Exosomal CircPRRX1 Enhances Doxorubicin Resistance in Gastric Cancer by Regulating MiR-3064-5p/PTPN14 Signaling

Shumin Wang,Mei Ping,Bin Song,Yarong Guo,Yuanfei Li,Junmei Jia 연세대학교의과대학 2020 Yonsei medical journal Vol.61 No.9

Purpose: Gastric cancer (GC) is a malignant tumor with a high mortality rate. Drug resistance is a major obstacle to GC therapy. This study aimed to investigate the role and mechanism of exosomal circPRRX1 in doxorubicin resistance in GC. Materials and Methods: HGC-27 and AGS cells were exposed to different doses of doxorubicin to construct doxorubicin-resistantcell lines. Levels of circPRRX1, miR-3064-5p, and nonreceptor tyrosine phosphatase 14 (PTPN14) were detected by quantitativereal-time PCR or Western blot assay. Then, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, transwell,and Western blot assays were used to explore the function of circPRRX1 in GC cells. Interactions among circPRRX1, miR-3064-5p,and PTPN14 were confirmed by dual-luciferase reporter assay. The in vivo function of circPRRX1 was analyzed in a xenograft tumormodel. Results: CircPRRX1 was highly expressed in doxorubicin-resistant GC cell lines. Knockdown of circPRRX1 reversed doxorubicinresistance in doxorubicin-resistant GC cells. Additionally, extracellular circPRRX1 was carried by exosomes to spread doxorubicinresistance. CircPRRX1 silencing reduced doxorubicin resistance by targeting miR-3064-5p or regulating PTPN14. In GC patients,high levels of circPRRX1 in serum exosomes were associated with poor responses to doxorubicin treatment. Moreover, depletionof circPRRX1 reduced doxorubicin resistance in vivo. Conclusion: CircPRRX1 strengthened doxorubicin resistance by modulating miR-3064-5p/PTPN14 signaling and might be atherapeutic target for GC patients.

LncSNHG3 promotes hepatocellular carcinoma epithelial mesenchymal transition progression through the miR-152-3p/JAK1 pathway

Li Hong,Wu Yu,Wang Runmei,Guo Junmei,Yu Qin,Zhang Lihe,Zhao Haiping,Yang Hao 한국유전학회 2022 Genes & Genomics Vol.44 No.1

Background: The dysregulation of LncRNAs is related to the malignant progression of many cancers. Objective: The study aimed to investigate the expression and the biological role of LncSNHG3 in hepatocellular carcinoma (HCC). Methods: The TCGA data of the LncSNHG3 in HCC were analyzed. The expression in HCC cell lines was detected by qRT-PCR. Proliferation, migration, and invasion of HepG2 and Huh7 were examined by cell counting kit-8, colony formation, transwell assays, and wound healing assays. At the same time, the interactions among LncSNHG3, miR-152-3p, and JAK1 were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation, subcellular distribution. Xenograft tumor-bearing mice models were used to measure the effect of LncSNHG3 on the growth of HCC in vivo. The apoptosis and epithelial mesenchymal transition (EMT)-associated proteins were checked by WB and IHC. Results: LncSNHG3 was overexpressed in HCC tissues and cell lines. In addition, it is correlated with the tumor stage and survival time of HCC patients. Down-regulated LncSNHG3 could significantly suppress the EMT progression of HCC in vivo and in vitro. LncSNHG3 could promote the JAK1 expression by sponging miR-152-3p. Conclusions: LncSNHG3 acted as an oncogene and promoted the EMT procession in HCC by binding miR-152-3p and promoting JAK1 expression. Predictably, LncSNHG3 was used as a potential marker and will be used as a novel therapy target for HCC in the future.

Omp16, a conserved peptidoglycan-associated lipoprotein, is involved in Brucella virulence in vitro

Feijie Zhi,Dong Zhou,Junmei Li,Lulu Tian,Guangdong Zhang,Yaping Jin,Aihua Wang 한국미생물학회 2020 The journal of microbiology Vol.58 No.9

