043155   HU C, WU Z, LI L (Zhejiang Univ, Hangzhou, Zhejiang, PR China, Email: ljli@zju.edu.cn) : Mesenchymal stromal cells promote liver regeneration through regulation of immune cells. Int J Biol Sci 2020, 16(5), 893-903.

The liver is sensitive to pathogen-induced acute or chronic liver injury, and liver transplantation (LT) is the only effective strategy for end-stage liver diseases. However, the clinical application is limited by a shortage of liver organs, immunological rejection and high cost. Mesenchymal stromal cell (MSC)-based therapy has gradually become a hot topic for promoting liver regeneration and repairing liver injury in various liver diseases, since MSCs are reported to migrate toward injured tissues, undergo hepatogenic differentiation, inhibit inflammatory factor release and enhance the proliferation of liver cells in vivo. MSCs exert immunoregulatory effects through cell-cell contact and the secretion of anti-inflammatory factors to inhibit liver inflammation and promote liver regeneration. In addition, MSCs are reported to effectively inhibit the activation of cells of the innate immune system, including macrophages, natural killer (NK) cells, dendritic cells (DCs), monocytes and other immune cells, and inhibit the activation of cells of the adaptive immune system, including T lymphocytes, B lymphocytes and subsets of T cells or B cells. In the current review, we mainly focus on the potential effects and mechanisms of MSCs in inhibiting the activation of immune cells to attenuate liver injury in models or patients with acute liver failure (ALF), nonalcoholic fatty liver disease (NAFLD), and liver fibrosis and in patients or models after LT. We highlight that MSC transplantation may replace general therapies for eliminating acute or chronic liver injury in the near future.

2 illus, 1 table, 110 ref

043154   LI J, CHEN Z, WANG Y (Harbin Institute of Technology, China, Email: jieli@hit.edu.cn) : Contents, construction methods, data resources, and functions comparative analysis of bacteria databases. Int J Biol Sci 2020, 16(5), 838-48.

Many bacterial-related databases are developed to meet the researchers’ needs of analysis and search for a number of bacterial information. However, these databases have different data resources, construction methods, data formats, and analysis tools. It’s difficult for researchers to select appropriate databases and analysis tools to promote their researches. In the paper, we compared the contents, construction methods, data sources, update frequency, scope and scale of data, analysis tools, and features of nine famous bacterial databases: CARD, EffectiveDB, MBGD, MPD, PATRCI, PHI-base, VFDB, gcMeta and SILVA, and help researchers to better make better use of these databases. In addition, we also hope this review can help researchers develop a more comprehensive database and better tools to meet the needs of researchers.

11 illus, 2 tables, 33 ref

043153   ZHANG C, MA L, NIU Y, WANG Z, XU X, LI Y, YU Y (Shanghai Jiao Tong Univ, Shanghai, 200030, P.R. China, Email: yyc2166@sjtu.edu.cn) : Circular RNA in lung cancer research: Biogenesis, functions, and roles. Int J Biol Sci 2020, 16(5), 803-14.

Lung cancer is one of the most common and deadly malignancies worldwide, in spite of advances in targeted therapy in recent years. An effective strategy for lung cancer prevention remains a major problem. Advances in next-generation sequencing have helped in understanding the RNA and identifying novel circular RNAs (circRNAs) that may have a broad impact on the early diagnosis and treatment of lung cancer. The circRNAs, exhibiting spatiotemporal-specific expression, are stable and conserved and present diverse biological functions in the normal and diseased states, including cancer. In this review, we summarize the recent advances in elucidating the functional role of circRNAs in lung cancer pathogenesis and discuss their potential mechanisms.

2 illus, 2 tables, 69 ref

043152   WU Y, LIU X, ZHENG H, ZHU H, MAI W, HUANG X, HUANG Y (Cardiology Dep, Shunde hospital, Southern Medical Univ, Guangdong, China, 523808, Email: hxhscience@163.com) : Multiple roles of sFRP2 in cardiac development and cardiovascular disease. Int J Biol Sci 2020, 16(5), 730-8.

The Wnt signaling pathway plays important roles in organ development and disease processes. Secreted frizzled-related protein 2 (sFRP2), a vital molecule of Wnt signaling, can regulate cardiac development and cardiovascular disease. Recent studies have suggested that sFRP2 is not only an antagonist of the canonical Wnt signaling pathway, but also has a more complex relationship in myocardial fibrosis, angiogenesis, cardiac hypertrophy and cardiac regeneration. Here, we review the role of sFRP2 and Wnt signaling in cardiac development and cardiovascular disease.

3 illus, 83 ref

043151   LIU M, HU Y, LU S, LU M, LI J, CHANG H, JIA H, ZHOU M, REN F, ZHONG J (Pathology Dep, Xinxiang Medical Univ, Henan, China, Email: renfeng@xxmu.edu.cn) : IC261, a specific inhibitor of CK1δ/ε, promotes aerobic glycolysis through p53-dependent mechanisms in colon cancer. Int J Biol Sci 2020, 16(5), 882-92.

Casein kinase 1δ (CK1δ) and casein kinase 1ε (CK1ε) have been proposed to be involved in DNA replication, differentiation and apoptosis, thus participating in the regulation of tumorigenesis. However, their functions in colon cancer and the underlying mechanism remain unclear. Here, we found that the expression of CK1ε and CK1δ increased significantly in cancer tissues and the upregulation of CK1ε and CK1δ were closely related to poor differentiation, advanced TNM stage and poor prognosis of colon cancer. CK1δ/ε inhibitor IC261 could induce a decrease in cell survival and proliferation, and an increase in apoptosis in colon cancer cells. Interestingly, IC261 increased the level of aerobic glycolysis in colon cancer cells. Meanwhile, IC261 caused the decrease of p53 protein level and the misregulation of glycolysis related genes (TIGAR, G6PD, GLUT1) which are closely related to the regulation of glycolysis by p53. Inhibiting p53 by siRNA or inhibitor could significantly attenuate the upregulation of aerobic glycolysis induced by IC261. Finally, inhibition of aerobic glycolysis can further increase the cytotoxicity induced by IC261. Collectively, our results revealed that IC261 could inhibit the growth of colon cancer cells and increase the level of aerobic glycolysis, which is regulated by p53-dependent manner. This result suggested that targeting CK1δ/ε and glycolysis might be a valuable strategy treatment and combination therapies for colon cancer.

7 illus, 2 tables, 48 ref

043150   GUO H, CAI J, WANG X, WANG B, WANG F, LI X, QU X, KONG X, GAO Y, WU H, et al. (Liver Diseases Dep, ShuGuang Hospital Affiliated to Shanghai Univ of Chinese Traditional Medicine, 528 Zhangheng Road, Shanghai, China, 201203, Email: xiaoni-kong@126.com) : Prognostic values of a novel multi-mRNA signature for predicting relapse of cholangiocarcinoma. Int J Biol Sci 2020, 16(5), 869- 81.

Cholangiocarcinoma (CCA) is an epithelial cancer and has high death and recurrence rates, current methods cannot satisfy the need for predicting cancer relapse effectively. So, we aimed at conducting a multi-mRNA signature to improve the relapse prediction of CCA. We analyzed mRNA expression profiling in large CCA cohorts from the Gene Expression Omnibus (GEO) database (GSE76297, GSE32879, GSE26566, GSE31370, and GSE45001) and The Cancer Genome Atlas (TCGA) database. The Least absolute shrinkage and selection operator (LASSO) regression model was used to establish a 7-mRNA-based signature that was significantly related to the recurrence-free survival (RFS) in two test series. Based on the 7-mRNA signature, the cohort TCGA patients could be divided into high-risk or low-risk subgroups with significantly different RFS [p < 0.001, hazard ratio (HR): 48.886, 95 % confidence interval (CI): 6.226-3.837E+02]. Simultaneously, the prognostic value of the 7-mRNA signature was confirmed in clinical samples of Ren Ji hospital (p < 0.001, HR: 4.558, 95 % CI: 1.829-11.357). Further analysis including multivariable and sub-group analyses revealed that the 7-mRNA signature was an independent prognostic value for recurrence of patients with CCA. In conclusion, our results might provide an efficient tool for relapse prediction and were beneficial to individualized management for CCA patients.

7 illus, 1 table, 44 ref

043149   XU Y, LI L, WANG C, YUE H, ZHANG H, GU J, HU W, LIU L, ZHANG Z (Osteoporosis and Bone Diseases Dep, Shanghai Jiao Tong Univ Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China, Email: chinallu@163.com) : Clinical and molecular characterization and discovery of novel genetic mutations of chinese patients with COL2A1-related dysplasia. Int J Biol Sci 2020, 16(5), 859-68.

COL2A1-related disorders represent a heterogeneous group of skeletal dysplasias with a wide phenotypic spectrum. Our aim is to characterize the clinical and molecular phenotypes of Chinese patients with COL2A1-related dysplasia and to explore their phenotype-genotype relations. Clinical data were collected, physical examinations were conducted, and X-ray radiography and genetic analyses were performed in ten families involving 29 patients with COL2A1-related dysplasia. Nine mutations were identified in COL2A1, including five novel (c.816+6C>T, p.Gly246Arg, p.Gly678Glu, p.Gly1014Val and p.Ter1488Gln) and four reported previously (p.Gly204Val, p.Arg275Cys, p.Gly504Ser and p.Arg719Cys). Based on clinical features and molecular mutations, the ten families were classified into five definite COL2A1-related disorders: four families with spondyloepiphyseal dysplasia congenita (SEDC), three with osteoarthritis with mild chondrodysplasia (OSCPD), one with Czech dysplasia, one with Kniest dysplasia, and one with epiphyseal dysplasia, multiple, with myopia and deafness (EDMMD). Based on genetic testing results, prenatal diagnosis and genetic counseling were accomplished for one female proband with OSCDP. Chinese patients with OSCDP, Czech dysplasia and EDMMD caused by COL2A1 mutations were first reported, expanding the spectrum of COL2A1 mutations and the phenotype of COL2A1-related disorders and providing further evidence for the phenotype-genotype relations, which may help improve procreative management of COL2A1-related disorders.

7 illus, 1 table, 30 ref

043148   ZHAO Z, YU Z, HOU Y, ZHANG L, FU A (Southwest Univ, Chongqing 400715, China, Email: fal@swu.edu.cn.) : Improvement of cognitive and motor performance with mitotherapy in aged mice. Int J Biol Sci 2020, 16(5), 849-58.

Changes in mitochondrial structure and function are mostly responsible for aging and age-related features. Whether healthy mitochondria could prevent aging is, however, unclear. Here we intravenously injected the mitochondria isolated from young mice into aged mice and investigated the mitotherapy on biochemistry metabolism and animal behaviors. The results showed that heterozygous mitochondrial DNA (mtDNA) of both aged and young mouse coexisted in tissues of aged mice after mitochondrial administration, and meanwhile, ATP content in tissues increased while reactive oxygen species (ROS) level reduced. Besides, the mitotherapy significantly improved cognitive and motor performance of aged mice. Our study, at the first report in aged animals, not only provides a useful approach to study mitochondrial function associated with aging, but also a new insight into anti-aging through mitotherapy.

