Publications by authors named "Yu-Zhu Wang"

47 Publications

The Anti-Tumor Effect and Mechanism of Triterpenoids in Mill. on Reversing Effector CD8+ T-cells Dysfunction by Targeting Glycolysis Pathways in Colorectal Cancer.

Integr Cancer Ther 2021 Jan-Dec;20:15347354211017219

Southeast University, Nanjing, Jiangsu, China.

Mill. is a traditional Chinese medicine (TCM) which is commonly used for cancer treatments. Our previous work had proven that triterpenoids of (TER) could effectively regulate glycolysis involved in colorectal cancer (CRC) and play an important role in the prevention of T-cells dysfunction. This study aimed to systematically investigate the effects and mechanisms of TER on glucose metabolism in CRC, while the regulatory mechanisms of TER on restoring T-cells function and activity in CRC were explored as well. The extract of triterpenoids from was obtained, and production of lactic acid and glucose uptake were assayed. Also, the expression of CD8+ T-cells surface markers, cytokines secreted by CD8+ T cells, and the expression of key glycolytic enzymes and glucose deprivation induced by tumor cells were further examined. Notably, results showed that TER prevented the dysfunction in CD8+ T cells by enhancing mTOR activity and subsequent cellular metabolism. Furthermore, our findings also demonstrated that TER promoted glycolytic gene expression in CD8+ T cells in vivo, and significantly inhibited tumor growth. Altogether, our studies suggested that TER not only reversed effector CD8+ T-cells dysfunction and enhanced T-cells recognition, but also improved tumor microenvironment, thereby providing new insight into the prevention and treatment of CRC with TCM.
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http://dx.doi.org/10.1177/15347354211017219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145606PMC
May 2021

Efficient tandem organic light-emitting diodes with non-doped structures.

Opt Lett 2020 Dec;45(23):6450-6453

Highly efficient tandem organic light-emitting diodes (TOLEDs) were achieved based on a non-doped charge generation unit (CGU) consisting of LiF/Al/C60/4,4',4"-tris(N-3-methylphenyl-N-phenyl-amino) triphenylamine (m-MTDATA) and ultrathin emitting layers. The current-voltage characteristics of the CGU devices and electron-only devices and the capacitance-voltage characteristics of the CGU-based capacitance devices were characterized to explore the charge generation and injection mechanisms. The charge generation process occurs at the interface of C60/m-MTDATA through electron transferring from the highest occupied molecular orbital of m-MTDATA to the lowest unoccupied molecular orbital of C60. It is found that the thinner C60 layer contributes to efficient electron injection. Under the optimal structure, the blue TOLEDs exhibit a maximum current efficiency () of 43.3 cd/A. The and maximum external quantum efficiency () of the white TOLEDs reach 84.6 cd/A and 26.7%, respectively.
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http://dx.doi.org/10.1364/OL.409613DOI Listing
December 2020

Effects and mechanisms of fatty acid metabolism‑mediated glycolysis regulated by betulinic acid‑loaded nanoliposomes in colorectal cancer.

Oncol Rep 2020 Dec 1;44(6):2595-2609. Epub 2020 Oct 1.

Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.

Although previous studies have demonstrated that triterpenoids, such as betulinic acid (BA), can inhibit tumor cell growth, their potential targets in colorectal cancer (CRC) metabolism have not been systematically investigated. In the present study, BA‑loaded nanoliposomes (BA‑NLs) were prepared, and their effects on CRC cell lines were evaluated. The aim of the present study was to determine the anticancer mechanisms of action of BA‑NLs in fatty acid metabolism‑mediated glycolysis, and investigate the role of key targets, such as acyl‑CoA synthetase (ACSL), carnitine palmitoyltransferase (CPT) and acetyl CoA, in promoting glycolysis, which is activated by inducing hexokinase (HK), phosphofructokinase‑1 (PFK‑1), phosphoenolpyruvate (PEP) and pyruvate kinase (PK) expression. The results demonstrated that BA‑NLs significantly suppressed the proliferation and glucose uptake of CRC cells by regulating potential glycolysis and fatty acid metabolism targets and pathways, which forms the basis of the anti‑CRC function of BA‑NLs. Moreover, the effects of BA‑NLs were further validated by demonstrating that the key targets of HK2, PFK‑1, PEP and PK isoenzyme M2 (PKM2) in glycolysis, and of ACSL1, CPT1a and PEP in fatty acid metabolism, were blocked by BA‑NLs, which play key roles in the inhibition of glycolysis and fatty acid‑mediated production of pyruvate and lactate. The results of the present study may provide a deeper understanding supporting the hypothesis that liposomal BA may regulate alternative metabolic pathways implicated in CRC adjuvant therapy.
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http://dx.doi.org/10.3892/or.2020.7787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640364PMC
December 2020

The effects and mechanisms of isoliquiritigenin loaded nanoliposomes regulated AMPK/mTOR mediated glycolysis in colorectal cancer.

Artif Cells Nanomed Biotechnol 2020 Dec;48(1):1231-1249

Department of General Surgery, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China.

In this study, isoliquiritigenin (ISL) incorporated nanoliposomes were prepared and their effects on colorectal cancer (CRC) cell lines were investigated. Herein, we sought to explore the anti-cancer mechanisms of ISL loaded nanoliposomes (ISL-NLs) on AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathways mediated glycolysis. Also, the key targets such as caveolin 1 (CAV1), glucose transporters and Akt/mTOR that promote glycolysis, and are activated via the induction of α-enolase (ENO1), fructose bisphosphate aldolase A (ALDOA) and monocarboxylate transporter 4 (MCT4) expressions were also investigated. It was shown that ISL-NLs significantly suppressed the proliferation and glucose uptake of CRC cell by potentially regulating the glycolysis and lactate targets as well as pathways that formed the basis of the anti-CRC effects of ISL-NLs. The mechanism underlying this effect was further validated via the regulation of some key targets such as ENO1, ALDOA, lactate dehydrogenase A (LDHA) and MCT4 in glycolysis coupled with cellular myelocytomatosis oncogene (c-myc), hypoxia-inducible factor 1-alpha (HIF-1α) in protein kinase B/mTOR (Akt/mTOR) pathways. Moreover, the AMPK proteins were identified to be up-regulated while the lactic acid production was suppressed by ISL-NLs in the CRC cells, indicating that ISL-NLs had an inhibitory effect on AMPK mediated glycolysis and lactate production. Altogether, these results have provided insights into the mechanism underlying the key role that liposomal ISL played in the multiple inhibition of AMPK and Akt/mTOR mediated glycolysis and lactate generation, which may be regulated as the alternative metabolic pathways of CRC as well as serve as adjuvant therapy for the disease.
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http://dx.doi.org/10.1080/21691401.2020.1825092DOI Listing
December 2020

Comparison between endovascular versus hybrid thrombectomy for arteriovenous graft under complete ultrasound guidance.

