to investigate the interactive effects. Proportions of genotypes among participants were 29.2% for , 47.4% for , and 23.4% for . Three dietary patterns were identified, namely, the balanced pattern, the snack pattern, and the high-meat pattern. Compared with the balanced pattern, the other two patterns were associated with an elevated risk of Hhcy [the snack pattern: odds ratio (OR) 1.2, 95% confidence interval (CI) 1.0-1.5; the high-meat pattern: OR 1.3, 95% CI 1.1-1.6] after adjustment for age group, gender, residential region, and genotypes. A multiplicative interaction between the high-meat pattern and genotype was observed, and synergistic effects between both the snack pattern and the high-meat pattern with were identified. Our results indicated that polymorphism and dietary patterns had interactive effects on Hhcy among the Chinese population. Subsequent targeted and appropriate dietary guidelines should be recommended for high-risk populations or patients of Hhcy carrying specific genotypes.
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http://dx.doi.org/10.3389/fcvm.2021.638322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263928PMC
June 2021

Two Cases of Well Controlled Chronic Spontaneous Urticaria Triggered by the Moderna COVID-19 Vaccine.

Allergy Rhinol (Providence) 2021 Jan-Dec;12:21526567211026271. Epub 2021 Jun 24.

Allergy/Immunology Associates Inc., Mayfield Heights, Ohio.

Chronic spontaneous urticaria (CSU, chronic idiopathic urticaria) is a clinical diagnosis characterized by recurrent urticaria of unknown origin, with or without angioedema, that occurs for six weeks or longer. Management of CSU includes a second-generation H1 antihistamine and/or elimination of exacerbating factors. If initial treatment is unsuccessful, trials of first generation H1 antihistamine, H2 blocking antihistamine, leukotriene-receptor antagonist, anti-inflammatory or immunosuppressive agents may be administered. Exacerbating factors include stress, environmental conditions, medications, physical stimuli, and infections. We report the first two cases of a COVID-19 vaccine triggered relapse of CSU that was previously well controlled on therapy.
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http://dx.doi.org/10.1177/21526567211026271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236777PMC
June 2021

Thymocytes induce renal tubular epithelial cells to undergo the epithelial-to-mesenchymal transition.

Asian Pac J Allergy Immunol 2021 Jul 11. Epub 2021 Jul 11.

Department of Pathology, The First Hospital of Jilin University, Changchun, China.

Background: Renal tubulointerstitial fibrosis is known to occur as a result of epithelial cell transformation into myofibroblasts via the epithelial-to-mesenchymal transition (EMT) process. It has been reported that macrophages, regulatory T (Treg) cells, and gamma delta T (γδ T) cells can promote fibrosis via EMT in vivo.

Objective: Our study intended to detect whether thymocytes can induce renal tubular cells to undergo the EMT.

Methods: Rat thymocytes were activated by phytohemagglutinin and concanavalin A. The rat renal tubular epithelial cells (NRK-52E) were incubated in a conditioned medium harvested from activated thymocytes or co-cultured with freshly isolated thymocytes for 48 hours. Real-time reverse transcription-polymerase chain reaction, immunofluorescence, and western blotting analysis were used to test the expression of the epithelial and mesenchymal markers in NRK-52E cells. Scratch assay was designed to test the cell migration abilities of NRK-52E cells. Student's t test and oneway analysis of variance test were used for statistical analysis.

Results: The combined stimulation with phytohemagglutinin and concanavalin A activated the primary isolated rat thymocytes. After treatment with conditioned medium or freshly isolated thymocytes, the expression levels of cytokeratin 19 and E-cadherin were downregulated in NRK-52E cells, while the mRNA and protein expression levels of alpha-smooth muscle actin, desmin, and vimentin were upregulated (P < 0.05). We found that the cell migration abilities of the induced NRK-52E cells were significantly improved.

Conclusions: Both activated rat thymocytes (more percentage of CD8+ T cells) and freshly isolated thymocytes have promoting effects on the EMT of NRK-52E cells.
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http://dx.doi.org/10.12932/AP-210221-1075DOI Listing
July 2021

Tunable room-temperature ferromagnetism in Co-doped two-dimensional van der Waals ZnO.

Nat Commun 2021 Jun 25;12(1):3952. Epub 2021 Jun 25.

Department of Materials Science and Engineering, University of California, Berkeley, CA, USA.

The recent discovery of ferromagnetism in two-dimensional van der Waals crystals has provoked a surge of interest in the exploration of fundamental spin interaction in reduced dimensions. However, existing material candidates have several limitations, notably lacking intrinsic room-temperature ferromagnetic order and air stability. Here, motivated by the anomalously high Curie temperature observed in bulk diluted magnetic oxides, we demonstrate room-temperature ferromagnetism in Co-doped graphene-like Zinc Oxide, a chemically stable layered material in air, down to single atom thickness. Through the magneto-optic Kerr effect, superconducting quantum interference device and X-ray magnetic circular dichroism measurements, we observe clear evidences of spontaneous magnetization in such exotic material systems at room temperature and above. Transmission electron microscopy and atomic force microscopy results explicitly exclude the existence of metallic Co or cobalt oxides clusters. X-ray characterizations reveal that the substitutional Co atoms form Co states in the graphitic lattice of ZnO. By varying the Co doping level, we observe transitions between paramagnetic, ferromagnetic and less ordered phases due to the interplay between impurity-band-exchange and super-exchange interactions. Our discovery opens another path to 2D ferromagnetism at room temperature with the advantage of exceptional tunability and robustness.
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http://dx.doi.org/10.1038/s41467-021-24247-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233323PMC
June 2021

Intestinal Flora is a Key Factor in Insulin Resistance and Contributes to the Development of Polycystic Ovary Syndrome.