7 illus, 47 ref

043147   BAO Y, ZHANG Y, LU Y, GUO H, DONG Z, CHEN Q, ZHANG X, SHEN W, CHEN W, WANG X (Huzhou Univ, huzhou 313000, China, Email: wangx2017@126.com) : Overexpression of microRNA-9 enhances cisplatin sensitivity in hepatocellular carcinoma by regulating EIF5A2-mediated epithelial–mesenchymal transition. Int J Biol Sci 2020, 16(5), 827-37.

We investigated the role of microRNA (miR)-9 in modulating chemoresistance in hepatocellular carcinoma (HCC) cells. MiR-9 was overexpressed or knocked down in HCC cell lines. Cell viability, cell proliferation, the expression of EIF5A2 and the epithelial–mesenchymal transition (EMT)-related proteins were examined. HCC cells overexpressing miR-9 were more sensitive to cisplatin; miR-9 knockdown yielded the opposite result. The in vivo nude mouse HCC xenograft tumors yielded the same results. EIF5A2 was identified as a potential target of miR-9, where miR-9 regulated EIF5A2 expression at mRNA and protein level. EIF5A2 knockdown reversed miR-9 inhibition–mediated cisplatin resistance. Altering miR-9 and EIF5A2 expression changed E-cadherin and vimentin expression. Furthermore, EIF5A2 mediated miR-9 EMT pathway regulation, indicating that miR-9 can enhance cisplatin sensitivity by targeting EIF5A2 and inhibiting the EMT pathway. Targeting miR-9 may be useful for overcoming drug resistance in HCC.

7 illus, 2 tables, 47 ref

043146   LI H, WANG Y, RONG S-K, LI L, CHEN T, FAN Y-Y, WANG Y-F, YANG C-R, YANG C, et al. (Colorectal Surgery Dep, Ningxia Medical Univ, Yinchuan, Ningxia 750004, China, Email: yangjiali_123@163.com) : Integrin α1 promotes tumorigenicity and progressive capacity of colorectal cancer. Int J Biol Sci 2020, 16(5), 815-26.

Colorectal cancer (CRC) is the second leading cause of death globally. Integrin α1 (ITGA1) belongs to integrin family and involves in regulating cell adhesion, invasion, proliferation and tumorigenicity, its expression is up-regulated in various cancers, including CRC. However, the molecular understanding and clinical relevance of ITGA1 in the development and progression of CRC remain unclear. In the present study, we detected ITGA1 in 50 CRC tissues and adjacent non-cancerous tissues, sera from 100 CRC patients and 50 healthy subjects, and four CRC cell lines using immunohistochemistry staining, enzyme-linked immunosorbent assay and Western blotting. We found that the ITGA1 protein was significantly higher in human CRC tissues and cell lines than both paired non-tumor tissues and normal cells, respectively. In addition, the serum concentration of ITGA1 was also higher in CRC patients compared to the healthy subjects (p<0.01) and was significantly associated with metastatic TNM stages (p<0.0001) and circulating carbohydrate antigen 199 (CA199) (p<0.022). Furthermore, down-regulation of ITGA1 with transfecting LV-shITGA1 inhibited the progressive capacity of cell migration and invasion in CRC SW480 cell line and the tumorgenicity in nude mice. In functional studies, ITGA1 knockdown also inhibited Ras/ERK signaling pathway by decreasing the expression of Ras, p-Erk1/2 and c-Myc in SW480. Contrastly, when evelated expression of ITGA1 in NCM460 coincided with the increased expression of Ras, p-Erk1/2 and c-Myc. Taken together, our findings suggest that ITGA1 is an oncogene with a capability to promote CRC cell migration, invasion and tumorigenicity by activating the Ras/Erk signaling, implying that it may be a novel target for the diagnosis and treatment of CRC, and warrants further investigation.

7 illus, 1 tables, 33 ref

043145   LIU J, LAI L, LIN J, ZHENG J, NIE X, ZHU X, XUE J, LIU T (Nephrology Div, Fudan Univ, Shanghai, China, 200040, Email: xuejun@fudan.edu.cn.) : Ranitidine and finasteride inhibit the synthesis and release of trimethylamine N-oxide and mitigates its cardiovascular and renal damage through modulating gut microbiota. Int J Biol Sci 2020, 16(5), 790-802.

Trimethylamine N-oxide (TMAO) leads to the development of cardiovascular and chronic kidney diseases, but there are currently no potent drugs that inhibit the production or toxicity of TMAO. In this study, high-fat diet–fed ApoE-/- mice were treated with finasteride, ranitidine, and andrioe. Subsequently, the distribution and quantity of gut microbiota in the faeces of the mice in each group were analysed using 16S rRNA sequencing of the V3+V4 regions. Pathological examination confirmed that both ranitidine and finasteride reduced atherosclerosis and renal damage in mice. HPLC analysis also indicated that ranitidine and finasteride significantly reduced the synthesis of TMAO and the TMAO precursor delta-Valerobetaine in their livers. The 16S rRNA sequencing showed that all 3 drugs significantly increased the richness and diversity of gut microbiota in the model mice. Bioinformatic analysis revealed that the faeces of mice treated with ranitidine and finasteride, had significant increases in the number of microbes in the families g_Helicobacter, f_Desulfovibrionaceae, Mucispirillum_schaedleri_ASF457, and g_Blautia, whereas the relative abundances of microbes in the families Enterobacter_sp._IPC1-8 and g_Bacteroides were significantly reduced. The microbiota metabolic pathways, such as nucleotide and cofactor and vitamin metabolism were also significantly increased, whereas the activities of metabolic signalling pathways related to glycan biosynthesis and metabolism and cardiovascular diseases were significantly reduced. Therefore, our study indicates that in addition to their known pharmacological effects, ranitidine and finasteride also exhibit potential cardiovascular and renal protective effects. They inhibit the synthesis and metabolism of TMAO and delay the deposition of lipids and endotoxins through improving the composition of the gut microbiota.

8 illus, 36 ref

043144   KE Y, WU C, ZHENG Y, CHEN M, LI Y, XIE C, ZHOU Y, ZHONG Y, YU H (Radiation and Medical Oncology Dep, Zhongnan Hospital of Wuhan Univ, Wuhan, China,430071, Email: haijunyu@whu.edu.cn) : Radiosensitization of clioquinol combined with zinc in the nasopharyngeal cancer stem-like cells by inhibiting autophagy in vitro and in vivo. Int J Biol Sci 2020, 16(5), 777-89.

Loco-regional recurrence of nasopharyngeal carcinoma (NPC) after radiation therapy is one of the main types of treatment failure. This study is aimed to explore the possible causes of inside-field recurrence of NPC patients in order to develop effective treatment methods. Our study indicated that CD44 and autophagy proteins in tumor tissues of patients with recurrent NPC are higher than that of the relapse free patients. The in vitro experiments further confirmed that cancer stem cells (CSCs) were more radioresistant with enhanced autophagy activity. Treatment with clioquinol (CQ) combined with zinc could obviously enhance the radiosensitivity of CNE-2s cells through autophagy inhibition, activation of the caspase system and impairment of DNA damage repair. The in vivo experiments have further consolidated our findings. Our results suggest that CSCs and enhanced autophagy activity may be involved in the inside-field recurrence of NPC, and CQ combined with zinc could be an important therapeutic approach for recurrent NPC.

7 illus, 1 table, 49 ref

043143   GE J, CHENG X, YUAN C, QIAN J, WU C, CAO C, YANG H, ZHOU F, ZOU J (Orthopaedic Surgery Dep, First Affiliated Hospital of Soochow Univ, 188 Shizi St., Suzhou, Jiangsu 215006, China, Email: liw72@126.com) : Syndecan-4 is a novel therapeutic target for intervertebral disc degeneration via Suppressing JNK/p53 pathway. Int J Biol Sci 2020, 16(5), 766-76.

Syndecan-4 is a member of the polysaccharide syndecan family and plays a vital role in intervertebral disc development. Several studies have demonstrated the positive relationship between syndecan-4 expression and intervertebral disc degeneration. However, the detailed molecular mechanism by which syndecan-4 affects the degeneration of nucleus pulposus cells (NPCs) remains unclear. In this study, cell viability was determined by CCK-8 assay, mRNA level was determined by qPCR, and protein expression was determined by western blot. Molecular interaction was determined by chromatin immunoprecipitation assay. A rabbit intervertebral disc degeneration model was established to test for syndecan in vivo. We found that the morphology and viability of NPCs were not affected by the expression of syndecan-4 in the long term. While the NPC function were affected, which results in the degeneration of intervertebral disc. Syndecan-4 overexpression promoted the degeneration of NPCs. Syndecan-4 also activated the JNK signaling pathway and downstream p53 pathways, and promoted degeneration. Inhibition of the JNK pathway, which down-regulated p53 expression, alleviated the degeneration. In an in vivo study, syndecan-4 siRNA injection stopped the development of rabbit disc degeneration, and even created a reverse effect, in which JNK/p53 played a role. Syndecan-4 may be a novel therapeutic target for intervertebral disc degeneration via suppressing the JNK/p53 pathway.

5 illus, 1 table, 32 ref

043142   SHU Y, HE D, LI W, WANG M, ZHAO S, LIU L, CAO Z, LIU R, HUANG Y, LI H, et al. (Beijing Univ of Chinese Medicine, Beijing, 100029, China, Email: yangxq0721@126.com) : Hepatoprotective effect of Citrus aurantium L. against APAP-induced liver injury by regulating liver lipid metabolism and apoptosis. Int J Biol Sci 2020, 16(5), 752-65.

Acetaminophen (APAP) refers to a medication used to manage pain and fever symptoms, but it always causes liver injury when overdosed. Zhishi, dried young fruit of Citrus aurantium L., is a famous Citrus herbal medicine in Asian countries which is rich in dietary phenolic substances. In this study, the mechanism of Zhishi protected against APAP-induced liver injury was studied more deeply by metabolomic strategy and pharmacological study. The metabolomics results demonstrated that Zhishi can prevent the APAP-induced liver injury model by regulating liver metabolic disorders in glycerophospholipid metabolism, fatty acid biosynthesis and glycerolipid metabolism. Moreover, it is confirmed that Zhishi blocked apoptosis of APAP-induced BRL-3A cell by simultaneously regulating p53 up-regulated apoptosis regulator (PUMA), AMPK-SIRT1 and JNK1 signaling pathways. Our findings indicated that Zhishi exhibited a hepaprotective effect against APAP-induced liver necrosis by inhibiting the PUMA and reversing disorder of liver lipid metabolism which could assist in improving the clinical outcomes of chemical-induced liver injury.