Int Angiol 2020 Dec 7;39(6):532-541. Epub 2020 Sep 7.

Department of Nephrology, Beijing Friendship Hospital, Capital Medical University, Beijing, China -

Background: Endovascular treatment of acute thrombosed arteriovenous grafts performed completely under ultrasound guidance has rarely been reported. We compared the efficacy of a new endovascular thrombectomy technique (percutaneous manual thromboaspiration through the introducer sheath) with classical hybrid thrombectomy (minimally invasive surgical thrombectomy combined with high-pressure angioplasty) performed completely under ultrasound guidance, for arteriovenous graft thrombosis.

Methods: This was a retrospective cohort study involving patients receiving hemodialysis who underwent arteriovenous graft thrombectomy between January 2014 and December 2017. We divided 130 participants into an intervention (endovascular) group (N.=65) and a control (classical hybrid) group (N.=65) according to the thrombectomy technique. The procedural success rate, immediate outcomes and patency were compared between the groups.

Results: There was no significant difference in the procedural success rate (92.31% vs. 89.23%, P=0.55) between the intervention and control groups, respectively. No major complications were noted, but two cases of vessel rupture occurred in the control group and three cases of vessel rupture occurred in the intervention group. The procedure time in the intervention group was significantly shorter than that in the control group (74±14.21 min vs. 109.05±19.20 min, respectively; P<0.05). During the 6-month follow-up, we found no significant difference in the postintervention primary patency rate (48.33% vs. 55.17%; P=0.51) or the postintervention second patency rate (83.33% vs. 84.49%; P=0.79) between the intervention and control groups, respectively. Dialysis clearance and ≥50% stenosis were predictors of postintervention primary patency (hazard ratio, 7.80; 95% confidence interval: 1.75-34.81; P=0.01; and hazard ratio, 6.43; 95% confidence interval: 2.43-17.03; P<0.001), respectively.

Conclusions: Completely ultrasound-guided percutaneous manual thromboaspiration through the introducer sheath can be used for thrombosed arteriovenous grafts. This approach has the advantage of shorter operative time compared with hybrid treatment.
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http://dx.doi.org/10.23736/S0392-9590.20.04423-5DOI Listing
December 2020

Cognitive impairment and associated risk factors in older adult hemodialysis patients: a cross-sectional survey.

Sci Rep 2020 07 27;10(1):12542. Epub 2020 Jul 27.

Department of Nephrology, Chinese PLA General Hospital, State Key Laboratory of Kidney Disease, Beijing, 100853, China.

The clinical epidemiological features of cognitive impairment in Chinese older adult patients undergoing hemodialysis are not clear, we aimed to identify the extent and patterns of cognitive impairment among those patients. We conducted a cross-sectional study of 613 hemodialysis patients aged 50 to 80 from 11 centers in Beijing. A neuropsychological battery of 11 tests covering domains of attention/processing speed, executive function, memory, language, and visuospatial function was applied, patients were classified as none, mild, or major cognitive impairment according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria for cognitive impairment. Compared with Chinese population norms, 37.2% of the participants had mild cognitive impairment, 43.7% had major cognitive impairment. Memory and language were the most severe impaired domains in the mild cognitive impairment group, attention and visuospatial function domains were the most serious impaired domains in the major cognitive impairment group. Concomitant impairment across multiple cognitive domains was common. Factors associated with major cognitive impairment included age, education level, history of stroke and hypertension, dialysis vintage, and single-pool Kt/V. There is a high frequency of cognitive impairment in Chinese older adult hemodialysis patients, with varying severity and concomitant impairment across multiple domains.
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http://dx.doi.org/10.1038/s41598-020-69482-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385128PMC
July 2020

The Antitumor Activity of Betulinic Acid-Loaded Nanoliposomes Against Colorectal Cancer and via Glycolytic and Glutaminolytic Pathways.

J Biomed Nanotechnol 2020 Feb;16(2):235-251

The purpose of this study is to develop betulinic acid loaded nanoliposomes to improve the chemotherapy effect of colorectal cancer. The cellular uptake and anti-tumor effects of betulinic acid loaded nanoliposomes were characterized and evaluated, and their effects on glycolysis, glutamine decomposition and key anti-cancer targets were analyzed. Moreover, their anticancer efficacy was assessed . Compared with free betulinic acid , the cellular uptake and anti-tumor activity of betulinic acid-loaded nanoliposomes were significantly enhanced; these nanoliposomes significantly suppressed the proliferation and glucose uptake of colorectal cancer cells. Mechanistically, the anti-colorectal cancer effect of betulinic acid-loaded nanoliposomes was confirmed by their triggering of cellular apoptosis and regulating the potential glycolytic and glutaminolytic targets and pathways. After tumor proliferation was inhibited and colorectal cancer cells apoptosis, the anticancer effect of betulinic acid loaded nanoliposomes was significantly enhanced. All in all, betulinic acid loaded nanoliposomes are expected to be an effective drug delivery system for colorectal cancer treatment.
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http://dx.doi.org/10.1166/jbn.2020.2888DOI Listing
February 2020

Transcriptomic analysis reveals recovery strategies in strawberry roots after using a soil amendment in continuous cropping soil.

BMC Plant Biol 2020 Jan 3;20(1). Epub 2020 Jan 3.

Beijing Academy of Forestry and Pomology Sciences, Beijing Academy of Agriculture and Forestry Science, Beijing, 100097, China.

Background: In strawberry cultivation, continuous cropping (CC) obstacles seriously threaten production. A patented soil amendment (SA) can effectively relieve the CC obstacles to strawberry cultivation, but knowledge of the recovery mechanisms underlying this phenomenon is limited.

Results: In this study, transcriptomic profiling of strawberry roots in soil with and without the SA was conducted using RNA-Seq technology to reveal gene expression changes in response to SA treatment. In total, 188 differentially expressed genes (DEGs), including 144 upregulated and 44 downregulated DEGs, were identified. SA treatment resulted in genotype-dependent responses, and the response pattern, including an overall increase in the expression of nutrient transport genes and a decrease in the expression of defense response genes, may be a possible mechanism underlying recovery strategies in strawberry roots after the application of the SA to CC soil. We also found that 9 Hsp genes involved in plant defense pathways were all downregulated in the SA-treated roots.

Conclusions: This research indicated that strawberry plants reallocated defense resources to development when SA treatment alleviated the stress caused by a CC soil environment. The present study provides an opportunity to reveal the fundamental mechanisms of the tradeoff between growth and defense in strawberry.
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http://dx.doi.org/10.1186/s12870-019-2216-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942283PMC
January 2020

The critical role of calcineurin/NFAT (C/N) pathways and effective antitumor prospect for colorectal cancers.

J Cell Biochem 2019 12 5;120(12):19254-19273. Epub 2019 Sep 5.

Department of General Surgery, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China.