Endocrinology 2021 Oct;162(10)

Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.

Context: The key gut microbial biomarkers for polycystic ovarian syndrome (PCOS) and how dysbiosis causes insulin resistance and PCOS remain unclear.

Objective: To assess the characteristics of intestinal flora in PCOS and explore whether abnormal intestinal flora can affect insulin resistance and promote PCOS and whether chenodeoxycholic acid (CDCA) can activate intestinal farnesoid X receptor (FXR), improving glucose metabolism in PCOS.

Setting And Design: The intestinal flora of treatment-naïve PCOS patients and hormonally healthy controls was analyzed. Phenotype analysis, intestinal flora analysis, and global metabolomic profiling of caecal contents were performed on a letrozole-induced PCOS mouse model; similar analyses were conducted after 35 days of antibiotic treatment on the PCOS mouse model, and glucose tolerance testing was performed on the PCOS mouse model after a 35-day CDCA treatment. Mice receiving fecal microbiota transplants from PCOS patients or healthy controls were evaluated after 10 weeks.

Results: Bacteroides was significantly enriched in treatment-naïve PCOS patients. The enrichment in Bacteroides was reproduced in the PCOS mouse model. Gut microbiota removal ameliorated the PCOS phenotype and insulin resistance and increased relative FXR mRNA levels in the ileum and serum fibroblast growth factor 15 levels. PCOS stool-transplanted mice exhibited insulin resistance at 10 weeks but not PCOS. Treating the PCOS mouse model with CDCA improved glucose metabolism.

Conclusions: Bacteroides is a key microbial biomarker in PCOS and shows diagnostic value. Gut dysbiosis can cause insulin resistance. FXR activation might play a beneficial rather than detrimental role in glucose metabolism in PCOS.
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http://dx.doi.org/10.1210/endocr/bqab118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375444PMC
October 2021

Structural, magnetic, and electronic evolution of the spin-ladder system BaFeS Se with isoelectronic substitution.

Phys Rev B 2020 Jun;101(23)

Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.

We report experimental studies of a series of BaFeS Se (0 ⩽ ⩽ 3) single crystals and powder specimens using x-ray diffraction, neutron-diffraction, muon-spin-relaxation, and electrical transport measurements. A structural transformation from (BaFeS) to (BaFeSe) was identified around = 0.7 - 1. Neutron-diffraction measurements on the samples with = 0.2, 0.4, and 0.7 reveal that the Néel temperature of the stripe antiferromagnetic order is gradually suppressed from ~120 to 85 K, while the magnitude of the ordered Fe moments shows very little variation. Similarly, the block antiferromagnetic order in BaFeSe remains robust for 1.5 ⩽ ⩽ 3 with negligible variation in the ordered moment and a slight decrease of the Néel temperature from 250 K ( = 3) to 225 K ( = 1.5). The sample with = 1 near the and border shows coexisting, two-dimensional, short-range stripe- and block-type antiferromagnetic correlations. The system remains insulating for all , but the thermal activation gap shows an abrupt increase when traversing the boundary from the stripe phase to the block phase. The results demonstrate that the crystal structure, magnetic order, and electronic properties are strongly coupled in the BaFeS Se system.
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http://dx.doi.org/10.1103/PhysRevB.101.235134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204408PMC
June 2020

Clinical features of NK/T-cell EBV-associated LPD manifested as gastrointestinal symptoms in patients with normal immunity: a case report and literature review.

BMC Gastroenterol 2021 Jun 10;21(1):254. Epub 2021 Jun 10.

Department of Gastroenterology, The Second Xiangya Hospital, Changsha, 410011, Hunan, China.

Background: Epstein-Barr virus (EBV)-associated NK/T-cell lymphoproliferative disorder (LPD) involving the gastrointestinal tract is rarely observed in individuals with normal immunity. The atypical clinical, colonoscopic manifestations often confuse clinicians, leading to misdiagnosis and delays in the treatment.

Case Presentation: Herein, we reported on a single case of a patient with gastrointestinal symptoms. Several colonoscopies showed multiple irregular ulcerations, while biopsies showed colitis with infiltration of neutrophils or lymphocytes. After 2 months follow-up, the patient was diagnosed with the extranodal NK/T-cell lymphoma, nasal type, and was treated with thalidomide. Later on, a second check was performed on his first pathological sample. Immunohistochemistry revealed EBV associated NK/T-cell LPD.

Conclusions: Multiple, multiform, and segmental gastrointestinal ulcers should be an indication for EBV infection, regardless of the presence of fever, lymphadenopathy, and hepatosplenomegaly. If EBV-associated NK/T-cell LPD is considered, serum EBV-DNA should be measured, and the tissue obtained by biopsy should be carefully analyzed for a positive expression of the EBER marker.
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http://dx.doi.org/10.1186/s12876-021-01718-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191100PMC
June 2021

Jackfruit Anaphylaxis in a Latex Allergic Non-Healthcare Worker.

Allergy Rhinol (Providence) 2021 Jan-Dec;12:21526567211009195. Epub 2021 May 26.

