Publications by authors named "Haiying Zhang"

338 Publications

The application of locking-taper implants in posterior area implant restoration with insufficient occlusal-gingival distances.

Am J Transl Res 2021 15;13(6):7221-7227. Epub 2021 Jun 15.

Department of Stomatology, Jiaozhou Central Hospital of Qingdao Qingdao, Shandong Province, China.

Objective: We aimed to investigate the effect of locking-taper implants on restoration in the posterior teeth area with insufficient occlusal-gingival distances.

Methods: Forty-five patients undergoing dental implants in our hospital with occlusal-gingival distances under 5 mm in the posterior teeth area were recruited for this retrospective study. A total of 78 locking-taper implants were implanted in these patients. The patients were followed up for two years to observe the implant retention rate, the implant bone heights at different time points after the restoration, and the effects of the different implant placement depths on the marginal bone mass at the implants. Meanwhile, we evaluated the peri-implant soft tissue status by measuring the modified plaque index, the gingival index, and probing the depths. The postoperative complications and the patient satisfaction levels were also analyzed.

Results: During the 2-year follow-up, the patients' implant retention rate was 100.00%. The implant placement depths did not affect the marginal bone masses at the implants at T0-T1 or T1-T2 (T0: the day after the restoration, T1: at one year after the restoration, T2: at two years after the restoration, all P>0.05). The peri-implant soft tissues in most of the patients were in good condition, and only a few patients had a small amount of plaque or slight gingival swelling. The average probe depth was 3.23±1.20 mm during the follow-up. Only one patient had abutment loosening, and one had a dental prosthesis fall off. The patients did not feel any numbness, continuous pain, or other abnormalities during the follow-up, and the overall patient satisfaction rate was over 97.78%.

Conclusion: Locking-taper implants can achieve good clinical outcomes in the restoration of the posterior area with insufficient occlusal-gingival distances. The implants can achieve a high implant retention rate, have no adverse effects on the peri-implant soft tissues, have a low complication rate, cause no significant marginal bone mass loss at the implants, and have a high patient satisfaction rate.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290773PMC
June 2021

Combined exposure to multiple metals and cognitive function in older adults.

Ecotoxicol Environ Saf 2021 Oct 2;222:112465. Epub 2021 Jul 2.

Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Department of Public Health, School of Medicine, Guangxi University of Science and Technology, Liuzhou, Guangxi, China. Electronic address:

Single toxic metal exposure has been reported to be associated with impaired cognitive function, but less is known about the effects of combined exposure to multiple metals. The aim of the study was to investigate the potential associations and interactions of multiple metals with cognitive function in older adults using multi-pollutants approach. A cross-sectional study was conducted in a total of 2879 participants aged ≥ 60 years old. We systematically measured levels of 22 blood metals and used the Mini-Mental State Examination (MMSE) to assess the cognitive function. The least absolute shrinkage and selection operator (LASSO) penalized regression was applied to identify independently main metals. Adjusted estimates of cognitive function with selected metals were investigated by generalized linear regression in the multi-metal model. We found that calcium, titanium, vanadium, copper, zinc, arsenic, selenium, rubidium, molybdenum, cadmium, barium, and lead were independently identified based on LASSO penalized regression. The multi-metal model showed a higher MMSE of 0.384 (95% CI: 0.122-0.646) for a 1-SD increment in log-transformed rubidium and a lower MMSE of 0.460 (95% CI: - 0.706 to - 0.214) for a 1-SD increment in log-transformed cadmium (P < 0.05). The significantly negative associations between cadmium and cognitive function were attenuated to null accompanying with increasing concentrations of rubidium (P = 0.256). Our findings suggested that blood rubidium and cadmium were mainly associated with cognitive function when accounting for co-exposure to other metals and higher level of rubidium appeared to attenuate the toxic effects of cadmium on cognitive function in older adults.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112465DOI Listing
October 2021

Abdominal wall mycobacterial spindle cell pseudotumor lesion.

Proc (Bayl Univ Med Cent) 2021 Mar 19;34(4):505-506. Epub 2021 Mar 19.

Department of Pathology, Baylor University Medical Center, Dallas, Texas.

Mycobacterial spindle cell pseudotumor is a rare entity that is histologically characterized by spindle-shaped histiocytes with acid-fast bacilli. It is primarily reported in immunocompromised patient in various body sites. We present a case of mycobacterial spindle cell pseudotumor in an abdominal wall mass from an immunosuppressed patient and discuss the characteristic findings.
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http://dx.doi.org/10.1080/08998280.2021.1897340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224204PMC
March 2021

Primaquine Diphosphate, a Known Antimalarial Drug, Blocks Vascular Leakage Acting Through Junction Stabilization.

Front Pharmacol 2021 4;12:695009. Epub 2021 Jun 4.

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.

Endothelial barrier integrity is important for vascular homeostasis, and hyperpermeability participates in the progression of many pathological states, such as diabetic retinopathy, ischemic stroke, chronic bowel disease, and inflammatory disease. Here, using drug repositioning, we discovered that primaquine diphosphate (PD), previously known as an antimalarial drug, was a potential blocker of vascular leakage. PD inhibited the linear pattern of vascular endothelial growth factors (VEGF)-induced disruption at the cell boundaries, blocked the formation of VEGF-induced actin stress fibers, and stabilized the cortactin actin rings in endothelial cells. PD significantly reduced leakage in the Miles assay and mouse model of streptozotocin (STZ)-induced diabetic retinopathy. Targeted prediction programs and deubiquitinating enzyme activity assays identified a potential mechanism of action for PD and demonstrated that this operates via ubiquitin specific protease 1 (USP1). USP1 inhibition demonstrated a conserved barrier function by inhibiting VEGF-induced leakage in endothelial permeability assays. Taken together, these findings suggest that PD could be used as a novel drug for vascular leakage by maintaining endothelial integrity.
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http://dx.doi.org/10.3389/fphar.2021.695009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211987PMC
June 2021

MiR-34a suppression targets Nampt to ameliorate bone marrow mesenchymal stem cell senescence by regulating NAD-Sirt1 pathway.