Transcription factors (TFs) like a nuclear factor of activated T-cells (NFAT) and its controller calcineurin are highly expressed in primary intestinal epithelial cells (IECs) due to delamination, damage by tumor-associated flora and selective activation in the intestinal tract tumor are crucial in the progression and growth of colorectal cancer (CRC). This study sought to summarize the current findings concerning the dysregulated calcineurin/NFAT (C/N) signaling involved in CRC initiation and progression. These signalings include proliferation, T-cell functions, and glycolysis with high lactate production that remodels the acidosis, which genes in tumor cells provide an evolutionary advantage, or even increased their attack phenotype. Moreover, the relationship between C/N and gut microbiome in CRC, especially role of NFAT and toll-like receptor signaling in regulating intestinal microbiota are also discussed. Furthermore, this review will discuss the proteins and genes relating to C/N induced acidosis in CRC, which includes ASIC2 regulated C/N1 and TFs associated with the glycolytic by-product that affect T-cell functions and CRC cell growth. It is revealed that calcineurin or NFAT targeting to antitumor, selective calcineurin inhibition or targets in NFAT signaling may be useful for clinical treatment of CRC. This can further aid in the identification of specific targets via cancer patient-personalized approach. Future studies should be focused on targeting to C/N or TLR signaling by the combination of therapeutic agents to regulate T-cell functions and gut microbiome for activating potent anticancer property with the prospect of potentiating the antitumor therapy for CRC.
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http://dx.doi.org/10.1002/jcb.29243DOI Listing
December 2019

Triterpenoids Extracted from Act Against Colorectal Cancer by Inhibiting Enzymes in Glycolysis and Glutaminolysis: Network Analysis and Experimental Validation.

Nutr Cancer 2020 3;72(2):293-319. Epub 2019 Jul 3.

Central laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

is a traditional Chinese medicine (TCM) mostly used to treat several cancer types. Although previous studies have found that certain ingredients of such as flavonoids can inhibit tumor cell proliferation [e.g. colorectal cancer (CRC)], systematic research on the mechanism underlying anticancer effect of active compounds like triterpenoids (TER) is lacking. Herein, the concept of "network pharmacology primarily based on active compounds" was applied to explore the anticancer mechanisms of TER extract from In this regard, potential targets and pathways of glycolysis and glutaminolysis form the basis for the anti-CRC effect of triterpenoids. Network pharmacology was used to predict several key proteins in the metabolic pathways, which were further verified via western blot and metabolomics methods. Our results showed that the total TER in remarkably inhibited the proliferation and apoptosis of SW620 cells. The top 4 compounds of TER (viz., betulinic acid-BTA, betulonic acid-BTOA, betulin-BT, and semialactic acid-SA) were confirmed through the detection of UPLC-MS and analysis of cell proliferation assays. Mechanistically, this study revealed that TER plays an anti-CRC role through key targets, such as ENO1, ALDOA, PFKFB3, PKM2, and LDHA, as well as key glycolytic and glutaminolytic pathways. Collectively, these results have provided new insights into the mechanism underlying anti-CRC effect of triterpenoids extract obtained from , mainly through combination of compositional quantitative analysis, network pharmacology, and experimental verification.
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http://dx.doi.org/10.1080/01635581.2019.1631858DOI Listing
December 2020

Role of SCFAs in gut microbiome and glycolysis for colorectal cancer therapy.

J Cell Physiol 2019 08 19;234(10):17023-17049. Epub 2019 Mar 19.

Department of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.

Increased risk of colorectal cancer (CRC) is associated with altered intestinal microbiota as well as short-chain fatty acids (SCFAs) reduction of output The energy source of colon cells relies mainly on three SCFAs, namely butyrate (BT), propionate, and acetate, while CRC transformed cells rely mainly on aerobic glycolysis to provide energy. This review summarizes recent research results for dysregulated glucose metabolism of SCFAs, which could be initiated by gut microbiome of CRC. Moreover, the relationship between SCFA transporters and glycolysis, which may correlate with the initiation and progression of CRC, are also discussed. Additionally, this review explores the linkage of BT to transport of SCFAs expressions between normal and cancerous colonocyte cell growth for tumorigenesis inhibition in CRC. Furthermore, the link between gut microbiota and SCFAs in the metabolism of CRC, in addition, the proteins and genes related to SCFAs-mediated signaling pathways, coupled with their correlation with the initiation and progression of CRC are also discussed. Therefore, targeting the SCFA transporters to regulate lactate generation and export of BT, as well as applying SCFAs or gut microbiota and natural compounds for chemoprevention may be clinically useful for CRCs treatment. Future research should focus on the combination these therapeutic agents with metabolic inhibitors to effectively target the tumor SCFAs and regulate the bacterial ecology for activation of potent anticancer effect, which may provide more effective application prospect for CRC therapy.
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http://dx.doi.org/10.1002/jcp.28436DOI Listing
August 2019

Inhibitory ASIC2-mediated calcineurin/NFAT against colorectal cancer by triterpenoids extracted from Rhus chinensis Mill.

J Ethnopharmacol 2019 May 14;235:255-267. Epub 2019 Feb 14.

Department of Pharmaceutics, Shanghai Eighth People's Hospital, Jiangsu University, Shanghai 200235, China.

Ethnopharmacological Relevance: Studies have shown that the etiology and pathogenesis of colorectal cancer are closely related to the tumor microenvironment, and the cancer tissue is still in the state of "energy deficit" and has to promote energy generation through high glycolysis. Rhus chinensis Mill is a Chinese herbal medicine used to treat various types of solid tumors in China. Colorectal cancer (CRC) is a heterogeneous disease group caused by abnormal changes in glucose metabolism resulted in lactic acid production, which remodels acidosis.

Aim Of The Study: Although previous studies have shown that the active compounds of Rhus chinensis Mill. can inhibit the proliferation of tumor cells, whether its triterpenoids could effectively regulate glycolysis involved in CRC have not been systematically investigated.

Materials And Methods: In this study, the extraction of triterpenoids extract from Rhus chinensis Mill. was obtained, and cell viability assay, the percentage of apoptosis for CRC cells were counted, and matrigel invasion assay and production of lactic acid and glucose uptake assay was determined. we further examined the expression of the key glycolytic enzymes and acid-sending ion channel (ASIC) family members of SW620 cells, and some key proteins in the glycolytic pathway were further verified.

Results: Notably, triterpenoids (TER) of Rhus chinensis Mill. showed effective anti-proliferative activity and significantly altered protein levels associated with CRC cell survival and glycolysis metabolism. TER could down-regulate the expression of ASIC2, in CRC SW620 cell line. Most importantly, the levels of ASIC2 and calcineurin/nuclear factor of activated T cells (NFAT) were also down-regulated by TER. Furthermore, inhibition of activated the ASIC2-mediated calcineurin/NFAT1 pathway and target gene transcript expression of MMP-2 and MMP-9 in parallel to reduce, and resulted in the reduced invasion ability by TER treatment.