Allergy/Immunology Associates Inc, Mayfield Heights, Ohio.

Introduction: Anaphylaxis to jackfruit (Artocarpus heterophyllus) is rare. Two previously reported cases have been published in two healthcare workers from jackfruit endemic regions. Latex allergy and birch pollen cross reactivity have both been associated with jackfruit anaphylaxis, providing two separate mechanisms of sensitization. We present a case of jackfruit anaphylaxis in a young latex allergic non-healthcare worker in a non-endemic region.

Case Report: A 21-year-old male had an anaphylactic reaction immediately after ingesting dried jackfruit. He had a history of allergic rhinitis and latex allergy. He was born premature and required neonatal intensive care and multiple surgeries in infancy, which could possibly be the source of his latex sensitization. Skin prick testing was positive for jackfruit and latex.

Discussion: Jackfruit anaphylaxis has only been described in conjunction with a latex allergy or a birch pollen allergy. As jackfruit becomes more available across the world, it is important for physicians and patients with these sensitivities to be aware of these possible cross reactions. Fruit sensitivities in latex allergic patients have been well established as Latex-fruit syndrome. Our case highlights the association of latex sensitization and jackfruit anaphylaxis.

Conclusion: We present a case of Jackfruit anaphylaxis associated with latex allergy in a non-healthcare worker from Midwestern United States. As jackfruit becomes more popular in non-endemic regions, its possible cross reactivity with latex, as well as birch pollen should be recognized.
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http://dx.doi.org/10.1177/21526567211009195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165822PMC
May 2021

A chromosome-level genome of a Kordofan melon illuminates the origin of domesticated watermelons.

Proc Natl Acad Sci U S A 2021 Jun;118(23)

Department of Animal and Plant Sciences, University of Sheffield, Sheffield S10 2TN, United Kingdom

Wild relatives or progenitors of crops are important resources for breeding and for understanding domestication. Identifying them, however, is difficult because of extinction, hybridization, and the challenge of distinguishing them from feral forms. Here, we use collection-based systematics, iconography, and resequenced accessions of and other species of to search for the potential progenitor of the domesticated watermelon. A Sudanese form with nonbitter whitish pulp, known as the Kordofan melon ( subsp. ), appears to be the closest relative of domesticated watermelons and a possible progenitor, consistent with newly interpreted Egyptian tomb paintings that suggest that the watermelon may have been consumed in the Nile Valley as a dessert by 4360 BP. To gain insights into the genetic changes that occurred from the progenitor to the domesticated watermelon, we assembled and annotated the genome of a Kordofan melon at the chromosome level, using a combination of Pacific Biosciences and Illumina sequencing as well as Hi-C mapping technologies. The genetic signature of bitterness loss is present in the Kordofan melon genome, but the red fruit flesh color only became fixed in the domesticated watermelon. We detected 15,824 genome structural variants (SVs) between the Kordofan melon and a typical modern cultivar, "97103," and mapping the SVs in over 400 accessions revealed shifts in allelic frequencies, suggesting that fruit sweetness has gradually increased over the course of watermelon domestication. That a likely progenitor of the watermelon still exists in Sudan has implications for targeted modern breeding efforts.
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http://dx.doi.org/10.1073/pnas.2101486118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201767PMC
June 2021

The GAR/RGG motif defines a family of nuclear alarmins.

Cell Death Dis 2021 05 12;12(5):477. Epub 2021 May 12.

Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Blk MD4, 5 Science Drive 2, Singapore, 117545, Singapore.

The nucleus is the target of autoantibodies in many diseases, which suggests intrinsic nuclear adjuvants that confer its high autoimmunogenicity. Nucleolin (NCL) is one abundant nucleolar autoantigen in systemic lupus erythematosus (SLE) patients and, in lupus-prone mice, it elicits autoantibodies early. With purified NCL, we observed that it was a potent alarmin that activated monocytes, macrophages and dendritic cells and it was a ligand for TLR2 and TLR4. NCL released by necrotic cells also exhibited alarmin activity. The NCL alarmin activity resides in its glycine/arginine-rich (GAR/RGG) motif and can be displayed by synthetic GAR/RGG peptides. Two more GAR/RGG-containing nucleolar proteins, fibrillarin (FBRL) and GAR1, were also confirmed to be novel alarmins. Therefore, the GAR/RGG alarmin motif predicts a family of nucleolar alarmins. The apparent prevalence of nucleolar alarmins suggests their positive contribution to tissue homeostasis by inducing self-limiting tissue inflammation with autoimmunity only occurring when surveillance is broken down.
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http://dx.doi.org/10.1038/s41419-021-03766-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116331PMC
May 2021

Identification of Key Genes for Hepatitis Delta Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis.

Turk J Gastroenterol 2021 02;32(2):169-177

Anhui Provincial Cancer Institute, The First Affiliated Hospital of Anhui Medical University, Anhui, China.

Background: It has been proposed that hepatitis delta virus (HDV) induces hepatic carcinogenesis by distinct molecular events compared with hepatocellular carcinoma (HCC) that is commonly induced by other hepatitis viruses. This study aimed to explore the underlying mechanism by identifying the key genes for HDV-HCC using bioinformatics analysis.