Stem Cell Res Ther 2021 05 6;12(1):271. Epub 2021 May 6.

The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, 126 Xin Min Street, Changchun, Jilin Province, People's Republic of China.

Background: Expansion-mediated replicative senescence and age-related natural senescence have adverse effects on mesenchymal stem cell (MSC) regenerative capability and functionality, thus severely impairing the extensive applications of MSC-based therapies. Emerging evidences suggest that microRNA-34a (miR-34a) has been implicated in the process of MSC senescence; however, the molecular mechanisms with regard to how miR-34a influencing MSC senescence remain largely undetermined.

Methods: MiR-34a expression in MSCs was evaluated utilizing RT-qPCR. The functional effects of miR-34a exerting on MSC senescence were investigated via gene manipulation. Relevant gene and protein expression levels were analyzed by RT-qPCR and western blot. Luciferase reporter assays were applied to confirm that Nampt is a direct target of miR-34a. The underlying regulatory mechanism of miR-34a targeting Nampt in MSC senescence was further explored by measuring intracellular NAD content, NAD/NADH ratio and Sirt1 activity.

Results: In contrast to Nampt expression, miR-34a expression incremented in senescent MSCs. MiR-34a overexpression in young MSCs resulted in senescence-associated characteristics as displayed by senescence-like morphology, prolonged cell proliferation, declined osteogenic differentiation potency, heightened senescence-associated-β-galactosidase activity, and upregulated expression levels of the senescence-associated factors. Conversely, miR-34a suppression in replicative senescent and natural senescent MSCs contributed to diminished senescence-related phenotypic features. We identified Nampt as a direct target gene of miR-34a. In addition, miR-34a repletion resulted in prominent reductions in Nampt expression levels, NAD content, NAD/NADH ratio, and Sirt1 activity, whereas anti-miR-34a treatment exerted the opposite effects. Furthermore, miR-34a-mediated MSC senescence was evidently rescued following the co-treatment with Nampt overexpression.

Conclusion: This study identifies a significant role of miR-34a playing in MSC replicative senescence and natural senescence via targeting Nampt and further mediating by NAD-Sirt1 pathway, carrying great implications for optimal strategies for MSC therapeutic applications.
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http://dx.doi.org/10.1186/s13287-021-02339-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101138PMC
May 2021

Single-cell transcriptomes reveal characteristic features of cell types within the human adrenal microenvironment.

J Cell Physiol 2021 May 2. Epub 2021 May 2.

Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang, China.

Various cells within the adrenal microenvironment are important in maintaining the body homeostasis. However, our understanding of adrenal disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ's multiple homeostatic functions. We report a cellular landscape of the human adrenal gland using single-cell RNA sequencing. We reveal characteristic features of cell types within the human adrenal microenvironment and found immune activation of nonimmune cells in the adrenal endothelial cells. We also reveal that abundant immune cells occupied a lot of space in adrenal gland. Additionally, Sex-related diversity in the adrenocortical cells and different gene expression profiles between the left and right adrenal gland are also observed at single-cell resolution. Together, at single-cell resolution, the transcriptomic map presents a comprehensive view of the human adrenal gland, which serves as a fundamental baseline description of this organ and paves a way for the further studies of adrenal diseases.
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http://dx.doi.org/10.1002/jcp.30398DOI Listing
May 2021

The SRSF1/circATP5B/miR-185-5p/HOXB5 feedback loop regulates the proliferation of glioma stem cells via the IL6-mediated JAK2/STAT3 signaling pathway.

J Exp Clin Cancer Res 2021 Apr 15;40(1):134. Epub 2021 Apr 15.

Department of Neurosurgery, the First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang City, 110001, China.

Background: Glioma is the most common and malignant tumor of central nervous system. The tumor initiation, self-renewal, and multi-lineage differentiation abilities of glioma stem cells (GSCs) are responsible for glioma proliferation and recurrence. Although circular RNAs (circRNAs) play vital roles in the progression of glioma, the detailed mechanisms remain unknown.

Methods: qRT-PCR, western blotting, immunohistochemistry, and bioinformatic analysis were performed to detect the expression of circATP5B, miR-185-5p, HOXB5, and SRSF1. Patient-derived GSCs were established, and MTS, EDU, neurosphere formation, and limiting dilution assays were used to detect the proliferation of GSCs. RNA-binding protein immunoprecipitation, RNA pull-down, luciferase reporter assays, and chromatin immunoprecipitation assays were used to detect these molecules' regulation mechanisms.

Results: We found circATP5B expression was significantly upregulated in GSCs and promoted the proliferation of GSCs. Mechanistically, circATP5B acted as miR-185-5p sponge to upregulate HOXB5 expression. HOXB5 was overexpressed in glioma and transcriptionally regulated IL6 expression and promoted the proliferation of GSCs via JAK2/STAT3 signaling. Moreover, RNA binding protein SRSF1 could bind to and promote circATP5B expression and regulate the proliferation of GSCs, while HOXB5 also transcriptionally regulated SRSF1 expression.

Conclusions: Our study identified the SRSF1/circATP5B/miR-185-5p/HOXB5 feedback loop in GSCs. This provides an effective biomarker for glioma diagnosis and prognostic evaluation.
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http://dx.doi.org/10.1186/s13046-021-01931-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051130PMC
April 2021

Relationship of gene variations with NAFLD risk in Chinese men.

Open Life Sci 2020 30;15(1):860-867. Epub 2020 Nov 30.

Department of chemotherapy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China.

Background: Fat mass and obesity-associated () gene is an obesity susceptibility gene and its relationship with the nonalcoholic fatty liver disease (NAFLD) remains unclear. This study aims to investigate the relationships of gene variations with NAFLD risk in a Chinese male population.