Conclusion: The potential pathways and targets that involved in glycolysis to excert the anti-CRC effects of main compounds in triterpenoids of Rhus chinensis Mill. were predicted by network pharmacology methods. Our findings thus provided rational evidence that inhibition of the ASIC2-induced calcineurin/NFAT pathway by triterpenoids in Rhus chinensis Mill. profoundly suppressed cell growth and invasion in CRC, which target alternative glycolysis in colorectal tumor cells, may be a useful adjuvant therapy in the treatment of colorectal cancer.
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http://dx.doi.org/10.1016/j.jep.2019.02.029DOI Listing
May 2019

Myricetin nanoliposomes induced SIRT3-mediated glycolytic metabolism leading to glioblastoma cell death.

Artif Cells Nanomed Biotechnol 2018 28;46(sup3):S180-S191. Epub 2019 Jan 28.

b Department of Medicine, Jiangsu University , Zhenjiang , China.

As the most aggressive and malignant glioma, glioblastoma multiforme (GBM) abnormally expresses genes that mediate glycolytic metabolism and tumour cell growth. In this study, we investigated myricetin incorporated nanoliposomes and ascertained their prospect in effectively treating cancer via the employment of the GBM cell line DBTRG-05MG. Notably, the myricetin nanoliposomes (MYR-NLs) displayed potent inhibition of proliferation and significantly regulated the levels of proteins related to both glycolytic metabolism and cell survival. Most importantly, SIRT3 and phosphorylated p53 were also down-regulated by MYR-NLs, indicating that the MYR-NLs inhibited GBM cell growth through the SIRT3/p53-mediated PI3K/Akt-ERK and mitochondrial pathways. Our findings thus provide rational evidence that liposomal myricetin targeted at alternative cell death pathways may be a useful adjuvant therapy in glioblastoma treatment.
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http://dx.doi.org/10.1080/21691401.2018.1489825DOI Listing
June 2019

Effects of rosemary (Rosmarinus officinalis L.) extracts and dry ice on the physicochemical stability of omega-3 fatty-acid-fortified surimi-like meat products.

J Sci Food Agric 2019 Jun 1;99(8):3843-3851. Epub 2019 Mar 1.

Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.

Background: Lipid peroxidation entails major quality degradation in omega-3 (ω-3) fatty-acid-fortified surimi-like meat products upon storage. Currently, the use of label-friendly alternatives to synthetic antioxidants is encouraged in the industry. Hence, we aimed to examine the applicability of the hurdle-technology concept, using an 80% (v/v) ethanol solution to obtain rosemary extracts (REs) containing substantial amounts of polyphenol, and dry ice (DI) which can create a cryogenic environment, on the physicochemical stabilities of ω-3 fatty-acid (FA)-fortified meat products after manufacturing and storage periods. The polyphenolic profiles of the REs were also investigated.

Results: Carnosol and rosmarinic acid are major phenolic components in REs. Furthermore, DI addition during the chopping procedure increased (P < 0.05) whiteness values and hardness of products, while total ω-3 and ω-6 FAs were relatively well preserved (P < 0.05) in products with flaxseed oil premixed with RE. During 14-day storage at 4 °C, combined treatment with RE and DI decreased (P < 0.05) thiobarbituric acid reactive substance (TBARS) levels and the centrifugation loss of products. Single or combined treatment with RE and/or DI decreased (P < 0.05) TBARS levels in products after 60 days of storage at -20 °C.

Conclusion: Due to the antioxidant-polyphenol profile of REs and a possible oxygen exclusion of DI treatment under atmospheric pressure during food manufacturing, application of the hurdle-technology concept, using treatment with both RE and DI, can reduce lipid peroxidation and maintain a greater water-holding capacity of ω-3 FA-fortified meat products upon storage. © 2019 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.9606DOI Listing
June 2019

Glucocorticoid receptor regulates expression of microRNA-22 and downstream signaling pathway in apoptosis of pancreatic acinar cells.

World J Gastroenterol 2018 Dec;24(45):5120-5130

Department of Hepatobiliary and Pancreatic Surgery, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), School of Medicine, Zhengzhou University, Zhengzhou 450003, Henan Province, China.

Aim: To elucidate the underlying mechanism that microRNA-22 (miR-22) promotes the apoptosis of rat pancreatic acinar cells (AR42J) and the elements that regulate the expression of miR-22.

Methods: One hundred nanomoles per liter of caerulein (Cae) was administrated to induce the apoptosis of AR42J cells and the apoptosis rate was detected by flow cytometry analysis. An amylase assay kit was used to measure the amylase expression level in the supernatant. Quantitative real-time PCR (qRT-PCR) was adopted to measure miR-22 expression. We used online tools to predict the potential transcription promoter of miR-22 and the binding sites, which was further identified by using luciferase reporter analysis, chromatin immunoprecipitation (ChIP) and ChIP-qPCR assays. Then, a mimic of miR-22, Nr3c1 plasmid encoding the glucocorticoid receptor (GR), and si-Nr3c1 were used to transfect AR42J cells, respectively. The mRNA expression of miR-22, Nr3c1, and Erb-b2 receptor tyrosine kinase 3 (ErbB3) was confirmed by qRT-PCR and the apoptosis rate of AR42J cells was detected by flow cytometry analysis. Western blot was used to detect the expression of ErbB3, GR, PI3k, PI3k-p85α, Akt, p-Akt, Bad, Bax, Bcl-xl, Bcl-2, and cleaved caspase3.

Results: After inducing apoptosis of AR42J cells , the expression of miR-22 was significantly increased by 2.20 ± 0.26 and 4.19 ± 0.54 times, respectively, at 3 h and 6 h in comparison with the control group. As revealed by qRT-PCR assay, the expression of miR-22 was 78.25 ± 6.61 times higher in the miR-22 mimic group relative to the miRNA control group, accompanied with an obviously increased acinar cell apoptosis rate (32.53 ± 1.15 18.07 ± 0.89, = 0.0006). The upregulation of miR-22 could suppress its target gene, ErbB3, and the phosphorylation of PI3k and Akt. Furthermore, we predicted the potential transcription promoter of miR-22 and the binding sites using online tools. Luciferase reporter analysis and site-directed mutagenesis indicated that the binding site (GACAGCCATGTACA) of the GR, which is encoded by the Nr3c1 gene. Downregulation of the expression of GR could upregulate the expression of miR-22, which further promoted the apoptosis of AR42J cells.

Conclusion: GR transcriptionally represses the expression of miR-22, which further promotes the apoptosis of pancreatic acinar cells by downregulating the downstream signaling pathway.
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http://dx.doi.org/10.3748/wjg.v24.i45.5120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288647PMC
December 2018

Space qualified microwave source for cold atom clock operating in orbit.

Rev Sci Instrum 2018 Nov;89(11):113115

Key Laboratory of Quantum Optics, Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, Shanghai 201800, China.