Methods: The GSE107170 dataset was downloaded and the differentially expressed genes (DEGs) were obtained by the online tool GEO2R. Gene otology (GO) functional analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using R packages. The protein-protein interaction (PPI) network was constructed by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Hub genes were selected by Cytoscape software according to degree algorithm. The hub genes were further validated in terms of expression and survival analysis based on public databases.

Results: A total of 93 commonly upregulated genes and 36 commonly downregulated genes were found. The top 5 upregulated hub genes were TFRC, ACTR2, ARPC1A, ARPC3, and ARPC2. The top 5 downregulated hub genes were CTNNB1, CCND1, CDKN1B, CDK4, and CDKN1A. In the validation analysis, the expressions of ARPC1A, ARPC3, and CDK4 were promoted in general liver cancer samples. Higher expressions of ARPC2 and CDK4 and lower expressions of CDKN1A, CCND1, and CDKN1B were associated with worse prognosis in general HCC patients.

Conclusion: The present study identifies a series of key genes that may be involved in the carcinogenesis of HDV-HCC and used as prognostic factors.
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http://dx.doi.org/10.5152/tjg.2020.191003DOI Listing
February 2021

Macrophage extracellular traps aggravate iron overload-related liver ischaemia/reperfusion injury.

Br J Pharmacol 2021 Sep 13;178(18):3783-3796. Epub 2021 Jun 13.

Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background And Purpose: Macrophages regulate iron homeostasis in the liver and play important role in hepatic ischaemia/reperfusion (I/R) injury. This study investigates the role of macrophages in iron overload-related hepatocyte damage during liver I/R.

Experimental Approach: Liver biopsies from patients undergoing partial hepatectomy with or without hepatic portal occlusion were recruited and markers of hepatocyte cell death and macrophage extracellular traps (METs) were detected. A murine hepatic I/R model was also established in high-iron diet-fed mice. Ferrostatin-1 and deferoxamine were administered to investigate the role of ferroptosis in hepatic I/R injury. The macrophage inhibitor liposome-encapsulated clodronate was used to investigate the interaction between macrophages and ferroptosis. AML12 hepatocytes and RAW264.7 macrophages were co-cultured in vitro. An inhibitor of macrophage extracellular traps was used to evaluate the role and mechanism of these traps and ferroptosis in hepatic I/R injury.

Key Results: Hepatocyte macrophage extracellular trap formation and ferroptosis were greater in patients who underwent hepatectomy with hepatic portal occlusion and in mice subjected to hepatic I/R. Macrophage extracellular traps increased when macrophages were subjected to hypoxia/reoxygenation and when they were co-cultured with hepatocytes. Ferroptosis increased and post-hypoxic hepatocyte survival decreased, which were reversed by inhibition of macrophage extracellular traps. Ferroptosis inhibition attenuated post-ischaemic liver damage. Moreover, iron overload induced hepatic ferroptosis and exacerbated post-ischaemic liver damage, which were reversed by the iron chelator.

Conclusion And Implications: Macrophage extracellular traps are in volved in regulating ferroptosis highlighting the therapeutic potential of macrophage extracellular traps and ferroptosis inhibition in reducing liver I/R injury.
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http://dx.doi.org/10.1111/bph.15518DOI Listing
September 2021

Analysis of the association between KIN17 expression and the clinical features/prognosis of epithelial ovarian cancer, and the effects of KIN17 in SKOV3 cells.

Oncol Lett 2021 Jun 15;21(6):475. Epub 2021 Apr 15.

Department of Recovery, Nursing School of Jilin University, Changchun, Jilin 130012, P.R. China.

DNA double-strand breaks (DSBs) are an important mechanism of chemotherapy in epithelial ovarian cancer (EOC). Kin17 DNA and RNA binding protein (KIN17) serves a crucial role in DSB repair. In the present study, the association between KIN17 and EOC, and the effects of KIN17 on EOC cells were evaluated. A bioinformatics method was used to determine the mRNA expression levels of KIN17 in EOC and its association with EOC prognosis including overall survival (OS) and progression free survival (PFS) time. Western blotting and immunohistochemical staining were used to evaluate the expression levels of KIN17 in EOC samples. Kaplan-Meier and Cox regression analyses were utilized to analyze risk factors for the OS of patients with EOC. A Cell Counting Kit-8 assay was performed to explore the roles of KIN17 in SKOV3 cells. Both the transcription and expression of KIN17 were upregulated in EOC tissues. Furthermore, the OS of patients with EOC with high mRNA expression levels of KIN17 was shorter than that of patients with EOC with low expression levels. High KIN17 expression was an independent risk factor for EOC prognosis. Furthermore, KIN17 knockdown inhibited the proliferation of SKOV3 cells, enhanced the sensitivity of the cells to cisplatin and inhibited the migration ability of the cells. These results suggested that KIN17 may act as an ideal candidate for therapy and as a prognostic biomarker of EOC, although the underlying mechanisms require further exploration.
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http://dx.doi.org/10.3892/ol.2021.12736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063336PMC
June 2021

The combined therapy of fecal microbiota transplantation and laxatives for functional constipation in adults: A systematic review and meta-analysis of randomized controlled trials.

Medicine (Baltimore) 2021 Apr;100(14):e25390

Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

Objective: Functional constipation is a prevalent, burdensome gastrointestinal disorder whose treatment remains challenging. Combined therapy uniting multiple treatments may be promising. Fecal microbiota transplantation (FMT) which tends to be an etiological treatment has been increasingly investigated in its management. Meanwhile, laxatives are widely used to relieve constipation temporarily, but their overall efficacy is poor. Therefore, we performed meta-analyses of randomized controlled trials to evaluate the joint efficacy of FMT and laxatives in functional constipation.