Brucella, the bacterial agent of common zoonotic brucellosis, primarily infects specific animal species. The Brucella outer membrane proteins (Omps) are particularly attractive for developing vaccine and improving diagnostic tests and are associated with the virulence of smooth Brucella strains. Omp16 is a homologue to peptidoglycan-associated lipoproteins (Pals), and an omp16 mutant has not been generated in any Brucella strain until now. Very little is known about the functions and pathogenic mechanisms of Omp16 in Brucella. Here, we confirmed that Omp16 has a conserved Pal domain and is highly conserved in Brucella. We attempted to delete omp16 in Brucella suis vaccine strain 2 (B. suis S2) without success, which shows that Omp16 is vital for Brucella survival. We acquired a B. suis S2 Omp16 mutant via conditional complementation. Omp16 deficiency impaired Brucella outer membrane integrity and activity in vitro. Moreover, inactivation of Omp16 decreased bacterial intracellular survival in macrophage RAW 264.7 cells. B. suis S2 and its derivatives induced marked expression of IL-1β, IL-6, and TNF-α mRNA in Raw 264.7 cells. Whereas inactivation of Omp16 in Brucella enhanced IL-1β and IL-6 expression in Raw 264.7 cells. Altogether, these findings show that the Brucella Omp16 mutant was obtained via conditional complementation and confirmed that Omp16 can maintain outer membrane integrity and be involved in bacterial virulence in Brucella in vitro and in vivo. These results will be important in uncovering the pathogenic mechanisms of Brucella.

Study on the performance of different discharging devices of a continuous production system

Zhenya Duan,Jie Wang,Shujie Sun,Wenchen Li,Haodong Zhang,Guoyue Qiao,Junmei Zhang,Jingtao Wang 한국화학공학회 2022 Korean Journal of Chemical Engineering Vol.39 No.4

Based on the developed continuous production system of sodium phenol carboxylation reaction, severaltypes of discharging devices are proposed, which are suitable for the case where the transported particles are not easyto maintain a stable state in the transported fluid. Numerical simulations of the gas-solid two-phase flow characteristicsand particle distribution were performed with DPM, and the particle retention ratio and fluid loss degree were proposedto investigate the performance of the discharging devices. The results of simulations and industrial experimentsshowed that a guide plate installed in the “B” discharging device can solve the accumulation problem, realize the efficientand continuous delivery of the particles, and maintain a uniform distribution of particles. This study can providea reference for the design of a gas-solid two-phase discharging device, and guide the industrial experimental operationand modification of continuous production systems for sodium phenol carboxylation.

Assimilating AOD retrievals from GOCI and VIIRS to forecast surface PM_2.5 episodes over Eastern China

Pang, Jiongming,Liu, Zhiquan,Wang, Xuemei,Bresch, Jamie,Ban, Junmei,Chen, Dan,Kim, Jhoon Elsevier 2018 Atmospheric environment Vol.179 No.-

<P><B>Abstract</B></P> <P>In this study, Geostationary Ocean Color Imager (GOCI) AOD and Visible Infrared Imaging Radiometer Suite (VIIRS) AOD data were assimilated to forecast surface PM<SUB>2.5</SUB> concentrations over Eastern China, by using the three–dimensional variational (3DAVR) data assimilation (DA) system, to compare DA impacts by assimilating AOD retrievals from these two types of satellites. Three experiments were conducted, including a CONTROL without the AOD assimilation, and GOCIDA and VIIRSDA with the assimilation of AOD retrievals from GOCI and VIIRS, respectively. By utilizing the Weather Research and Forecasting with Chemistry (WRF/Chem) model, 48-h forecasts were initialized at each 06 UTC from 19 November to 06 December 2013. These forecasts were evaluated with 248 ground-based measurements from the air quality monitoring network across 67 China cities. The results show that overall the CONTROL underestimated surface PM<SUB>2.5</SUB> concentrations, especially over Jing–Jin–Ji (JJJ) region and Yangtze River Delta (YRD) region. Both the GOCIDA and VIIRSDA produced higher surface PM<SUB>2.5</SUB> concentrations mainly over Eastern China, which fits well with the PM<SUB>2.5</SUB> measurements at these eastern sites, with more than 8% error reductions (ER). Moreover, compared to CONTROL, GOCIDA reduced 14.0% and 6.4% error on JJJ region and YRD region, respectively, while VIIRSDA reduced respectively 2.0% and 13.4% error over the corresponding areas. During the heavy polluted period, VIIRSDA improved all sites within YRD region, and GOCIDA enhanced 84% sites. Meanwhile, GOCIDA improved 84% sites on JJJ region, while VIIRSDA did not affect that region. These geographic distinctions might result from spatial dissimilarity between GOCI AOD and VIIRS AOD at time intervals. Moreover, the larger increment produced by AOD DA under stable meteorological conditions could lead to a longer duration (e.g., 1–2 days, > 2 days) of AOD DA impacts. Even though with AOD DA, surface PM<SUB>2.5</SUB> concentrations were still underestimated clearly over heavy polluted periods. And 3% sites performed worse, where low PM<SUB>2.5</SUB> values were observed and CONTROL performed well. With this study, the results indicate that AOD DA can partially improve the accuracy of PM<SUB>2.5</SUB> forecasts. And the obvious geographic differences on forecasts emphasize the potential and importance of combining AOD retrievals from GOCI and VIIRS into data assimilation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> AOD retrievals from two types of satellites were assimilated solely. </LI> <LI> Assimilating different AOD produced prominent geographic differences on forecast. </LI> <LI> Larger increment under stable meteorological conditions lead to a longer duration. </LI> <LI> The results emphasize the potential of combining different AOD retrievals. </LI> </UL> </P>