7 illus, 1 table, 47 ref

043141   ZHANG Y, DU P, LI Y, ZHU Q, SONG X, LIU S, HAO J, LIU L, LIU F, HU Y, et al. (General Surgery Dep, Xinhua Hospital Affiliated to Shanghai Jiao Tong Univ School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China, Email: liuyingbin@xinhuamed.com.cn) : TASP1 promotes gallbladder cancer cell proliferation and metastasis by up-regulating FAM49B via PI3K/AKT pathway. Int J Biol Sci 2020, 16(5), 739-51.

The highly conserved protease TASP1 not only takes part in critical site-specific proteolysis, but also plays an important role in numerous liquid and solid malignancies. However, the TASP1 expression and its biological regulation function in malignant gallbladder carcinoma (GBC) remain fully unknown. Here we observed that TASP1 levels were substantially overexpressed in GBC samples compared with non-tumor tissues. High TASP1 level was closely associated with T stage and metastasis, and was also correlated with poor prognosis in GBC patients. The depletion of TASP1 inhibited GBC cell proliferation and metastasis in vitro and in vivo. Furthermore, we first revealed that FAM49B had biological function and was positively regulated by TASP1 activating PI3K/AKT signaling pathway in GBC. At the same time, FAM49B also promoted GBC cell proliferation and migration. Inhibition of PI3K/AKT with LY294002 or FAM49B expression abrogated Myc-TASP1/Lv-shTASP1-induced GBC cell proliferation and motility. In conclusion, these findings demonstrate that TASP1 is critical for GBC progression via TASP1-PI3K/AKT-FAM49B axis and it may be a novel prognostic factor. The therapeutic targeting TASP1 may be a potential treatment approach for GBC patients.

7 illus, 2 tables, 37 ref

043140   TIAN J, CASELLA G, ZHANG Y, ROSTAMI A, LI X (Shaanxi Normal Univ, Xi’an, Shaanxi 710119, China, Email: xingli_xian@126.com) : Potential roles of extracellular vesicles in the pathophysiology, diagnosis, and treatment of autoimmune diseases. Int J Biol Sci 2020, 16(4), 620-32.

Since extracellular vesicles (EVs) were discovered in 1983 in sheep reticulocytes samples, they have gradually attracted scientific attention and become a topic of great interest in the life sciences field. EVs are small membrane particles, released by virtually every cell that carries a variety of functional molecules. Their main function is to deliver messages to the surrounding area in both physiological and pathological conditions. Initially, they were thought to be either cell debris, signs of cell death, or unspecific structures. However, accumulating evidence support a theory that EVs are a universal mechanism of communication. Thanks to their biological characteristics and functions, EVs are likely to represent a promising strategy for obtaining pathogen information, identifying therapeutic targets and selecting specific biomarkers for a variety of diseases, such as autoimmune diseases. In this review, we provide a brief overview of recent progress in the study of the biology and functions of EVs. We also discuss their roles in diagnosis and therapy, with particular emphasis on autoimmune diseases.

2 illus, 4 tables, 155 ref

043139   WANG W, ZHOU Z, XIANG L, LV M, NI T, DENG J, WANG H, MASATARA S, ZHOU Y, LIU Y (Oncology Dep, Yixing Hospital Affiliated to Medical College of Yangzhou Univ, Yixing, Jiangsu, 214200, PR China, Email: dryzhou@163.com) : CHIP-mediated ubiquitination of galectin-1 predicts colorectal cancer prognosis. Int J Biol Sci 2020, 16(4), 719-29.

CHIP and Galectin-1 are associated with the development of metastasis in cancer. However, the precise roles of CHIP or Gal1 in colorectal cancer are uncertain. Here, our study explored the relationship and clinical significance of CHIP or Gal1 in CRC. CHIP or Gal1 expression was significantly decreased or up-regulated in CRC compared with adjacent noncancerous tissues by immunohistochemistry on a CRC tissue microarray, respectively. Low CHIP or high Gal1 expression significantly correlated with clinicopathological characteristics in patients, as well as with shorter overall survival. Multivariate Cox regression analysis revealed that CHIP or Gal1 expression was an independent prognostic factor for CRC patients. Moreover, CHIP associated with Gal1 has a synergistic effect on the prediction of CRC prognosis. In vitro and vivo, high CHIP or low Gal1 expression inhibit CRC growth or metastasis. Our results found that CHIP could degradate Gal1 by ubiquitination. In summary, CHIP could inhibit CRC growth or metastasis through promoting Gal1 ubiquitination and degradation by proteasome. CHIP and Gal1 expressions are novel candidate prognostic markers in CRC. A combined effect of CHIP and Gal1 as efficient prognostic indicators was found for the first time.

4 illus, 3 tables, 31 ref

043138   ZHANG N, ZHANG Y, YOU S, TIAN Y, LU S, CAO L, SUN Y (Cardiology Dep, First Hospital of China Medical Univ, Shenyang, 110001, Liaoning Province, People’s Republic of China, Email: yxsun@cmu.edu.cn) : Septin4 prevents PDGF-BB-induced HAVSMC phenotypic transformation, proliferation and migration by promoting SIRT1-STAT3 deacetylation and dephosphorylation. Int J Biol Sci 2020, 16(4), 708-18.

SIRT1 and STAT3 are key to human aortic vascular smooth muscle cells (HAVSMCs) proliferation, migration and phenotypic transformation, but the regulatory mechanism of SIRT1-STAT3 in this process is still unclear. Septin4 is a cytoskeleton-related protein that regulates oxidative stress-vascular endothelial injury. However, the role and underlying mechanism of Septin4 in atherosclerosis remains unknown. Here, we revealed the role and mechanism of Septin4 in regulating SIRT1-STAT3 in atherosclerosis. We determined that the expression of Septin4 were markedly increased in Apoe-/- atherosclerosis mice and PDGF-BB-induced HAVSMCs. Knockdown of Septin4 significantly increased PDGF-BB-induced HAVSMCs proliferation, migration and phenotypic transformation, while overexpression of Septin4 had the opposite effects. Mechanically, co-immunoprecipitation results demonstrated that Septin4 was a novel interacting protein of STAT3 and SIRT1. Septin4 formed a complex with SIRT1-STAT3, enhancing the interaction between SIRT1 and STAT3, ensuing promoting SIRT1-regulated STAT3-K685 deacetylation and STAT3-Y705 dephosphorylation, which inhibited PDGF-BB-induced HAVSMCs proliferation, migration and phenotype transformation. Therefore, our findings provide novel insights into the prevention and treatment of atherosclerosis.

5 illus, 28 ref

043137   MIN K, KIM J Y, LEE S K (Medical Life Sciences Dep, The Catholic Univ of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea, Email: sukklee@catholic.ac.kr) : Epstein-Barr virus miR-BART1-3p suppresses apoptosis and promotes migration of gastric carcinoma cells by targeting DAB2. Int J Biol Sci 2020, 16(4), 694-707.

Although Epstein-Barr virus (EBV) is known to encode over 40 different miRNAs of its own, the roles of most EBV miRNAs remain unknown. Disabled homolog 2 (DAB2) is a putative tumor suppressor, but its role in gastric carcinoma (GC), especially in EBV-associated GC, needs to be clarified. Our qRT-PCR and mRNA microarray results showed that DAB2 expression was down-regulated in EBV-positive GC cells compared to EBV-negative cells. Four BART miRNAs that might target DAB2 were predicted, and we found, using a luciferase reporter assay, that miR-BART1-3p directly targeted the 3’-UTR of DAB2. The miR-BART1-3p transfection decreased DAB2 expression at both mRNA and protein levels, while transfection of an inhibitor of miR-BART1-3p, miR-BART1-3p(i), increased DAB2 expression. In addition, miR-BART1-3p as well as siDAB2 increased migration and decreased apoptosis. Meanwhile, miR-BART1-3p(i) or pcDNA3.1-DAB2 transfection decreased migration and increased apoptosis in EBV-infected GC cells. Furthermore, decreased migration by miR-BART1-3p(i) was abrogated by co-transfected siDAB2, while decreased migration by miR-BART1-3p(i) was further suppressed by a co-transfected DAB2 over-expression vector. Our data suggest that miR-BART1-3p plays an important role in the tumorigenesis of EBV-associated GC by directly targeting DAB2.

6 illus, 47 ref

043136   RUAN B, LIU W, CHEN P, CUI R, LI Y, JI M, HOU P, YANG Q (Endocrinology Dep, The First Affiliated Hospital of Xi’an Jiaotong Univ, Xi’an 710061, P.R. China, Email: yangqi2015@xjtu.edu.cn) : NVP-BEZ235 inhibits thyroid cancer growth by p53- dependent/independent p21 upregulation. Int J Biol Sci 2020, 16(4), 682-93.

NVP-BEZ235 is a novel dual PI3K/mTOR inhibitor, currently in phase 1/2 clinical trials, exhibiting clinical efficiency in treatment of numerous malignancies including thyroid cancer. Cancer cells harboring mutant p53 was widely reported to be blunt to pharmaceutical therapies. However, whether this genotype dependent effect also presents in thyroid cancer when treated with NVP-BEZ235 remains unknown. Therefore, in this study, the tumor suppressing effects of NVP-BEZ235 in thyroid cancer cell lines and in-vivo xenograft mouse model harboring different p53 status were examined. The antitumor effects were confirmed in p53 mutant thyroid cancer cells, though less prominent than p53 wild type cells. And for the p53 mutant cells, p53-independent upregulation of p21 plays a critical role in their response to NVP-BEZ235. Moreover, GSK3β/β-catenin signaling inhibition was implicated in the p21-mediated G₀/G₁ cell cycle arrest in both p53 wild type and mutant thyroid cancer cells treated with NVP-BEZ235.

7 illus, 1 table, 40 ref

043135   WU B, LIU J-D, BIAN E, HU W, HUANG C, MENG X, LEI Z, LV X, LI J (Anhui Medical Univ, 81 Meishan Road, Hefei, 230032, China, Email: lj@ahmu.edu.cn) : Blockage of Kv1.3 regulates macrophage migration in acute liver injury by targeting δ-catenin through RhoA signaling. Int J Biol Sci 2020, 16(4), 671-81.