The space cold atom clock (CAC) suffers more degradation of frequency stability from the local oscillator noise compared with fountain clocks operating on the ground because of the larger dead time of the clock cycle. Therefore, low phase noise is required for the microwave source of the space CAC in addition to robustness, compactness, and adaptability to the space environment. This paper presents the design and measurements of a low-phase-noise space qualified microwave source for the cold atom clock experiment in space CAC operating in the Tiangong-2 Chinese space laboratory. At frequencies near the carrier, a phase noise level of 10 × rad/Hz ( is the Fourier frequency) is achieved. This guarantees a frequency stability of 1.4 × 10 ( is the average time in seconds) for the typical space CAC operation cycle.
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http://dx.doi.org/10.1063/1.5048848DOI Listing
November 2018

Strategies for targeting energy metabolism in Kirsten rat sarcoma viral oncogene homolog -mutant colorectal cancer.

J Cell Biochem 2018 Oct 26. Epub 2018 Oct 26.

Department of Medicine, Jiangsu University, Zhenjiang City, Jiangsu Province, China.

Alterations in cellular energy metabolism play critical roles in colorectal cancer (CRC). These alterations, which correlate to KRAS mutations, have been identified as energy metabolism signatures. This review summarizes the relationship between colorectal tumors associated with mutated KRAS and energy metabolism, especially for the deregulated energy metabolism that affects tumor cell proliferation, invasion, and migration. Furthermore, this review will concentrate on the role of metabolic genes, factors and signaling pathways, which are coupled with the primary energy source connected with the KRAS mutation that induces metabolic alterations. Strategies for targeting energy metabolism in mutated KRAS CRC are also introduced. In conclusion, deregulated energy metabolism has a close relationship with KRAS mutations in colorectal tumors. Therefore, selective inhibitors, agents against metabolic targets or KRAS signaling, may be clinically useful for colorectal tumor treatment through a patient-personalized approach.
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http://dx.doi.org/10.1002/jcb.27558DOI Listing
October 2018

Strategies to target energy metabolism in consensus molecular subtype 3 along with Kirsten rat sarcoma viral oncogene homolog mutations for colorectal cancer therapy.

J Cell Physiol 2019 05 20;234(5):5601-5612. Epub 2018 Oct 20.

Department of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.

Alterations in cellular energy metabolism play a critical role in colorectal cancer (CRC), which has been identified as the definition of consensus molecular subtypes (CMSs), and CMS3 tumors exhibit energy metabolism signatures along with Kirsten rat sarcoma viral oncogene homolog (KRAS)-activating mutations. This review summarizes the relationship between CMS3 tumors associated with mutated KRAS and energy metabolism in CRC, especially for the dysregulated energy metabolism that affects tumor cell proliferation, invasion, and migration. Furthermore, this review concentrates on the role of metabolic genes and factors and signaling pathways, which coupled with a primary energy source connected with the CMS3 associated with mutated KRAS, induce metabolic alterations. The strategies to target energy metabolism for the metabolic alterations in mutated KRAS CRC are also introduced. In conclusion, dysregulated energy metabolism has a close relationship with mutated KRAS in CMS3 tumors. Therefore, selective inhibitors or agents against metabolic targets or KRAS signaling may be clinically useful for CMS3 tumor treatment through a personalized approach for patients with cancer.
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http://dx.doi.org/10.1002/jcp.27388DOI Listing
May 2019

New strategies for targeting glucose metabolism-mediated acidosis for colorectal cancer therapy.

J Cell Physiol 2018 01 1;234(1):348-368. Epub 2018 Aug 1.

Department of Medicine, Jiangsu University, Zhenjiang, China.

Colorectal cancer (CRC) is a heterogeneous group of diseases that are the result of abnormal glucose metabolism alterations with high lactate production by pyruvate to lactate conversion, which remodels acidosis and offers an evolutional advantage for tumor cells, even enhancing their aggressive phenotype. This review summarizes recent findings that involve multiple genes, molecules, and downstream signaling in the dysregulated glycolytic pathway, which can allow a tumor to initiate acid byproducts and to progress, thereby resulting in acidosis commonly found in the tumor microenvironment of CRC. Moreover, the relationship between CRC cells and the tumor acidic microenvironment, especially for regulating lactate production and lactate dehydrogenase A levels, is also discussed, as well as comprehensively defining different aspects of glycolytic pathways that affect cancer cell proliferation, invasion, and migration. Furthermore, this review concentrates on glucose metabolism-mediated transduction factors in CRC, which include acid-sensing ion channels, triosephosphate isomerase and key glycolysis-related enzymes that regulate glycolytic metabolites, coupled with the effect on tumor cell glycolysis as well as signaling pathways. In conclusion, glucose metabolism mediated by glycolytic pathways that are integral to tumor acidosis in CRC is demonstrated. Therefore, selective metabolic inhibitors or agents against these targets in glucose metabolism through glycolytic pathways may be clinically useful to regulate the tumor's acidic microenvironment for CRC treatment and to identify specific targets that regulate tumor acidosis through a cancer patient-personalized approach. Furthermore, strategies for modifying the metabolic processes that effectively inhibit cancer cell growth and tumor progression and activate potent anticancer effects may provide more effective antitumor prospects for CRC therapy.
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http://dx.doi.org/10.1002/jcp.26917DOI Listing
January 2018

In-orbit operation of an atomic clock based on laser-cooled Rb atoms.

Nat Commun 2018 07 24;9(1):2760. Epub 2018 Jul 24.

Key Laboratory of Quantum Optics, Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, Shanghai, 201800, China.

Atomic clocks based on laser-cooled atoms are widely used as primary frequency standards. Deploying such cold atom clocks (CACs) in space is foreseen to have many applications. Here we present tests of a CAC operating in space. In orbital microgravity, the atoms are cooled, trapped, launched, and finally detected after being interrogated by a microwave field using the Ramsey method. Perturbing influences from the orbital environment on the atoms such as varying magnetic fields and the passage of the spacecraft through Earth's radiation belt are also controlled and mitigated. With appropriate parameters settings, closed-loop locking of the CAC is realized in orbit and an estimated short-term frequency stability close to 3.0 × 10τ has been attained. The demonstration of the long-term operation of cold atom clock in orbit opens possibility on the applications of space-based cold atom sensors.
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http://dx.doi.org/10.1038/s41467-018-05219-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057979PMC
July 2018

Brain Transport Profiles of Ginsenoside Rb by Glucose Transporter 1: and .

Front Pharmacol 2018 19;9:398. Epub 2018 Apr 19.

Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China.