Genome shuffling improved acid-tolerance and succinic acid production of Actinobacillus succinogenes

Shumeng Hu,Ying You,Feifei Xia,Junmei Liu,Weichang Dai,Jingsheng Liu,Yuhua Wang 한국식품과학회 2019 Food Science and Biotechnology Vol.28 No.3

Succinic acid is widely applied to chemical,pharmaceutical, food, and agricultural industries. With therapid development of these industries, a great demand ofsuccinic acid is required. The acid-tolerance and succinicacid production of Actinobacillus succinogenes strain wereimproved by using genome shuffling. Results showed thatone modified strain AS-F32, with the best acid resistanceand the highest succinic acid production, was obtained after3 cycles of genome shuffling. The minimum growth pH ofAS-F32 was 3.5, and the acid production and cell dryweight were 5.1 and 4.8 g/L in flask, improved 2.6 and1.85 times over the start strain As-R2. Furthermore, thesuccinic acid yield of As-32 was 31.2 g/L and the dry cellweight was increased 44.4% by maintaining pH 4.8 with7.0 M NH4OH in 5 L bioreactor, increased 1.1 times thanthe original strain As-R2.

Effect on Viability of Microencapsulated Lactobacillus rhamnosus with the Whey Proteinpullulan Gels in Simulated Gastrointestinal Conditions and Properties of Gels

Minghao Zhang,Dan Cai,Qiumei Song,Yu Wang,Haiyue Sun,Chunhong Piao,Hansong Yu,Junmei Liu,Jingsheng Liu,Yuhua Wang 한국축산식품학회 2019 한국축산식품학회지 Vol.39 No.3

Lactobacillus rhamnosus GG (LGG) has low resistance to low pH and bile salt in the gastrointestinal juice. In this study, the gel made from whey protein concentrate (WPC) and pullulan (PUL) was used as the wall material to prepare the microencapsulation for LGG protection. The gelation process was optimized and the properties of gel were also determined. The results showed the optimal gel was made from 10% WPC and 8.0% PUL at pH 7.5, which could get the best protective effect; the viable counts of LGG were 6.61 Log CFU/g after exposure to simulated gastric juice (SGJ) and 9.40 Log CFU/g to simulated intestinal juice (SIJ) for 4 h. Sodium dodecyl sulphite polyacrylamide gel electrophoresis (SDS-PAGE) confirmed that the WPC-PUL gel had low solubility in SGJ, but dissolved well in SIJ, which suggested that the gel can protect LGG under SGJ condition and release probiotics in the SIJ. Moreover, when the gel has highest hardness and water-holding capacity, the viable counts of LGG were not the best, suggesting the relationship between the protection and the properties of the gel was non-linear.

Lactobacillus rhamnosus Granules Dose-Dependently Balance Intestinal Microbiome Disorders and Ameliorate Chronic Alcohol-Induced Liver Injury

Zelin Gu,Yanfeng Wu,Yu Wang,Haiyue Sun,Ying You,Chunhong Piao,Junmei Liu,Yuhua Wang 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.2