Methods: We performed a systematic literature search of 6 electronic databases as of August 11, 2020. Randomized controlled trial of FMT together with laxatives vs laxatives alone in functional constipation in adults were included. Two reviewers independently performed the screening, data extraction, and bias assessment. Dichotomous outcome data were synthesized by risk ratio, and measurement data by weighted mean difference (WMD).

Results: A total of 1400 records were identified, of which 5 were eligible (409 patients). Overall, compared to laxatives alone, combined therapy of FMT and laxatives more significantly improved total effective rate (risk ratio: 1.35; 95% confidence interval [CI]: 1.14, 1.60; I2 = 13%), Bristol stool form scale score (WMD: 1.04; 95% CI: 0.57, 1.51; I2 = 76%), reduce Wexner score (WMD: -3.25; 95% CI: -5.58, -0.92; I2 = 92%), Knowles-Eccersley-Scott-Symptom (KESS) score (WMD: -5.65; 95% CI: -7.62, -3.69; I2 = 0%) and patient assessment of constipation quality of life score (WMD: -18.56; 95%; CI: -26.43, -10.68; I2 = 78%). No serious adverse events were reported. The majority of included studies had poor methodological quality.

Conclusion: Combined therapy of FMT and laxatives may be a reasonably effective and safe treatment for people with functional constipation. However, caution is needed with the interpretation of these data due to the small sample size, high heterogeneity, and low quality of the studies. Besides, we expect that more studies will be performed exploring the efficacy and safety of combined therapy for functional constipation.
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http://dx.doi.org/10.1097/MD.0000000000025390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036125PMC
April 2021

Local vibration induced vascular pathological structural changes and abnormal levels of vascular damage indicators.

Microvasc Res 2021 07 6;136:104163. Epub 2021 Apr 6.

Guangdong Provincial Engineering Research Center of Public Health Detection and Assessment, Guangdong Pharmaceutical University, Guangzhou 510310, China; Guangdong Pharmaceutical University, China, NO. 283, Jianghai Dadao Street, Haizhu District, Guangzhou City 510300, China. Electronic address:

Background: The vascular component of the hand-arm-vibration syndrome (HAVS) is often characterized by vibration-induced white fingers (VWF). Active substances secreted by the vascular endothelial cells (VEC) maintain a dynamic balance but damage to the blood vessels may occur when the equilibrium is altered, thus forming an important pathological basis for VWF. This study was aimed at investigating vascular damage indicators as a basis for an early detection of disorders caused by vibration, using the rat tail model.

Methods And Results: Experiments were conducted using a control group of rats not exposed to vibration while two exposed groups having different exposure durations of 7 and 14 days were randomly formed. Following exposure, the structural changes of tail tissue samples in anesthetized rats were observed. Enzyme-linked immunosorbent assay (ELISA) was used for analyzing four vascular damage indicators myosin regulatory light chain (MLC2), endothelin-1 (ET-1), vinculin (VCL) and 5-hydroxytryptamine (5-HT) in tail blood samples. We found that both vascular smooth muscle and endothelial cells displayed changes in morphology characterized by vacuolization and swelling in the vibration-exposed group. The levels of vascular damage indicators were altered under the vibration.

Conclusion: The degree of vascular pathology increased with the longer duration exposure. Furthermore, the levels of MLC2, ET-1 and 5-HT in rat plasma were associated with vascular injury caused by local vibration.
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http://dx.doi.org/10.1016/j.mvr.2021.104163DOI Listing
July 2021

Incorporation of Urinary Neutrophil Gelatinase-Associated Lipocalin and Computed Tomography Quantification to Predict Acute Kidney Injury and In-Hospital Death in COVID-19 Patients.

Kidney Dis (Basel) 2021 Mar 15;7(2):120-130. Epub 2020 Sep 15.

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

Background: The prevalence of acute kidney injury (AKI) in COVID-19 patients is high, with poor prognosis. Early identification of COVID-19 patients who are at risk for AKI and may develop critical illness and death is of great importance.

Objective: The aim of this study was to develop and validate a prognostic model of AKI and in-hospital death in patients with COVID-19, incorporating the new tubular injury biomarker urinary neutrophil gelatinase-associated lipocalin (u-NGAL) and artificial intelligence (AI)-based chest computed tomography (CT) analysis.

Methods: A single-center cohort of patients with COVID-19 from Wuhan Leishenshan Hospital were included in this study. Demographic characteristics, laboratory findings, and AI-assisted chest CT imaging variables identified on hospital admission were screened using least absolute shrinkage and selection operator (LASSO) and logistic regression to develop a model for predicting the AKI risk. The accuracy of the AKI prediction model was measured using the concordance index (C-index), and the internal validity of the model was assessed by bootstrap resampling. A multivariate Cox regression model and Kaplan-Meier curves were analyzed for survival analysis in COVID-19 patients.