Ginsenoside Rb (Rb) has been demonstrated its protection for central nervous system and is apparently highly distributed to the brain. The objective of this study was to characterize Rb transport at the blood-brain barrier (BBB) using primary cultured rat brain microvascular endothelial cells (rBMEC), an BBB model. The initial uptake velocity of Rb in rBMEC was temperature- and concentration-dependent, and was significantly reduced by phloretin, an inhibitor of GLUT1 transporter, but was independent of metabolic inhibitor. Furthermore, the transport of Rb into rBMEC was significantly diminished in the presence of natural substrate α-D-glucose, suggesting a facilitated transport of Rb via GLUT1 transporter. The impact of GLUT1 on the distribution of Rb between brain and plasma was studied experimentally in rats. Administration of phloretin (5 mg/kg, i.v.) to normal rats for consecutive 1 week before Rb (10 mg/kg, i.v.) at 0.5, 2, and 6 h did not alter Rb concentrations in plasma, but resulted in significant decreased brain concentrations of Rb compared to in the phloretin-untreated normal rats (489.6 ± 58.3 versus 105.1 ± 15.1 ng/g, 193.8 ± 11.1 versus 84.8 ± 4.1 ng/g, and 114.2 ± 24.0 versus 39.9 ± 4.9 ng/g, respectively). The expression of GLUT1 in the phloretin-treated group by western blotting analysis and experiments was significantly decreased, indicating that the decreased transport of Rb in brain was well related to the down-regulated function and level of GLUT1. Therefore, our and results indicate that the transport of Rb at the BBB is at least partly mediated by GLUT1 transporter.
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http://dx.doi.org/10.3389/fphar.2018.00398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5917093PMC
April 2018

miR-29a up-regulation in AR42J cells contributes to apoptosis via targeting TNFRSF1A gene.

World J Gastroenterol 2016 May;22(20):4881-90

Qiang Fu, Tao Qin, Lin Chen, Chuan-Jiang Liu, Xu Zhang, Yu-Zhu Wang, Ming-Xing Hu, Hao-Yuan Chu, Hong-Wei Zhang, Department of Hepatobiliary Pancreatic Surgery, People's Hospital of Zhengzhou University, School of Medicine, Zhengzhou University, Zhengzhou 450003, Henan Province, China.

Aim: To investigate the expression of miR-29a in rat acute pancreatitis and its functional role in AR42J cell apoptosis.

Methods: Twelve SD rats were divided into a control group and an acute edematous pancreatitis (AEP) group randomly. AEP was induced by intraperitoneal injection of L-arginine (150 mg/kg) in the AEP group and equal volume of 0.9% NaCl was injected in the control group. The apoptosis of acinar cells in pancreatic tissue was determined by TUNEL assay. miRNA chip assay was performed to examine the expression of miRNAs in two groups. Besides, to further explore the role of miR-29a in apoptosis in vitro, recombinant rat TNF-α (50 ng/mL) was administered to treat the rat pancreatic acinar cell line AR42J for inducing AR42J cell apoptosis. Quantitative real-time PCR (qRT-PCR) was adopted to measure miR-29a expression. Then, miRNA mimic, miRNA antisense oligonucleotide (AMO) and control vector were used to transfect AR42J cells. The expression of miR-29a was confirmed by qRT-PCR and the apoptosis rate of AR42J cells was detected by flow cytometry analysis. Western blot was used to detect the expression of activated caspase3. Moreover, we used bioinformatics software and luciferase assay to test whether TNFRSF1A was the target gene of miR-29a. After transfection, qRT-PCR and Western blot was used to detect the expression of TNFRSF1A in AR42J cells after transfection.

Results: The expression of miR-29a was much higher in the AEP group compared with the control group as displayed by the miRNA chip assay. After inducing apoptosis of AR42J cells in vitro, the expression of miR-29a was significantly increased by 1.49 ± 0.04 times in comparison with the control group. As revealed by qRT-PCR assay, the expression of miR-29a was 2.68 ± 0.56 times higher in the miR-29a mimic group relative to the control vector group, accompanied with an obviously increased acinar cell apoptosis rate (42.83 ± 1.25 vs 24.97 ± 0.15, P < 0.05). Moreover, the expression of miR-29a in the miRNA AMO group was 0.46 ± 0.05 times lower than the control vector group, and the cell apoptosis rate was much lower accordingly (17.27 ± 1.36 vs 24.97 ± 0.15, P < 0.05). The results of bioinformatics software and luciferase assay showed that TNFRSF1A might be a target gene of miR-29a. TNFRSF1A expression was up-regulated in the miR-29a mimic group, while the miR-29a AMO group showed the reverse trend.

Conclusion: miR-29a might promote the apoptosis of AR42J cells via up-regulating the expression of its target gene TNFRSF1A.
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http://dx.doi.org/10.3748/wjg.v22.i20.4881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873880PMC
May 2016

Functional role of MicroRNA-19b in acinar cell necrosis in acute necrotizing pancreatitis.

J Huazhong Univ Sci Technolog Med Sci 2016 Apr 13;36(2):221-225. Epub 2016 Apr 13.

Department of Hepatobiliary Pancreatic Surgery, Shandong Qilu Hospital, Shandong University, Jinan, 250000, China.

The expression of microRNA-19b (miR-19b) in acute necrotizing pancreatitis (ANP) and its functional role in acinar cell necrosis of SD rats were investigated. Twelve SD rats were divided into two groups randomly, including control group and ANP group. The rat ANP models were established by intraperitoneal injection of L-arginine (2400 mg/kg body weight), and equal volume of 0.9% NaCl was injected in the control group. MiRNA chip assay was performed to examine the expression of miRNAs in the pancreas in two different groups. Besides, to further explore the role of miR-19b in ANP in vitro, taurolithocholic acid 3-sulfate disodium salt (TLC-S) (200 μmol/L) was administrated to treat the rat pancreatic acinar cell line, AR42J, for establishing the ANP cells model. The quantitative real-time PCR (qRT-PCR) was adopted to measure the miR-19b expression. Moreover, the mimic miRNA, miRNA antisense oligonucleotide (AMO) and control vector were used to transfect AR42J cells, the expression of miR-19b was confirmed by qRT-PCR and the necrotizing rate of AR42J cells was detected with AO/EB method. The expression of miR-19b was significantly higher in ANP group than in control group as displayed by the miRNA chip assay. Furthermore, after inducing necrosis of AR42J cells in vitro, the expression of miR-19b was significantly increased by 2.51±0.14 times in comparison with the control group. As revealed by qRT-PCR assay, the expression of miR-19b was 5.94±0.95 times higher in the mimic miRNA group than in the control vector group, companied with an obviously increased acinar cell necrotizing rate (50.3%±1.5% vs. 39.6%±2.3%, P<0.05). Moreover, the expression of miR-19b in the miRNA AMO group was 0.38±0.15 times lower than in the control vector group, and the cell necrosis rate was much lower accordingly (23.1%±3.3% vs. 39.6%±2.3%, P<0.05). Besides, there was no significant difference between the control vector cells and the cells without treatment (P>0.05). The expression of miR-19b was significantly induced in ANP. In addition, up-regulation of miR-19b could promote the necrosis of pancreatic acinar cells and miR-19b deficiency could decrease the rate of pancreatic acinar cell necrosis.
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http://dx.doi.org/10.1007/s11596-016-1570-2DOI Listing
April 2016

[Distribution and Dynamics of Cropland Soil Organic Carbon in Jianghan Plain: A Case Study of Qianjiang City].