Activation of macrophages and infiltration are key events in acute liver injury (ALI). Kv1.3 plays an important role in regulating immunologic functions of macrophages and is extensively recognized as a potential ion channel for immunological diseases. We hypothesized that blockage of Kv1.3 may influence ALI by inhibiting macrophages infiltration in damaged liver tissues. Margatoxin was administered into the peritoneal cavity of ALI mice. The impact of this treatment on ALI and macrophage migration in vivo and in vitro was determined using immunohistochemistry, transwell migration, and wound healing assays. MgTX treatment alleviated ALI in mice, as evidenced by reduced macrophage infiltration in liver tissues and lower serum levels of liver ALT and AST. RNA-seq profiling analysis showed that the most obvious change by MgTX treatment was downregulation of δ-catenin, a protein known to be associated with macrophage migration. The effect of MgTX on macrophage migration and involvement of δ-catenin was confirmed by transwell and wound healing assays. Overexpression of δ-catenin in RAW264.7 cells promoted migration, an event that was suppressed upon silencing of δ-catenin. Mechanistically, the expression of RhoA was regulated by the overexpression or knockdown of δ-catenin. These findings suggest a role for blockage of Kv1.3 channel in macrophage migration and reveal a new target in the treatment of ALI.

6 illus, 28 ref

045072   REDDY K P, DEVI M U, RAMULU V, MADHAVI M (Jayashankar Telangana State Agricultural Univ, Hyderabad- 500 030, Telangana) : Water productivity and economics of rabi sunflower as influenced by nitrogen and potassium fertigation schedules. J Crop Weed 2020, 16(2), 244-8.

The present study was conducted to identify the optimum nitrogen and potassium fertigation schedules for rabi sunflower (variety DRSH-1) under semi-arid climate of Hyderabad in 2017-18. The experiment was conducted in a randomized block design with nine treatments replicated thrice. The nine treatments were combinations of N (75 kg ha^-1) and K (30 kg ha^-1) fertilizers applied by fertigation through ventury at different intervals viz., 3 days and 4 days. Drip irrigation was scheduled once in 2 days at 0.8 E pan. Fertigation was imposed at 16 DAS to 88 DAS and completed in 19 and 10 splits in 4 and 8 days interval, respectively. The sources of N and K fertilizers were urea and potassium sulphate, respectively. The amount of total irrigation water applied was 3188 m³ and 4666 m³ in drip irrigation and furrow irrigation treatments, respectively. Application of 75 kg N and 30 kg K₂ O ha^-1, at 4 days interval (T₇ ) has recorded higher seed yield (2623 kg ha^-1), water productivity (0.82 kg m^-3) and was at par with (T₈ ) 75 -30 kg N-P₂ O5 kg ha^-1 applied at 8 days interval (0.76 kg m^-3), Significantly lower water productivity (0.38 kg m^-3) was noticed in furrow irrigation with conventional manual application of fertilisers (T₉ ). The highest net returns (Rs. 66,103 ha^-1) and benefit cost ratio (2.59) were recorded in N and K at 4 days interval (T₇ ) followed by N and K at 8 days interval (T₈ ) (2.44).

2 illus, 3 tables, 9 ref

043134   KONG L, ZUO R, WANG M, WANG W, XU J, CHAI Y, GUAN J, KANG Q (Orthopedics Dep, Shanghai Jiao Tong Univ Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, P.R. China, Email: orthokang@163.com) : Silencing microRNA-137-3p, which targets RUNX2 and CXCL12 prevents steroid-induced osteonecrosis of the femoral head by facilitating osteogenesis and angiogenesis. Int J Biol Sci 2020, 16(4), 655-70.

The main pathogenesis of steroid-induced osteonecrosis of the femoral head (SONFH) includes decreased osteogenic capacity of bone marrow-derived mesenchymal stem cells (BMSCs) and damaged blood supply to the femoral head. MicroRNAs (miRNAs) have been shown to play prominent roles in SONFH development. However, there is no report that a specific miRNA targeting two genes in two different pathogenic pathways has been applied to this disease. The present study investigated the effects of transplantation of miR-137-3p-silenced BMSCs on the prevention and early treatment of SONFH. First, western blotting and dual luciferase assays were employed to verify that miR-137-3p directly targets Runx2 and CXCL12. Then, silencing of miR-137-3p was found to facilitate osteogenic differentiation of BMSCs, which was confirmed by alkaline phosphatase (ALP) staining, alizarin red staining and qRT-PCR. Silencing of miR-137-3p also promoted angiogenesis by human umbilical vein endothelial cells (HUVECs) in the presence or absence of glucocorticoids. Thereafter, overexpression of Runx2 and CXCL12 without the 3′ untranslated region (3′UTR) partially rescued the effects of miR-137-3p on osteogenesis and angiogenesis, respectively. This finding further supported the hypothesis that miR-137-3p exerts its functions partly by regulating the genes, Runx2 and CXCL12. We also demonstrated that SONFH was partially prevented by transplantation of miR-137-3p-silenced BMSCs into a rat model. Micro-CT and histology showed that the transplantation of miR-137-3p-silenced BMSCs significantly improved bone regeneration. Additionally, the results of enzyme-linked immunosorbent assays (ELISA) and flow cytometry suggested that stromal cell-derived factor-1α (SDF-1α) and endothelial progenitor cells (EPCs) participated in the process of vascular repair. Taken together, these findings show that silencing of miR-137-3p directly targets the genes, Runx2 and CXCL12, which can play critical roles in SONFH repair by facilitating osteogenic differentiation and mobilizing EPCs.

8 illus, 48 ref

043133   WEI L, ZHOU Q, TIAN H, SU Y, FU G-H, SUN T (Cardiology Dep, Shanghai Ninth People’s Hospital Affiliated with Shanghai Jiaotong Univ School of Medicine, Shanghai 200025, China, Email: beibeisun2008@163.com) : Integrin β3 promotes cardiomyocyte proliferation and attenuates hypoxia-induced apoptosis via regulating the PTEN/Akt/mTOR and ERK1/2 pathways. Int J Biol Sci 2020, 16(4), 644-54.

Integrin β3 is one of the main integrin heterodimer receptors on the surface of cardiac myocytes. Our previous studies showed that hypoxia induces apoptosis and increases integrin β3 expression in cardiomyocytes. However, the exact mechanism by which integrin β3 protects against apoptosis remains unclear. Hence, the present investigation aimed to explore the mechanism of integrin β3 in cardiomyocyte proliferation and hypoxia-induced cardiomyocyte apoptosis. Stable cells and in vivo acute and chronic heart failure rat models were generated to reveal the essential role of integrin β3 in cardiomyocyte proliferation and apoptosis. Western blotting and immunohistochemistry were employed to detect the expression of integrin β3 in the stable cells and rat cardiac tissue. Flow cytometer was used to investigate the role of integrin β3 in hypoxia-induced cardiomyocyte apoptosis. Confocal microscopy was used to detect the localization of integrin β3 and integrin αv in cardiomyocytes. A cobaltous chloride-induced hypoxic microenvironment stimulated cardiomyocyte apoptosis and increased integrin β3 expression in H9C2 cells, AC16 cells, and cardiac tissue from acute and chronic heart failure rats. The overexpression of integrin β3 promoted cardiomyocyte proliferation, whereas silencing integrin β3 expression resulted in decreased cell proliferation in vitro. Furthermore, knocking down integrin β3 expression using shRNA or the integrin β3 inhibitor cilengitide exacerbated cobaltous chloride-induced cardiomyocyte apoptosis, whereas overexpression of integrin β3 weakened cobaltous chloride-induced cardiomyocytes apoptosis. We found that integrin β3 promoted cardiomyocytes proliferation through the regulation of the PTEN/Akt/mTOR and ERK1/2 signaling pathways. In addition, we found that knockdown of integrin αv or integrin β1 weakened the effect of integrin β3 in cardiomyocyte proliferation. Our findings revealed the molecular mechanism of the role of integrin β3 in cardiomyocyte proliferation and hypoxia-induced cardiomyocyte apoptosis, providing new insights into the mechanisms underlying myocardial protection.

7 illus, 26 ref

043132   WANG C, HUANG X, WU Y, WANG J, LI F, GUO G (Jinan Univ, 1017 Dongmen North Road, Shenzhen 518020, China) : Tumor cell-associated exosomes robustly elicit anti-tumor immune responses through modulating dendritic cell vaccines in lung tumor. Int J Biol Sci 2020, 16(4), 633-43.

DC vaccine-based immunotherapy is emerging as a novel therapeutic strategy for cancer treatment, however, antitumor effect of DC vaccines based on tumor cell lysates (TCLs) remains unsatisfactory due to poor immunogenicity of tumor antigens. Although tumor-associated exosomes (TAEs) have been reported as a promising antigen for DC vaccines, it remains unclear how TAE-based DC vaccine induced antitumor immunity in lung cancer. In the present study, we extracted TAEs from the supernatant of tumor cell culture medium, and compared the effect of TAEs with TCLs on DCs. To further evaluate the therapeutic effect of DC_TAE, we used immunofluorescence and flow cytometry to evaluate the apoptosis of tumor tissue, tumor-infiltrating CD8⁺ T cells and Tregs in TDLNs and spleen. Then the levels of cytokines of IL-12, IFN-γ, L-10 and TGF-β were quantified by ELISA assays. Our data showed that TAEs were more potent than TCLs to promote DC maturation and enhance MHC cross presentation, which directly contributed to more robust tumor-specific cytotoxic T lymphocyte (CTL) response. More importantly, TAEs reduced the expression of PD-L1 of DCs, thereby led to down-regulated population of Tregs in vitro. Moreover, DC^TAE remarkably suppressed the tumor growth and prolonged survival rate in vivo, due to participance of CD8⁺ T cells and decreased Tregs in TDLNs and spleen. TAEs could serve to improve vaccine-elicited immunotherapy by triggering stronger DC-mediated immune responses and decreasing Tregs in the tumor microenvironment. 

7 illus, 46 ref

043131   LIU R, CHEN H, ZHAO P, CHEN C-H, LIANG H, YANG C, ZHOU Z, ZHI X, LIU S, et al. (Fuzhou Univ, Fuzhou, Fujian 350108, China, Email: chenc@mail.kiz.ac.cn) : Mifepristone derivative FZU-00,003 suppresses triple-negative breast cancer cell growth partially via miR-153-KLF5 axis. Int J Biol Sci 2020, 16(4), 611-9.

Triple-negative breast cancer (TNBC) is one of the most malignant breast cancers lacking targeted therapeutics currently. We recently reported that mifepristone (MIF), a drug regularly used for abortion, suppresses TNBC cell growth by inhibiting KLF5 expression via inducing miR-153. However, its anticancer efficacy is only modest at high dose. In order to enhance the anticancer activities, a focused compound library containing 17 compounds by altering the sensitive metabolic region of mifepristone has been designed and synthesized. We first tested the cell growth inhibitory effects of these compounds in TNBC cell lines. Among them, FZU-00,003 displayed the most potent efficiency. FZU-00,003 suppresses TNBC cell growth, cell cycle progression and induces apoptosis more effectively than MIF does. Consistently, FZU-00,003 induces miR-153 expression and suppressed KLF5 expression at much lower dosages than MIF does. Furthermore, FZU-00,003 inhibits tumor growth more potently than MIF does. Taken together, the MIF derivative, FZU-00,003 may serve as a better therapeutic compound for TNBC than MIF.