Results: One hundred seventy-four patients were included. The median (±SD) age of the patients was 63.59 ± 13.79 years, and 83 (47.7%) were men.u-NGAL, serum creatinine, serum uric acid, and CT ground-glass opacity (GGO) volume were independent predictors of AKI, and all were selected in the nomogram. The prediction model was validated by internal bootstrapping resampling, showing results similar to those obtained from the original samples (i.e., 0.958; 95% CI 0.9097-0.9864). The C-index for predicting AKI was 0.955 (95% CI 0.916-0.995). Multivariate Cox proportional hazards regression confirmed that a high u-NGAL level, an increased GGO volume, and lymphopenia are strong predictors of a poor prognosis and a high risk of in-hospital death.

Conclusions: This model provides a useful individualized risk estimate of AKI in patients with COVID-19. Measurement of u-NGAL and AI-based chest CT quantification are worthy of application and may help clinicians to identify patients with a poor prognosis in COVID-19 at an early stage.
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http://dx.doi.org/10.1159/000511403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573910PMC
March 2021

Short-Range Nematic Fluctuations in Sr_{1-x}Na_{x}Fe_{2}As_{2} Superconductors.

Phys Rev Lett 2021 Mar;126(10):107001

Department of Physics, University of California, Berkeley, California 94720, USA.

Interactions between nematic fluctuations, magnetic order and superconductivity are central to the physics of iron-based superconductors. Here we report on in-plane transverse acoustic phonons in hole-doped Sr_{1-x}Na_{x}Fe_{2}As_{2} measured via inelastic x-ray scattering, and extract both the nematic susceptibility and the nematic correlation length. By a self-contained method of analysis, for the underdoped (x=0.36) sample, which harbors a magnetically ordered tetragonal phase, we find it hosts a short nematic correlation length ξ∼10  Å and a large nematic susceptibility χ_{nem}. The optimal-doped (x=0.55) sample exhibits weaker phonon softening effects, indicative of both reduced ξ and χ_{nem}. Our results suggest short-range nematic fluctuations may favor superconductivity, placing emphasis on the nematic correlation length for understanding the iron-based superconductors.
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http://dx.doi.org/10.1103/PhysRevLett.126.107001DOI Listing
March 2021

The effectiveness and safety of Tuina for tension-type headache: A systematic review and meta-analysis.

Complement Ther Clin Pract 2021 May 19;43:101293. Epub 2021 Jan 19.

The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, China. Electronic address:

Background And Purpose: Tension-type headache (TTH) is one of the most common primary headache diseases in the world and has a serious negative impact on the physical and mental health of patients. Tuina is now widely used to treat tension-type headaches. This article aims to systematically review the evidence about the effectiveness of Tuina on the effectiveness rate, pain intensity, and impact of headache in individuals with TTH.

Methods: Eight databases for randomized controlled trials (RCTs) of Tuina were included in treatments for TTH. Cochrane Collaboration's tool was applied to evaluate the quality of the studies. Confidence in the effect estimates was determined with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. We use the software STATA 12.0 for meta-analysis and TSA software for test sequence analysis.

Results: Seven studies were included with a total sample of 1228 individuals. Meta-analysis results showed that Tuina was superior to drugs for improving the effectiveness rate (RR = 1.49, 95%CI: 1.25 to 1.77, p < 0.01, low evidence). A visual analog scale (VAS) score of Tuina was significantly lower than that of drugs (WMD = -0.738, 95% CI: -1.128 to -0.349, p < 0.01, moderate evidence). The trial sequential analysis showed that the effectiveness of Tuina for TTH was accurate. Adverse events were tolerable.

Conclusion: Tuina has a certain effect in treating tension headache. However, due to the low level of methodological quality included in the article, this conclusion should be considered cautiously. More studies are necessary to strengthen the evidence regarding the effectiveness and safety of Tuina for subjects with TTH.
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http://dx.doi.org/10.1016/j.ctcp.2020.101293DOI Listing
May 2021

The role of early video capsule endoscopy in the diagnosis and prognosis of obscure gastrointestinal bleeding: A multi-center propensity score matching study.

J Gastroenterol Hepatol 2021 Sep 14;36(9):2540-2548. Epub 2021 Apr 14.

Division of Gastroenterology and Hepatology, School of Medicine, Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Jiao Tong University, Renji Hospital, Shanghai, China.

Background And Aim: Video capsule endoscopy (VCE) is a first-line procedure for the diagnosis of obscure gastrointestinal bleeding (OGIB). The opinions on the timing for such diagnostic evaluation remain unclear. We aimed to explore the role of early VCE in OGIB patients.

Methods: A total of 997 patients that underwent VCE at Renji Hospital and Nagoya University from May 15, 2002, to December 28, 2016, were included in this study. We matched patients that underwent early VCE within 14 days of bleeding (early group, n = 678) to patients that did not (late group, n = 319) via 1:1 propensity score matching (PSM). We then compared VCE diagnostic rates and the prevalence of post-VCE rebleeding in patients with initial negative VCE findings within 1 year between these groups before and after PSM.

Results: Following PSM, early VCE was associated with a significantly higher rate of OGIB diagnosis (56.4% vs 45.5%, P = 0.001) and with a significantly lower incidence of rebleeding within 1 year following treatment (24.7% vs 36.7%, P = 0.041). In univariate and multivariate analyses, VCE timing (odds ratio 0.648; 95% confidence interval 0.496-0.847, P = 0.001 and odds ratio 0.666; 95% confidence interval 0.496-0.894, P = 0.007, respectively) was found to be linked with a higher rate of positive findings.