Methods: A 1:2 matched case-control study was performed on 275 cases of NAFLD and 550 controls matched for age. Nine of the gene single nucleotide polymorphisms (SNPs) were genotyped.

Results: Logistic regression analysis found that rs1477196 was significantly associated with the susceptibility to NAFLD in recessive genetic models [unadjusted odds ratio (OR) = 2.52, 95% confidence interval (CI): 1.22-5.19, = 0.012] and the relativity weakened after further adjustment for body mass index (BMI), uric acid, metabolic syndrome, smoking, and drinking (adjusted OR = 2.18, 95% CI: 0.96-4.99, = 0.06). In the obese group, the AA + AG genotypes of rs1121980 and rs9940128 were associated with a decreased risk of NAFLD, when compared with the GG genotype, respectively (rs1121980: adjusted OR = 0.62, 95% CI = 0.39-0.99, = 0.044; rs9940128: adjusted OR = 0.61, 95% CI = 0.38-0.97, = 0.038). Furthermore, rs1477196 was associated with the severity of NAFLD (OR = 2.95, 95% CI = 1.09-7.94, = 0.034).

Conclusions: Our results demonstrated that the gene was related to the presence and severity of NAFLD in a Chinese male population, and the relationships of the tested SNPs with NAFLD are most probably mediated by BMI.
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http://dx.doi.org/10.1515/biol-2020-0081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874577PMC
November 2020

Randomized controlled clinical trial of a highly filled flowable composite in non-carious cervical lesions: 3-year results.

Clin Oral Investig 2021 Apr 2. Epub 2021 Apr 2.

Department of Endodontics, Beijing Stomatological Hospital, Capital Medical University, Beijing, China.

Objectives: This prospective, randomized, split-mouth clinical trial assessed the 3-year clinical performance of a highly filled flowable composite and a conventional paste-type composite in non-carious cervical lesions (NCCLs).

Materials And Methods: A total of 84 NCCLs in 27 subjects were included in this split-mouth design study and randomly divided into two groups: a highly filled flowable composite Clearfil Majesty ES Flow group (ES, n = 42) and a conventional paste-type composite Majesty group (MJ, n = 42). Clearfil SE Bond was used following the manufacturer's instructions. The restorations were evaluated at baseline (BL) and 1, 2, and 3 years using FDI (World Dental Federation) criteria. Data were analysed by a paired chi-squared test for intergroup comparisons and the Friedman test for intragroup comparisons (α = 0.05).

Results: Both groups had a 97.3% retention rate at the 3-year evaluation. The acceptable scores (FDI scores 1-3) for each criterion exhibited no significant difference between the MJ and ES groups at any time point (p = 1.00). The marginal adaptation performance of ES was significantly better than that of MJ at every evaluation point (p < 0.05).

Conclusions: The 3-year clinical performance of ES in NCCLs was similar to that of MJ. When the restorations were clinically acceptable, ES showed better marginal adaptation than MJ.

Clinical Relevance: Compared with conventional paste-type composites, highly filled flowable composites showed similar clinical performance and better marginal adaptation for restoring NCCLs after 3 years.

Trial Registration: TRN: ChiCTR1900028484 . Date of registration: December 22, 2019, retrospectively registered.
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http://dx.doi.org/10.1007/s00784-021-03901-zDOI Listing
April 2021

Sulforaphane prevents angiotensin II-induced cardiomyopathy by activation of Nrf2 through epigenetic modification.

J Cell Mol Med 2021 May 1;25(9):4408-4419. Epub 2021 Apr 1.

Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China.

Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of cellular antioxidant defence. We previously showed that SFN prevented Ang II-induced cardiac damage via activation of Nrf2. However, the underlying mechanism of SFN's persistent cardiac protection remains unclear. This study aimed to explore the potential of SFN in activating cardiac Nrf2 through epigenetic mechanisms. Wild-type mice were injected subcutaneously with Ang II, with or without SFN. Administration of chronic Ang II-induced cardiac inflammatory factor expression, oxidative damage, fibrosis and cardiac remodelling and dysfunction, all of which were effectively improved by SFN treatment, coupled with an up-regulation of Nrf2 and downstream genes. Bisulfite genome sequencing and chromatin immunoprecipitation (ChIP) were performed to detect the methylation level of the first 15 CpGs and histone H3 acetylation (Ac-H3) status in the Nrf2 promoter region, respectively. The results showed that SFN reduced Ang II-induced CpG hypermethylation and promoted Ac-H3 accumulation in the Nrf2 promoter region, accompanied by the inhibition of global DNMT and HDAC activity, and a decreased protein expression of key DNMT and HDAC enzymes. Taken together, SFN exerts its cardioprotective effect through epigenetic modification of Nrf2, which may partially contribute to long-term activation of cardiac Nrf2.
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http://dx.doi.org/10.1111/jcmm.16504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093985PMC
May 2021

CRISPR/Cas9-mediated mutagenesis of ClBG1 decreased seed size and promoted seed germination in watermelon.

Hortic Res 2021 Apr 1;8(1):70. Epub 2021 Apr 1.

National Watermelon and Melon Improvement Center, Beijing Academy of Agricultural and Forestry Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops (North China), Beijing Key Laboratory of Vegetable Germplasm Improvement, Beijing, 100097, China.