5 illus, 30 ref

043130   XIE J, LIN L-S, HUANG X-Y, GAN R-H, DING L-C, SU B-H, ZHAO Y, LU Y-G, ZHENG D-L (Fujian Medical Univ, 88 Jiao Tong Road, Fuzhou 350004, China, Email: dalizheng@fjmu.edu.cn) : The NOTCH1-HEY1 pathway regulates self-renewal and epithelial-mesenchymal transition of salivary adenoid cystic carcinoma cells. Int J Biol Sci 2020, 16(4), 598-610.

Our previous study demonstrated a close relationship between the NOTCH signaling pathway and salivary adenoid cystic carcinoma (SACC). Its receptor gene, NOTCH1, and its downstream gene, HES1, contribute to the proliferation, invasion and metastasis of SACC. Accumulating evidence supports HEY1 as another effector of the signaling pathway. The purpose of this study was to explore the effects of the NOTCH1-HEY1 pathway on the proliferation, invasion and metastasis of SACC cells. Our results verified that HEY1 is a specific molecular target of the NOTCH signaling pathway in SACC cells and that its expression in carcinoma is much higher than that in paracarcinoma tissues. The expression of NOTCH1 and HEY1 are positively correlated in the salivary adenoid cystic carcinoma tissues. NOTCH1 is significantly related to the activation of HEY1 in SACC, and that HEY1 reciprocally regulates NOTCH1 expression in SACC. HEY1 promotes cell proliferation and spheroid formation and inhibits cell apoptosis in vitro. In addition, HEY1 enhances the tumorigenicity of SACC in vivo. Furthermore, HEY1 increases cell invasion and metastasis by driving the expression of epithelial-mesenchymal transition (EMT)-related genes and MMPs. The results of this study indicate that the NOTCH1-HEY1 pathway is specifically upregulated in SACC and promotes cell proliferation, self-renewal, invasion, metastasis and the expression of EMT-related genes and MMPs. Our findings suggest that a NOTCH1-HEY1 pathway inhibitor might therefore have potential therapeutic applications in treating SACC patients by inhibiting cancer cell growth and metastasis.

6 illus, 2 tables, 57 ref

043129   WU Y, YAN B, XU W, GUO L, WANG Z, LI G, HOU N, ZHANG J, LING R (Thyroid Dep, Fourth Military Medical Univ, Xi’an, Shaanxi, China, Email: lingrui@fmmu.edu.cn) : Compound C enhances the anticancer effect of aspirin in HER-2-positive breast cancer by regulating lipid metabolism in an AMPK-independent pathway. Int J Biol Sci 2020, 16(4), 583-97.

Various clinical studies have determined that aspirin shows anticancer effects in many human malignant cancers, including human epidermal growth factor receptor-2 (HER-2)-positive breast cancer. However, the anti-tumor mechanism of aspirin has not been fully defined. The aim of this study was to determine the role of Compound C in enhancing the anticancer effect of aspirin. HER-2-positive breast cancer cell lines were treated with aspirin with or without Compound C pre-treatment; their phenotypes and mechanisms were then analyzed in vitro and in vivo. Aspirin exhibited anticancer effects in HER-2-positive breast cancer by inhibiting cell growth and inducing apoptosis through the activation of AMP-activated protein kinase (AMPK). Unexpectedly, pre-treatment with Compound C, a widely used AMPK inhibitor, induced robust anticancer effects in cells compared to aspirin monotherapy. This anticancer effect was not distinct in HER-2 negative breast cancer MDA-MB-231 cells and may be due to the inhibition of lipid metabolism mediated by c-myc. Besides, c-myc re-expression or palmitic acid supply could partially restored cell proliferation. Aspirin exhibits anticancer effects in HER-2-positive breast cancer by regulating lipid metabolism mediated by c-myc, and Compound C strengthens these effects in an AMPK-independent manner. Our results potentially provide a novel therapeutic strategy exploiting combined aspirin and Compound C therapy for HER-2-positive breast cancer, which acts by reducing de novo lipid synthesis.

7 illus, 42 ref

043128   LI D, XIANG S, SHEN J, XIAO M, ZHAO Y, WU X, DU F, JI H, LI M, ZHAO Q, ZHAO Q , et al. (Pharmacology Dep, Southwest Medical Univ, Luzhou, 646000, Sichuan, PR China, Email: xzg555898@hotmail.com) : Comprehensive understanding of B7 family in gastric cancer. Expression profile, association with clinicopathological parameters and downstream targets. Int J Biol Sci 2020, 16(4), 568-82.

B7 family members were identified as co-stimulators or co-inhibitors of the immune response and played important roles in cancer immunotherapy; however, their dysregulation in gastric cancer is still unclear. Data were obtained from TCGA and GTEX database. B7 mutations, association with DNA methylation and affected proteins were analyzed in cBioportal. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology (GO) project was studied by DAVID to find the downstream signaling pathway and important metabolic process, respectively. Protein-protein interaction network was analyzed in STRING and Cytoscape. A total of 160 paired specimens in tissue microarray from patients with gastric cancer were used to detect the expression levels of seven B7 family members via immunohistochemical analysis. Bioinformatics studies revealed dysregulation of B7 members in gastric cancer. Gene and protein alteration were found in B7 family members. Furthermore, DNA methylation and gene alteration may be both involved in B7 member dysregulation in gastric cancer. Importantly, the high expression of B7-H6 is associated with good overall patient survival. B7 family members primarily affect the EGFR tyrosine kinase inhibitor resistance signaling pathway in gastric cancer and TP53 may be an important target of the family. The low expression of B7-1 and high expression of B7-H3 and B7-H7 were validated by IHC staining. Our results provide insight into B7 family member expression in gastric cancer and stress their importance in stomach tumorigenesis, which may be beneficial for designing future cancer treatments.

6 illus, 1 table, 39 ref

043128   LI D, XIANG S, SHEN J, XIAO M, ZHAO Y, WU X, DU F, JI H, LI M, ZHAO Q, ZHAO Q , et al. (Pharmacology Dep, Southwest Medical Univ, Luzhou, 646000, Sichuan, PR China, Email: xzg555898@hotmail.com) : Comprehensive understanding of B7 family in gastric cancer. Expression profile, association with clinicopathological parameters and downstream targets. Int J Biol Sci 2020, 16(4), 568-82.

B7 family members were identified as co-stimulators or co-inhibitors of the immune response and played important roles in cancer immunotherapy; however, their dysregulation in gastric cancer is still unclear. Data were obtained from TCGA and GTEX database. B7 mutations, association with DNA methylation and affected proteins were analyzed in cBioportal. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology (GO) project was studied by DAVID to find the downstream signaling pathway and important metabolic process, respectively. Protein-protein interaction network was analyzed in STRING and Cytoscape. A total of 160 paired specimens in tissue microarray from patients with gastric cancer were used to detect the expression levels of seven B7 family members via immunohistochemical analysis. Bioinformatics studies revealed dysregulation of B7 members in gastric cancer. Gene and protein alteration were found in B7 family members. Furthermore, DNA methylation and gene alteration may be both involved in B7 member dysregulation in gastric cancer. Importantly, the high expression of B7-H6 is associated with good overall patient survival. B7 family members primarily affect the EGFR tyrosine kinase inhibitor resistance signaling pathway in gastric cancer and TP53 may be an important target of the family. The low expression of B7-1 and high expression of B7-H3 and B7-H7 were validated by IHC staining. Our results provide insight into B7 family member expression in gastric cancer and stress their importance in stomach tumorigenesis, which may be beneficial for designing future cancer treatments.

6 illus, 1 table, 39 ref

043127   CHENG Y, ZHANG X, MA F, SUN W, WANG W, YU J, SHI Y, CAI L, XU Z (Nephrology Dep, The First Hospital of Jilin Univ, 71 Xinmin Street, Changchun, China, 130021, Email: chengyanli@jlu.edu.cn) : The role of Akt2 in the protective effect of fenofibrate against diabetic nephropathy. Int J Biol Sci 2020, 16(4), 553-67.

Fenofibrate (FF) protects against diabetic nephropathy (DN) in type 1 diabetic (T1D) mice by upregulating the expression of fibroblast growth factor 21 (FGF21), leading to the activation of the Akt-mediated Nrf2 antioxidant pathways. Here, we examined which isoforms of Akt contribute to FF activation of FGF21-mediated renal protection by examining the phosphorylation and expression of three isoforms, Akt1, Akt2, and Akt3. T1D induced by a single intraperitoneal dose of streptozotocin (STZ) resulted in reduced phosphorylation of one isoform, Akt2, but FF treatment increased renal Akt2 phosphorylation in these and normal mice, suggesting a potential and specific role for renal Akt2 in FF protection against T1D. This was further confirmed using in vitro cultured HK-2 human kidney tubule cells exposed to high glucose (HG) with siRNA silencing of the Akt2 gene and STZ-induced diabetic Akt2-knockout mice with and without 3-month FF treatment. In normal HK-2 cells exposed to HG for 24 hours, FF completely prevented cell death, reduced total Akt expression and glycogen synthase kinase (GSK)-3β phosphorylation, increased nuclear accumulation of Fyn, and reduced nuclear Nrf2 levels. These positive effects of FF were partially abolished by silencing Akt2 expression. Similarly, FF abolished T1D-induced renal oxidative stress, inflammation, and renal dysfunction in wild-type mice, but was only partially effective in Akt2-KO mice. Furthermore, FF treatment stimulated phosphorylation of AMPKα, an important lipid metabolism mediator, which in parallel with Akt2 plays an important role in FF protection against HG-induced HK-2 cells oxidative stress and damage. These results suggest that FF protects against DN through FGF21 to activate both Akt2/GSK-3β/Fyn/Nrf2 antioxidants and the AMPK pathway. Therefore, FF could be repurposed for the prevention of DN in T1D patients.

8 illus, 43 ref

043126   GAO Y, ZHU H, WANG Q, FENG Y, ZHANG C (Orthopaedic Surgery Dep, Shanghai Jiao Tong Univ Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, China, Email: fengyongxsh@gmail.com) : Inhibition of PERK signaling prevents against glucocorticoid-induced endotheliocyte apoptosis and osteonecrosis of the femoral head. Int J Biol Sci 2020, 16(4), 543-52.

Vascular injury is considered an important pathological process during glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). In this study, we tried to investigate whether the endoplasmic reticulum (ER) stress is triggered in the GC-induced endotheliocyte (EC) apoptosis and ONFH. The results showed that a GC upregulated the expression of ER stress-related proteins, and PERK-CHOP signaling played an important role and induced EC apoptosis. The inhibition of PERK by GSK2656157 significantly decreased the GC-induced EC apoptosis in vitro and in vivo, thus protecting a rat model from vascular injury and significantly preventing GC-induced ONFH.