As the functions of Lactobacilli become better understood, there are increasing numbers of applications for Lactobacillus products. Previously, we have demonstrated that Lactobacillus rhamnosus GG (LGG) can prevent alcoholic liver injury. LGG granules were produced by fluid bed granulation with a media composed of starch, skimmed milk powder, whey powder, microcrystalline cellulose and maltose, and LGG fermented liquid that comprised 30–50% of the total weight. We found LGG granules dose-dependently protected against chronic alcoholic liver disease. When alcohol was consumed for 8 weeks with LGG treatment during the last 2 weeks, we demonstrated that the dose dependence of LGG granules can improve alcohol-induced liver injury through decreasing the levels of lipopolysaccharide and tumor necrosis factor-α in serum and prevent liver steatosis by suppressing triglyceride, free fatty acid, and malondialdehyde production in liver. Alcohol feeding caused a decline in the number of both Lactobacillus and Bifidobacterium, with a proportional increase in the number of Clostridium perfringens in ileum, and expansion of the Gram-negative bacteria Proteobacteria, Campylobacterales, and Helicobacter in cecum. However, LGG granule treatment restored the content of these microorganisms. In conclusion, LGG granule supplementation can improve the intestinal microbiota, reduce the number of gram-negative bacteria, and ameliorate alcoholic liver injury.

A Brucella Omp16 Conditional Deletion Strain Is Attenuated in BALB/c Mice

( Feijie Zhi ),( Jiaoyang Fang ),( Weifang Zheng ),( Junmei Li ),( Guangdong Zhang ),( Dong Zhou ),( Yaping Jin ),( Aihua Wang ) 한국미생물 · 생명공학회 2022 Journal of microbiology and biotechnology Vol.32 No.1

Brucella spp. are facultative intracellular pathogens that invade, survive and proliferate in numerous phagocytic and non-phagocytic cell types, thereby leading to human and animal brucellosis. Outer membrane proteins (Omps) are major immunogenic and protective antigens that are implicated in Brucella virulence. A strain deleted of the omp16 gene has not been obtained which suggests that the Omp16 protein is vital for Brucella survival. Nevertheless, we previously constructed an omp16 conditional deletion strain of Brucella, ΔOmp16. Here, the virulence and immune response elicted by this strain were assessed in a mouse model of infection. Splenomegaly was significantly reduced at two weeks post-infection in ΔOmp16-infected mice compared to infection with the parental strain. The bacterial load in the spleen also was significantly decreased at this post-infection time point in ΔOmp16-infected mice. Histopathological changes in the spleen were observed via hematoxylineosin staining and microscopic examination which showed that infection with the ΔOmp16 strain alleviated spleen histopathological alterations compared to mice infected with the parental strain. Moreover, the levels of humoral and cellular immunity were similar in both ΔOmp16-infected mice and parental strain-infected mice. The results overall show that the virulence of ΔOmp16 is attenuated markedly, but that the immune responses mediated by the deletion and parental strains in mice are indistinguishable. The data provide important insights that illuminate the pathogenic strategies adopted by Brucella.

MondoA Is Required for Normal Myogenesis and Regulation of the Skeletal Muscle Glycogen Content in Mice

Hui Ran,Yao Lu,Qi Zhang,Qiuyue Hu,Junmei Zhao,Kai Wang,Xuemei Tong,Qing Su 대한당뇨병학회 2021 Diabetes and Metabolism Journal Vol.45 No.3

Background: Skeletal muscle is the largest tissue in the human body, and it plays a major role in exerting force and maintaining metabolism homeostasis. The role of muscle transcription factors in the regulation of metabolism is not fully understood. MondoA is a glucose-sensing transcription factor that is highly expressed in skeletal muscle. Previous studies suggest that MondoA can influence systemic metabolism homeostasis. However, the function of MondoA in the skeletal muscle remains unclear. Methods: We generated muscle-specific MondoA knockout (MAKO) mice and analyzed the skeletal muscle morphology and glycogen content. Along with skeletal muscle from MAKO mice, C2C12 myocytes transfected with small interfering RNA against MondoA were also used to investigate the role and potential mechanism of MondoA in the development and glycogen metabolism of skeletal muscle. Results: MAKO caused muscle fiber atrophy, reduced the proportion of type II fibers compared to type I fibers, and increased the muscle glycogen level. MondoA knockdown inhibited myoblast proliferation, migration, and differentiation by inhibiting the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway. Further mechanistic experiments revealed that the increased muscle glycogen in MAKO mice was caused by thioredoxin-interacting protein (TXNIP) downregulation, which led to upregulation of glucose transporter 4 (GLUT4), potentially increasing glucose uptake. Conclusion: MondoA appears to mediate mouse myofiber development, and MondoA decreases the muscle glycogen level. The findings indicate the potential function of MondoA in skeletal muscle, linking the glucose-related transcription factor to myogenesis and skeletal myofiber glycogen metabolism.