Abscisic acid (ABA) is a critical regulator of seed development and germination. β-glucosidases (BGs) have been suggested to be contributors to increased ABA content because they catalyze the hydrolysis of ABA-glucose ester to release free ABA. However, whether BGs are involved in seed development is unclear. In this study, a candidate gene, ClBG1, in watermelon was selected for targeted mutagenesis via the CRISPR/Cas9 system. Seed size and weight were significantly reduced in the Clbg1-mutant watermelon lines, which was mainly attributed to decreased cell number resulting from decreased ABA levels. A transcriptome analysis showed that the expression of 1015 and 1429 unique genes was changed 10 and 18 days after pollination (DAP), respectively. Cytoskeleton- and cell cycle-related genes were enriched in the differentially expressed genes of wild type and Clbg1-mutant lines during seed development. Moreover, the expression of genes in the major signaling pathways of seed size control was also changed. In addition, seed germination was promoted in the Clbg1-mutant lines due to decreased ABA content. These results indicate that ClBG1 may be critical for watermelon seed size regulation and germination mainly through the modulation of ABA content and thereby the transcriptional regulation of cytoskeleton-, cell cycle- and signaling-related genes. Our results lay a foundation for dissecting the molecular mechanisms of controlling watermelon seed size, a key agricultural trait of significant economic importance.
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http://dx.doi.org/10.1038/s41438-021-00506-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012358PMC
April 2021

Extracellular vesicle and particle isolation from human and murine cell lines, tissues, and bodily fluids.

STAR Protoc 2021 Mar 22;2(1):100225. Epub 2020 Dec 22.

Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10021, USA.

We developed a modified protocol, based on differential ultracentrifugation (dUC), to isolate extracellular vesicles and particles (specifically exomeres) (EVPs) from various human and murine sources, including cell lines, surgically resected tumors and adjacent tissues, and bodily fluids, such as blood, lymphatic fluid, and bile. The diversity of these samples requires robust and highly reproducible protocols and refined isolation technology, such as asymmetric-flow field-flow fractionation (AF4). Our isolation protocol allows for preparation of EVPs for various downstream applications, including proteomic profiling. For complete details on the use and execution of this protocol, please refer to Hoshino et al. (2020).
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http://dx.doi.org/10.1016/j.xpro.2020.100225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988237PMC
March 2021

Grafting Delays Watermel on Fruit Ripening by Altering Gene Expression of ABA Centric Phytohormone Signaling.

Front Plant Sci 2021 25;12:624319. Epub 2021 Feb 25.

National Watermelon and Melon Improvement Center, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops (North China), Beijing Key Laboratory of Vegetable Germplasm Improvement, National Engineering Research Center for Vegetables, Beijing Academy of Agriculture and Forestry Sciences, Beijing, China.

Grafting cultivation is implemented worldwide mainly to resist abiotic and biotic stresses and is an effective method to improve watermelon production. However, grafting may affect fruit development and quality. In our experiment, pumpkin-grafted (PG) watermelon fruits developed slower and the ripening period was extended compared to self-grafted (SG) fruits. We found that the concentrations of abscisic acid (ABA) among endogenous phytohormones were dramatically reduced by pumpkin grafting. In order to understand these changes at the gene expression level, we performed a comprehensive analysis of the fruit flesh transcriptomes between PG and SG during fruit development and ripening. A total of 1,675 and 4,102 differentially expressed genes (DEGs) were identified between PG and SG. Further functional enrichment analysis revealed that these DEGs were associated with carbohydrate biosynthesis, phytohormone signaling transmission, and cell wall metabolism categories. ABA centric phytohormone signaling and fruit quality-related genes including ABA receptor, PP2C proteins, AP2-EREBP transcription factors, sucrose transporter, and carotenoid isomerase were co-expressed with fruit ripening. These results provide the valuable resource for understanding the mechanism of pumpkin grafting effect on watermelon fruit ripening and quality development.
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http://dx.doi.org/10.3389/fpls.2021.624319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947309PMC
February 2021

Mediated relationships between multiple metals exposure and fasting blood glucose by reproductive hormones in Chinese men.

Environ Pollut 2021 Jun 19;278:116791. Epub 2021 Feb 19.

Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, Guangxi, China; Department of Public Health, School of Medicine, Guangxi University of Science and Technology, Liuzhou, Guangxi, China. Electronic address:

Previous studies have reported metals exposure contribute to the change of fasting blood glucose (FBG) level. However, the roles of reproductive hormones in their associations have not been fully elucidated. The aim of the study is to investigate the associations of multiple serum metals with reproductive hormones, and to further explore potential roles of reproductive hormones in relationships between metals exposure and FBG level. A total of 1911 Chinese Han men were analyzed by a cross-sectional study. We measured serum levels of 22 metals by inductively coupled plasma mass spectrometer (ICP-MS). FBG, total testosterone (TT), estradiol (E2), follicle stimulating hormone (FSH), and sex hormone-binding globulin (SHBG) levels were determined. Least absolute shrinkage and selection operator (LASSO) regression models were conducted to select important metals, and restricted cubic spline models were then used to estimate dose-response relationships between selected metals and reproductive hormones. We also conducted mediation analyses to evaluate whether reproductive hormones played mediating roles in the associations between metals and FBG. We found significant inverse dose-dependent trends of copper, tin and zinc with E2; zinc with SHBG; copper and nickel with TT, while significant positive dose-dependent trend of iron with E2, respectively. Moreover, approximately inverted U-shaped associations existed between lead and SHBG, iron and TT. In addition, E2, SHBG and TT were negatively associated with FBG level. In mediation analyses, the association of copper with FBG was mediated by E2 and TT, with a mediation ratio of 10.4% and 22.1%, respectively. Furthermore, E2 and SHBG mediated the relationship of zinc with FBG, with a mediation ratio of 7.8% and 14.5%, respectively. E2 mediated 11.5% of positive relationship between tin with FBG. Our study suggested that the associations of metals exposure with FBG may be mediated by reproductive hormones.
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http://dx.doi.org/10.1016/j.envpol.2021.116791DOI Listing
June 2021

Runx3 Induces a Cell Shape Change and Suppresses Migration and Metastasis of Melanoma Cells by Altering a Transcriptional Profile.

Int J Mol Sci 2021 Feb 23;22(4). Epub 2021 Feb 23.

Institute of Genetics and Cell Biology, School of Life Sciences, Northeast Normal University, No. 5268, Renmin St., Changchun 130024, China.