Huan Jing Ke Xue 2015 Sep;36(9):3422-8

Taking an example of Qianjiang City in Jianghan Plain, the distribution and dynamics of soil organic carbon (SOC) in croplands was studied in present study. The cropland included both paddy field and dry land. SOC contents were analyzed by taking soil samples of topsoil (0-20 cm) in 2011 according to land uses and soil types, and then compared with the initial SOC conducted in the period of the second soil survey (1983). The results showed that SOC density and storage in 2011 was 30.50 t . hm-2and 452. 82 x 10(4) t, respectively. During the past 28 years, the cropland SOC density was decreased at a rate of 0. 10 t . (hm2.a)-1, and SOC storage was reduced by 9% with the decreasing rate of 1. 53 t.a-1. SOC density and storage in paddy field was about 1. 6 and 1. 3 times over that in dry land in the two selected periods. However, the dynamics of SOC in paddy field and dry land were quite the opposite. In paddy field, SOC was lost by 16% (52. 83 x 10(4) t), with a decreasing rate of 0. 23 t . (hm2.a)-1; whereas in dry land, SOC was increased by 5% (8. 57 x 10(4) t), with an increasing rate of 0. 05 t . (hm2.a)-1. The loss of SOC in paddy field was mainly resulted from gleyed paddy soil, which suffered a fast decrease of SOC density and accounted for 80% of SOC lost in paddy field. In addition, Hydromorphic paddy soil, accounting for 50% of the area of paddy field, tended to loss another 15% of SOC in paddy field. While in dry land, the minor SOC storage increased was dominantly attributed to grey fluvo aquic soil, which accounted for 96% of the area of dry land. Thus, the dynamics of cropland SOC in Jianghan Plain was dominantly controlled by SOC changes in paddy field. Our findings suggest that effective management should be considered to enhance the capacity of SOC accumulation and sequestration in the low-yield paddy field and the types of soils that are large in area.
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September 2015

Nuciferine downregulates Per-Arnt-Sim kinase expression during its alleviation of lipogenesis and inflammation on oleic acid-induced hepatic steatosis in HepG2 cells.

Front Pharmacol 2015 21;6:238. Epub 2015 Oct 21.

Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine Shanghai, China.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease associated with lipotoxicity, lipid peroxidation, oxidative stress, and inflammation. Nuciferine, an active ingredient extracted from the natural lotus leaf, has been reported to be effective for the prevention and treatment of NAFLD. Per-Arnt-Sim kinase (PASK) is a nutrient responsive protein kinase that regulates lipid and glucose metabolism, mitochondrial respiration, and gene expression. The aim of the present study was to investigate the protective effect of nuciferine against NAFLD and its inhibitory effect on PASK, exploring the possible underlying mechanism of nuciferine-mediated inhibition on NAFLD. Relevant biochemical parameters (lipid accumulation, extent of oxidative stress and release of inflammation cytokines) in oleic acid (OA)-induced HepG2 cells that mimicked steatosis in vitro were measured and compared with the control. It was found that nuciferine and silenced-PASK (siRNA PASK) both inhibited triglyceride (TG) accumulation and was effective in decreasing fatty acid (FFAs). The content of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) were increased respectively by nuciferine and siRNA PASK without increase in glutathione (GSH). Malondialdehyde (MDA) was decreased respectively by nuciferine and siRNA PASK. In addition, nuciferine decreased TNF-a, IL-6 and IL-8 as well as the siRNA PASK group. IL-10 was increased by nuciferine and siRNA PASK respectively. Further investigation revealed that nuciferine and siRNA PASK could respectively regulate the expression of target genes involved in lipogenesis and inflammation, suggesting that nuciferine may be a potential therapeutic treatment for NAFLD. Furthermore, the modulated effect of nuciferine on (OA)-induced HepG2 cells lipogenesis and inflammation, which was accompanied with PASK inhibition, was also consistent with siRNA PASK, implying that PASK might play a role in nuciferine-mediated regulation on NAFLD.
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http://dx.doi.org/10.3389/fphar.2015.00238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612658PMC
November 2015

Incarvine C suppresses proliferation and vasculogenic mimicry of hepatocellular carcinoma cells via targeting ROCK inhibition.

BMC Cancer 2015 Oct 28;15:814. Epub 2015 Oct 28.

Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of medicine, No. 100 Haining Road, Shanghai, 200080, P. R. China.

Background: Studies have described vasculogenic mimicry (VM) as an alternative circulatory system to blood vessels in multiple malignant tumor types, including hepatocellular carcinoma (HCC). In the current study, we aimed to seek novel and more efficient treatment strategies by targeting VM and explore the underlying mechanisms in HCC cells.

Methods: Cell counting kit-8 (CCK-8) assay and colony survival assay were performed to explore the inhibitory effect of incarvine C (IVC) on human cancer cell proliferation. Flow cytometry was performed to analyze the cell cycle distribution after DNA staining and cell apoptosis by the Annexin V-PE and 7-AAD assay. The effect of IVC on Rho-associated, coiled-coil-containing protein kinase (ROCK) was determined by western blotting and stress fiber formation assay. The inhibitory role of IVC on MHCC97H cell VM formation was determined by formation of tubular network structures on Matrigel in vitro, real time-qPCR, confocal microscopy and western blotting techniques.

Results: We explored an anti-metastatic HCC agent, IVC, derived from traditional Chinese medicinal herbs, and found that IVC dose-dependently inhibited the growth of MHCC97H cells. IVC induced MHCC97H cell cycle arrest at G1 transition, which was associated with cyclin-dependent kinase 2 (CDK-2)/cyclin-E1 degradation and p21/p53 up-regulation. In addition, IVC induced apoptotic death of MHCC97H cells. Furthermore, IVC strongly suppressed the phosphorylation of the ROCK substrate myosin phosphatase target subunit-1 (MYPT-1) and ROCK-mediated actin fiber formation. Finally, IVC inhibited cell-dominant tube formation in vitro, which was accompanied with the down-regulation of VM-key factors as detected by real time-qPCR and immunofluorescence.

Conclusions: Taken together, the effective inhibitory effect of IVC on MHCC97H cell proliferation and neovascularization was associated with ROCK inhibition, suggesting that IVC may be a new potential drug candidate for the treatment of HCC.
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http://dx.doi.org/10.1186/s12885-015-1809-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625643PMC
October 2015

Per-Arnt-Sim Kinase (PASK): An Emerging Regulator of Mammalian Glucose and Lipid Metabolism.

Nutrients 2015 Sep 7;7(9):7437-50. Epub 2015 Sep 7.

Department of Clinical Pharmacy, Shanghai General Hospital, School of medicine, Shanghai Jiaotong University, No.100 Haining Road, Shanghai 200025, China.