5 illus, 48 ref

043125   ZHANG Y, DONG D, WANG H (Gastroenterology Dep, The First Affiliated Hospital of Anhui Medical Univ, Hefei, Anhui, 230032, China, Email: kongderun168@163.com) : Mucosal-associated Invariant T cell in liver diseases. Int J Biol Sci 2020, 16(3), 460-70.

Mucosal-associated invariant T cells (MAIT cells) are a new population of innate immune cells, which are abundant in the liver and play complex roles in various liver diseases. In this review, we summarize MAIT cells in the liver diseases in recent studies, figure out the role of MAIT cells in various liver disease, including Alcoholic liver disease, Non-alcoholic liver disease, Autoimmune liver diseases, Viral hepatitis and Liver Cancer. Briefly, MAIT cells are involved in anti-bacteria responses in the alcoholic liver diseases. Besides, the activated MAIT cells promote the liver inflammation by secreting inflammatory cytokines and produce regulatory cytokines, which induces anti-inflammatory macrophage polarization. MAIT cells participate in the liver fibrosis via enhancing hepatic stellate cell activation. In viral hepatitis, MAIT cells exhibit a flawed and exhausted phenotype, which results in little effect on controlling the virus and bacteria. In liver cancer, MAIT cells indicate the disease progression and the outcome of therapy. In summary, MAIT cells are attractive biomarkers and therapeutic targets for liver disease.

2 illus, 1 table, 92 ref

043124   CHEN H, HE Y, JIA W (Hepatic Surgery Dep, Science and Technology of China Univ, HeFei, 230001, China, Email: ch2446@ustc.edu.cn) : Precise hepatectomy in the intelligent digital era. Int J Biol Sci 2020, 16(3), 365-73.

In the past 20 years, the concept of surgery has undergone profound changes. Surgical practice has shifted from emphasizing the complete elimination of lesions to achieving optimal rehabilitation in patients. Collaborative optimization of surgery consists of three core elements, removal of lesions, organ protection and injury close monitoring, and controlled surgical intervention. As a result, the traditional surgical paradigm has quietly transformed into a modern precision surgical paradigm. In this review, we summarized the latest breakthroughs and applications of precision medicine in liver surgery. In addition, we also outlined the progresses that have been made in precision liver surgery, the opportunities and challenges that may encountered in the future.

2 illus, 44 ref

043123   LU Y-H, CHENG Y-P, LI T, HAN F, LI C-J, LI X-Y, XUE M, CHEN Y, MENG Z-Y, HAN Z, et al. (Tianjin Medical Univ, Tianjin 300134, China, Email: xfx22081@vip.163.com) : Empagliflozin attenuates hyperuricemia by upregulation of ABCG2 via AMPK/AKT/CREB signaling pathway in Type 2 diabetic mice. Int J Biol Sci 2020, 16(3), 529- 42.

Hyperuricemia (HUA) is a metabolic disease characterized by elevated serum uric acid (SUA). Empagliflozin, a kind of sodium-glucose cotransporter 2 inhibitors, has recently emerged as a new antidiabetic agent by facilitating glucose excretion in urine. Moreover, there was evidence of SUA reduction following treatment with empagliflozin in addition to glycaemic control, while the molecular mechanisms remain unknown. To investigate the potential mechanisms, the model of type 2 diabetes (T2DM) with HUA was established by combination of peritoneal injection of potassium oxonate and intragastric administration of hypoxanthine in KK-Ay mice. A series of method such as RT-PCR, western blot, immunochemistry, immunofluorescence were conducted to explore the mechanism. Our results showed that empagliflozin significantly ameliorated the levels of SUA and blood glucose in T2DM mice with HUA. Furthermore, in both kidney and ileum, empagliflozin obviously promoted protein expression of uric acid (UA) transporter ABCG2, p-AMPK, p-AKT and p-CREB. The same trend was observed in human tubular epithelial (HK-2) cells. Additionally, through application of an AMPK inhibitor (Compound C), it was further confirmed empagliflozin exerted its anti-hyperuricemic effects in an AMPK dependent manner. Meanwhile, with the help of ChIP assay and luciferase reporter gene assay, we found that CREB further activated ABCG2 via binding to the promoter of ABCG2 to induce transcription. Taken together, our study demonstrated that empagliflozin treatment played an essential role in attenuating HUA by upregulation of ABCG2 via AMPK/AKT/CREB signaling pathway.

8 illus, 2 tables, 45 ref

043122   FAN J, FAN X, GUANG H, SHAN X, TIAN Q, ZHANG F, CHEN R, YE F, QUAN H, ZHANG H, DINH L, et al. (Wenzhou Medical Univ, Wenzhou, Zhejiang, 325035, China, Email: fxbwzmc@126.com ) : Upregulation of miR-335-3p by NF-κB transcriptional regulation contributes to the induction of pulmonary arterial hypertension via apj during hypoxia. Int J Biol Sci 2020, 16(3), 515-28.

Pulmonary arterial hypertension (PAH) is a cardiopulmonary disease that can lead to heart failure and eventually death. MicroRNAs (miRs) play essential roles during PAH progression; however, their exact mechanism of action remains unclear. Apelin is a small bioactive peptide with a key protective function in the pathogenesis of PAH mediated by binding to the APJ gene. The aim of the present study was to investigate the role of miR-335-3p in chronic normobaric hypoxia (CNH)-induced PAH in mice and the potential underlying regulatory mechanism. Adult male C57BL/6 mice were exposed to normoxia (~21 % O₂) or CNH (~10 % O₂, 23 h/d) for 5 weeks. MiR-335-3p was significantly increased in lung tissue of CNH-induced PAH mice. Blocking miR-335-3p attenuated CNH-induced PAH and alleviated pulmonary vascular remodeling. Bioinformatics analysis and luciferase reporter assay indicated that nuclear factor-kappa beta (NF-κB) acted as a transcriptional regulator upstream of miR-335-3p. Pyrrolidine dithiocarbamate treatment reversed the CNH-induced increase in miR-335-3p expression and diminished CNH-induced PAH. Moreover, p50^-/- mice were resistant to CNH-induced PAH. Finally, APJ was identified as a direct targeting gene downstream of miR-335-3p, and pharmacological activation of APJ by its ligand apelin-13 reduced CNH-induced PAH and improved pulmonary vascular remodeling. Our results indicate that NF-κB-mediated transcriptional upregulation of miR-335-3p contributes to the inhibition of APJ and induction of PAH during hypoxia; hence, miR-335-3p could be a potential therapeutic target for hypoxic PAH.

8 illus, 52 ref

043121   GUOREN Z, ZHAOHUI F, WEI Z, MEI W, YUAN W, LIN S, XIAOYUE X, XIAOMEI Z, BO S (Nanjing Medical Univ, 42 Baiziting, Nanjing, Jiangsu, 210009, China, Email: shenbo987@njmu.edu.cn) : TFAP2A induced ITPKA serves as an oncogene and interacts with DBN1 in lung adenocarcinoma. Int J Biol Sci 2020, 16(3), 504-14.

The inositol polyphosphate kinase (IPK) family member ITPKA (inositol 1,4,5-trisphosphate 3-kinase) regulates the levels of many inositol polyphosphates which are important in cellular signaling. Several recent studies reported the aberrant expression of ITPKA in malignancy disease and usually made cancer more aggressive. However, the contribution of the inositol polyphosphate kinase ITPKA to lung cancer development remains unclear. Here we report that ITPKA is overexpressed in lung adenocarcinoma (LUAD) and positively correlated with advanced clinical parameters. ITPKA contributes to the malignant phenotypes in-vitro. Mechanistically, ITPKA executed its action through the inducting of epithelial–mesenchymal transition (EMT) and interacting with Drebrin 1 (which is related to cancer metastasis). Moreover, the hyper-expression of ITPKA in LUAD is transcriptionally activated by the transcription factor TFAP2A. In survival analysis by using tissue microarray (TMA), we indicate that ITPKA is hyper-expressed in LUAD tissues compared to adjacent normal tissues, and increased expression of ITPKA is associated with poor prognosis. Collectively, this study indicates that TFAP2A induced ITPKA hyperexpression promotes LUAD via interacting with Drebrin 1 and activating epithelial–mesenchymal transition (EMT). ITPKA might represent a potent candidate for the treatment and prognostic prediction of LUAD.

6 illus, 1 table, 20 ref

043120   CHEN R, CHENG Q, OWUSU-ANSAH K G, SONG G, ZHOU L, XU X, WU J , et al. (Surgery Dep, Zhejiang Univ, Hangzhou 310000, China, Email: drwujian@zju.edu.cn) : NKILA, a prognostic indicator, inhibits tumor metastasis by suppressing NF-κB/Slug mediated epithelialmesenchymal transition in hepatocellular carcinoma. Int J Biol Sci 2020, 16(3), 495- 503.

The metastasis of hepatocellular carcinoma (HCC) is one of the major obstacles hindering its therapeutic efficacy, leading to low surgical resection rate, high mortality and poor prognosis. Accumulating evidence has shown that both long noncoding RNA (lncRNA) and NF-κB play vital roles in the regulation of cancer metastasis. However, the clinical significance and biological function of NKILA (NF-κB interacting lncRNA) and its interaction with NF-κB in HCC remain unknown. In this study, we demonstrated that NKILA was down-regulated in HCC tissues and cell lines, and decreased NKILA expression was significantly associated with larger tumor size and positive vascular invasion in HCC patients. NKILA reduction was an independent risk factor of HCC patients’ poor prognosis, and the 5-year overall survival (OS) rates of patients with low and high NKILA expression were 15.6% and 60.0%, respectively. Moreover, NKILA inhibits migration and invasion of HCC cells both in vitro and in vivo. Mechanistically, NKILA prevents Slug/epithelial to mesenchymal transition (EMT) pathway via suppressing phosphorylation of IκBα, p65 nuclear translocation and NF-κB activation. In conclusion, these results indicate that NKILA might serve as an effective prognostic biomarker and a promising therapeutic target against HCC metastasis.

5 illus, 2 tables, 31 ref

043119   XIA S, SUN Q, ZOU Z, LIU Y, FANG X, SUN B, WEI S, WANG D, ZHANG A, LIU Q (Toxicology Dep, Guizhou Medical Univ, Guiyang 550025, Guizhou, China, Email: aihuagzykd@163.com) : Ginkgo biloba extract attenuates the disruption of pro-and anti-inflammatory T-cell balance in peripheral blood of arsenicosis patients. Int J Biol Sci 2020, 16(3), 483-94.