Runt-related transcription factor-3 (Runx3) is a tumor suppressor, and its contribution to melanoma progression remains unclear. We previously demonstrated that Runx3 re-expression in B16-F10 melanoma cells changed their shape and attenuated their migration. In this study, we found that Runx3 re-expression in B16-F10 cells also suppressed their pulmonary metastasis. We performed microarray analysis and uncovered an altered transcriptional profile underlying the cell shape change and the suppression of migration and metastasis. This altered transcriptional profile was rich in Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) annotations relevant to adhesion and the actin cytoskeleton and included differentially expressed genes for some major extracellular matrix (ECM) proteins as well as genes that were inversely associated with the increase in the metastatic potential of B16-F10 cells compared to B16-F0 melanoma cells. Further, we found that this altered transcriptional profile could have prognostic value, as evidenced by myelin and lymphocyte protein () and vilin-like (). Finally, gene expression was correlated with metastatic potential among the cells and was targeted by histone deacetylase (HDAC) inhibitors in B16-F10 cells, and the knockdown of gene expression in B16-F0 cells changed their shape and enhanced the migratory and invasive traits of their metastasis. Our study suggests that self-entrapping of metastatic Runx3-negative melanoma cells via adhesion and the actin cytoskeleton could be a powerful therapeutic strategy.
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http://dx.doi.org/10.3390/ijms22042219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926509PMC
February 2021

Mutation Is Associated with Increased Risk of Recurrence in Surgically Resected Lung Adenocarcinoma.

Clin Cancer Res 2021 May 16;27(9):2604-2612. Epub 2021 Feb 16.

Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: is the most common mutation in primary lung adenocarcinoma. Phase I clinical trials have demonstrated encouraging clinical activity of inhibitors in the metastatic setting. We investigated disease-free survival (DFS) and tumor genomic features in patients with surgically resected -mutant lung adenocarcinoma.

Experimental Design: Patients who underwent resection of stage I-III lung adenocarcinoma and next-generation sequencing (NGS) were evaluated. Exclusion criteria were receipt of induction therapy, incomplete resection, and low-quality NGS. Mutations were classified as wild-type ( ), G12C ( ), or non-G12C ( ). DFS was compared between groups using the log-rank test; factors associated with DFS were assessed using Cox regression. Mutual exclusivity and cooccurrence, tumor clonality, and mutational signatures were assessed.

Results: In total, 604 patients were included: 374 (62%), 95 (16%), and 135 (22%). Three-year DFS was not different between -mutant and tumors. However, 3-year DFS was worse in patients with than tumors (log-rank = 0.029). tumors had more lymphovascular invasion (51% vs. 37%; = 0.032) and higher tumor mutation burden [median (interquartile range), 7.0 (5.3-10.8) vs. 6.1 (3.5-9.7); = 0.021], compared with tumors. mutation was independently associated with worse DFS on multivariable analysis. Our DFS findings were externally validated in an independent The Cancer Genome Atlas cohort.

Conclusions: mutations are associated with worse DFS after complete resection of stage I-III lung adenocarcinoma. These tumors harbor more aggressive clinicopathologic and genomic features than other -mutant tumors. We identified a high-risk group for whom inhibitors may be investigated to improve survival.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102372PMC
May 2021

CU06-1004-Induced Vascular Normalization Improves Immunotherapy by Modulating Tumor Microenvironment Cytotoxic T Cells.

Front Immunol 2020 26;11:620166. Epub 2021 Jan 26.

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.

Blocking the immune evasion mechanism of tumor cells has become an attractive means for treating cancers. However, the usage of a drug such as nivolumab (αPD-1), which blocks programmed cell death protein 1 (PD-1), turned out to be only effective against certain types of cancer. Especially, vascular abnormal structures of which deter delivery route by leakage and cause the poor perfusion were considered to be environment unfavorable to T cells and immune checkpoint blockade (ICB) delivery within the tumor microenvironment (TME). Herein, we report stabilization of tumor blood vessels by endothelial dysfunctional blocker CU06-1004, which modified the TME and showed synergistic effects with immunotherapy anti-PD-1 antibody. CU06-1004 combination therapy consistently prolonged the survival of tumor-bearing mice by decreasing tumor growth. T-cell infiltration increased in the tumors of the combination group, with cytotoxic CD8 T cell activity within the tumor parenchyma upregulated compared with anti-PD-1 monotherapy. Tumor inhibition was associated with reduced hypoxia and reduced vessel density in the central region of the tumor. These effects correlated significantly with enhanced expression of IFN gamma and PD-L1 in tumors. Taken together, our findings suggest that CU06-1004 is a potential candidate drug capable of improving therapeutic efficacy of anti-PD-1 through beneficial changes in the TME.
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http://dx.doi.org/10.3389/fimmu.2020.620166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874050PMC
July 2021

Transcriptomic and genome-wide association study reveal long noncoding RNAs responding to nitrogen deficiency in maize.

BMC Plant Biol 2021 Feb 12;21(1):93. Epub 2021 Feb 12.

Maize Research Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.

Background: Long noncoding RNAs (lncRNAs) play important roles in essential biological processes. However, our understanding of lncRNAs as competing endogenous RNAs (ceRNAs) and their responses to nitrogen stress is still limited.

Results: Here, we surveyed the lncRNAs and miRNAs in maize inbred line P178 leaves and roots at the seedling stage under high-nitrogen (HN) and low-nitrogen (LN) conditions using lncRNA-Seq and small RNA-Seq. A total of 894 differentially expressed lncRNAs and 38 different miRNAs were identified. Co-expression analysis found that two lncRNAs and four lncRNA-targets could competitively combine with ZmmiR159 and ZmmiR164, respectively. To dissect the genetic regulatory by which lncRNAs might enable adaptation to limited nitrogen availability, an association mapping panel containing a high-density single-nucleotide polymorphism (SNP) array (56,110 SNPs) combined with variable LN tolerant-related phenotypes obtained from hydroponics was used for a genome-wide association study (GWAS). By combining GWAS and RNA-Seq, 170 differently expressed lncRNAs within the range of significant markers were screened. Moreover, 40 consistently LN-responsive genes including those involved in glutamine biosynthesis and nitrogen acquisition in root were identified. Transient expression assays in Nicotiana benthamiana demonstrated that LNC_002923 could inhabit ZmmiR159-guided cleavage of Zm00001d015521.