Per-Arnt-Sim Kinase (PASK) is an evolutionarily-conserved nutrient-responsive protein kinase that regulates lipid and glucose metabolism, mitochondrial respiration, phosphorylation, and gene expression. Recent data suggests that mammalian PAS kinase is involved in glucose metabolism and acts on pancreatic islet α/β cells and glycogen synthase (GS), affecting insulin secretion and blood glucose levels. In addition, PASK knockout mice (PASK-/-) are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet, implying that PASK may be a new target for metabolic syndrome (MetS) treatment as well as the cellular nutrients and energy sensors-adenosine monophosphate (AMP)-activated protein kinase (AMPK) and the targets of rapamycin (m-TOR). In this review, we will briefly summarize the regulation of PASK on mammalian glucose and lipid metabolism and its possible mechanism, and further explore the potential targets for MetS therapy.
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http://dx.doi.org/10.3390/nu7095347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586542PMC
September 2015

ROCK is involved in vasculogenic mimicry formation in hepatocellular carcinoma cell line.

PLoS One 2014 19;9(9):e107661. Epub 2014 Sep 19.

Department of Pharmacy, Shanghai First People's Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.

Ras homolog family member A (RhoA) and Rho-associated coiled coil-containing protein kinases 1 and 2 (ROCK1 and 2) are key regulators of focal adhesion, actomyosin contraction and cell motility. RhoA/ROCK signaling has emerged as an attractive target for the development of new cancer therapeutics. Whether RhoA/ROCK is involved in regulating the formation of tumor cell vasculogenic mimicry (VM) is largely unknown. To confirm this hypothesis, we performed in vitro experiments using hepatocellular carcinoma (HCC) cell lines. Firstly, we demonstrated that HCC cells with higher active RhoA/ROCK expression were prone to form VM channels, as compared with RhoA/ROCK low-expressing cells. Furthermore, Y27632 (a specific inhibitor of ROCK) rather than exoenzyme C3 (a specific inhibitor of RhoA) effectively inhibited the formation of tubular network structures in a dose-dependent manner. To elucidate the possible mechanism of ROCK on VM formation, real-time qPCR, western blot and immunofluorescence were used to detect changes of the key VM-related factors, including VE-cadherin, erythropoietin-producing hepatocellular carcinoma-A2 (EphA2), phosphoinositide 3-kinase (PI3K), matrix metalloproteinase (MMP)14, MMP2, MMP9 and laminin 5γ2-chain (LAMC2), and epithelial-mesenchymal-transition (EMT) markers: E-cadherin and Vimentin. The results showed that all the expression profiles were attenuated by blockage of ROCK. In addition, in vitro cell migration and invasion assays showed that Y27632 inhibited the migration and invasion capacity of HCC cell lines in a dose-dependent manner markedly. These data indicate that ROCK is an important mediator in the formation of tumor cell VM, and suggest that ROCK inhibition may prove useful in the treatment of VM in HCC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0107661PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169566PMC
June 2015

Optimization of storage condition for maintaining long-term viability of nematophagous fungus Esteya vermicola as biocontrol agent against pinewood nematode.

World J Microbiol Biotechnol 2014 Nov 29;30(11):2805-10. Epub 2014 Jul 29.

Department of Food Science and Technology, College of Agriculture and Biotechnology, Chungnam National University, Taejon, 305-764, Republic of Korea,

The fungus, Esteya vermicola has been proposed as biocontrol agent against pine wilting disease caused by Bursaphelenchus xylophilus. In this study, we reported the effects of temperature and different additives on the viability and biocontrol efficacy of E. vermicola formulated by alginate-clay. The viability of the E. vermicola formulation was determined for six consecutive months at temperature ranged from -70 to 25 °C. The fresh conidia without any treatment were used as control. Under the optimal storage conditions with E. vermicola alginate-clay formulation, the results suggested that E. vermicola alginate-clay formulation with a long shelf life could be a non-vacuum-packed formulation that contains 2 % sodium alginate and 5 % clay at 4 °C. Three conidial formulations prepared with additives of 15 % glycerol, 0.5 % yeast extract and 0.5 % herbal extraction, respectively significantly improved the shelf life. In addition, these tested formulations retained the same biocontrol efficacy as the fresh conidial against pinewood nematode. This study provided a tractable and low-cost method to preserve the shelf life of E. vermicola.
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http://dx.doi.org/10.1007/s11274-014-1704-2DOI Listing
November 2014

Expressions of miR-22 and miR-135a in acute pancreatitis.

J Huazhong Univ Sci Technolog Med Sci 2014 Apr 8;34(2):225-233. Epub 2014 Apr 8.

Department of Hepatobiliary Pancreatic Surgery, People's Hospital of Zhengzhou University, School of Medicine, Zhengzhou University, Zhengzhou, 450003, China.

This study examined the expressions of miR-22 and miR-135a in rats with acute edematous pancreatitis (AEP) and their target genes in order to shed light on the involvement of miR-22 and miR-135a in the pathogenesis of acute pancreatitis (AP). The in vivo model of AEP was established by introperitoneal injection of L-arginine (150 mg/kg) in rats. The miRNA microarray analysis was used to detect the differential expression of miRNAs in pancreatic tissue in AEP and normal rats. The in vitro AEP model was established by inducing the rat pancreatic acinar cell line (AR42J) with 50 ng/mL recombinant rat TNF-α. Real-time quantitative RT-PCR was employed to detect the expression of miR-22 and miR-135a in AR42J cells. Lentiviruses carrying the miRNA mimic and anti-miRNA oligonucleotide (AMO) of miR-22 and miR-135a were transfected into the AR42J cells. The AR42J cells transfected with vehicle served as control. Western blotting was used to measure the expression of activated caspase3 and flow cytometry analysis to detect the apoptosis of AR42J cells. Targets of miR-22 and miR-135a were predicted by using TargetScan, miRanda, and TarBase. Luciferase reporter assay and quantitative real-time RT-PCR were performed to confirm whether ErbB3 and Ptk2 were the target gene of miR-22 and miR-135a, respectively. The results showed that the expression levels of miR-22 and miR-135a were obviously increased in AEP group compared with the control group in in-vivo and in-vitro models. The expression levels of miR-22 and miR-135a were elevated conspicuously and the expression levels of their target genes were reduced significantly in AR42J cells transfected with lentiviruses carrying the miRNA mimic. The apoptosis rate was much higher in the TNF-α-induced cells than in non-treated cells. The AR42J cells transfected with miRNA AMOs expressed lower level of miR-22 and miR-135a and had lower apoptosis rate, but the expression levels of ErbB3 and Ptk2 were increased obviously. It was concluded that the expression levels of miR-22 and miR-135a were elevated in AEP. Up-regulating the expression of miR-22 and miR-135a may promote the apoptosis of pancreatic acinar cells by repressing ErbB3 and Ptk2 expression in AEP.
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http://dx.doi.org/10.1007/s11596-014-1263-7DOI Listing
April 2014
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