Conclusion: Early VCE can improve the reliability of OGIB diagnosis while also reducing rates of post-VCE rebleeding. This suggests that timely and accurate diagnosis can help to improve OGIB patient treatment and prognosis.
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http://dx.doi.org/10.1111/jgh.15491DOI Listing
September 2021

Sugar modulation of anaerobic-response networks in maize root tips.

Plant Physiol 2021 03;185(2):295-317

Plant Molecular and Cellular Biology, University of Florida, Gainesville, Florida 32611, USA.

Sugar supply is a key component of hypoxia tolerance and acclimation in plants. However, a striking gap remains in our understanding of mechanisms governing sugar impacts on low-oxygen responses. Here, we used a maize (Zea mays) root-tip system for precise control of sugar and oxygen levels. We compared responses to oxygen (21 and 0.2%) in the presence of abundant versus limited glucose supplies (2.0 and 0.2%). Low-oxygen reconfigured the transcriptome with glucose deprivation enhancing the speed and magnitude of gene induction for core anaerobic proteins (ANPs). Sugar supply also altered profiles of hypoxia-responsive genes carrying G4 motifs (sources of regulatory quadruplex structures), revealing a fast, sugar-independent class followed more slowly by feast-or-famine-regulated G4 genes. Metabolite analysis showed that endogenous sugar levels were maintained by exogenous glucose under aerobic conditions and demonstrated a prominent capacity for sucrose re-synthesis that was undetectable under hypoxia. Glucose abundance had distinctive impacts on co-expression networks associated with ANPs, altering network partners and aiding persistence of interacting networks under prolonged hypoxia. Among the ANP networks, two highly interconnected clusters of genes formed around Pyruvate decarboxylase 3 and Glyceraldehyde-3-phosphate dehydrogenase 4. Genes in these clusters shared a small set of cis-regulatory elements, two of which typified glucose induction. Collective results demonstrate specific, previously unrecognized roles of sugars in low-oxygen responses, extending from accelerated onset of initial adaptive phases by starvation stress to maintenance and modulation of co-expression relationships by carbohydrate availability.
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http://dx.doi.org/10.1093/plphys/kiaa029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133576PMC
March 2021

Hyperglycemia aggravates monocyte-endothelial adhesion in human umbilical vein endothelial cells from women with gestational diabetes mellitus by inducing Cx43 overexpression.

Ann Transl Med 2021 Feb;9(3):234

Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: Gestational diabetes mellitus (GDM) is among the most common metabolic diseases during pregnancy and inevitably leads to maternal and fetal complications. Hyperglycemia results in injury to vascular endothelial cells, including monocyte-endothelial adhesion, which is considered to be the initiating factor of vascular endothelial cell injury. Connexin 43 (Cx43) plays a key role in this adhesion process. Therefore, this study aimed to explore the effects of Cx43 on monocyte-endothelial adhesion in GDM-induced injury of vascular endothelial cells.

Methods: Human umbilical vein endothelial cells (HUVECs) were isolated from umbilical cords from pregnant women with and without GDM. THP-1 cells (a human leukemia monocytic cell line) adhering to HUVECs, related molecules [intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)], and the activity of the phosphoinositide 3-kinase/protein kinase B/Nuclear factor- kappa B (PI3K/AKT/NF-κB) signaling pathway were compared between the normal and GDM-HUVECs. Oleamide and specific small interfering ribonucleic acids (siRNAs) were used to inhibit Cx43 expression in GDM-HUVECs to observe the effects of Cx43 on the adhesion of THP-1 cells and HUVECs.

Results: A much higher number of THP-1 cells adhered to GDM-HUVECs than to normal HUVECs. This was accompanied by an increased expression of Cx43, ICAM-1, and VCAM-1, as well as activation of the PI3K/AKT/NF-κB signaling pathway. After the inhibition of Cx43 expression in GDM-HUVECs with oleamide and specific siRNA, THP-1-HUVEC adhesion, ICAM-1 and VCAM-1 expression, and activation of PI3K/AKT/NF-κB signaling pathway were all attenuated. Hyperglycemia was able to increase expression of Cx43 in HUVECs.

Conclusions: For the first time, Cx43 expression was found to be substantially higher in GDM-HUVECs than in normal HUVECs. Hyperglycemia caused the overexpression of Cx43 in HUVECs, which resulted in the activation of the PI3K/AKT/NF-κB signaling pathway and the increase of its downstream adhesion molecules, including ICAM-1 and VCAM-1, ultimately leading to increased monocyte-endothelial adhesion.
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http://dx.doi.org/10.21037/atm-19-4738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940931PMC
February 2021

Short-Term HRV Analysis Using Nonparametric Sample Entropy for Obstructive Sleep Apnea.

Entropy (Basel) 2021 Feb 24;23(3). Epub 2021 Feb 24.

School of Biomedical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.