Conclusions: These lncRNAs containing trait-associated significant SNPs could consider to be related to root development and nutrient utilization. Taken together, the results of our study can provide new insights into the potential regulatory roles of lncRNAs in response to LN stress, and give valuable information for further screening of candidates as well as the improvement of maize resistance to LN stress.
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http://dx.doi.org/10.1186/s12870-021-02847-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879672PMC
February 2021

Evolutionary gain of oligosaccharide hydrolysis and sugar transport enhanced carbohydrate partitioning in sweet watermelon fruits.

Plant Cell 2021 Jul;33(5):1554-1573

National Watermelon and Melon Improvement Center, Beijing Academy of Agriculture and Forestry Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops (North China), Beijing Key Laboratory of Vegetable Germplasm Improvement, Beijing 100097, China.

How raffinose (Raf) family oligosaccharides, the major translocated sugars in the vascular bundle in cucurbits, are hydrolyzed and subsequently partitioned has not been fully elucidated. By performing reciprocal grafting of watermelon (Citrullus lanatus) fruits to branch stems, we observed that Raf was hydrolyzed in the fruit of cultivar watermelons but was backlogged in the fruit of wild ancestor species. Through a genome-wide association study, the alkaline alpha-galactosidase ClAGA2 was identified as the key factor controlling stachyose and Raf hydrolysis, and it was determined to be specifically expressed in the vascular bundle. Analysis of transgenic plants confirmed that ClAGA2 controls fruit Raf hydrolysis and reduces sugar content in fruits. Two single-nucleotide polymorphisms (SNPs) within the ClAGA2 promoter affect the recruitment of the transcription factor ClNF-YC2 (nuclear transcription factor Y subunit C) to regulate ClAGA2 expression. Moreover, this study demonstrates that C. lanatus Sugars Will Eventually Be Exported Transporter 3 (ClSWEET3) and Tonoplast Sugar Transporter (ClTST2) participate in plasma membrane sugar transport and sugar storage in fruit cell vacuoles, respectively. Knocking out ClAGA2, ClSWEET3, and ClTST2 affected fruit sugar accumulation. Genomic signatures indicate that the selection of ClAGA2, ClSWEET3, and ClTST2 for carbohydrate partitioning led to the derivation of modern sweet watermelon from non-sweet ancestors during domestication.
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http://dx.doi.org/10.1093/plcell/koab055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254481PMC
July 2021

Tumour-regulated anorexia preceding cachexia.

Nat Cell Biol 2021 02;23(2):111-113

Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

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http://dx.doi.org/10.1038/s41556-021-00635-8DOI Listing
February 2021

Cell-free DNA (cfDNA) and Exosome Profiling from a Year-Long Human Spaceflight Reveals Circulating Biomarkers.

iScience 2020 Dec 25;23(12):101844. Epub 2020 Nov 25.

Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.

Liquid biopsies based on cell-free DNA (cfDNA) or exosomes provide a noninvasive approach to monitor human health and disease but have not been utilized for astronauts. Here, we profile cfDNA characteristics, including fragment size, cellular deconvolution, and nucleosome positioning, in an astronaut during a year-long mission on the International Space Station, compared to his identical twin on Earth and healthy donors. We observed a significant increase in the proportion of cell-free mitochondrial DNA (cf-mtDNA) inflight, and analysis of post-flight exosomes in plasma revealed a 30-fold increase in circulating exosomes and patient-specific protein cargo (including brain-derived peptides) after the year-long mission. This longitudinal analysis of astronaut cfDNA during spaceflight and the exosome profiles highlights their utility for astronaut health monitoring, as well as cf-mtDNA levels as a potential biomarker for physiological stress or immune system responses related to microgravity, radiation exposure, and the other unique environmental conditions of spaceflight.
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http://dx.doi.org/10.1016/j.isci.2020.101844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756145PMC
December 2020

Recent Advances in Experimental Models of Breast Cancer Exosome Secretion, Characterization and Function.

J Mammary Gland Biol Neoplasia 2020 12 22;25(4):305-317. Epub 2020 Dec 22.

Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medical College, New York, NY, USA.

Breast cancer (BC) is responsible for 15% of all the cancer deaths among women in the USA. The tumor microenvironment (TME) has the potential to act as a driver of breast cancer progression and metastasis. The TME is composed of stromal cells within an extracellular matrix and soluble cytokines, chemokines and extracellular vesicles and nanoparticles that actively influence cell behavior. Extracellular vesicles include exosomes, microvesicles and large oncosomes that orchestrate fundamental processes during tumor progression through direct interaction with target cells. Long before tumor cell spread to future metastatic sites, tumor-secreted exosomes enter the circulation and establish distant pre-metastatic niches, hospitable and permissive milieus for metastatic colonization. Emerging evidence suggests that breast cancer exosomes promote tumor progression and metastasis by inducing vascular leakiness, angiogenesis, invasion, immunomodulation and chemoresistance. Exosomes are found in almost all physiological fluids including plasma, urine, saliva, and breast milk, providing a valuable resource for the development of non-invasive cancer biomarkers. Here, we review work on the role of exosomes in breast cancer progression and metastasis, and describe the most recent advances in models of exosome secretion, isolation, characterization and functional analysis. We highlight the potential applications of plasma-derived exosomes as predictive biomarkers for breast cancer diagnosis, prognosis and therapy monitoring. We finally describe the therapeutic approaches of exosomes in breast cancer.
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http://dx.doi.org/10.1007/s10911-020-09473-0DOI Listing
December 2020

Outcomes of Tofacitinib Dose Reduction in Patients with Ulcerative Colitis in Stable Remission from the Randomised RIVETING Trial.