Endemic arsenicosis is a public health problem that affects thousands of people worldwide. However, the biological mechanism involved is not well characterized, and there is no specific treatment. Exposure to arsenic may be associated with immune-related problems. In the present work, we performed an investigation to determine whether the Th17/Treg balance was abnormal in peripheral blood mononuclear cells (PBMCs) of patients with arsenicosis caused by burning coal. Furthermore, we investigated the effect of Ginkgo biloba extract (GBE) on the Th17/Treg imbalance in patients with arsenicosis. In this trial, 81 arsenicosis patients and 37 controls were enrolled. The numbers of Th17 and Treg cells, as well as related transcription factors and serum cytokines, were determined at the beginning and end of the study. Patients with arsenicosis exhibited higher levels of Th17 cells, Th17-related cytokines (IL-17A and IL-6), and the transcription factor RORγt. There were lower levels of Treg cells, a Treg-related cytokine (IL-10), and the transcription factor Foxp3 as compared with controls. There was a positive correlation between the levels of Th17 cells and IL-17A and the levels of arsenic in hair. Arsenicosis patients were randomly assigned to a GBE treatment group or a placebo group. After 3 months of follow-up, 74 patients completed the study (39 cases in the GBE group and 35 in the placebo group). Administration of GBE to patient upregulated the numbers of Treg cells and the level of IL-10 and downregulated the numbers of Th17 cells and the levels of cytokines associated with Th17 cells. The mRNA levels of Foxp3 and RORγt were increased and decreased, respectively. These results indicated that exposure to arsenic is associated with immune-related problems. The present investigation describes a previously unknown mechanism showing that an imbalance of pro- and anti-inflammatory T cells is involved in the pathogenesis of arsenicosis and that a GBE exerts effects on arsenicosis through regulation of the pro- and anti-inflammatory T cell balance.

6 illus, 2 tables, 67 ref

043118   TAO Y, TANG Y, YANG Z, WU F, WANG L, YANG L, LEI L, JING Y, JIANG X, HONGJUN JIN H (Chongqing Medical Univ, Yixueyuan Road, Chongqing, 400016, China, Email: lingzhang@cqmu.edu.cn) : Exploration of serum exosomal LncRNA TBILA and AGAP2-AS1 as promising biomarkers for diagnosis of non-small cell lung cancer. Int J Biol Sci 2020, 16(3), 471-82.

Non-small cell lung cancer is the most common type of cancer with a poor prognosis, and development of an effective diagnostic method is urgently needed. Exosomal lncRNAs, a class of transcripts longer than 200 nucleotides packaged into exosomes, have been defined as an ideal diagnostic biomarker for cancer. However, little is known about the clinical utility of exosomal lncRNAs in NSCLC. Here, we aimed to identify exosomal lncRNAs as promising biomarkers for NSCLC diagnosis. First, serum exosomes from NSCLC patients were successfully isolated by a polymer precipitation kit and then identified by TEM, NTA and western blot analysis. A total of nine candidate lncRNAs were detected by qRT-PCR in a training set. The two exosomal lncRNA TBILA and AGAP2-AS1 were screened out for the higher levels in NSCLC patients than that of healthy controls in a validation set. And there was a significant positive correlation between these exosomal lncRNAs levels and tumor size, lymph node metastasis and TNM stage. Additionally, we validated that these exosomal lncRNAs were stable in serum. Next, we evaluated the diagnostic efficiency of exosomal lncRNAs in NSCLC patients by ROC curve analysis. The data showed that individual TBILA or AGAP2-AS1 exhibited better diagnostic efficiency in NSCLC patients with different tumor pathologic subtypes and early stage, whereas the combination of lncRNAs did not provide better results than individual lncRNAs. Notably, the combination of two exosomal lncRNAs and the serum tumor biomarker Cyfra21-1 widely used in clinical practices further improved the diagnostic accuracy for NSCLC patients. This study suggests that exosomal lncRNA TBILA and AGAP2-AS1 may be promising biomarkers for diagnosis of NSCLC.

7 illus, 5 tables, 46 ref

043117   YE T, LI J, SUN Z, LIU D, ZENG B, ZHAO Q, WANG J, XING H R (Chongqing Medical Univ, Chongqing, China, Email: wjy2003123@163.com ) : Cdh1 functions as an oncogene by inducing self-renewal of lung cancer stem-like cells via oncogenic pathways. Int J Biol Sci 2020, 16(3), 447-59.

The mortality rate of lung cancer remains the highest amongst all cancers despite of new therapeutic developments. While cancer stem cells (CSCs) may play a pivotal role in cancer, mechanisms underlying CSCs self-renewal and their relevance to cancer progression have not been clearly elucidated due to the lack of reliable and stable CSC cellular models. In the present study, we unveiled the novel oncogene function of cadherin 1 (Cdh1) via bioinformatic analysis in a broad spectrum of human cancers including lung adenocarcinoma (LUAD), adding a new dimension to the widely reported tumor suppressor function of Cdh1. Experimentally, we show for the first time that Cdh1 promotes the self-renewal of lung CSCs, consistent with its function in embryonic and normal stem cells. Using the LLC-Symmetric Division (LLC-SD) model, we have revealed an intricate cross-talk between the oncogenic pathway and stem cell pathway in which Cdh1 functions as an oncogene by promoting lung CSC renewal via the activation of the Phosphoinositide 3-kinase (PI3K) and inhibition of Mitogen-activated protein kinase (MAPK) pathways, respectively. In summary, this study has provided evidence demonstrating effective utilization of the normal stem cell renewal mechanisms by CSCs to promote oncogenesis and progression.

5 illus, 2 tables, 47 ref

043116   ZHANG C, GEORGE S K, WU R, THAKKER P U, ABOLBASHARI M, KIM T-H, KO I K, ZHANG Y, SUN Y (Wake Forest School of Medicine, Winston-Salem, NC, USA, Email: yzhang@wakehealth.edu) : Reno-protection of urine-derived stem cells in a chronic kidney disease rat model induced by renal ischemia and nephrotoxicity. Int J Biol Sci 2020, 16(3), 435-46.

Drug-induced nephrotoxicity can occur in patients with pre-existing renal dysfunction or renal ischemia, potentially leading to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Prompt treatment of CKD and the related side effects is critical in preventing progression to ESRD. The goal of this study was to demonstrate the therapeutic potential of urine-derived stem cells (USC) to treat chronic kidney disease-induced by nephrotoxic drugs and renal ischemia. Human USC were collected, expanded and characterized by flow cytometry. A CKD model was induced by creating an ischemia-reperfusion injury and gentamicin administration. Twenty-eight adult immunodeficient rats were divided into three groups: PBS-treated group (n=9), USC-treated group (n=9), and sham group with age-matched control animals (n=10). Cell suspension of USC (5 x 106 / 100µl / kidney) or PBS was injected bilaterally into the renal parenchyma 9 weeks after CKD model creation. Renal function was evaluated by collection blood and urine samples to measure serum creatinine and glomerulus filtration rate. The kidneys were harvested 12 weeks after cell injection. Histologically, the extent of glomerulosclerosis and tubular atrophy, the amount of collagen deposition, interstitial fibrosis, inflammatory monocyte infiltration, and expression of transforming growth factor beta 1 (TGF-ß1), and superoxide dismutase 1 (SOD-1) were examined. USC expressed renal parietal epithelial cells (CD24, CD29 and CD44). Renal function, measured by GFR and serum Cr in USC-treated group were significantly improved compared to PBS-treated animals (p<0.05). The degree of glomerular sclerosis and atrophic renal tubules, the amount of fibrosis, and monocyte infiltration significantly decreased in USC-treated group compared to the PBS group (p<0.05). The level of TGF-ß1 expression in renal tissues was also significantly lower in the PBS group, while the level of SOD-1 expression was significantly elevated in the USC group, compared to PBS group (p<0.05). The present study demonstrates the nephron-protective effect of USC on renal function via anti-inflammatory, anti-oxidative stress, and anti-fibrotic activity in a dual-injury CKD rat model. This provides an alternative treatment for CKD in certain clinical situations, such as instances where CKD is due to drug-induced nephrotoxicity and renal ischemia.

10 illus, 2 tables, 34 ref

043115   WU W, LIN C-Y, CHANG L-C, LEE C-C, CHIU C-Y, HSU H-J, SUN C-Y, CHEN Y-C, KUO Y-L, YANG C-W (Chang Gung Memorial Hospital, Mai-Chin Road, Keelung 20401, Taiwan, Email: ssu1@cgmh.org.tw) : Gut microbiota as diagnostic tools for mirroring disease progression and circulating nephrotoxin levels in chronic kidney disease: Discovery and validation study. Int J Biol Sci 2020, 16(3), 420-34.

The interplay of the gut microbes with gut-producing nephrotoxins and the renal progression remains unclear in large human cohort. Significant compositional and functional differences in the intestinal microbiota (by 16S rRNA gene sequencing) were noted among 30 controls and 92 (31 mild, 30 moderate and 31 advanced) patients at different chronic kidney disease (CKD) stages (discovery cohort). A core CKD-associated microbiota consisted of 7 genera (Escherichia_Shigella, Dialister, Lachnospiraceae_ND3007_group, Pseudobutyrivibrio, Roseburia, Paraprevotella and Ruminiclostridium) and 2 species (Collinsella stercoris and Bacteroides eggerthii) were identified to be highly correlated with the stages of CKD. Paraprevotella, Pseudobutyrivibrio and Collinsella stercoris were superior in discriminating CKD from the controls than the use of urine protein/creatinine ratio, even at early-stage of disease. The performance was further confirmed in a validation cohort comprising 22 controls and 76 peritoneal dialysis patients. Bacterial genera highly correlated with indoxyl sulfate and p-cresyl sulfate levels were identified. Prediction of the functional capabilities of microbial communities showed that microbial genes related to the metabolism of aromatic amino acids (phenylalanine, tyrosine, and tryptophan) were differentially enriched among the control and different CKD stages. Collectively, our results provide solid human evidence of the impact of gut-metabolite-kidney axis on the severity of chronic kidney disease and highlight a usefulness of specific gut microorganisms as possible disease differentiate marker of this global health burden.

7 illus, 4 tables, 53 ref

041285   MANE A N, SHIVAKUMAR K M, KADASHETTI V (Public Health Dentistry Dep, Krishna Institute of Medical Sciences Deemed Univ, Satara - 415 110, Maharashtra, Email: shivakumarkm1@gmail.com) : Feasibility assessment for using telehealth technology among dentists and general population in Satara District, Maharashtra. Indian J Dent Sci 2020, 12(4), 258-62.