Obstructive sleep apnea (OSA) is associated with reduced heart rate variability (HRV) and autonomic nervous system dysfunction. Sample entropy (SampEn) is commonly used for regularity analysis. However, it has limitations in processing short-term segments of HRV signals due to the extreme dependence of its functional parameters. We used the nonparametric sample entropy (NPSampEn) as a novel index for short-term HRV analysis in the case of OSA. The manuscript included 60 6-h electrocardiogram recordings (20 healthy, 14 mild-moderate OSA, and 26 severe OSA) from the PhysioNet database. The NPSampEn value was compared with the SampEn value and frequency domain indices. The empirical results showed that NPSampEn could better differentiate the three groups ( < 0.01) than the ratio of low frequency power to high frequency power (LF/HF) and SampEn. Moreover, NPSampEn (83.3%) approached a higher OSA screening accuracy than the LF/HF (73.3%) and SampEn (68.3%). Compared with SampEn (|r| = 0.602, < 0.05), NPSampEn (|r| = 0.756, < 0.05) had a significantly stronger association with the apnea-hypopnea index (AHI). Hence, NPSampEn can fully overcome the influence of individual differences that are prevalent in biomedical signal processing, and might be useful in processing short-term segments of HRV signal.
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http://dx.doi.org/10.3390/e23030267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996273PMC
February 2021

Ferroptosis inducer erastin downregulates androgen receptor and its splice variants in castration‑resistant prostate cancer.

Oncol Rep 2021 04 2;45(4). Epub 2021 Mar 2.

Department of Recovery, Nursing School, Jilin University, Changchun, Jilin 130021, P.R. China.

To date, there is no effective therapy available for the treatment of castration‑resistant prostate cancer (CRPC), and patients generally succumb to the disease within 2 to 4 years. In the progression of CRPC, androgen receptor (AR) and its splice variants play critical roles. Hence, it is necessary to develop a drug to inhibit the expression and activity of the full‑length and splice variants of AR for the treatment of CRPC. Erastin, as the first discovered drug to induce ferroptosis, has been studied in various types of cancer. However, there are few studies focusing on the relationship between erastin and AR. In the present study, western blotting, and sulforhodamine B cell viability, glutathione, lipid peroxidation and reactive oxygen species assays were performed to verify the ferroptosis of CRPC cells; reverse transcription‑quantitative polymerase chain reaction, dual‑luciferase reporter, and lentiviral packaging and lentivirus‑infected cell assays were employed to evaluate how erastin affects AR. A mouse xenograft assay was used to determine the underlying mechanism in vivo. Erastin, as a classical inducer of ferroptosis, can suppress the transcriptional activities of both the full‑length and splice variants in AR models in vitro and in vivo. In addition, when erastin was used for CRPC treatment combined with docetaxel, the growth inhibitory efficacy of docetaxel was found to be enhanced. Thus, these findings indicated that ferroptosis inducer erastin has potential in the treatment of CRPC via targeting AR.
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http://dx.doi.org/10.3892/or.2021.7976DOI Listing
April 2021

Genome-wide association studies provide insights into the genetic determination of fruit traits of pear.

Nat Commun 2021 02 18;12(1):1144. Epub 2021 Feb 18.

Centre of Pear Engineering Technology Research, State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, Jiangsu, China.

Pear is a major fruit tree crop distributed worldwide, yet its breeding is a very time-consuming process. To facilitate molecular breeding and gene identification, here we have performed genome-wide association studies (GWAS) on eleven fruit traits. We identify 37 loci associated with eight fruit quality traits and five loci associated with three fruit phenological traits. Scans for selective sweeps indicate that traits including fruit stone cell content, organic acid and sugar contents might have been under continuous selection during breeding improvement. One candidate gene, PbrSTONE, identified in GWAS, has been functionally verified to be involved in the regulation of stone cell formation, one of the most important fruit quality traits in pear. Our study provides insights into the complex fruit related biology and identifies genes controlling important traits in pear through GWAS, which extends the genetic resources and basis for facilitating molecular breeding in perennial trees.
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http://dx.doi.org/10.1038/s41467-021-21378-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892570PMC
February 2021

The Arabidopsis sucrose non-fermenting-1-related protein kinase AtSnRK2.4 interacts with a transcription factor, AtMYB21, that is involved in salt tolerance.

Plant Sci 2021 Feb 19;303:110685. Epub 2020 Sep 19.

Asian Natural Environment Science Center (ANESC), The University of Tokyo, 1-1-1 Midori Cho, Nishitokyo-shi, Tokyo 188-0002, Japan.

Sucrose non-fermenting-1-related protein kinase 2 s (SnRK2 s) are important stress-related plant protein kinases in plants. The interaction partners and phosphorylation substrates of group II and III SnRK2 s in Arabidopsis thaliana have been identified, but similar data for group I SnRK2 s are very limited. Here, we used a yeast two-hybrid (Y2H) screen to find proteins that interact with Arabidopsis AtSnRK2.4, a group I SnRK2. The transcription factor AtMYB21 was identified as an AtSnRK2.4 interaction partner, and its interaction with AtSnRK2.4 was confirmed by an in vitro pull-down assay and a bimolecular fluorescence complementation (BiFC) assay. A subcellular localization assay demonstrated that AtSnRK2.4 and AtMYB21 were located in the cytoplasm and nucleus of onion epidermal cells. AtSnRK2.4 and AtMYB21 were expressed in many tissues and upregulated in response to NaCl stress. Transgenic plants that overexpressed AtSnRK2.4 or AtMYB21 gene exhibited enhanced tolerance to salt stress at germination and post-germination stages. Moreover, the expression of downstream stress-responsive genes was upregulated in salt-stressed AtSnRK2.4 and AtMYB21 transgenic Arabidopsis. These results suggest that AtSnRK2.4 may act synergistically with AtMYB21 to mediate the response to salt stress through the upregulation of downstream stress-responsive genes.
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http://dx.doi.org/10.1016/j.plantsci.2020.110685DOI Listing
February 2021
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