J Crohns Colitis 2021 Jul;15(7):1130-1141

Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.

Background And Aims: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present primary completion analysis from RIVETING, an ongoing, double-blind, randomised, parallel-group trial evaluating efficacy and safety of tofacitinib dose reduction to 5 mg twice daily [BID] versus remaining on 10 mg BID in patients in stable remission on tofacitinib 10 mg BID maintenance therapy.

Methods: Patients had received tofacitinib 10 mg BID for ≥ 2 consecutive years and been in stable remission for ≥ 6 months before enrolment. The primary endpoint was modified Mayo score remission at Month 6. Safety was assessed up to February 20, 2020 [data cut-off].

Results: In all, 140 patients were randomised [1:1] to tofacitinib 5 or 10 mg BID; 77.1% and 90.0% of patients in the 5 and 10 mg BID groups, respectively, were in modified Mayo score remission at Month 6 (adjusted difference 12.9%; 95% confidence interval [CI] 0.5-25.0). Smaller differences between treatment groups were seen in patients with baseline endoscopic subscore of 0 versus 1 [9.8%; -3.0-22.6, and 21.1%; -6.1-48.2, respectively], and in patients without versus with prior tumour necrosis factor inhibitor [TNFi] failure [9.5%; -6.6-25.6, and 17.4%; -1.6-36.3, respectively]. Adverse events [AE] and serious AE rates were similar across treatment groups; no deaths were reported.

Conclusions: Most patients in stable remission on 10 mg BID maintenance therapy maintained remission following dose de-escalation. For patients who dose de-escalated, those in deep endoscopic remission and those without prior TNFi failure were more likely to maintain remission. Efficacy data were limited to the first 6 months; a longer duration of follow-up during RIVETING will further characterise the impact of dose reduction on maintenance of remission. Safety findings were consistent with the established safety profile of tofacitinib.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256630PMC
July 2021

The endothelial dysfunction blocker CU06-1004 ameliorates choline-deficient L-amino acid diet-induced non-alcoholic steatohepatitis in mice.

PLoS One 2020 4;15(12):e0243497. Epub 2020 Dec 4.

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.

Non-alcoholic steatohepatitis (NASH) is a severe, advanced form of non-alcoholic fatty liver disease (NAFLD) that is associated with features of metabolic syndrome and characterized by hepatic steatosis, inflammation, and fibrosis. In addition, NASH is associated with endothelial dysfunction within the hepatic vasculature. Treatment with CU06-1004 (previously called Sac-1004) ameliorates endothelial dysfunction by inhibiting hyperpermeability and inflammation. In this study, we investigated the protective effects of CU06-1004 in a choline-deficient L-amino acid (CDAA)-induced mouse model of NASH for 3 or 6 weeks. Specifically, we evaluated the effects of CU06-1004 on lipid accumulation, inflammation, hepatic fibrosis, and liver sinusoidal endothelial cell (LSEC) capillarization through biochemical analysis, immunohistochemistry, and real-time PCR. We found that the administration of CU06-1004 to mice improved liver triglyceride (TG) and serum alanine aminotransferase (ALT) in this CDAA-induced model of NASH for 6 weeks. In groups of NASH induced mice for both 3 and 6 weeks, CU06-1004 significantly reduced the hepatic expression of genes related to lipogenesis, inflammation, and cell adhesion. However, expression of genes related to hepatic fibrosis and vascular endothelial changes were only decreased in animals with mild NASH. These results suggest that the administration of CU06-1004 suppresses hepatic steatosis, inflammation, fibrosis, and LSEC capillarization in a CDAA-induced mouse model of NASH. This suggests that CU06-1004 has therapeutic potential for the treatment of mild NASH.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243497PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717513PMC
January 2021

Histologic patterns of lung injury in patients using e-cigarettes.

Proc (Bayl Univ Med Cent) 2020 Jul 6;33(4):619-620. Epub 2020 Jul 6.

Department of Pathology, Baylor University Medical Center, Dallas, Texas.

In recent years, e-cigarette use has become more popular. Until recently, it was considered safer than smoking. We report two cases of acute pulmonary illness associated with vaping, focusing on their histologic patterns.
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http://dx.doi.org/10.1080/08998280.2020.1775052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549899PMC
July 2020

Co-exposure of serum calcium, selenium and vanadium is nonlinearly associated with increased risk of type 2 diabetes mellitus in a Chinese population.

Chemosphere 2021 Jan 26;263:128021. Epub 2020 Aug 26.

Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China. Electronic address:

Background: Metals play an important role in type 2 diabetes mellitus (T2DM). This study aimed to explore the association of T2DM risk with single metal exposure and multi-metal co-exposure.

Methods: A case-control study with 223 T2DM patients and 302 controls was conducted. Serum concentrations of 19 metals were determined by inductively coupled plasma mass spectrometry (ICP-MS). Those metals with greater effects were screened out and co-exposure effects of metals were assessed by least absolute shrinkage and selection operator (LASSO) regression.

Results: Serum calcium (Ca), selenium (Se) and vanadium (V) were found with greater effects. Higher levels of Ca and Se were associated with increased T2DM risk (OR = 2.23, 95%CI: 1.38-3.62, P = 0.002; OR = 3.16, 95%CI: 1.82-5.50, P < 0.001), but higher V level was associated with decreased T2DM risk (OR = 0.58, 95%CI: 0.34-0.97, P < 0.001). Serum Ca and V concentrations were nonlinearly associated with T2DM risk (P < 0.001, P < 0.001); however, Se concentration was linearly associated with T2DM risk (P < 0.001, P = 0.389). High co-exposure score of serum Ca, Se and V was associated with increased T2DM risk (OR = 3.50, 95%CI: 2.08-5.89, P < 0.001) as a non-linear relationship (P < 0.001, P = 0.003).