In this era of modern medicine, teledentistry has been constantly changing with the advent of information and technology. Teledentistry is a part of telemedicine. Teledentistry has many branches such as telestomatology, teleradiology, telepathology, tele oral surgery, and teleorthodontics. Teledentistry uses information technologies and communication system to deliver health‑care services to people. A cross‑sectional analytical study was conducted among the all dental specialist and people related to dental health service of Satara district. Respondents were given a brief introduction to the purpose of survey in an electronic format (dentist) and physical format (general population). Bulk of questions were focused on two domains (1) need for telehealth technology (2) interest in using telehealth technology for dental care delivery. The Collected information is subjected to descriptive statistical analysis. The Chi‑square test was used to test the association of variables for dentists and general population. Results showed great need of telehealth technology to overcome the obstacle in providing sufficient oral health services to the rural and underserved population as well as positive response from the dentist toward teledentistry. Out of 196 general population and 60 dentists, it is not easy for 67 % general population to visit dentist due to difficulty of basic transportation services. Moreover, 56 % people have no access to dentist only. 80 % of dentist is willing to participate in teledentistry program if it ever comes and 83.33 % dentists think it can improve overall efficiency of dental health‑care services. Unwillingness and attitude among local dental practitioners can be changed through increasing scope of education regarding teledentistry at the central government level through preparing legislation.

4 illus, 27 ref

041284   MITTAL R, MAHESHWARI R, TRIPATHI S, PANDEY S (Prosthodontics Dep, Kothiwal Dental Coll and Research Centre, Moradabad, Uttar Pradesh, Email: reenamt2006@gmail.com) : Eco Friendly dentistry: Preventing pollution to promoting sustainability. Indian J Dent Sci 2020, 12(4), 251-7.

In today’s world, being eco‑friendly is a part of every profession. Medical profession is concerned with maintaining general health and well‑being of the individual. Dentistry is dedicated toward maintenance of oral health and enhancing function. However, it has a huge impact on environment due to generation of large amount of waste including metallic waste and excessive use of water and electricity. Practicing green dentistry involves judicious use of water and electricity, decreasing waste production, and decreasing pollution with the use of the latest technologies. Oral health workers should recognize the significance of contributing in the interests of sustainability. They share the moral responsibility toward the society to provide optimal oral health services, maintain patient safety as well as reduce their impact on natural resources. This study reviews some practical suggestions for making dental practice eco‑friendly by enhancing the use of newer technologies and reducing the use of disposables and paper and eco‑friendly waste management.

2 illus, 2 tables, 29 ref

041283   BANSAL A, KAUR N, YADAV P K, SHARMA V K, JAIN P, AGRAWAL G (Periodontics and Community Dentistry Dep, AMU, Aligarh, Uttar Pradesh, Email: pramod468@gmail.com) : Prevalence of dental caries among 12-15 years old school children of government and private schools in Agra city. Indian J Dent Sci 2020, 12(4), 232-6.

Oral health is an important component of general health, with dental caries affecting a person’s ability to eat, speak, or socialize. Dental caries is one of the most prevalent diseases affecting human beings and persists till date as a challenge to the medical and dental profession in particular and the society in general. The study aims to assess the prevalence of dental caries among 12–15‑years‑old school‑going children of government and private schools in Agra city, Uttar Pradesh, India. A crosssectional study was conducted among 12–15–years‑old school‑going children of government and private schools in Agra city, Uttar Pradesh, India. A total of 1600 school children were through a multistage random sampling procedure. The children were examined according to the World Health Organization criteria, 2013. Information regarding a patient’s demographic profile was recorded using a self–administered questionnaire. Chi‑square test was used to find the significance of study parameters. The level of significance (P value) was fixed at 0.05. The present study reveals a prevalence of dental caries was almost of the same magnitude in the 12 and 13 years of age group, and it was found to be 28.6 % and 28.9 %, respectively among government and private school children. It was found that among 14 and 15 years of age groups, dental caries affected 22.9 % and 19.6 % of the study participants, respectively from both government and private school children. The results were found to be highly statistically significant between government and private school children regarding the number of carious teeth. The prevalence of dental caries was found to be the major public health problem among both the government and private school children of Agra city, which need immediate attention. Therefore, there is a need to develop preventive and promotional oral health strategies to combat this disease.

6 tables, 18 ref

041282   PATEL B S, CHOUDHARI S R, GOYAL S, PATEL C B, WAGHELA S A (Pediatric and Preventive Dentistry Dep, Government Dental Coll and Hospital, Ahmedabad - 380 016, Gujarat, Email: bhrgvi1994@gmail.com) : Clinical and radiographical evaluation of single versus multiple visit pulpectomy treatment in primary teeth with apical periodontitis. Indian J Dent Sci 2020, 12(4), 225-31.

This study highlights success rate as well as advantages and disadvantages of single‑ versus multiple‑visit pulpectomy in children. This study was aimed to compare the success rate of single‑ and multiple‑visit pulpectomy in primary teeth with apical periodontitis. It was a randomized, double‑blind study. The study was conducted in children with one or more restorable sixty primary molars with deep carious lesions and requiring pulpectomy in the age group of 4–8 years. Selected teeth were divided into two groups of thirty each and treated either in single visit or multiple visits. Follow‑up was done at the period of 1 month, 3 months, and 6 months and evaluated using Gutmann criteria. The normality of data was checked by Shapiro– Wilk test. Intragroup comparison was made by using Friedman test and post hoc‑Wilcoxon test. Mann–Whitney U‑test was used for inter group comparison. Clinical and radiographical success for both group showed statistically significant (P < 0.001) improvement when the baseline score (preoperative) was compared with other time intervals. No statistically significant difference (P > 0.05) was obtained when clinical outcome was compared between two groups. Although radiographical success for multiple‑visit group is slightly more than the single‑visit group at all time intervals, statistically it was not significant (P > 0.05). Single‑visit can be considered a viable alternative to multiple‑visit pulpectomy considering its various advantages, especially in children.

1 illus, 5 tables, 30 ref

041280   RAZA M, JAIN S, SHARMA P, KUMAR P, SHETTY D, JUNEJA A (Orthodontics and Dentofacial Orthopaedics Dep, I.T.S. Center for Dental Studies and Research, Ghaziabad - 201 206, Uttar Pradesh, Email: monis8raza@gmail.com) : Awareness related to COVID 19 among dental health-care students and professionals of national capital region: A cross sectional study. Indian J Dent Sci 2020, 12(4), 209-15.

The Coronavirus 2 syndrome (SARS CoV 2) or COVID‑19 pandemic’s rapid and widespread reach has become a major cause of concern to the dental health‑care profession. The goal of this study was to assess the knowledge among dental students and professionals about COVID‑19 disease and related infection management practices in the region of Delhi‑National Capital Region, India. An online questionnaire was created, and it was divided into six sections to assess the awareness with respect to the facts, diagnostic aspects of the disease, and its importance in dental treatment. Convenient sampling method was used for data collection. Comparison was done among the following four groups: Bachelor of Dental Surgery (BDS) students, Master of Dental Surgery (MDS) students, academicians (teaching in a dental college), and academicians + practitioners (teaching/not teaching but working in a private dental clinic) over a total of 500 responses for a period of 10 days. The data were coded, entered, and analyzed using SPSS 20.0 version. Descriptive statistics, frequencies, and percentages were used to summarize the data. ANOVA test was used to determine the association of study disciplines among BDS, MDS, practitioners, and academicians and practitioners. P < 0.05 was considered statistically significant. The average correct responses among various sections among all groups came out to be 60.64 %, with the highest score being 64.91 % among academicians + practitioners and the lowest score being 57.45 % among BDS students. Among the sections, 72.4 % was highest (section 1: what is coronavirus) and 41.2 % was lowest (section 5: diagnosis/tests). Comparison of the overall sections among various groups showed a nonsignificant result although some individual questions showed a statistically significant result. Dental health professionals need regular educational activities and training programs on infection prevention practices with respect to COVID‑19 infection to serve not just their own practice but also to help the health‑care sector in case the demand arises.

1 illus, 3 tables, 22 ref

041279   SRIVASTAVA S, TANDON P, SHARMA H, GUPTA S (Periodontology Dep, Sharda Univ, Greater Noida, Uttar Pradesh, Email: srnsh92@gmail.com) : Comparative evaluation of gingival response following the placement of light cured dressing and noneugenol dressing after periodontal flap surgery: A clinical study. Indian J Dent Sci 2020, 12(4), 204-8.

The aim of the study was to compare light‑cured dressing with most widely used noneugenol pack in the perspective of esthetics, acceptance, and healing following periodontal flap surgery. Fifty‑eight patients suffering from generalized chronic periodontitis, requiring periodontal flap surgery on contralateral sides of the arch, were selected and divided randomly into Group I (control) and Group II (test). In Group I, a noneugenol dressing and in Group II light‑cured dressing were applied after flap surgery. Clinical parameters such as debris index, plaque index, and modified gingival index were recorded at baseline (day 0) and 10 days postoperatively (after removal of the dressing). The data were collected and statistically analyzed. Group II showed better results than Group I when debris index, plaque index, and modified gingival index scores were compared though the differences were not statistically significant. Patients found no unpleasant taste/smell and perceived the light‑cured dressing to be better. The noneugenol dressing retained more plaque on its undersurface than light‑cure dressing. However, this did not have much influence on the healing outcome and clinical gingival parameters, which were optimal and comparable in both groups. The greater number of patients showed a preference for light‑cure dressing, based on its superior esthetics and taste.

6 illus, 3 tables, 9 ref

041278   GUPTA R, SHREE S, SIDDHARTH M, KANSAL H M (Periodontology Dep, Sharda Univ, Greater Noida, Uttar Pradesh, Email: radhika_aaryan@yahoo.co.in) : Association between periodontal disease and chronic obstructive pulmonary disease: A case–control study. Indian J Dent Sci 2020, 12(4), 198-203.

It has been recognized that oral infections, especially periodontal diseases, may affect the course and pathogenesis of a number of systemic diseases. The present study is done with an aim to determine the association between chronic obstructive pulmonary disease (COPD) and periodontal disease. The study included 130 individuals consisting of 65 patients (case group) having COPD and 65 individuals as controls. Individuals in the case group were well‑functioning and ambulatory patients having COPD as determined by their history and by performing pulmonary function test, who were then graded into mild, moderate, severe, and very severe. Periodontal status was evaluated by the following indices: simplified oral hygiene index (OHI‑S), plaque index (PI), gingival index (GI), pocket probing depth (PPD), and clinical attachment level (CAL). Individuals in the case group had significantly higher OHI‑S, PI, GI, PPD, and CAL (P < 0.0001) compared with the control group. A significant positive relationship was observed between COPD subgroup P values and PI, thus indicating a trend in which severity of lung obstruction increased as these periodontal indices worsened. The patients with COPD showed poor oral hygiene and higher prevalence of periodontal disease. The lack of awareness and negligence toward oral health care was noted, which increased as the severity of COPD increased. The dental community’s awareness of poor health within this population should be elevated. Prevention and treatment of periodontal disease could be included in planned intervention campaigns designed to help patients with COPD.

4 tables, 23 ref