Conclusions: This study suggest that higher levels of serum Ca and Se were associated with increased T2DM risk, but higher serum V level was associated with decreased T2DM risk. Moreover, co-exposure of serum Ca, Se and V was nonlinearly associated with T2DM risk, and high co-exposure score was positively associated with T2DM risk.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128021DOI Listing
January 2021

CU06-1004 Alleviates Experimental Colitis by Modulating Colonic Vessel Dysfunction.

Front Pharmacol 2020 15;11:571266. Epub 2020 Sep 15.

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.

Inflammatory bowel disease is an autoimmune disease that causes chronic inflammation of the gastrointestinal tract. Endothelial dysfunction, defined by a reduced endothelial barrier and an increase in the expression of adhesion molecules, is part of the pathology of inflammatory bowel disease. In this study, we assessed the therapeutic effect of CU06-1004, an endothelial dysfunction blocker that reduces vascular hyperpermeability and inflammation in a mouse model of colitis. Acute colitis was induced in mice using 3% (w/v) dextran sodium sulfate added to their drinking water for 7 days. Twenty-four hours after the addition of dextran sodium sulfate, either mesalazine or CU06-1004 was administered orally each day. Administration of CU06-1004 significantly reduced the clinical manifestations (weight loss, diarrhea, and bloody stool) and histological changes (epithelium loss, inflammatory cell infiltration, and crypt destruction) induced by dextran sodium sulfate. Proinflammatory cytokines were also reduced, indicating that inflammation was ameliorated. From a vascular perspective, CU06-1004 reduced interrupted and tortuous vessels, enhanced junction protein expression, and reduced inflammatory adhesion molecules, indicating a broad improvement of endothelial dysfunction. Endothelial protection induced epithelial barrier restoration and decreased epithelial inflammation. Blocking endothelial dysfunction with CU06-1004 significantly ameliorated the progression of inflammatory bowel disease. Therefore, CU06-1004 may represent a potential therapeutic agent for the treatment of inflammatory bowel disease as well as other inflammatory diseases.
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http://dx.doi.org/10.3389/fphar.2020.571266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523507PMC
September 2020

Maintenance of Remission With Tofacitinib Therapy in Patients With Ulcerative Colitis.

Clin Gastroenterol Hepatol 2020 Oct 9. Epub 2020 Oct 9.

Medical University of Vienna, Vienna, Austria.

Background & Aims: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib in patients with moderate to severe UC, up to 1 year, have been reported. We investigated maintenance of efficacy in patients in remission after 52 weeks of maintenance treatment in the pivotal phase 3 study (OCTAVE Sustain); these patients received open-label, long-term treatment with tofacitinib 5 mg twice daily.

Methods: Patients with moderate to severe UC who completed a 52-week, phase 3 maintenance study (OCTAVE Sustain) were eligible to enroll into the ongoing, phase 3, multicenter, open-label, long-term extension (OCTAVE Open). We analyzed data from 142 patients who were in remission following tofacitinib treatment in OCTAVE Sustain who received tofacitinib 5 mg twice daily during OCTAVE Open. We assessed efficacy (including remission [based on total Mayo score], endoscopic improvement, clinical response, and partial Mayo score up to month 36 of OCTAVE Open) and safety data.

Results: After 12 months of tofacitinib 5 mg twice daily in OCTAVE Open, 68.3% of patients were in remission, 73.9% had endoscopic improvement, and 77.5% had a clinical response. At month 36, 50.4%, of the patients were in remission, 55.3% had endoscopic improvement, and 56.0% had a clinical response. The safety profile of tofacitinib 5 mg twice daily revealed no new safety risks associated with long-term exposure up to 36 months.

Conclusions: Efficacy endpoints were maintained for up to 36 months, regardless of prior tofacitinib dose, including patients who reduced from tofacitinib 10 mg to 5 mg twice daily upon OCTAVE Open entry. No new safety risks were identified. ClinicalTrials.gov: OCTAVE Sustain (NCT01458574); OCTAVE Open (NCT01470612).
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http://dx.doi.org/10.1016/j.cgh.2020.10.004DOI Listing
October 2020

Associations Between Serum Multiple Metals Exposures and Metabolic Syndrome: a Longitudinal Cohort Study.

Biol Trace Elem Res 2021 Jul 3;199(7):2444-2455. Epub 2020 Oct 3.

Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China.

Although many studies have confirmed metabolic syndrome (MetS) is correlated with metal exposures, few studies have elucidated the associations of multiple metals with MetS risk. We aim to explore the relationship between serum 22 metals and MetS. We determined serum 22 metals using ICP-MS and used LASSO regression to select metals independently related with MetS to construct multiple-metals model. We further explored the dose-response relationship between positive metals and MetS by the restricted cubic spline regression. After screening by LASSO regression, serum 11 metals were selected to construct multiple-metals model in cross-sectional analysis, while 5 metals in longitudinal analysis. In the 11-metal model, only tin and zinc were associated with MetS in cross-sectional analysis (OR = 2.22, 95% CI:1.43, 3.45; OR = 2.17, 95% CI: 1.42, 3.32; both P < 0.05). Besides, the same results were found in the 5-metal model in longitudinal analysis (HR = 1.66, 95% CI: 0.87, 3.17; HR = 1.83, 95% CI: 1.07, 3.14; both P < 0.05). Moreover, there were positive linear relationships between serum tin and zinc concentrations and the increasing risk of MetS (both P < 0.05, P > 0.05). Furthermore, the interaction between high tin and high zinc was also associated with increasing MetS risk (P < 0.05). We found that serum tin and zinc were independently and interactively associated with MetS in the southern Chinese men. Our results suggested that high tin and zinc may be the risk factors of MetS.
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http://dx.doi.org/10.1007/s12011-020-02371-wDOI Listing
July 2021
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